Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment option for several hematologic malignancies and other congenital diseases including immunodeficiencies or hemoglobinopathies. When the first allografts were performed, most patients given bone marrow (BM) from donors other than homozygotic twins developed skin, gut, and/or liver injury. This disease was defined by Billingham in 1966 as graft-versushost disease (GVHD). He also described 3 standard tenets for GVHD pathophysiology, which remain valid today even with rapid advances in this area: (1) donor graft must have immune-competent cells, (2) recipient must be incapable of rejecting the graft, and (3) recipient must have tissue antigens not present in the donor.

To read the full article in PDF:

Click here

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment option for several hematologic malignancies and other congenital diseases including immunodeficiencies or hemoglobinopathies. When the first allografts were performed, most patients given bone marrow (BM) from donors other than homozygotic twins developed skin, gut, and/or liver injury. This disease was defined by Billingham in 1966 as graft-versushost disease (GVHD). He also described 3 standard tenets for GVHD pathophysiology, which remain valid today even with rapid advances in this area: (1) donor graft must have immune-competent cells, (2) recipient must be incapable of rejecting the graft, and (3) recipient must have tissue antigens not present in the donor.

To read the full article in PDF:

Click here

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment option for several hematologic malignancies and other congenital diseases including immunodeficiencies or hemoglobinopathies. When the first allografts were performed, most patients given bone marrow (BM) from donors other than homozygotic twins developed skin, gut, and/or liver injury. This disease was defined by Billingham in 1966 as graft-versushost disease (GVHD). He also described 3 standard tenets for GVHD pathophysiology, which remain valid today even with rapid advances in this area: (1) donor graft must have immune-competent cells, (2) recipient must be incapable of rejecting the graft, and (3) recipient must have tissue antigens not present in the donor.

To read the full article in PDF:

Click here

You have spent several days checking on a patient hospitalized for an acute exacerbation of heart failure. You have straightened out her medications and diet and discussed a plan for follow-up with the patient and a family member, and now she is being wheeled out the door. What happens to her next?

Too often, not your desired plan. If she is going home, maybe she understands what she needs to do, maybe not. Maybe she will get your prescriptions filled and take the medications as directed, maybe not. If she is going to a nursing home, maybe the physician covering the nursing home will get your plan, maybe not. There is a good chance she will be back in the emergency room soon, all because of a poor transition of care.

Transitions of care are changes in the level, location, or providers of care as patients move within the health care system. These can be critical junctures in patients’ lives, and if poorly executed can result in many adverse effects—including rehospitalization.¹

Although high rehospitalization rates gained national attention in 2009 after a analysis of Medicare data,² health care providers have known about the lack of coordinated care transitions for more than 50 years.³ Despite some progress, improving care transitions remains a national challenge. As the health system evolves from a fee-for-service financial model to payment-for-value,⁴ it is especially important that health care providers improve care for patients by optimizing care transitions.

In this article, we summarize the factors contributing to poor care transitions, highlight programs that improve them, and discuss strategies for successful transitions.

TRANSITION PROBLEMS ARE COMMON

Transitions of care occur when patients move to short-term and long-term acute care hospitals, skilled nursing facilities, primary and specialty care offices, community health centers, rehabilitation facilities, home health agencies, hospice, and their own homes.⁵ Problems can arise at any of these transitions, but the risk is especially high when patients leave the hospital to receive care in another setting or at home.

In the past decade, one in five Medicare patients was rehospitalized within 30 days of discharge from the hospital,² and up to 25% were rehospitalized after being discharged to a skilled nursing facility.⁶ Some diagnoses (eg, sickle cell anemia, gangrene) and procedures (eg, kidney transplantation, ileostomy) are associated with readmission rates of nearly one in three.^7,8

The desire of policymakers to “bend the cost curve” of health care has led to efforts to enhance care coordination by improving transitions between care venues. Through the Patient Protection and Affordable Care Act, a number of federal initiatives are promoting strategies to improve care transitions and prevent readmissions after hospital discharge.

The Hospital Readmission Reduction Program⁹ drives much of this effort. In fiscal year 2013 (beginning October 1, 2012), more than 2,000 hospitals incurred financial penalties of up to 1% of total Medicare diagnosis-related group payments (about $280 million the first year) for excess readmissions.¹⁰ The penalty’s maximum rose to 2% in fiscal year 2014 and could increase to 3% in 2015. The total penalty for 2014 is projected to be $227 million, with 2,225 hospitals affected.¹¹

The Centers for Medicare and Medicaid Innovation has committed hundreds of millions of dollars to Community-based Care Transitions Programs¹² and more than $200 million to Hospital Engagement Networks¹³ to carry out the goals of the Partnership for Patients,¹⁴ aiming to reduce rehospitalizations and other adverse events.

At first, despite these efforts, readmission rates did not appear to change substantially.¹⁵ However, the Centers for Medicare and Medicaid Services reported that hospital readmission rates for Medicare fee-for-service beneficiaries declined in 2012 to 18.4%,¹⁶ although some believe that the reduction is related to an increase in the number of patients admitted for observation in recent years.¹⁷

TRANSITIONS ARE OFTEN POORLY COORDINATED

Although some readmissions are unavoidable—resulting from the inevitable progression of disease or worsening of chronic conditions¹⁸—they may also result from a fumbled transition between care settings. Our current system of care transition has serious deficiencies that endanger patients. Areas that need improvement include communication between providers, patient education about medications and treatments, monitoring of medication adherence and complications, follow-up of pending tests and procedures after discharge, and outpatient follow-up soon after discharge.^19–21

Traditional health care does not have dependable mechanisms for coordinating care across settings; we are all ensconced in “silos” that generally keep the focus within individual venues.²² Lack of coordination blurs the lines of responsibility for patients in the period between discharge from one location and admission to another, leaving them confused about whom to contact for care, especially if symptoms worsen.^23,24

Gaps in coordination are not surprising, given the complexity of the US health care system and the often remarkable number of physicians caring for an individual patient.⁵ Medicare beneficiaries see an average of two primary care physicians and five specialists during a 2-year period; patients with chronic conditions may see up to 16 physicians in 1 year.²⁵ Coordinating care between so many providers in different settings, combined with possible patient factors such as disadvantaged socioeconomic status, lack of caregiver support, and inadequate health literacy, provides many opportunities for failures.

Research has identified several root causes behind most failed care transitions:

Poor provider communication

Multiple studies associate adverse events after discharge with a lack of timely communication between hospital and outpatient providers.²⁶ One study estimated that 80% of serious medical errors involve miscommunication during the hand-off between medical providers.²⁷ Discharge summaries often lack important information such as test results, hospital course, discharge medications, patient counseling, and follow-up plans. Most adverse drug events after hospital discharge result directly from breakdown in communication between hospital staff and patients or primary care physicians.²⁸ Approximately 40% of patients have test results pending at the time of discharge and 10% of these require some action; yet outpatient physicians and patients are often unaware of them.²¹

Ineffective patient and caregiver education

The Institute of Medicine report, Crossing the Quality Chasm: A New Health System for the 21st Century,²⁹ noted that patients leaving one setting for another receive little information on how to care for themselves, when to resume activities, what medication side effects to watch out for, and how to get answers to questions. Of particular concern is that patients and caregivers are sometimes omitted from transition planning and often must suddenly assume new self-care responsibilities upon going home that hospital staff managed before discharge. Too often, patients are discharged with inadequate understanding of their medical condition, self-care plan,^23,24 and who should manage their care.³⁰

Up to 36% of adults in the United States have inadequate health literacy (defined as the inability to understand basic health information needed to make appropriate decisions), hindering patient education efforts.^31–33 Even if they understand, patients and their caregivers must be engaged or “activated” (ie, able and willing to manage one’s health) if we expect them to adhere to appropriate care and behaviors. A review found direct correlations between patient activation and healthy behavior, better health outcomes (eg, achieving normal hemoglobin A_1c and cholesterol levels), and better care experiences.³⁴ This review also noted that multiple studies have documented improved activation scores as a result of specific interventions.

No follow-up with primary care providers

The risk of hospital readmission is significantly lower for patients with chronic obstructive pulmonary disease or heart failure who receive follow-up within 7 days of discharge.^35–38 Of Medicare beneficiaries readmitted to the hospital within 30 days of discharge in 2003–2004, half had no contact with an outpatient physician in the interval between their discharge and their readmission,² and one in three adult patients discharged from a hospital to the community does not see a physician within 30 days of discharge.³⁹ The dearth of primary care providers in many communities can make follow-up care difficult to coordinate.

Failure to address chronic conditions

Analyses of national data sets reveal that patients are commonly rehospitalized for conditions unrelated to their initial hospitalization. According to the Center for Studying Health System Change, more than a quarter of readmissions in the 30 days after discharge are for conditions unrelated to those identified in the index admission, the proportion rising to more than one-third at 1 year.³⁹ Among Medicare beneficiaries readmitted within 30 days of discharge, the proportion readmitted for the same condition was just 35% after hospitalization for heart failure, 10% after hospitalization for acute myocardial infarction, and 22% after hospitalization for pneumonia.⁴⁰

Lack of community support

Multiple social and environmental factors contribute to adverse postdischarge events.^41–43 For socioeconomically disadvantaged patients, care-transition issues are compounded by insufficient access to outpatient care, lack of social support, and lack of transportation. Some studies indicate that between 40% to 50% of readmissions are linked to social problems and inadequate access to community resources.^44–47 Psychosocial issues such as limited health literacy, poor self-management skills, inadequate social support, and living alone are associated with adverse outcomes, including readmission and death.^48,49 Such factors may help explain high levels of “no-shows” to outpatient follow-up visits.

NATIONAL MODELS OF BEST PRACTICES

Efforts to reduce readmissions have traditionally focused on hospitals, but experts now recognize that multiple factors influence readmissions and must be comprehensively addressed. Several evidence-based models seek to improve patient outcomes with interventions aimed at care transitions:

Project BOOST

Project BOOST (Better Outcomes by Optimizing Safe Transitions)⁵⁰ is a national initiative developed by the Society of Hospital Medicine to standardize and optimize the care of patients discharged from hospital to home. The program includes evidence-based clinical interventions that can easily be adopted by any hospital. Interventions are aimed at:

• Identifying patients at high risk on admission
• Targeting risk-specific situations
• Improving information flow between inpatient and outpatient providers
• Improving patient and caregiver education by using the teach-back method
• Achieving timely follow-up after discharge.

The program includes a year of technical support provided by a physician mentor.

Preliminary results from pilot sites showed a 14% reduction in 30-day readmission rates in units using BOOST compared with control units in the same hospital.⁵¹ Mentored implementation was recognized by the Joint Commission and the National Quality Forum with the 2011 John M. Eisenberg Award for Innovation in Patient Safety and Quality.⁵²

Project RED

Project RED (Re-Engineered Discharge)⁵³ evolved from efforts by Dr. Brian Jack and colleagues to re-engineer the hospital workflow process to improve patient safety and reduce rehospitalization rates at Boston Medical Center. The intervention has 12 mutually reinforcing components aimed at improving the discharge process.

In a randomized controlled trial, Project RED led to a 30% decrease in emergency department visits and readmissions within 30 days of discharge from a general medical service of an urban academic medical center.⁵⁴ This study excluded patients admitted from a skilled nursing facility or discharged to one, but a recent study demonstrated that Project RED also led to a lower rate of hospital admission within 30 days of discharge from a skilled nursing facility.⁵⁵

The STAAR initiative

The STAAR initiative (State Action on Avoidable Re-hospitalizations)⁵⁶ was launched in 2009 by the Institute for Healthcare Improvement with the goal of reducing avoidable readmissions in the states of Massachusetts, Michigan, and Washington. Hospital teams focus on improving:

• Assessment of needs after hospital discharge
• Teaching and learning
• Real-time hand-off communication
• Timely follow-up after hospital discharge.

As yet, no published studies other than case reports show a benefit from STAAR.⁵⁷

The Care Transitions Program

The Care Transitions Program,⁵⁸ under the leadership of Dr. Eric Coleman, aims to empower patients and caregivers, who meet with a “transition coach.” The program provides assistance with medication reconciliation and self-management, a patient-centered record owned and maintained by the patient to facilitate cross-site information transfer, timely outpatient follow-up with primary or specialty care, a list of red flags to indicate a worsening condition, and instructions on proper responses.

A randomized controlled trial of the program demonstrated a reduction in hospital readmissions at 30, 90, and 180 days, and lower hospital costs at 90 and 180 days.⁵⁹ This approach also proved effective in a real-world setting.⁶⁰

The Transitional Care Model

Developed by Dr. Mary Naylor and colleagues, the Transitional Care Model⁶¹ also aims at patient and family empowerment, focusing on patients’ stated goals and priorities and ensuring patient engagement. In the program, a transitional care nurse has the job of enhancing patient and caregiver understanding, facilitating patient self-management, and overseeing medication management and transitional care.

A randomized controlled trial demonstrated improved outcomes after hospital discharge for elderly patients with complex medical illnesses, with overall reductions in medical costs through preventing or delaying rehospitalization.⁶² A subsequent real-world study validated this approach.⁶³

The Bridge Model

The Illinois Transitional Care Consortium’s Bridge Model⁶⁴ is for older patients discharged home after hospitalization. It is led by social workers (“bridge care coordinators”) who address barriers to implementing the discharge plan, coordinate resources, and intervene at three points: before discharge, 2 days after discharge, and 30 days after discharge.

An initial study showed no impact on the 30-day rehospitalization rate,⁶⁵ but larger studies are under way with a modified version.

Guided Care

Developed at the Johns Hopkins Bloomberg School of Public Health, Guided Care⁶⁶ involves nurses who work in partnership with physicians and others in primary care to provide patient-centered, cost-effective care to patients with multiple chronic conditions. Nurses conduct in-home assessments, facilitate care planning, promote patient self-management, monitor conditions, coordinate the efforts of all care professionals, and facilitate access to community resources.

A cluster-randomized controlled trial found that this program had mixed results, reducing the use of home health care but having little effect on the use of other health services in the short run. However, in the subgroup of patients covered by Kaiser-Permanente, those who were randomized to the program accrued, on average, 52% fewer skilled nursing facility days, 47% fewer skilled nursing facility admissions, 49% fewer hospital readmissions, and 17% fewer emergency department visits.⁶⁷

The GRACE model

The GRACE model (Geriatric Resources for Assessment and Care of Elders)⁶⁸ was developed to improve the quality of geriatric care, reduce excess health care use, and prevent long-term nursing home placement. Each patient is assigned a support team consisting of a nurse practitioner and a social worker who make home visits, coordinate health care and community services, and develop an individualized care plan.

In one study,⁶⁹ GRACE reduced hospital admission rates for participants at high risk of hospitalization by 12% in the first year of the program and 44% in the second year. GRACE participants also reported higher quality of life compared with the control group.⁶⁹

INTERACT tools

Led by Dr. Joseph Ouslander, INTERACT (Interventions to Reduce Acute Care Transfers)⁷⁰ is a quality-improvement initiative for skilled nursing facilities, designed to facilitate the early identification, evaluation, documentation, and communication of changes in the status of residents. Visitors to its website can download a set of tools and strategies to help them manage conditions before they become serious enough to require a hospital transfer. The tools assist in promoting important communication among providers and enhancing advance-care planning.

A 6-month study in 25 nursing homes showed a 17% reduction in self-reported hospital admissions with this program compared with the same period the previous year.⁷¹

Additional home-based care interventions

Additional innovations are under way in home-based care.

The Home Health Quality Improvement National Campaign is a patient-centered movement to improve the quality of care received by patients residing at home.⁷² Through its Best Practices Intervention Packages, it offers evidence-based educational tools, resources, and interventions for reducing avoidable hospitalizations, improving medication management, and coordinating transitional care.

The Center for Medicare and Medicaid Innovation Independence at Home Demonstration⁷³ is testing whether home-based comprehensive primary care can improve care and reduce hospitalizations for Medicare beneficiaries with multiple chronic conditions.

NO SINGLE INTERVENTION: MULTIPLE STRATEGIES NEEDED

A 2011 review found no single intervention that regularly reduced the 30-day risk of re-hospitalization.⁷⁴ However, other studies have shown that multifaceted interventions can reduce 30-day readmission rates. Randomized controlled trials in short-stay, acute care hospitals indicate that improvement in the following areas can directly reduce hospital readmission rates:

• Comprehensive planning and risk assessment throughout hospitalization
• Quality of care during the initial admission
• Communication with patients, their caregivers, and their clinicians
• Patient education
• Predischarge assessment
• Coordination of care after discharge.

In randomized trials, successful programs reduced the 30-day readmission rates by 20% to 40%,^{54,62,75–79} and a 2011 meta-analysis of randomized clinical trials found evidence that interventions associated with discharge planning helped to reduce readmission rates.⁸⁰

Methods developed by the national care transition models described above can help hospitals optimize patient transitions (Table 1). Although every model has its unique attributes, they have several strategies in common:

Engage a team of key stakeholders that may include patients and caregivers, hospital staff (physicians, nurses, case managers, social workers, and pharmacists), community physicians (primary care, medical homes, and specialists), advance practice providers (physician assistants and nurse practitioners), and postacute care facilities and services (skilled nursing facilities, home health agencies, assisted living residences, hospice, and rehabilitation facilities).

Develop a comprehensive transition plan throughout hospitalization that includes attention to factors that may affect self-care, such as health literacy, chronic conditions, medications, and social support.

Enhance medication reconciliation and management. Obtain the best possible medication history on admission, and ensure that patients understand changes in their medications, how to take each medicine correctly, and important side effects.

Institute daily interdisciplinary communication and care coordination by everyone on the health care team with an emphasis on the care plan, discharge planning, and safety issues.⁸¹

Standardize transition plans, procedures and forms. All discharging physicians should use a standard discharge summary template that includes pertinent diagnoses, active issues, a reconciled medication list with changes highlighted, results from important tests and consultations, pending test results, planned follow-up and required services, warning signs of a worsening condition, and actions needed if a problem arises.

Always send discharge summaries directly to the patient’s primary care physician or next care setting at the time of discharge.

Give the patient a discharge plan that is easy to understand. Enhance patient and family education using health literacy standards⁸² and interactive methods such as teach-back,⁸³ in which patients demonstrate comprehension and skills required for self-care immediately after being taught. Such tools actively teach patients and caregivers to follow a care plan, including managing medications.

Follow up and coordinate support in a timely manner after a patient leaves the care setting. Follow-up visits should be arranged before discharge. Within 1 to 3 days after discharge, the patient should be called or visited by a case manager, social worker, nurse, or other health care provider.

CHALLENGES TO IMPROVING TRANSITIONS

Although several models demonstrated significant reductions of hospital readmissions in trials, challenges remain. Studies do not identify which features of the models are necessary or sufficient, or how applicable they are to different hospital and patient characteristics. A 2012 analysis⁸⁴ of a program designed to reduce readmissions in three states identified key obstacles to successfully improving care transitions:

Collaborative relationships across settings are critical, but very difficult to achieve. It takes time to develop the relationships and trust among providers, and little incentive exists for skilled nursing facilities and physicians outside the hospital to engage in the process.

Infrastructure is lacking, as is experience to implement quality improvements.

We lack proof that models work on a large scale. Confusion exists about which readmissions are preventable and which are not. More evidence is needed to help guide hospitals’ efforts to improve transitions of care and reduce readmissions.

You have spent several days checking on a patient hospitalized for an acute exacerbation of heart failure. You have straightened out her medications and diet and discussed a plan for follow-up with the patient and a family member, and now she is being wheeled out the door. What happens to her next?

Too often, not your desired plan. If she is going home, maybe she understands what she needs to do, maybe not. Maybe she will get your prescriptions filled and take the medications as directed, maybe not. If she is going to a nursing home, maybe the physician covering the nursing home will get your plan, maybe not. There is a good chance she will be back in the emergency room soon, all because of a poor transition of care.

Transitions of care are changes in the level, location, or providers of care as patients move within the health care system. These can be critical junctures in patients’ lives, and if poorly executed can result in many adverse effects—including rehospitalization.¹

Although high rehospitalization rates gained national attention in 2009 after a analysis of Medicare data,² health care providers have known about the lack of coordinated care transitions for more than 50 years.³ Despite some progress, improving care transitions remains a national challenge. As the health system evolves from a fee-for-service financial model to payment-for-value,⁴ it is especially important that health care providers improve care for patients by optimizing care transitions.

In this article, we summarize the factors contributing to poor care transitions, highlight programs that improve them, and discuss strategies for successful transitions.

TRANSITION PROBLEMS ARE COMMON

Transitions of care occur when patients move to short-term and long-term acute care hospitals, skilled nursing facilities, primary and specialty care offices, community health centers, rehabilitation facilities, home health agencies, hospice, and their own homes.⁵ Problems can arise at any of these transitions, but the risk is especially high when patients leave the hospital to receive care in another setting or at home.

In the past decade, one in five Medicare patients was rehospitalized within 30 days of discharge from the hospital,² and up to 25% were rehospitalized after being discharged to a skilled nursing facility.⁶ Some diagnoses (eg, sickle cell anemia, gangrene) and procedures (eg, kidney transplantation, ileostomy) are associated with readmission rates of nearly one in three.^7,8

The desire of policymakers to “bend the cost curve” of health care has led to efforts to enhance care coordination by improving transitions between care venues. Through the Patient Protection and Affordable Care Act, a number of federal initiatives are promoting strategies to improve care transitions and prevent readmissions after hospital discharge.

The Hospital Readmission Reduction Program⁹ drives much of this effort. In fiscal year 2013 (beginning October 1, 2012), more than 2,000 hospitals incurred financial penalties of up to 1% of total Medicare diagnosis-related group payments (about $280 million the first year) for excess readmissions.¹⁰ The penalty’s maximum rose to 2% in fiscal year 2014 and could increase to 3% in 2015. The total penalty for 2014 is projected to be $227 million, with 2,225 hospitals affected.¹¹

The Centers for Medicare and Medicaid Innovation has committed hundreds of millions of dollars to Community-based Care Transitions Programs¹² and more than $200 million to Hospital Engagement Networks¹³ to carry out the goals of the Partnership for Patients,¹⁴ aiming to reduce rehospitalizations and other adverse events.

At first, despite these efforts, readmission rates did not appear to change substantially.¹⁵ However, the Centers for Medicare and Medicaid Services reported that hospital readmission rates for Medicare fee-for-service beneficiaries declined in 2012 to 18.4%,¹⁶ although some believe that the reduction is related to an increase in the number of patients admitted for observation in recent years.¹⁷

TRANSITIONS ARE OFTEN POORLY COORDINATED

Although some readmissions are unavoidable—resulting from the inevitable progression of disease or worsening of chronic conditions¹⁸—they may also result from a fumbled transition between care settings. Our current system of care transition has serious deficiencies that endanger patients. Areas that need improvement include communication between providers, patient education about medications and treatments, monitoring of medication adherence and complications, follow-up of pending tests and procedures after discharge, and outpatient follow-up soon after discharge.^19–21

Traditional health care does not have dependable mechanisms for coordinating care across settings; we are all ensconced in “silos” that generally keep the focus within individual venues.²² Lack of coordination blurs the lines of responsibility for patients in the period between discharge from one location and admission to another, leaving them confused about whom to contact for care, especially if symptoms worsen.^23,24

Gaps in coordination are not surprising, given the complexity of the US health care system and the often remarkable number of physicians caring for an individual patient.⁵ Medicare beneficiaries see an average of two primary care physicians and five specialists during a 2-year period; patients with chronic conditions may see up to 16 physicians in 1 year.²⁵ Coordinating care between so many providers in different settings, combined with possible patient factors such as disadvantaged socioeconomic status, lack of caregiver support, and inadequate health literacy, provides many opportunities for failures.

Research has identified several root causes behind most failed care transitions:

Poor provider communication

Multiple studies associate adverse events after discharge with a lack of timely communication between hospital and outpatient providers.²⁶ One study estimated that 80% of serious medical errors involve miscommunication during the hand-off between medical providers.²⁷ Discharge summaries often lack important information such as test results, hospital course, discharge medications, patient counseling, and follow-up plans. Most adverse drug events after hospital discharge result directly from breakdown in communication between hospital staff and patients or primary care physicians.²⁸ Approximately 40% of patients have test results pending at the time of discharge and 10% of these require some action; yet outpatient physicians and patients are often unaware of them.²¹

Ineffective patient and caregiver education

The Institute of Medicine report, Crossing the Quality Chasm: A New Health System for the 21st Century,²⁹ noted that patients leaving one setting for another receive little information on how to care for themselves, when to resume activities, what medication side effects to watch out for, and how to get answers to questions. Of particular concern is that patients and caregivers are sometimes omitted from transition planning and often must suddenly assume new self-care responsibilities upon going home that hospital staff managed before discharge. Too often, patients are discharged with inadequate understanding of their medical condition, self-care plan,^23,24 and who should manage their care.³⁰

Up to 36% of adults in the United States have inadequate health literacy (defined as the inability to understand basic health information needed to make appropriate decisions), hindering patient education efforts.^31–33 Even if they understand, patients and their caregivers must be engaged or “activated” (ie, able and willing to manage one’s health) if we expect them to adhere to appropriate care and behaviors. A review found direct correlations between patient activation and healthy behavior, better health outcomes (eg, achieving normal hemoglobin A_1c and cholesterol levels), and better care experiences.³⁴ This review also noted that multiple studies have documented improved activation scores as a result of specific interventions.

No follow-up with primary care providers

The risk of hospital readmission is significantly lower for patients with chronic obstructive pulmonary disease or heart failure who receive follow-up within 7 days of discharge.^35–38 Of Medicare beneficiaries readmitted to the hospital within 30 days of discharge in 2003–2004, half had no contact with an outpatient physician in the interval between their discharge and their readmission,² and one in three adult patients discharged from a hospital to the community does not see a physician within 30 days of discharge.³⁹ The dearth of primary care providers in many communities can make follow-up care difficult to coordinate.

Failure to address chronic conditions

Analyses of national data sets reveal that patients are commonly rehospitalized for conditions unrelated to their initial hospitalization. According to the Center for Studying Health System Change, more than a quarter of readmissions in the 30 days after discharge are for conditions unrelated to those identified in the index admission, the proportion rising to more than one-third at 1 year.³⁹ Among Medicare beneficiaries readmitted within 30 days of discharge, the proportion readmitted for the same condition was just 35% after hospitalization for heart failure, 10% after hospitalization for acute myocardial infarction, and 22% after hospitalization for pneumonia.⁴⁰

Lack of community support

Multiple social and environmental factors contribute to adverse postdischarge events.^41–43 For socioeconomically disadvantaged patients, care-transition issues are compounded by insufficient access to outpatient care, lack of social support, and lack of transportation. Some studies indicate that between 40% to 50% of readmissions are linked to social problems and inadequate access to community resources.^44–47 Psychosocial issues such as limited health literacy, poor self-management skills, inadequate social support, and living alone are associated with adverse outcomes, including readmission and death.^48,49 Such factors may help explain high levels of “no-shows” to outpatient follow-up visits.

NATIONAL MODELS OF BEST PRACTICES

Efforts to reduce readmissions have traditionally focused on hospitals, but experts now recognize that multiple factors influence readmissions and must be comprehensively addressed. Several evidence-based models seek to improve patient outcomes with interventions aimed at care transitions:

Project BOOST

Project BOOST (Better Outcomes by Optimizing Safe Transitions)⁵⁰ is a national initiative developed by the Society of Hospital Medicine to standardize and optimize the care of patients discharged from hospital to home. The program includes evidence-based clinical interventions that can easily be adopted by any hospital. Interventions are aimed at:

• Identifying patients at high risk on admission
• Targeting risk-specific situations
• Improving information flow between inpatient and outpatient providers
• Improving patient and caregiver education by using the teach-back method
• Achieving timely follow-up after discharge.

The program includes a year of technical support provided by a physician mentor.

Preliminary results from pilot sites showed a 14% reduction in 30-day readmission rates in units using BOOST compared with control units in the same hospital.⁵¹ Mentored implementation was recognized by the Joint Commission and the National Quality Forum with the 2011 John M. Eisenberg Award for Innovation in Patient Safety and Quality.⁵²

Project RED

Project RED (Re-Engineered Discharge)⁵³ evolved from efforts by Dr. Brian Jack and colleagues to re-engineer the hospital workflow process to improve patient safety and reduce rehospitalization rates at Boston Medical Center. The intervention has 12 mutually reinforcing components aimed at improving the discharge process.

In a randomized controlled trial, Project RED led to a 30% decrease in emergency department visits and readmissions within 30 days of discharge from a general medical service of an urban academic medical center.⁵⁴ This study excluded patients admitted from a skilled nursing facility or discharged to one, but a recent study demonstrated that Project RED also led to a lower rate of hospital admission within 30 days of discharge from a skilled nursing facility.⁵⁵

The STAAR initiative

The STAAR initiative (State Action on Avoidable Re-hospitalizations)⁵⁶ was launched in 2009 by the Institute for Healthcare Improvement with the goal of reducing avoidable readmissions in the states of Massachusetts, Michigan, and Washington. Hospital teams focus on improving:

• Assessment of needs after hospital discharge
• Teaching and learning
• Real-time hand-off communication
• Timely follow-up after hospital discharge.

As yet, no published studies other than case reports show a benefit from STAAR.⁵⁷

The Care Transitions Program

The Care Transitions Program,⁵⁸ under the leadership of Dr. Eric Coleman, aims to empower patients and caregivers, who meet with a “transition coach.” The program provides assistance with medication reconciliation and self-management, a patient-centered record owned and maintained by the patient to facilitate cross-site information transfer, timely outpatient follow-up with primary or specialty care, a list of red flags to indicate a worsening condition, and instructions on proper responses.

A randomized controlled trial of the program demonstrated a reduction in hospital readmissions at 30, 90, and 180 days, and lower hospital costs at 90 and 180 days.⁵⁹ This approach also proved effective in a real-world setting.⁶⁰

The Transitional Care Model

Developed by Dr. Mary Naylor and colleagues, the Transitional Care Model⁶¹ also aims at patient and family empowerment, focusing on patients’ stated goals and priorities and ensuring patient engagement. In the program, a transitional care nurse has the job of enhancing patient and caregiver understanding, facilitating patient self-management, and overseeing medication management and transitional care.

A randomized controlled trial demonstrated improved outcomes after hospital discharge for elderly patients with complex medical illnesses, with overall reductions in medical costs through preventing or delaying rehospitalization.⁶² A subsequent real-world study validated this approach.⁶³

The Bridge Model

The Illinois Transitional Care Consortium’s Bridge Model⁶⁴ is for older patients discharged home after hospitalization. It is led by social workers (“bridge care coordinators”) who address barriers to implementing the discharge plan, coordinate resources, and intervene at three points: before discharge, 2 days after discharge, and 30 days after discharge.

An initial study showed no impact on the 30-day rehospitalization rate,⁶⁵ but larger studies are under way with a modified version.

Guided Care

Developed at the Johns Hopkins Bloomberg School of Public Health, Guided Care⁶⁶ involves nurses who work in partnership with physicians and others in primary care to provide patient-centered, cost-effective care to patients with multiple chronic conditions. Nurses conduct in-home assessments, facilitate care planning, promote patient self-management, monitor conditions, coordinate the efforts of all care professionals, and facilitate access to community resources.

A cluster-randomized controlled trial found that this program had mixed results, reducing the use of home health care but having little effect on the use of other health services in the short run. However, in the subgroup of patients covered by Kaiser-Permanente, those who were randomized to the program accrued, on average, 52% fewer skilled nursing facility days, 47% fewer skilled nursing facility admissions, 49% fewer hospital readmissions, and 17% fewer emergency department visits.⁶⁷

The GRACE model

The GRACE model (Geriatric Resources for Assessment and Care of Elders)⁶⁸ was developed to improve the quality of geriatric care, reduce excess health care use, and prevent long-term nursing home placement. Each patient is assigned a support team consisting of a nurse practitioner and a social worker who make home visits, coordinate health care and community services, and develop an individualized care plan.

In one study,⁶⁹ GRACE reduced hospital admission rates for participants at high risk of hospitalization by 12% in the first year of the program and 44% in the second year. GRACE participants also reported higher quality of life compared with the control group.⁶⁹

INTERACT tools

Led by Dr. Joseph Ouslander, INTERACT (Interventions to Reduce Acute Care Transfers)⁷⁰ is a quality-improvement initiative for skilled nursing facilities, designed to facilitate the early identification, evaluation, documentation, and communication of changes in the status of residents. Visitors to its website can download a set of tools and strategies to help them manage conditions before they become serious enough to require a hospital transfer. The tools assist in promoting important communication among providers and enhancing advance-care planning.

A 6-month study in 25 nursing homes showed a 17% reduction in self-reported hospital admissions with this program compared with the same period the previous year.⁷¹

Additional home-based care interventions

Additional innovations are under way in home-based care.

The Home Health Quality Improvement National Campaign is a patient-centered movement to improve the quality of care received by patients residing at home.⁷² Through its Best Practices Intervention Packages, it offers evidence-based educational tools, resources, and interventions for reducing avoidable hospitalizations, improving medication management, and coordinating transitional care.

The Center for Medicare and Medicaid Innovation Independence at Home Demonstration⁷³ is testing whether home-based comprehensive primary care can improve care and reduce hospitalizations for Medicare beneficiaries with multiple chronic conditions.

NO SINGLE INTERVENTION: MULTIPLE STRATEGIES NEEDED

A 2011 review found no single intervention that regularly reduced the 30-day risk of re-hospitalization.⁷⁴ However, other studies have shown that multifaceted interventions can reduce 30-day readmission rates. Randomized controlled trials in short-stay, acute care hospitals indicate that improvement in the following areas can directly reduce hospital readmission rates:

• Comprehensive planning and risk assessment throughout hospitalization
• Quality of care during the initial admission
• Communication with patients, their caregivers, and their clinicians
• Patient education
• Predischarge assessment
• Coordination of care after discharge.

In randomized trials, successful programs reduced the 30-day readmission rates by 20% to 40%,^{54,62,75–79} and a 2011 meta-analysis of randomized clinical trials found evidence that interventions associated with discharge planning helped to reduce readmission rates.⁸⁰

Methods developed by the national care transition models described above can help hospitals optimize patient transitions (Table 1). Although every model has its unique attributes, they have several strategies in common:

Engage a team of key stakeholders that may include patients and caregivers, hospital staff (physicians, nurses, case managers, social workers, and pharmacists), community physicians (primary care, medical homes, and specialists), advance practice providers (physician assistants and nurse practitioners), and postacute care facilities and services (skilled nursing facilities, home health agencies, assisted living residences, hospice, and rehabilitation facilities).

Develop a comprehensive transition plan throughout hospitalization that includes attention to factors that may affect self-care, such as health literacy, chronic conditions, medications, and social support.

Enhance medication reconciliation and management. Obtain the best possible medication history on admission, and ensure that patients understand changes in their medications, how to take each medicine correctly, and important side effects.

Institute daily interdisciplinary communication and care coordination by everyone on the health care team with an emphasis on the care plan, discharge planning, and safety issues.⁸¹

Standardize transition plans, procedures and forms. All discharging physicians should use a standard discharge summary template that includes pertinent diagnoses, active issues, a reconciled medication list with changes highlighted, results from important tests and consultations, pending test results, planned follow-up and required services, warning signs of a worsening condition, and actions needed if a problem arises.

Always send discharge summaries directly to the patient’s primary care physician or next care setting at the time of discharge.

Give the patient a discharge plan that is easy to understand. Enhance patient and family education using health literacy standards⁸² and interactive methods such as teach-back,⁸³ in which patients demonstrate comprehension and skills required for self-care immediately after being taught. Such tools actively teach patients and caregivers to follow a care plan, including managing medications.

Follow up and coordinate support in a timely manner after a patient leaves the care setting. Follow-up visits should be arranged before discharge. Within 1 to 3 days after discharge, the patient should be called or visited by a case manager, social worker, nurse, or other health care provider.

CHALLENGES TO IMPROVING TRANSITIONS

Although several models demonstrated significant reductions of hospital readmissions in trials, challenges remain. Studies do not identify which features of the models are necessary or sufficient, or how applicable they are to different hospital and patient characteristics. A 2012 analysis⁸⁴ of a program designed to reduce readmissions in three states identified key obstacles to successfully improving care transitions:

Collaborative relationships across settings are critical, but very difficult to achieve. It takes time to develop the relationships and trust among providers, and little incentive exists for skilled nursing facilities and physicians outside the hospital to engage in the process.

Infrastructure is lacking, as is experience to implement quality improvements.

We lack proof that models work on a large scale. Confusion exists about which readmissions are preventable and which are not. More evidence is needed to help guide hospitals’ efforts to improve transitions of care and reduce readmissions.

You have spent several days checking on a patient hospitalized for an acute exacerbation of heart failure. You have straightened out her medications and diet and discussed a plan for follow-up with the patient and a family member, and now she is being wheeled out the door. What happens to her next?

Too often, not your desired plan. If she is going home, maybe she understands what she needs to do, maybe not. Maybe she will get your prescriptions filled and take the medications as directed, maybe not. If she is going to a nursing home, maybe the physician covering the nursing home will get your plan, maybe not. There is a good chance she will be back in the emergency room soon, all because of a poor transition of care.

Transitions of care are changes in the level, location, or providers of care as patients move within the health care system. These can be critical junctures in patients’ lives, and if poorly executed can result in many adverse effects—including rehospitalization.¹

Although high rehospitalization rates gained national attention in 2009 after a analysis of Medicare data,² health care providers have known about the lack of coordinated care transitions for more than 50 years.³ Despite some progress, improving care transitions remains a national challenge. As the health system evolves from a fee-for-service financial model to payment-for-value,⁴ it is especially important that health care providers improve care for patients by optimizing care transitions.

In this article, we summarize the factors contributing to poor care transitions, highlight programs that improve them, and discuss strategies for successful transitions.

TRANSITION PROBLEMS ARE COMMON

Transitions of care occur when patients move to short-term and long-term acute care hospitals, skilled nursing facilities, primary and specialty care offices, community health centers, rehabilitation facilities, home health agencies, hospice, and their own homes.⁵ Problems can arise at any of these transitions, but the risk is especially high when patients leave the hospital to receive care in another setting or at home.

In the past decade, one in five Medicare patients was rehospitalized within 30 days of discharge from the hospital,² and up to 25% were rehospitalized after being discharged to a skilled nursing facility.⁶ Some diagnoses (eg, sickle cell anemia, gangrene) and procedures (eg, kidney transplantation, ileostomy) are associated with readmission rates of nearly one in three.^7,8

The desire of policymakers to “bend the cost curve” of health care has led to efforts to enhance care coordination by improving transitions between care venues. Through the Patient Protection and Affordable Care Act, a number of federal initiatives are promoting strategies to improve care transitions and prevent readmissions after hospital discharge.

The Hospital Readmission Reduction Program⁹ drives much of this effort. In fiscal year 2013 (beginning October 1, 2012), more than 2,000 hospitals incurred financial penalties of up to 1% of total Medicare diagnosis-related group payments (about $280 million the first year) for excess readmissions.¹⁰ The penalty’s maximum rose to 2% in fiscal year 2014 and could increase to 3% in 2015. The total penalty for 2014 is projected to be $227 million, with 2,225 hospitals affected.¹¹

The Centers for Medicare and Medicaid Innovation has committed hundreds of millions of dollars to Community-based Care Transitions Programs¹² and more than $200 million to Hospital Engagement Networks¹³ to carry out the goals of the Partnership for Patients,¹⁴ aiming to reduce rehospitalizations and other adverse events.

At first, despite these efforts, readmission rates did not appear to change substantially.¹⁵ However, the Centers for Medicare and Medicaid Services reported that hospital readmission rates for Medicare fee-for-service beneficiaries declined in 2012 to 18.4%,¹⁶ although some believe that the reduction is related to an increase in the number of patients admitted for observation in recent years.¹⁷

TRANSITIONS ARE OFTEN POORLY COORDINATED

Although some readmissions are unavoidable—resulting from the inevitable progression of disease or worsening of chronic conditions¹⁸—they may also result from a fumbled transition between care settings. Our current system of care transition has serious deficiencies that endanger patients. Areas that need improvement include communication between providers, patient education about medications and treatments, monitoring of medication adherence and complications, follow-up of pending tests and procedures after discharge, and outpatient follow-up soon after discharge.^19–21

Traditional health care does not have dependable mechanisms for coordinating care across settings; we are all ensconced in “silos” that generally keep the focus within individual venues.²² Lack of coordination blurs the lines of responsibility for patients in the period between discharge from one location and admission to another, leaving them confused about whom to contact for care, especially if symptoms worsen.^23,24

Gaps in coordination are not surprising, given the complexity of the US health care system and the often remarkable number of physicians caring for an individual patient.⁵ Medicare beneficiaries see an average of two primary care physicians and five specialists during a 2-year period; patients with chronic conditions may see up to 16 physicians in 1 year.²⁵ Coordinating care between so many providers in different settings, combined with possible patient factors such as disadvantaged socioeconomic status, lack of caregiver support, and inadequate health literacy, provides many opportunities for failures.

Research has identified several root causes behind most failed care transitions:

Poor provider communication

Multiple studies associate adverse events after discharge with a lack of timely communication between hospital and outpatient providers.²⁶ One study estimated that 80% of serious medical errors involve miscommunication during the hand-off between medical providers.²⁷ Discharge summaries often lack important information such as test results, hospital course, discharge medications, patient counseling, and follow-up plans. Most adverse drug events after hospital discharge result directly from breakdown in communication between hospital staff and patients or primary care physicians.²⁸ Approximately 40% of patients have test results pending at the time of discharge and 10% of these require some action; yet outpatient physicians and patients are often unaware of them.²¹

Ineffective patient and caregiver education

The Institute of Medicine report, Crossing the Quality Chasm: A New Health System for the 21st Century,²⁹ noted that patients leaving one setting for another receive little information on how to care for themselves, when to resume activities, what medication side effects to watch out for, and how to get answers to questions. Of particular concern is that patients and caregivers are sometimes omitted from transition planning and often must suddenly assume new self-care responsibilities upon going home that hospital staff managed before discharge. Too often, patients are discharged with inadequate understanding of their medical condition, self-care plan,^23,24 and who should manage their care.³⁰

Up to 36% of adults in the United States have inadequate health literacy (defined as the inability to understand basic health information needed to make appropriate decisions), hindering patient education efforts.^31–33 Even if they understand, patients and their caregivers must be engaged or “activated” (ie, able and willing to manage one’s health) if we expect them to adhere to appropriate care and behaviors. A review found direct correlations between patient activation and healthy behavior, better health outcomes (eg, achieving normal hemoglobin A_1c and cholesterol levels), and better care experiences.³⁴ This review also noted that multiple studies have documented improved activation scores as a result of specific interventions.

No follow-up with primary care providers

The risk of hospital readmission is significantly lower for patients with chronic obstructive pulmonary disease or heart failure who receive follow-up within 7 days of discharge.^35–38 Of Medicare beneficiaries readmitted to the hospital within 30 days of discharge in 2003–2004, half had no contact with an outpatient physician in the interval between their discharge and their readmission,² and one in three adult patients discharged from a hospital to the community does not see a physician within 30 days of discharge.³⁹ The dearth of primary care providers in many communities can make follow-up care difficult to coordinate.

Failure to address chronic conditions

Analyses of national data sets reveal that patients are commonly rehospitalized for conditions unrelated to their initial hospitalization. According to the Center for Studying Health System Change, more than a quarter of readmissions in the 30 days after discharge are for conditions unrelated to those identified in the index admission, the proportion rising to more than one-third at 1 year.³⁹ Among Medicare beneficiaries readmitted within 30 days of discharge, the proportion readmitted for the same condition was just 35% after hospitalization for heart failure, 10% after hospitalization for acute myocardial infarction, and 22% after hospitalization for pneumonia.⁴⁰

Lack of community support

Multiple social and environmental factors contribute to adverse postdischarge events.^41–43 For socioeconomically disadvantaged patients, care-transition issues are compounded by insufficient access to outpatient care, lack of social support, and lack of transportation. Some studies indicate that between 40% to 50% of readmissions are linked to social problems and inadequate access to community resources.^44–47 Psychosocial issues such as limited health literacy, poor self-management skills, inadequate social support, and living alone are associated with adverse outcomes, including readmission and death.^48,49 Such factors may help explain high levels of “no-shows” to outpatient follow-up visits.

NATIONAL MODELS OF BEST PRACTICES

Efforts to reduce readmissions have traditionally focused on hospitals, but experts now recognize that multiple factors influence readmissions and must be comprehensively addressed. Several evidence-based models seek to improve patient outcomes with interventions aimed at care transitions:

Project BOOST

Project BOOST (Better Outcomes by Optimizing Safe Transitions)⁵⁰ is a national initiative developed by the Society of Hospital Medicine to standardize and optimize the care of patients discharged from hospital to home. The program includes evidence-based clinical interventions that can easily be adopted by any hospital. Interventions are aimed at:

• Identifying patients at high risk on admission
• Targeting risk-specific situations
• Improving information flow between inpatient and outpatient providers
• Improving patient and caregiver education by using the teach-back method
• Achieving timely follow-up after discharge.

The program includes a year of technical support provided by a physician mentor.

Preliminary results from pilot sites showed a 14% reduction in 30-day readmission rates in units using BOOST compared with control units in the same hospital.⁵¹ Mentored implementation was recognized by the Joint Commission and the National Quality Forum with the 2011 John M. Eisenberg Award for Innovation in Patient Safety and Quality.⁵²

Project RED

Project RED (Re-Engineered Discharge)⁵³ evolved from efforts by Dr. Brian Jack and colleagues to re-engineer the hospital workflow process to improve patient safety and reduce rehospitalization rates at Boston Medical Center. The intervention has 12 mutually reinforcing components aimed at improving the discharge process.

In a randomized controlled trial, Project RED led to a 30% decrease in emergency department visits and readmissions within 30 days of discharge from a general medical service of an urban academic medical center.⁵⁴ This study excluded patients admitted from a skilled nursing facility or discharged to one, but a recent study demonstrated that Project RED also led to a lower rate of hospital admission within 30 days of discharge from a skilled nursing facility.⁵⁵

The STAAR initiative

The STAAR initiative (State Action on Avoidable Re-hospitalizations)⁵⁶ was launched in 2009 by the Institute for Healthcare Improvement with the goal of reducing avoidable readmissions in the states of Massachusetts, Michigan, and Washington. Hospital teams focus on improving:

• Assessment of needs after hospital discharge
• Teaching and learning
• Real-time hand-off communication
• Timely follow-up after hospital discharge.

As yet, no published studies other than case reports show a benefit from STAAR.⁵⁷

The Care Transitions Program

The Care Transitions Program,⁵⁸ under the leadership of Dr. Eric Coleman, aims to empower patients and caregivers, who meet with a “transition coach.” The program provides assistance with medication reconciliation and self-management, a patient-centered record owned and maintained by the patient to facilitate cross-site information transfer, timely outpatient follow-up with primary or specialty care, a list of red flags to indicate a worsening condition, and instructions on proper responses.

A randomized controlled trial of the program demonstrated a reduction in hospital readmissions at 30, 90, and 180 days, and lower hospital costs at 90 and 180 days.⁵⁹ This approach also proved effective in a real-world setting.⁶⁰

The Transitional Care Model

Developed by Dr. Mary Naylor and colleagues, the Transitional Care Model⁶¹ also aims at patient and family empowerment, focusing on patients’ stated goals and priorities and ensuring patient engagement. In the program, a transitional care nurse has the job of enhancing patient and caregiver understanding, facilitating patient self-management, and overseeing medication management and transitional care.

A randomized controlled trial demonstrated improved outcomes after hospital discharge for elderly patients with complex medical illnesses, with overall reductions in medical costs through preventing or delaying rehospitalization.⁶² A subsequent real-world study validated this approach.⁶³

The Bridge Model

The Illinois Transitional Care Consortium’s Bridge Model⁶⁴ is for older patients discharged home after hospitalization. It is led by social workers (“bridge care coordinators”) who address barriers to implementing the discharge plan, coordinate resources, and intervene at three points: before discharge, 2 days after discharge, and 30 days after discharge.

An initial study showed no impact on the 30-day rehospitalization rate,⁶⁵ but larger studies are under way with a modified version.

Guided Care

Developed at the Johns Hopkins Bloomberg School of Public Health, Guided Care⁶⁶ involves nurses who work in partnership with physicians and others in primary care to provide patient-centered, cost-effective care to patients with multiple chronic conditions. Nurses conduct in-home assessments, facilitate care planning, promote patient self-management, monitor conditions, coordinate the efforts of all care professionals, and facilitate access to community resources.

A cluster-randomized controlled trial found that this program had mixed results, reducing the use of home health care but having little effect on the use of other health services in the short run. However, in the subgroup of patients covered by Kaiser-Permanente, those who were randomized to the program accrued, on average, 52% fewer skilled nursing facility days, 47% fewer skilled nursing facility admissions, 49% fewer hospital readmissions, and 17% fewer emergency department visits.⁶⁷

The GRACE model

The GRACE model (Geriatric Resources for Assessment and Care of Elders)⁶⁸ was developed to improve the quality of geriatric care, reduce excess health care use, and prevent long-term nursing home placement. Each patient is assigned a support team consisting of a nurse practitioner and a social worker who make home visits, coordinate health care and community services, and develop an individualized care plan.

In one study,⁶⁹ GRACE reduced hospital admission rates for participants at high risk of hospitalization by 12% in the first year of the program and 44% in the second year. GRACE participants also reported higher quality of life compared with the control group.⁶⁹

INTERACT tools

Led by Dr. Joseph Ouslander, INTERACT (Interventions to Reduce Acute Care Transfers)⁷⁰ is a quality-improvement initiative for skilled nursing facilities, designed to facilitate the early identification, evaluation, documentation, and communication of changes in the status of residents. Visitors to its website can download a set of tools and strategies to help them manage conditions before they become serious enough to require a hospital transfer. The tools assist in promoting important communication among providers and enhancing advance-care planning.

A 6-month study in 25 nursing homes showed a 17% reduction in self-reported hospital admissions with this program compared with the same period the previous year.⁷¹

Additional home-based care interventions

Additional innovations are under way in home-based care.

The Home Health Quality Improvement National Campaign is a patient-centered movement to improve the quality of care received by patients residing at home.⁷² Through its Best Practices Intervention Packages, it offers evidence-based educational tools, resources, and interventions for reducing avoidable hospitalizations, improving medication management, and coordinating transitional care.

The Center for Medicare and Medicaid Innovation Independence at Home Demonstration⁷³ is testing whether home-based comprehensive primary care can improve care and reduce hospitalizations for Medicare beneficiaries with multiple chronic conditions.

NO SINGLE INTERVENTION: MULTIPLE STRATEGIES NEEDED

A 2011 review found no single intervention that regularly reduced the 30-day risk of re-hospitalization.⁷⁴ However, other studies have shown that multifaceted interventions can reduce 30-day readmission rates. Randomized controlled trials in short-stay, acute care hospitals indicate that improvement in the following areas can directly reduce hospital readmission rates:

• Comprehensive planning and risk assessment throughout hospitalization
• Quality of care during the initial admission
• Communication with patients, their caregivers, and their clinicians
• Patient education
• Predischarge assessment
• Coordination of care after discharge.

In randomized trials, successful programs reduced the 30-day readmission rates by 20% to 40%,^{54,62,75–79} and a 2011 meta-analysis of randomized clinical trials found evidence that interventions associated with discharge planning helped to reduce readmission rates.⁸⁰

Methods developed by the national care transition models described above can help hospitals optimize patient transitions (Table 1). Although every model has its unique attributes, they have several strategies in common:

Engage a team of key stakeholders that may include patients and caregivers, hospital staff (physicians, nurses, case managers, social workers, and pharmacists), community physicians (primary care, medical homes, and specialists), advance practice providers (physician assistants and nurse practitioners), and postacute care facilities and services (skilled nursing facilities, home health agencies, assisted living residences, hospice, and rehabilitation facilities).

Develop a comprehensive transition plan throughout hospitalization that includes attention to factors that may affect self-care, such as health literacy, chronic conditions, medications, and social support.

Enhance medication reconciliation and management. Obtain the best possible medication history on admission, and ensure that patients understand changes in their medications, how to take each medicine correctly, and important side effects.

Institute daily interdisciplinary communication and care coordination by everyone on the health care team with an emphasis on the care plan, discharge planning, and safety issues.⁸¹

Standardize transition plans, procedures and forms. All discharging physicians should use a standard discharge summary template that includes pertinent diagnoses, active issues, a reconciled medication list with changes highlighted, results from important tests and consultations, pending test results, planned follow-up and required services, warning signs of a worsening condition, and actions needed if a problem arises.

Always send discharge summaries directly to the patient’s primary care physician or next care setting at the time of discharge.

Give the patient a discharge plan that is easy to understand. Enhance patient and family education using health literacy standards⁸² and interactive methods such as teach-back,⁸³ in which patients demonstrate comprehension and skills required for self-care immediately after being taught. Such tools actively teach patients and caregivers to follow a care plan, including managing medications.

Follow up and coordinate support in a timely manner after a patient leaves the care setting. Follow-up visits should be arranged before discharge. Within 1 to 3 days after discharge, the patient should be called or visited by a case manager, social worker, nurse, or other health care provider.

CHALLENGES TO IMPROVING TRANSITIONS

Although several models demonstrated significant reductions of hospital readmissions in trials, challenges remain. Studies do not identify which features of the models are necessary or sufficient, or how applicable they are to different hospital and patient characteristics. A 2012 analysis⁸⁴ of a program designed to reduce readmissions in three states identified key obstacles to successfully improving care transitions:

Collaborative relationships across settings are critical, but very difficult to achieve. It takes time to develop the relationships and trust among providers, and little incentive exists for skilled nursing facilities and physicians outside the hospital to engage in the process.

Infrastructure is lacking, as is experience to implement quality improvements.

We lack proof that models work on a large scale. Confusion exists about which readmissions are preventable and which are not. More evidence is needed to help guide hospitals’ efforts to improve transitions of care and reduce readmissions.

African Americans are disproportionately affected by heart failure and have not experienced the same benefit from treatment as white patients have. Much of the disparity can be blamed on modifiable risk factors such as uncontrolled hypertension and on suboptimal health care. When African Americans are treated according to guidelines, discrepant outcomes can be minimized.

In this article, we review the processes contributing to heart failure in African Americans, its management, and challenges with regard to disparities.

HEART FAILURE IS INCREASING

Despite 20 years of progress in understanding the pathophysiology of heart failure and developing medical and surgical therapies for it, its prevalence and associated morbidity are increasing in the United States. In 2010, 6.6 million (2.8%) of the adults in the United States had heart failure,¹ and the prevalence is expected to increase by about 25% by 2030.

DISPARITIES IN INCIDENCE, OUTCOMES

Heart failure is more prevalent in African Americans than in whites, imposes higher rates of death and morbidity, and has a more malignant course.^1–6

According to American Heart Association statistics, the annual incidence of heart failure in whites is approximately 6 per 1,000 person-years, while in African Americans it is 9.1 per 1,000 person-years.¹ In the Atherosclerosis Risk in Communities study, the incidence of new heart failure was 1.0 per 1,000 person-years in Chinese Americans, 2.4 in whites, 3.5 in Hispanics, and 4.6 in African Americans.²

Moreover, when hospitalized for heart failure, African Americans have a 45% greater risk of death or decline in functional status than whites.⁷

Heart failure also occurs earlier in African Americans. Bibbins-Domingo et al⁸ reported that heart failure before age 50 was 20 times more frequent in African Americans than in whites. Functional and structural cardiac changes appeared an average of 10 years before the onset of symptoms and were strongly associated with the development of subsequent heart failure.⁸

In the Women’s Health Initiative, African American women had higher rates of heart failure than white women, perhaps in part because of higher rates of diabetes.⁹

Heart failure with preserved ejection fraction

About half of patients who have signs and symptoms of heart failure have a normal (“preserved”) ejection fraction. The incidence of this condition, previously called diastolic heart failure, appears to be similar between African Americans and whites. However, African Americans appear to have a greater incidence of factors that predispose to it and tend to present later in the course.¹⁰ For example, African Americans have higher left ventricular mass and wall thickness and a higher incidence of left ventricular hypertrophy than white patients.^11–13 In addition, those with heart failure with preserved ejection fraction tend to be younger, female, more likely to have hypertension and diabetes, and less likely to have coronary artery disease, and tend to have worse renal function than their white counterparts.^14,15 The predisposition to diastolic impairment persists even after adjusting for risk factors.^11–15 The mortality rate in African Americans with heart failure with preserved ejection fraction and without coronary artery disease may also be higher than that of comparable white patients.¹⁶

WHY DO AFRICAN AMERICANS HAVE MORE HEART FAILURE?

Modifiable risk factors

In African Americans, the higher percentage of cases of heart failure is attributable to modifiable risk factors such as hypertension, hyperglycemia, left ventricular hypertrophy, and smoking, and fewer cases are due to ischemic heart disease.^2,3 Nonischemic cardiomyopathy predominates in African Americans, whereas ischemic cardiomyopathy predominates in whites.

Hypertension, diabetes, obesity, and chronic kidney disease all portend subsequent heart failure and are common in African Americans, but hypertension is the main culprit.^{3,5,8,17–21} The prevalence of hypertension in African Americans is among the highest in the world, and because African Americans are more likely to have poorer control of their hypertension, they consequently have more target-organ damage.²² Indeed, in many hypertensive African Americans who develop heart failure, the hypertension is poorly controlled. However, even after adjusting for risk factors, and particularly blood pressure control, African Americans remain at higher risk of heart failure.²³

The specific mechanistic links between hypertension and heart failure remain to be identified. Despite having a higher prevalence of left ventricular hypertrophy and left ventricular remodeling, African Americans with heart failure tend toward systolic heart failure, as opposed to heart failure with preserved ejection fraction.

Neurohormonal imbalances and endothelial dysfunction

Derangements in the renin-angiotensin-aldosterone and adrenergic axes are likely the main pathophysiologic mechanisms in the genesis of heart failure in all populations. However, other factors may underlie the enhanced disease burden in African Americans.

Impaired endothelial function, as evidenced by impaired digital and brachial artery vasomotion, is very common in African Americans.^24–26 The small arteries of African Americans are less elastic than those of whites and Chinese.²⁷ The underlying mechanism may be related to increased oxidative stress, decreased nitric oxide availability, exaggerated vasoconstrictor response, and attenuated responsiveness to vasodilators and nitric oxide.^28–31

Genetic polymorphisms

An important caveat in discussing racial differences in heart failure is that “race” is completely arbitrary and is based on sociopolitical rather than scientific or physiologic definitions. Perceived genetic influences are likely to represent complex gene-gene, gene-environment, and gene-drug interactions.

This is especially true for African Americans, who are a markedly heterogeneous group. The US Office of Management and Budget defines “black” or “African American” as having origins in any of the black racial groups of Africa (www.census.gov/2010census/data). Thus, “African American” includes sixth-generation descendants of African slaves, recently immigrated Jamaicans, and black descendants of French and Spanish people.

Most African Americans have some European ancestry. In one study, the estimated proportion of European ancestry ranged from 7% in Jamaicans of African descent to approximately 23% in African Americans in New Orleans.³²

Nevertheless, several polymorphisms associated with the risk of heart failure may provide insight into some of the “race-based” differences in pathophysiology and response to medications and, it is hoped, may eventually serve as the basis for tailored therapy. Genes of interest include those for:

• Beta 1 adrenergic receptor
• Alpha 2c receptor³³
• Aldosterone synthase³⁴
• G protein
• Transforming growth factor beta
• Nitric oxide synthase³⁵
• Transthyrectin.^36,37

Socioeconomic factors and quality of care

Heart failure patients—and especially African Americans—have high rates of hospital readmission, and socioeconomic factors have been implicated. In more than 40,000 patients with heart failure, lower income was a significant predictor of hospital readmission.³⁸ Socioeconomic factors in turn could account for delay in seeking treatment for worsening symptoms, failure to recognize symptoms, limited disease awareness, inadequate access to health care, noncompliance with follow-up appointments, and poor adherence to recommended treatment, all of which are common in African American patients.^38,39

African Americans also report more discrimination from health care providers, have more concerns about blood pressure medications, and are more likely to have misperceptions about high blood pressure (eg, that it is not serious), all of which may interfere with optimal blood pressure control.⁴⁰ Managing heart failure in African Americans should include trying to identify and eliminate barriers to attaining treatment goals.

PREVENTING HEART FAILURE BY REDUCING RISK FACTORS

The American College of Cardiology Foundation and American Heart Association, in their 2013 guidelines, underscored the progressive nature of heart failure by defining four stages of the disease, from stage A (at risk) through stage D (refractory heart failure) (Figure 1).⁴¹ They also emphasized the importance of preventing it.

A thorough clinical assessment, with appropriate assessment for risk factors and intervention at stage A, is critical in preventing left ventricular remodeling and heart failure. These risk factors include hypertension, hyperlipidemia, atherosclerosis, diabetes mellitus, valvular disease, obesity, physical inactivity, excessive alcohol intake, poor diet, and smoking.

Hypertension is especially important in African Americans and requires vigorous screening and aggressive treatment. Antihypertensive drugs should be prescribed early, with a lower threshold for escalating therapy with combinations of drugs, as most patients require more than one.

There is considerable debate about the appropriate blood pressure thresholds for diagnosing hypertension and the optimal target blood pressures in African Americans. The 2014 report of the Joint National Committee recommends a similar hypertension treatment target of 140/90 mm Hg for all patients except older adults (for whom 150/90 mm Hg is acceptable), and no separate target for African Americans.⁴² Previous guidelines from this committee recommended thiazide-type diuretics as first-line therapy for hypertension in African Americans⁴³; the new ones recommend thiazide-type diuretics or calcium channel blockers. However, in those with left ventricular systolic dysfunction, hypertension treatment should include drugs shown to reduce the risk of death in heart failure—ie, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, hydralazine, nitrates, and aldosterone receptor antagonists.

Salt intake should be reduced to less than 3 g per day (1,200 mg of sodium per day), which has been shown to substantially reduce rates of cardiovascular morbidity and mortality and health care costs.⁴⁴ Since most Americans consume 7 to 10 g of salt per day, strict salt restriction should be encouraged as a preventive measure.

Diabetes should be screened for and treated in African Americans per current American Diabetes Association guidelines.

Dyslipidemia should also be screened for and treated per guidelines.⁴⁵

Smoking cessation, moderation of alcohol intake, and avoidance of illicit drugs should be encouraged. Given that African Americans develop heart failure at a relatively early age, the level of vigilance should be high and the threshold for screening should be low.

Healthy neighborhoods, healthy people

Neighborhoods can be designed and built with wellness in mind, incorporating features such as access to healthy food and walkability. Living in such neighborhoods leads to more physical activity and less obesity, although this relationship may be less robust in African Americans.^46–49

Environmental factors are multifactorial in African Americans and extend beyond those afforded by the built environment. For instance, lack of safety may hinder the potential benefit of an otherwise walkable neighborhood. These interactions are highly complex, and more investigation is needed to determine the effect of built environments on risk factors in African Americans.

DRUG THERAPY FOR HEART FAILURE IN AFRICAN AMERICANS

Use standard therapies

ACE inhibitors, beta-blockers, and aldosterone antagonists are the standard of care in heart failure, with digoxin (Lanoxin) and diuretics used as adjuncts to control symptoms.

African Americans may respond differently than whites to some of these drugs (Table 1). However, these findings should be interpreted with caution, since most of them came from subgroup analyses of trials in which African Americans accounted for as many as 28% to as few as 1%.⁵⁰ To date, no data unequivocally show that we should use standard heart failure therapies any differently in African Americans than in whites.

Digoxin: Limited role to control symptoms

Post hoc analysis of the Digitalis Investigation Group trial, in which 14% of the patients were nonwhite, revealed that compared with placebo, digitalis (and achieving a serum digitalis concentration of 0.5 to 0.9 ng/mL) was associated with lower rates of all-cause mortality in most subgroups—except nonwhites.⁵¹

In general, digoxin has a limited role in heart failure, since other drugs are available that substantially modify outcomes. However, it can be considered in patients who have persistent heart failure symptoms.

ACE inhibitors, ARBs are recommended

ACE inhibitors are recommended for patients with New York Heart Association (NYHA) class I, II, III, or IV heart failure (class I recommendation, ie, “recommended”; level of evidence A on a scale of A, B, and C) and as part of standard therapy for African American patients with heart failure with symptomatic or asymptomatic left ventricular systolic dysfunction (class I recommendation; level of evidence C).⁴¹

Although African American patients did not appear to derive any benefit from enalapril (Vasotec) in the Studies of Left Ventricular Dysfunction (SOLVD) trial,⁵² a subsequent analysis that involved the SOLVD Prevention Trial did not find any differences between African Americans and whites in response to this agent.⁶ Similarly, a meta-analysis did not suggest differences in ACE-inhibitor efficacy in reducing adverse cardiovascular outcomes in heart failure between African Americans and non–African Americans.⁵³

Of note: African Americans have a 3% to 4% higher incidence of angioedema from ACE inhibitors than whites.^54,55

Angiotensin receptor blockers (ARBs) can be used as substitute therapy in African Americans who cannot tolerate ACE inhibitors (class IIa recommendation, ie, “reasonable”; level of evidence B).⁴¹

Beta-blockers also recommended

Beta-blockers are recommended in NYHA class I, II, III, and IV heart failure (class I recommendation; level of evidence A) and as part of standard therapy for African Americans with heart failure due to symptomatic left ventricular systolic dysfunction (class I recommendation; level of evidence B) and asymptomatic left ventricular systolic dysfunction (level of evidence C).⁴¹

Carvedilol (Coreg) and metoprolol (Lopressor) are the standard beta-blockers used to treat heart failure, and these drugs should be used in African Americans as well as in whites.^{15,53,56–59} Of interest, however, race-specific differences may exist in the beta-adrenergic pathway.^60,61

Aldosterone antagonists: More study needed

Aldosterone antagonists, also called mineralocorticoid antagonists, ie, spironolactone (Aldactone) and eplerenone (Inspra), are recommended in addition to beta-blockers and ACE inhibitors for NYHA class II–IV heart failure, unless contraindicated (class I recommendation; level of evidence A).

However, trials of aldosterone antagonists to date have enrolled few African Americans.^62–64 The limited data suggest that African Americans with heart failure may be less responsive to the renal effects of spironolactone, demonstrating less of an increase in serum potassium levels, and there are essentially no data to guide the use of these drugs in African Americans with heart failure.⁶⁵ Further study is needed. But in the absence of data to the contrary, these agents, should also be used in African American patients with class III or IV heart failure.

Hydralazine plus nitrates: Recommended for African Americans

Hydralazine plus isosorbide dinitrate (available as BiDil) is recommended as part of standard therapy, in addition to beta-blockers and ACE inhibitors specifically for African Americans with left ventricular systolic dysfunction and NYHA class III or IV heart failure (class I recommendation; level of evidence A), as well as NYHA class II heart failure (class I recommendation; level of evidence B).⁴¹

Preliminary evidence for this combination came from the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials.⁶⁶

Subsequently, the African-American Heart Failure Trial⁶⁷ was conducted in self-identified African American patients with NYHA class III or IV heart failure on standard heart failure therapy, including an ACE inhibitor if tolerated. Patients were randomly assigned to receive a fixed combination of isosorbide 20 mg and hydralazine 37.5 mg, one or two tablets three times a day, or placebo. The target dose of isosorbide dinitrate was 120 mg, and the target dose of hydralazine was 225 mg daily. Follow-up was up to 18 months. The study was terminated early because of a significant 43% improvement in overall survival for the patients in the isosorbide-hydralazine group. In addition, the rate of first hospitalization was 39% lower and the mean improvement in quality-of-life scores was 52% greater with isosorbide-hydralazine than with placebo.⁶⁷

There has been much debate about whether the benefit seen in this trial was the result of a hemodynamic effect, blood pressure response, or neurohormonal modulation. The benefit is less likely from a reduction in blood pressure, as the patients who had low blood pressure derived a mortality benefit similar to those with higher blood pressure, despite no further reduction in their blood pressure.⁶⁸

Treatment for heart failure with preserved ejection fraction

Although there are no data on how to manage heart failure with preserved ejection fraction that are specific to African Americans, the ACCF/AHA guideline⁴¹ recommends treating systolic and diastolic hypertension (class I, level of evidence B) according to published clinical practice guidelines and using diuretics to alleviate volume overload (class I; level of evidence C). Revascularization and management of atrial fibrillation are also “reasonable,” as are the use of ARBs, ACE inhibitors, and beta-blockers in the management of hypertension (class IIa; level of evidence C). ARBs may also be considered to reduce hospitalization in symptomatic patients with heart failure with preserved ejection fraction (class IIb, ie, “may be considered”; level of evidence B).

For acute decompensated heart failure

One of the greatest challenges in heart failure is treating patients who present with acute decompensated heart failure.

As in the general population, the major precipitating factor for hospitalization with decompensated heart failure in African Americans is nonadherence to prescribed dietary and medication regimens.³⁵ African Americans with acute decompensated heart failure tend to be younger and to have nonischemic cardiomyopathy, hypertension, diabetes, and obesity, but a lower risk of death.^35,69,70 Up to 44% have uncontrolled hypertension.³⁵

Inotropes and vasodilators have undergone multiple trials in the acutely decompensated state in the general population, but no trial has demonstrated a reduction in the mortality rate, and some showed a higher mortality rate. Thus, the treatment of acute decompensated heart failure remains primarily consensus-guided and symptom-focused.

Loop diuretics have been the mainstay in managing fluid retention and congestion in heart failure. The Diuretic Optimization Strategies Evaluation trial tested low-dose vs high-dose intravenous furosemide (Lasix) given either as a continuous infusion or as intermittent intravenous boluses. All strategies were safe and effective.⁷¹

Although ultrafiltration is an effective method of decongestion in heart failure and has been associated with a reduction in hospitalization, it is also associated with worsening renal function.⁷² The Cardiorenal Rescue Study in Acute Decompensated Heart Failure⁷³ compared ultrafiltration vs stepped diuretic therapy. In this trial, which enrolled approximately 26% nonwhites, stepped diuretic therapy was superior to ultrafiltration in preserving renal function in acute decompensated heart failure, although the efficacy of fluid removal was similar.

Both studies were small, and subgroup analyses are not likely to yield useful information. Nevertheless, these data support the use of intravenous diuretics, by continuous infusion or bolus, in acute decompensated heart failure.

Despite no benefit in terms of the mortality rate, inotropes continue to be used in some cases of acute decompensated heart failure, and African Americans appear to have a response to milrinone (Primacor IV) similar to that in whites.⁶⁹

In a nonrandomized study in which most patients were black, high-dose intravenous nitroglycerin appeared to be safe and associated with less need for ventilator support and intensive care unit admission, compared retrospectively with a population that did not receive high-dose nitroglycerin.⁷⁴

Given the different profile of the African American patient with acute decompensated heart failure, prospective studies would be useful in determining the best management strategy.

TREATMENTS FOR ADVANCED HEART FAILURE

Cardiac resynchronization and implantable cardioverter-defibrillators

Cardiac resynchronization therapy is indicated for patients with NYHA class II, III, and ambulatory class IV heart failure and left ventricular ejection fraction less than or equal to 35%, sinus rhythm, left bundle branch block, and a QRS duration greater than or equal to 150 ms (class I recommendation; level of evidence A for class NYHA III and IV; level of evidence B for NYHA class II).⁴¹

An implantable cardioverter-defibrillator is recommended in patients with NYHA class II or III heart failure for primary prevention of sudden cardiac death in selected patients with nonischemic dilated cardiomyopathy or ischemic heart disease (class I recommendation; level of evidence A).

However, few members of racial and ethnic minorities were included in trials of implantable cardioverter-defibrillators^75,76 or cardiac resynchronization,^7,77,78 so that subgroup analysis is limited. Use of an implantable cardioverter-defibrillator showed similar reduction in mortality between African Americans and whites, and compliance with device implantation and medical therapy was comparable.⁷⁹

Among patients discharged from hospitals in the American Heart Association’s Get With the Guidelines–Heart Failure Quality Improvement Program, fewer than 40% of potentially eligible patients received an implantable cardioverter-defibrillator, and rates were significantly lower for African Americans.⁸⁰ When they can get cardiac resynchronization therapy, African Americans appear to experience similar benefit from it.⁸¹

Heart transplantation: Poorer outcomes in African Americans?

Heart transplantation remains the most effective and durable therapy for advanced heart failure. Median survival approaches 14 years.⁸²

However, a retrospective study found that African American recipients had an 11.5% lower 10-year survival rate than whites, which persisted after adjusting for risk, donor-recipient matching by race, and censoring of deaths in the first year.⁸³ Although socioeconomic factors and poor human leukocyte antigen matching have been implicated, a retrospective cohort study showed that African American recipients had a higher risk of death than white recipients even after adjustment for recipient, transplant, and socioeconomic factors.^84–87 African Americans were more likely to die of graft failure or of a cardiovascular cause than white patients, but were less likely to die of infection or malignancy. Although mortality rates decreased over time for all transplant recipients, the disparity in mortality rates between African Americans and whites remained essentially unchanged.⁸⁴

Among all donor-recipient combinations, African American recipients of hearts from African American donors had the highest risk of death.⁸⁸

Limited access to transplantation persists, particularly for African Americans of lower socioeconomic status. African Americans are more likely than whites to be uninsured, and the funding requirement to be placed on the transplantation list disproportionately affects African Americans.^89,90

Left-ventricular assist devices

Left-ventricular assist devices (LVADs) improve survival in heart transplantation candidates and heart failure patients who do not qualify for transplantation. After LVAD implantation, African American patients have similar 1- and 2-year survival rates and no difference in readmission rates compared with whites.^91,92

Access to LVAD implantation, however, is significantly influenced by race, and African Americans are significantly less likely to receive one (OR = 0.29).⁹³ Further investigation is required to identify disparities in outcome, access, and contributing factors.

DISPARITIES CAN BE MINIMIZED

In general, heart failure in African Americans is characterized by a high prevalence of hypertension as a major risk factor and potentially different pathogenesis than in the general population. Furthermore, heart failure in African Americans is more prevalent, occurs at an early age, and has a more severe course than in whites, perhaps because of a higher prevalence of risk factors such as diabetes mellitus, obesity, and again, hypertension. These disparities are multifactorial and involve a complex interplay between genes, environment, and socioeconomic factors.

For now, heart failure in African Americans should be treated according to standard evidenced-based strategies, which include a combination of isosorbide dinitrate and hydralazine in addition to other neurohormonal modifying agents (ACE inhibitors, beta-blockers, aldosterone antagonists), a strategy demonstrated to reduce mortality rates in African Americans. When treated according to guidelines, disparities in outcomes can be minimized.

However, many questions about managing heart failure remain unanswered, since African Americans have been markedly underrepresented in clinical trials. Clinical trials need to enroll enough African Americans to answer the questions of interest. Disparities in outcomes must be investigated in a scientific and hypothesis-driven manner. The effect of the built environment on African Americans needs more study as well, as success with these strategies may be impeded by unrecognized factors.

Preventing heart failure should be a priority. Efforts should be directed toward detecting and modifying risk factors early, managing hypertension aggressively, and identifying left ventricular dysfunction early.

African Americans are disproportionately affected by heart failure and have not experienced the same benefit from treatment as white patients have. Much of the disparity can be blamed on modifiable risk factors such as uncontrolled hypertension and on suboptimal health care. When African Americans are treated according to guidelines, discrepant outcomes can be minimized.

In this article, we review the processes contributing to heart failure in African Americans, its management, and challenges with regard to disparities.

HEART FAILURE IS INCREASING

Despite 20 years of progress in understanding the pathophysiology of heart failure and developing medical and surgical therapies for it, its prevalence and associated morbidity are increasing in the United States. In 2010, 6.6 million (2.8%) of the adults in the United States had heart failure,¹ and the prevalence is expected to increase by about 25% by 2030.

DISPARITIES IN INCIDENCE, OUTCOMES

Heart failure is more prevalent in African Americans than in whites, imposes higher rates of death and morbidity, and has a more malignant course.^1–6

According to American Heart Association statistics, the annual incidence of heart failure in whites is approximately 6 per 1,000 person-years, while in African Americans it is 9.1 per 1,000 person-years.¹ In the Atherosclerosis Risk in Communities study, the incidence of new heart failure was 1.0 per 1,000 person-years in Chinese Americans, 2.4 in whites, 3.5 in Hispanics, and 4.6 in African Americans.²

Moreover, when hospitalized for heart failure, African Americans have a 45% greater risk of death or decline in functional status than whites.⁷

Heart failure also occurs earlier in African Americans. Bibbins-Domingo et al⁸ reported that heart failure before age 50 was 20 times more frequent in African Americans than in whites. Functional and structural cardiac changes appeared an average of 10 years before the onset of symptoms and were strongly associated with the development of subsequent heart failure.⁸

In the Women’s Health Initiative, African American women had higher rates of heart failure than white women, perhaps in part because of higher rates of diabetes.⁹

Heart failure with preserved ejection fraction

About half of patients who have signs and symptoms of heart failure have a normal (“preserved”) ejection fraction. The incidence of this condition, previously called diastolic heart failure, appears to be similar between African Americans and whites. However, African Americans appear to have a greater incidence of factors that predispose to it and tend to present later in the course.¹⁰ For example, African Americans have higher left ventricular mass and wall thickness and a higher incidence of left ventricular hypertrophy than white patients.^11–13 In addition, those with heart failure with preserved ejection fraction tend to be younger, female, more likely to have hypertension and diabetes, and less likely to have coronary artery disease, and tend to have worse renal function than their white counterparts.^14,15 The predisposition to diastolic impairment persists even after adjusting for risk factors.^11–15 The mortality rate in African Americans with heart failure with preserved ejection fraction and without coronary artery disease may also be higher than that of comparable white patients.¹⁶

WHY DO AFRICAN AMERICANS HAVE MORE HEART FAILURE?

Modifiable risk factors

In African Americans, the higher percentage of cases of heart failure is attributable to modifiable risk factors such as hypertension, hyperglycemia, left ventricular hypertrophy, and smoking, and fewer cases are due to ischemic heart disease.^2,3 Nonischemic cardiomyopathy predominates in African Americans, whereas ischemic cardiomyopathy predominates in whites.

Hypertension, diabetes, obesity, and chronic kidney disease all portend subsequent heart failure and are common in African Americans, but hypertension is the main culprit.^{3,5,8,17–21} The prevalence of hypertension in African Americans is among the highest in the world, and because African Americans are more likely to have poorer control of their hypertension, they consequently have more target-organ damage.²² Indeed, in many hypertensive African Americans who develop heart failure, the hypertension is poorly controlled. However, even after adjusting for risk factors, and particularly blood pressure control, African Americans remain at higher risk of heart failure.²³

The specific mechanistic links between hypertension and heart failure remain to be identified. Despite having a higher prevalence of left ventricular hypertrophy and left ventricular remodeling, African Americans with heart failure tend toward systolic heart failure, as opposed to heart failure with preserved ejection fraction.

Neurohormonal imbalances and endothelial dysfunction

Derangements in the renin-angiotensin-aldosterone and adrenergic axes are likely the main pathophysiologic mechanisms in the genesis of heart failure in all populations. However, other factors may underlie the enhanced disease burden in African Americans.

Impaired endothelial function, as evidenced by impaired digital and brachial artery vasomotion, is very common in African Americans.^24–26 The small arteries of African Americans are less elastic than those of whites and Chinese.²⁷ The underlying mechanism may be related to increased oxidative stress, decreased nitric oxide availability, exaggerated vasoconstrictor response, and attenuated responsiveness to vasodilators and nitric oxide.^28–31

Genetic polymorphisms

An important caveat in discussing racial differences in heart failure is that “race” is completely arbitrary and is based on sociopolitical rather than scientific or physiologic definitions. Perceived genetic influences are likely to represent complex gene-gene, gene-environment, and gene-drug interactions.

This is especially true for African Americans, who are a markedly heterogeneous group. The US Office of Management and Budget defines “black” or “African American” as having origins in any of the black racial groups of Africa (www.census.gov/2010census/data). Thus, “African American” includes sixth-generation descendants of African slaves, recently immigrated Jamaicans, and black descendants of French and Spanish people.

Most African Americans have some European ancestry. In one study, the estimated proportion of European ancestry ranged from 7% in Jamaicans of African descent to approximately 23% in African Americans in New Orleans.³²

Nevertheless, several polymorphisms associated with the risk of heart failure may provide insight into some of the “race-based” differences in pathophysiology and response to medications and, it is hoped, may eventually serve as the basis for tailored therapy. Genes of interest include those for:

• Beta 1 adrenergic receptor
• Alpha 2c receptor³³
• Aldosterone synthase³⁴
• G protein
• Transforming growth factor beta
• Nitric oxide synthase³⁵
• Transthyrectin.^36,37

Socioeconomic factors and quality of care

Heart failure patients—and especially African Americans—have high rates of hospital readmission, and socioeconomic factors have been implicated. In more than 40,000 patients with heart failure, lower income was a significant predictor of hospital readmission.³⁸ Socioeconomic factors in turn could account for delay in seeking treatment for worsening symptoms, failure to recognize symptoms, limited disease awareness, inadequate access to health care, noncompliance with follow-up appointments, and poor adherence to recommended treatment, all of which are common in African American patients.^38,39

African Americans also report more discrimination from health care providers, have more concerns about blood pressure medications, and are more likely to have misperceptions about high blood pressure (eg, that it is not serious), all of which may interfere with optimal blood pressure control.⁴⁰ Managing heart failure in African Americans should include trying to identify and eliminate barriers to attaining treatment goals.

PREVENTING HEART FAILURE BY REDUCING RISK FACTORS

The American College of Cardiology Foundation and American Heart Association, in their 2013 guidelines, underscored the progressive nature of heart failure by defining four stages of the disease, from stage A (at risk) through stage D (refractory heart failure) (Figure 1).⁴¹ They also emphasized the importance of preventing it.

A thorough clinical assessment, with appropriate assessment for risk factors and intervention at stage A, is critical in preventing left ventricular remodeling and heart failure. These risk factors include hypertension, hyperlipidemia, atherosclerosis, diabetes mellitus, valvular disease, obesity, physical inactivity, excessive alcohol intake, poor diet, and smoking.

Hypertension is especially important in African Americans and requires vigorous screening and aggressive treatment. Antihypertensive drugs should be prescribed early, with a lower threshold for escalating therapy with combinations of drugs, as most patients require more than one.

There is considerable debate about the appropriate blood pressure thresholds for diagnosing hypertension and the optimal target blood pressures in African Americans. The 2014 report of the Joint National Committee recommends a similar hypertension treatment target of 140/90 mm Hg for all patients except older adults (for whom 150/90 mm Hg is acceptable), and no separate target for African Americans.⁴² Previous guidelines from this committee recommended thiazide-type diuretics as first-line therapy for hypertension in African Americans⁴³; the new ones recommend thiazide-type diuretics or calcium channel blockers. However, in those with left ventricular systolic dysfunction, hypertension treatment should include drugs shown to reduce the risk of death in heart failure—ie, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, hydralazine, nitrates, and aldosterone receptor antagonists.

Salt intake should be reduced to less than 3 g per day (1,200 mg of sodium per day), which has been shown to substantially reduce rates of cardiovascular morbidity and mortality and health care costs.⁴⁴ Since most Americans consume 7 to 10 g of salt per day, strict salt restriction should be encouraged as a preventive measure.

Diabetes should be screened for and treated in African Americans per current American Diabetes Association guidelines.

Dyslipidemia should also be screened for and treated per guidelines.⁴⁵

Smoking cessation, moderation of alcohol intake, and avoidance of illicit drugs should be encouraged. Given that African Americans develop heart failure at a relatively early age, the level of vigilance should be high and the threshold for screening should be low.

Healthy neighborhoods, healthy people

Neighborhoods can be designed and built with wellness in mind, incorporating features such as access to healthy food and walkability. Living in such neighborhoods leads to more physical activity and less obesity, although this relationship may be less robust in African Americans.^46–49

Environmental factors are multifactorial in African Americans and extend beyond those afforded by the built environment. For instance, lack of safety may hinder the potential benefit of an otherwise walkable neighborhood. These interactions are highly complex, and more investigation is needed to determine the effect of built environments on risk factors in African Americans.

DRUG THERAPY FOR HEART FAILURE IN AFRICAN AMERICANS

Use standard therapies

ACE inhibitors, beta-blockers, and aldosterone antagonists are the standard of care in heart failure, with digoxin (Lanoxin) and diuretics used as adjuncts to control symptoms.

African Americans may respond differently than whites to some of these drugs (Table 1). However, these findings should be interpreted with caution, since most of them came from subgroup analyses of trials in which African Americans accounted for as many as 28% to as few as 1%.⁵⁰ To date, no data unequivocally show that we should use standard heart failure therapies any differently in African Americans than in whites.

Digoxin: Limited role to control symptoms

Post hoc analysis of the Digitalis Investigation Group trial, in which 14% of the patients were nonwhite, revealed that compared with placebo, digitalis (and achieving a serum digitalis concentration of 0.5 to 0.9 ng/mL) was associated with lower rates of all-cause mortality in most subgroups—except nonwhites.⁵¹

In general, digoxin has a limited role in heart failure, since other drugs are available that substantially modify outcomes. However, it can be considered in patients who have persistent heart failure symptoms.

ACE inhibitors, ARBs are recommended

ACE inhibitors are recommended for patients with New York Heart Association (NYHA) class I, II, III, or IV heart failure (class I recommendation, ie, “recommended”; level of evidence A on a scale of A, B, and C) and as part of standard therapy for African American patients with heart failure with symptomatic or asymptomatic left ventricular systolic dysfunction (class I recommendation; level of evidence C).⁴¹

Although African American patients did not appear to derive any benefit from enalapril (Vasotec) in the Studies of Left Ventricular Dysfunction (SOLVD) trial,⁵² a subsequent analysis that involved the SOLVD Prevention Trial did not find any differences between African Americans and whites in response to this agent.⁶ Similarly, a meta-analysis did not suggest differences in ACE-inhibitor efficacy in reducing adverse cardiovascular outcomes in heart failure between African Americans and non–African Americans.⁵³

Of note: African Americans have a 3% to 4% higher incidence of angioedema from ACE inhibitors than whites.^54,55

Angiotensin receptor blockers (ARBs) can be used as substitute therapy in African Americans who cannot tolerate ACE inhibitors (class IIa recommendation, ie, “reasonable”; level of evidence B).⁴¹

Beta-blockers also recommended

Beta-blockers are recommended in NYHA class I, II, III, and IV heart failure (class I recommendation; level of evidence A) and as part of standard therapy for African Americans with heart failure due to symptomatic left ventricular systolic dysfunction (class I recommendation; level of evidence B) and asymptomatic left ventricular systolic dysfunction (level of evidence C).⁴¹

Carvedilol (Coreg) and metoprolol (Lopressor) are the standard beta-blockers used to treat heart failure, and these drugs should be used in African Americans as well as in whites.^{15,53,56–59} Of interest, however, race-specific differences may exist in the beta-adrenergic pathway.^60,61

Aldosterone antagonists: More study needed

Aldosterone antagonists, also called mineralocorticoid antagonists, ie, spironolactone (Aldactone) and eplerenone (Inspra), are recommended in addition to beta-blockers and ACE inhibitors for NYHA class II–IV heart failure, unless contraindicated (class I recommendation; level of evidence A).

However, trials of aldosterone antagonists to date have enrolled few African Americans.^62–64 The limited data suggest that African Americans with heart failure may be less responsive to the renal effects of spironolactone, demonstrating less of an increase in serum potassium levels, and there are essentially no data to guide the use of these drugs in African Americans with heart failure.⁶⁵ Further study is needed. But in the absence of data to the contrary, these agents, should also be used in African American patients with class III or IV heart failure.

Hydralazine plus nitrates: Recommended for African Americans

Hydralazine plus isosorbide dinitrate (available as BiDil) is recommended as part of standard therapy, in addition to beta-blockers and ACE inhibitors specifically for African Americans with left ventricular systolic dysfunction and NYHA class III or IV heart failure (class I recommendation; level of evidence A), as well as NYHA class II heart failure (class I recommendation; level of evidence B).⁴¹

Preliminary evidence for this combination came from the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials.⁶⁶

Subsequently, the African-American Heart Failure Trial⁶⁷ was conducted in self-identified African American patients with NYHA class III or IV heart failure on standard heart failure therapy, including an ACE inhibitor if tolerated. Patients were randomly assigned to receive a fixed combination of isosorbide 20 mg and hydralazine 37.5 mg, one or two tablets three times a day, or placebo. The target dose of isosorbide dinitrate was 120 mg, and the target dose of hydralazine was 225 mg daily. Follow-up was up to 18 months. The study was terminated early because of a significant 43% improvement in overall survival for the patients in the isosorbide-hydralazine group. In addition, the rate of first hospitalization was 39% lower and the mean improvement in quality-of-life scores was 52% greater with isosorbide-hydralazine than with placebo.⁶⁷

There has been much debate about whether the benefit seen in this trial was the result of a hemodynamic effect, blood pressure response, or neurohormonal modulation. The benefit is less likely from a reduction in blood pressure, as the patients who had low blood pressure derived a mortality benefit similar to those with higher blood pressure, despite no further reduction in their blood pressure.⁶⁸

Treatment for heart failure with preserved ejection fraction

Although there are no data on how to manage heart failure with preserved ejection fraction that are specific to African Americans, the ACCF/AHA guideline⁴¹ recommends treating systolic and diastolic hypertension (class I, level of evidence B) according to published clinical practice guidelines and using diuretics to alleviate volume overload (class I; level of evidence C). Revascularization and management of atrial fibrillation are also “reasonable,” as are the use of ARBs, ACE inhibitors, and beta-blockers in the management of hypertension (class IIa; level of evidence C). ARBs may also be considered to reduce hospitalization in symptomatic patients with heart failure with preserved ejection fraction (class IIb, ie, “may be considered”; level of evidence B).

For acute decompensated heart failure

One of the greatest challenges in heart failure is treating patients who present with acute decompensated heart failure.

As in the general population, the major precipitating factor for hospitalization with decompensated heart failure in African Americans is nonadherence to prescribed dietary and medication regimens.³⁵ African Americans with acute decompensated heart failure tend to be younger and to have nonischemic cardiomyopathy, hypertension, diabetes, and obesity, but a lower risk of death.^35,69,70 Up to 44% have uncontrolled hypertension.³⁵

Inotropes and vasodilators have undergone multiple trials in the acutely decompensated state in the general population, but no trial has demonstrated a reduction in the mortality rate, and some showed a higher mortality rate. Thus, the treatment of acute decompensated heart failure remains primarily consensus-guided and symptom-focused.

Loop diuretics have been the mainstay in managing fluid retention and congestion in heart failure. The Diuretic Optimization Strategies Evaluation trial tested low-dose vs high-dose intravenous furosemide (Lasix) given either as a continuous infusion or as intermittent intravenous boluses. All strategies were safe and effective.⁷¹

Although ultrafiltration is an effective method of decongestion in heart failure and has been associated with a reduction in hospitalization, it is also associated with worsening renal function.⁷² The Cardiorenal Rescue Study in Acute Decompensated Heart Failure⁷³ compared ultrafiltration vs stepped diuretic therapy. In this trial, which enrolled approximately 26% nonwhites, stepped diuretic therapy was superior to ultrafiltration in preserving renal function in acute decompensated heart failure, although the efficacy of fluid removal was similar.

Both studies were small, and subgroup analyses are not likely to yield useful information. Nevertheless, these data support the use of intravenous diuretics, by continuous infusion or bolus, in acute decompensated heart failure.

Despite no benefit in terms of the mortality rate, inotropes continue to be used in some cases of acute decompensated heart failure, and African Americans appear to have a response to milrinone (Primacor IV) similar to that in whites.⁶⁹

In a nonrandomized study in which most patients were black, high-dose intravenous nitroglycerin appeared to be safe and associated with less need for ventilator support and intensive care unit admission, compared retrospectively with a population that did not receive high-dose nitroglycerin.⁷⁴

Given the different profile of the African American patient with acute decompensated heart failure, prospective studies would be useful in determining the best management strategy.

TREATMENTS FOR ADVANCED HEART FAILURE

Cardiac resynchronization and implantable cardioverter-defibrillators

Cardiac resynchronization therapy is indicated for patients with NYHA class II, III, and ambulatory class IV heart failure and left ventricular ejection fraction less than or equal to 35%, sinus rhythm, left bundle branch block, and a QRS duration greater than or equal to 150 ms (class I recommendation; level of evidence A for class NYHA III and IV; level of evidence B for NYHA class II).⁴¹

An implantable cardioverter-defibrillator is recommended in patients with NYHA class II or III heart failure for primary prevention of sudden cardiac death in selected patients with nonischemic dilated cardiomyopathy or ischemic heart disease (class I recommendation; level of evidence A).

However, few members of racial and ethnic minorities were included in trials of implantable cardioverter-defibrillators^75,76 or cardiac resynchronization,^7,77,78 so that subgroup analysis is limited. Use of an implantable cardioverter-defibrillator showed similar reduction in mortality between African Americans and whites, and compliance with device implantation and medical therapy was comparable.⁷⁹

Among patients discharged from hospitals in the American Heart Association’s Get With the Guidelines–Heart Failure Quality Improvement Program, fewer than 40% of potentially eligible patients received an implantable cardioverter-defibrillator, and rates were significantly lower for African Americans.⁸⁰ When they can get cardiac resynchronization therapy, African Americans appear to experience similar benefit from it.⁸¹

Heart transplantation: Poorer outcomes in African Americans?

Heart transplantation remains the most effective and durable therapy for advanced heart failure. Median survival approaches 14 years.⁸²

However, a retrospective study found that African American recipients had an 11.5% lower 10-year survival rate than whites, which persisted after adjusting for risk, donor-recipient matching by race, and censoring of deaths in the first year.⁸³ Although socioeconomic factors and poor human leukocyte antigen matching have been implicated, a retrospective cohort study showed that African American recipients had a higher risk of death than white recipients even after adjustment for recipient, transplant, and socioeconomic factors.^84–87 African Americans were more likely to die of graft failure or of a cardiovascular cause than white patients, but were less likely to die of infection or malignancy. Although mortality rates decreased over time for all transplant recipients, the disparity in mortality rates between African Americans and whites remained essentially unchanged.⁸⁴

Among all donor-recipient combinations, African American recipients of hearts from African American donors had the highest risk of death.⁸⁸

Limited access to transplantation persists, particularly for African Americans of lower socioeconomic status. African Americans are more likely than whites to be uninsured, and the funding requirement to be placed on the transplantation list disproportionately affects African Americans.^89,90

Left-ventricular assist devices

Left-ventricular assist devices (LVADs) improve survival in heart transplantation candidates and heart failure patients who do not qualify for transplantation. After LVAD implantation, African American patients have similar 1- and 2-year survival rates and no difference in readmission rates compared with whites.^91,92

Access to LVAD implantation, however, is significantly influenced by race, and African Americans are significantly less likely to receive one (OR = 0.29).⁹³ Further investigation is required to identify disparities in outcome, access, and contributing factors.

DISPARITIES CAN BE MINIMIZED

In general, heart failure in African Americans is characterized by a high prevalence of hypertension as a major risk factor and potentially different pathogenesis than in the general population. Furthermore, heart failure in African Americans is more prevalent, occurs at an early age, and has a more severe course than in whites, perhaps because of a higher prevalence of risk factors such as diabetes mellitus, obesity, and again, hypertension. These disparities are multifactorial and involve a complex interplay between genes, environment, and socioeconomic factors.

For now, heart failure in African Americans should be treated according to standard evidenced-based strategies, which include a combination of isosorbide dinitrate and hydralazine in addition to other neurohormonal modifying agents (ACE inhibitors, beta-blockers, aldosterone antagonists), a strategy demonstrated to reduce mortality rates in African Americans. When treated according to guidelines, disparities in outcomes can be minimized.

However, many questions about managing heart failure remain unanswered, since African Americans have been markedly underrepresented in clinical trials. Clinical trials need to enroll enough African Americans to answer the questions of interest. Disparities in outcomes must be investigated in a scientific and hypothesis-driven manner. The effect of the built environment on African Americans needs more study as well, as success with these strategies may be impeded by unrecognized factors.

Preventing heart failure should be a priority. Efforts should be directed toward detecting and modifying risk factors early, managing hypertension aggressively, and identifying left ventricular dysfunction early.

African Americans are disproportionately affected by heart failure and have not experienced the same benefit from treatment as white patients have. Much of the disparity can be blamed on modifiable risk factors such as uncontrolled hypertension and on suboptimal health care. When African Americans are treated according to guidelines, discrepant outcomes can be minimized.

In this article, we review the processes contributing to heart failure in African Americans, its management, and challenges with regard to disparities.

HEART FAILURE IS INCREASING

Despite 20 years of progress in understanding the pathophysiology of heart failure and developing medical and surgical therapies for it, its prevalence and associated morbidity are increasing in the United States. In 2010, 6.6 million (2.8%) of the adults in the United States had heart failure,¹ and the prevalence is expected to increase by about 25% by 2030.

DISPARITIES IN INCIDENCE, OUTCOMES

Heart failure is more prevalent in African Americans than in whites, imposes higher rates of death and morbidity, and has a more malignant course.^1–6

According to American Heart Association statistics, the annual incidence of heart failure in whites is approximately 6 per 1,000 person-years, while in African Americans it is 9.1 per 1,000 person-years.¹ In the Atherosclerosis Risk in Communities study, the incidence of new heart failure was 1.0 per 1,000 person-years in Chinese Americans, 2.4 in whites, 3.5 in Hispanics, and 4.6 in African Americans.²

Moreover, when hospitalized for heart failure, African Americans have a 45% greater risk of death or decline in functional status than whites.⁷

Heart failure also occurs earlier in African Americans. Bibbins-Domingo et al⁸ reported that heart failure before age 50 was 20 times more frequent in African Americans than in whites. Functional and structural cardiac changes appeared an average of 10 years before the onset of symptoms and were strongly associated with the development of subsequent heart failure.⁸

In the Women’s Health Initiative, African American women had higher rates of heart failure than white women, perhaps in part because of higher rates of diabetes.⁹

Heart failure with preserved ejection fraction

About half of patients who have signs and symptoms of heart failure have a normal (“preserved”) ejection fraction. The incidence of this condition, previously called diastolic heart failure, appears to be similar between African Americans and whites. However, African Americans appear to have a greater incidence of factors that predispose to it and tend to present later in the course.¹⁰ For example, African Americans have higher left ventricular mass and wall thickness and a higher incidence of left ventricular hypertrophy than white patients.^11–13 In addition, those with heart failure with preserved ejection fraction tend to be younger, female, more likely to have hypertension and diabetes, and less likely to have coronary artery disease, and tend to have worse renal function than their white counterparts.^14,15 The predisposition to diastolic impairment persists even after adjusting for risk factors.^11–15 The mortality rate in African Americans with heart failure with preserved ejection fraction and without coronary artery disease may also be higher than that of comparable white patients.¹⁶

WHY DO AFRICAN AMERICANS HAVE MORE HEART FAILURE?

Modifiable risk factors

In African Americans, the higher percentage of cases of heart failure is attributable to modifiable risk factors such as hypertension, hyperglycemia, left ventricular hypertrophy, and smoking, and fewer cases are due to ischemic heart disease.^2,3 Nonischemic cardiomyopathy predominates in African Americans, whereas ischemic cardiomyopathy predominates in whites.

Hypertension, diabetes, obesity, and chronic kidney disease all portend subsequent heart failure and are common in African Americans, but hypertension is the main culprit.^{3,5,8,17–21} The prevalence of hypertension in African Americans is among the highest in the world, and because African Americans are more likely to have poorer control of their hypertension, they consequently have more target-organ damage.²² Indeed, in many hypertensive African Americans who develop heart failure, the hypertension is poorly controlled. However, even after adjusting for risk factors, and particularly blood pressure control, African Americans remain at higher risk of heart failure.²³

The specific mechanistic links between hypertension and heart failure remain to be identified. Despite having a higher prevalence of left ventricular hypertrophy and left ventricular remodeling, African Americans with heart failure tend toward systolic heart failure, as opposed to heart failure with preserved ejection fraction.

Neurohormonal imbalances and endothelial dysfunction

Derangements in the renin-angiotensin-aldosterone and adrenergic axes are likely the main pathophysiologic mechanisms in the genesis of heart failure in all populations. However, other factors may underlie the enhanced disease burden in African Americans.

Impaired endothelial function, as evidenced by impaired digital and brachial artery vasomotion, is very common in African Americans.^24–26 The small arteries of African Americans are less elastic than those of whites and Chinese.²⁷ The underlying mechanism may be related to increased oxidative stress, decreased nitric oxide availability, exaggerated vasoconstrictor response, and attenuated responsiveness to vasodilators and nitric oxide.^28–31

Genetic polymorphisms

An important caveat in discussing racial differences in heart failure is that “race” is completely arbitrary and is based on sociopolitical rather than scientific or physiologic definitions. Perceived genetic influences are likely to represent complex gene-gene, gene-environment, and gene-drug interactions.

This is especially true for African Americans, who are a markedly heterogeneous group. The US Office of Management and Budget defines “black” or “African American” as having origins in any of the black racial groups of Africa (www.census.gov/2010census/data). Thus, “African American” includes sixth-generation descendants of African slaves, recently immigrated Jamaicans, and black descendants of French and Spanish people.

Most African Americans have some European ancestry. In one study, the estimated proportion of European ancestry ranged from 7% in Jamaicans of African descent to approximately 23% in African Americans in New Orleans.³²

Nevertheless, several polymorphisms associated with the risk of heart failure may provide insight into some of the “race-based” differences in pathophysiology and response to medications and, it is hoped, may eventually serve as the basis for tailored therapy. Genes of interest include those for:

• Beta 1 adrenergic receptor
• Alpha 2c receptor³³
• Aldosterone synthase³⁴
• G protein
• Transforming growth factor beta
• Nitric oxide synthase³⁵
• Transthyrectin.^36,37

Socioeconomic factors and quality of care

Heart failure patients—and especially African Americans—have high rates of hospital readmission, and socioeconomic factors have been implicated. In more than 40,000 patients with heart failure, lower income was a significant predictor of hospital readmission.³⁸ Socioeconomic factors in turn could account for delay in seeking treatment for worsening symptoms, failure to recognize symptoms, limited disease awareness, inadequate access to health care, noncompliance with follow-up appointments, and poor adherence to recommended treatment, all of which are common in African American patients.^38,39

African Americans also report more discrimination from health care providers, have more concerns about blood pressure medications, and are more likely to have misperceptions about high blood pressure (eg, that it is not serious), all of which may interfere with optimal blood pressure control.⁴⁰ Managing heart failure in African Americans should include trying to identify and eliminate barriers to attaining treatment goals.

PREVENTING HEART FAILURE BY REDUCING RISK FACTORS

The American College of Cardiology Foundation and American Heart Association, in their 2013 guidelines, underscored the progressive nature of heart failure by defining four stages of the disease, from stage A (at risk) through stage D (refractory heart failure) (Figure 1).⁴¹ They also emphasized the importance of preventing it.

A thorough clinical assessment, with appropriate assessment for risk factors and intervention at stage A, is critical in preventing left ventricular remodeling and heart failure. These risk factors include hypertension, hyperlipidemia, atherosclerosis, diabetes mellitus, valvular disease, obesity, physical inactivity, excessive alcohol intake, poor diet, and smoking.

Hypertension is especially important in African Americans and requires vigorous screening and aggressive treatment. Antihypertensive drugs should be prescribed early, with a lower threshold for escalating therapy with combinations of drugs, as most patients require more than one.

There is considerable debate about the appropriate blood pressure thresholds for diagnosing hypertension and the optimal target blood pressures in African Americans. The 2014 report of the Joint National Committee recommends a similar hypertension treatment target of 140/90 mm Hg for all patients except older adults (for whom 150/90 mm Hg is acceptable), and no separate target for African Americans.⁴² Previous guidelines from this committee recommended thiazide-type diuretics as first-line therapy for hypertension in African Americans⁴³; the new ones recommend thiazide-type diuretics or calcium channel blockers. However, in those with left ventricular systolic dysfunction, hypertension treatment should include drugs shown to reduce the risk of death in heart failure—ie, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, hydralazine, nitrates, and aldosterone receptor antagonists.

Salt intake should be reduced to less than 3 g per day (1,200 mg of sodium per day), which has been shown to substantially reduce rates of cardiovascular morbidity and mortality and health care costs.⁴⁴ Since most Americans consume 7 to 10 g of salt per day, strict salt restriction should be encouraged as a preventive measure.

Diabetes should be screened for and treated in African Americans per current American Diabetes Association guidelines.

Dyslipidemia should also be screened for and treated per guidelines.⁴⁵

Smoking cessation, moderation of alcohol intake, and avoidance of illicit drugs should be encouraged. Given that African Americans develop heart failure at a relatively early age, the level of vigilance should be high and the threshold for screening should be low.

Healthy neighborhoods, healthy people

Neighborhoods can be designed and built with wellness in mind, incorporating features such as access to healthy food and walkability. Living in such neighborhoods leads to more physical activity and less obesity, although this relationship may be less robust in African Americans.^46–49

Environmental factors are multifactorial in African Americans and extend beyond those afforded by the built environment. For instance, lack of safety may hinder the potential benefit of an otherwise walkable neighborhood. These interactions are highly complex, and more investigation is needed to determine the effect of built environments on risk factors in African Americans.

DRUG THERAPY FOR HEART FAILURE IN AFRICAN AMERICANS

Use standard therapies

ACE inhibitors, beta-blockers, and aldosterone antagonists are the standard of care in heart failure, with digoxin (Lanoxin) and diuretics used as adjuncts to control symptoms.

African Americans may respond differently than whites to some of these drugs (Table 1). However, these findings should be interpreted with caution, since most of them came from subgroup analyses of trials in which African Americans accounted for as many as 28% to as few as 1%.⁵⁰ To date, no data unequivocally show that we should use standard heart failure therapies any differently in African Americans than in whites.

Digoxin: Limited role to control symptoms

Post hoc analysis of the Digitalis Investigation Group trial, in which 14% of the patients were nonwhite, revealed that compared with placebo, digitalis (and achieving a serum digitalis concentration of 0.5 to 0.9 ng/mL) was associated with lower rates of all-cause mortality in most subgroups—except nonwhites.⁵¹

In general, digoxin has a limited role in heart failure, since other drugs are available that substantially modify outcomes. However, it can be considered in patients who have persistent heart failure symptoms.

ACE inhibitors, ARBs are recommended

ACE inhibitors are recommended for patients with New York Heart Association (NYHA) class I, II, III, or IV heart failure (class I recommendation, ie, “recommended”; level of evidence A on a scale of A, B, and C) and as part of standard therapy for African American patients with heart failure with symptomatic or asymptomatic left ventricular systolic dysfunction (class I recommendation; level of evidence C).⁴¹

Although African American patients did not appear to derive any benefit from enalapril (Vasotec) in the Studies of Left Ventricular Dysfunction (SOLVD) trial,⁵² a subsequent analysis that involved the SOLVD Prevention Trial did not find any differences between African Americans and whites in response to this agent.⁶ Similarly, a meta-analysis did not suggest differences in ACE-inhibitor efficacy in reducing adverse cardiovascular outcomes in heart failure between African Americans and non–African Americans.⁵³

Of note: African Americans have a 3% to 4% higher incidence of angioedema from ACE inhibitors than whites.^54,55

Angiotensin receptor blockers (ARBs) can be used as substitute therapy in African Americans who cannot tolerate ACE inhibitors (class IIa recommendation, ie, “reasonable”; level of evidence B).⁴¹

Beta-blockers also recommended

Beta-blockers are recommended in NYHA class I, II, III, and IV heart failure (class I recommendation; level of evidence A) and as part of standard therapy for African Americans with heart failure due to symptomatic left ventricular systolic dysfunction (class I recommendation; level of evidence B) and asymptomatic left ventricular systolic dysfunction (level of evidence C).⁴¹

Carvedilol (Coreg) and metoprolol (Lopressor) are the standard beta-blockers used to treat heart failure, and these drugs should be used in African Americans as well as in whites.^{15,53,56–59} Of interest, however, race-specific differences may exist in the beta-adrenergic pathway.^60,61

Aldosterone antagonists: More study needed

Aldosterone antagonists, also called mineralocorticoid antagonists, ie, spironolactone (Aldactone) and eplerenone (Inspra), are recommended in addition to beta-blockers and ACE inhibitors for NYHA class II–IV heart failure, unless contraindicated (class I recommendation; level of evidence A).

However, trials of aldosterone antagonists to date have enrolled few African Americans.^62–64 The limited data suggest that African Americans with heart failure may be less responsive to the renal effects of spironolactone, demonstrating less of an increase in serum potassium levels, and there are essentially no data to guide the use of these drugs in African Americans with heart failure.⁶⁵ Further study is needed. But in the absence of data to the contrary, these agents, should also be used in African American patients with class III or IV heart failure.

Hydralazine plus nitrates: Recommended for African Americans

Hydralazine plus isosorbide dinitrate (available as BiDil) is recommended as part of standard therapy, in addition to beta-blockers and ACE inhibitors specifically for African Americans with left ventricular systolic dysfunction and NYHA class III or IV heart failure (class I recommendation; level of evidence A), as well as NYHA class II heart failure (class I recommendation; level of evidence B).⁴¹

Preliminary evidence for this combination came from the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials.⁶⁶

Subsequently, the African-American Heart Failure Trial⁶⁷ was conducted in self-identified African American patients with NYHA class III or IV heart failure on standard heart failure therapy, including an ACE inhibitor if tolerated. Patients were randomly assigned to receive a fixed combination of isosorbide 20 mg and hydralazine 37.5 mg, one or two tablets three times a day, or placebo. The target dose of isosorbide dinitrate was 120 mg, and the target dose of hydralazine was 225 mg daily. Follow-up was up to 18 months. The study was terminated early because of a significant 43% improvement in overall survival for the patients in the isosorbide-hydralazine group. In addition, the rate of first hospitalization was 39% lower and the mean improvement in quality-of-life scores was 52% greater with isosorbide-hydralazine than with placebo.⁶⁷

There has been much debate about whether the benefit seen in this trial was the result of a hemodynamic effect, blood pressure response, or neurohormonal modulation. The benefit is less likely from a reduction in blood pressure, as the patients who had low blood pressure derived a mortality benefit similar to those with higher blood pressure, despite no further reduction in their blood pressure.⁶⁸

Treatment for heart failure with preserved ejection fraction

Although there are no data on how to manage heart failure with preserved ejection fraction that are specific to African Americans, the ACCF/AHA guideline⁴¹ recommends treating systolic and diastolic hypertension (class I, level of evidence B) according to published clinical practice guidelines and using diuretics to alleviate volume overload (class I; level of evidence C). Revascularization and management of atrial fibrillation are also “reasonable,” as are the use of ARBs, ACE inhibitors, and beta-blockers in the management of hypertension (class IIa; level of evidence C). ARBs may also be considered to reduce hospitalization in symptomatic patients with heart failure with preserved ejection fraction (class IIb, ie, “may be considered”; level of evidence B).

For acute decompensated heart failure

One of the greatest challenges in heart failure is treating patients who present with acute decompensated heart failure.

As in the general population, the major precipitating factor for hospitalization with decompensated heart failure in African Americans is nonadherence to prescribed dietary and medication regimens.³⁵ African Americans with acute decompensated heart failure tend to be younger and to have nonischemic cardiomyopathy, hypertension, diabetes, and obesity, but a lower risk of death.^35,69,70 Up to 44% have uncontrolled hypertension.³⁵

Inotropes and vasodilators have undergone multiple trials in the acutely decompensated state in the general population, but no trial has demonstrated a reduction in the mortality rate, and some showed a higher mortality rate. Thus, the treatment of acute decompensated heart failure remains primarily consensus-guided and symptom-focused.

Loop diuretics have been the mainstay in managing fluid retention and congestion in heart failure. The Diuretic Optimization Strategies Evaluation trial tested low-dose vs high-dose intravenous furosemide (Lasix) given either as a continuous infusion or as intermittent intravenous boluses. All strategies were safe and effective.⁷¹

Although ultrafiltration is an effective method of decongestion in heart failure and has been associated with a reduction in hospitalization, it is also associated with worsening renal function.⁷² The Cardiorenal Rescue Study in Acute Decompensated Heart Failure⁷³ compared ultrafiltration vs stepped diuretic therapy. In this trial, which enrolled approximately 26% nonwhites, stepped diuretic therapy was superior to ultrafiltration in preserving renal function in acute decompensated heart failure, although the efficacy of fluid removal was similar.

Both studies were small, and subgroup analyses are not likely to yield useful information. Nevertheless, these data support the use of intravenous diuretics, by continuous infusion or bolus, in acute decompensated heart failure.

Despite no benefit in terms of the mortality rate, inotropes continue to be used in some cases of acute decompensated heart failure, and African Americans appear to have a response to milrinone (Primacor IV) similar to that in whites.⁶⁹

In a nonrandomized study in which most patients were black, high-dose intravenous nitroglycerin appeared to be safe and associated with less need for ventilator support and intensive care unit admission, compared retrospectively with a population that did not receive high-dose nitroglycerin.⁷⁴

Given the different profile of the African American patient with acute decompensated heart failure, prospective studies would be useful in determining the best management strategy.

TREATMENTS FOR ADVANCED HEART FAILURE

Cardiac resynchronization and implantable cardioverter-defibrillators

Cardiac resynchronization therapy is indicated for patients with NYHA class II, III, and ambulatory class IV heart failure and left ventricular ejection fraction less than or equal to 35%, sinus rhythm, left bundle branch block, and a QRS duration greater than or equal to 150 ms (class I recommendation; level of evidence A for class NYHA III and IV; level of evidence B for NYHA class II).⁴¹

An implantable cardioverter-defibrillator is recommended in patients with NYHA class II or III heart failure for primary prevention of sudden cardiac death in selected patients with nonischemic dilated cardiomyopathy or ischemic heart disease (class I recommendation; level of evidence A).

However, few members of racial and ethnic minorities were included in trials of implantable cardioverter-defibrillators^75,76 or cardiac resynchronization,^7,77,78 so that subgroup analysis is limited. Use of an implantable cardioverter-defibrillator showed similar reduction in mortality between African Americans and whites, and compliance with device implantation and medical therapy was comparable.⁷⁹

Among patients discharged from hospitals in the American Heart Association’s Get With the Guidelines–Heart Failure Quality Improvement Program, fewer than 40% of potentially eligible patients received an implantable cardioverter-defibrillator, and rates were significantly lower for African Americans.⁸⁰ When they can get cardiac resynchronization therapy, African Americans appear to experience similar benefit from it.⁸¹

Heart transplantation: Poorer outcomes in African Americans?

Heart transplantation remains the most effective and durable therapy for advanced heart failure. Median survival approaches 14 years.⁸²

However, a retrospective study found that African American recipients had an 11.5% lower 10-year survival rate than whites, which persisted after adjusting for risk, donor-recipient matching by race, and censoring of deaths in the first year.⁸³ Although socioeconomic factors and poor human leukocyte antigen matching have been implicated, a retrospective cohort study showed that African American recipients had a higher risk of death than white recipients even after adjustment for recipient, transplant, and socioeconomic factors.^84–87 African Americans were more likely to die of graft failure or of a cardiovascular cause than white patients, but were less likely to die of infection or malignancy. Although mortality rates decreased over time for all transplant recipients, the disparity in mortality rates between African Americans and whites remained essentially unchanged.⁸⁴

Among all donor-recipient combinations, African American recipients of hearts from African American donors had the highest risk of death.⁸⁸

Limited access to transplantation persists, particularly for African Americans of lower socioeconomic status. African Americans are more likely than whites to be uninsured, and the funding requirement to be placed on the transplantation list disproportionately affects African Americans.^89,90

Left-ventricular assist devices

Left-ventricular assist devices (LVADs) improve survival in heart transplantation candidates and heart failure patients who do not qualify for transplantation. After LVAD implantation, African American patients have similar 1- and 2-year survival rates and no difference in readmission rates compared with whites.^91,92

Access to LVAD implantation, however, is significantly influenced by race, and African Americans are significantly less likely to receive one (OR = 0.29).⁹³ Further investigation is required to identify disparities in outcome, access, and contributing factors.

DISPARITIES CAN BE MINIMIZED

In general, heart failure in African Americans is characterized by a high prevalence of hypertension as a major risk factor and potentially different pathogenesis than in the general population. Furthermore, heart failure in African Americans is more prevalent, occurs at an early age, and has a more severe course than in whites, perhaps because of a higher prevalence of risk factors such as diabetes mellitus, obesity, and again, hypertension. These disparities are multifactorial and involve a complex interplay between genes, environment, and socioeconomic factors.

For now, heart failure in African Americans should be treated according to standard evidenced-based strategies, which include a combination of isosorbide dinitrate and hydralazine in addition to other neurohormonal modifying agents (ACE inhibitors, beta-blockers, aldosterone antagonists), a strategy demonstrated to reduce mortality rates in African Americans. When treated according to guidelines, disparities in outcomes can be minimized.

However, many questions about managing heart failure remain unanswered, since African Americans have been markedly underrepresented in clinical trials. Clinical trials need to enroll enough African Americans to answer the questions of interest. Disparities in outcomes must be investigated in a scientific and hypothesis-driven manner. The effect of the built environment on African Americans needs more study as well, as success with these strategies may be impeded by unrecognized factors.

Preventing heart failure should be a priority. Efforts should be directed toward detecting and modifying risk factors early, managing hypertension aggressively, and identifying left ventricular dysfunction early.

A 20-year-old woman presents to the emergency department with fatigue and the sudden onset of palpitations. She reports no history of significant illness or surgery. She says she is not currently taking prescription or over-the-counter medications. She does not smoke, drink alcohol, or use illicit drugs.

Her weight is 52 kg (115 lb), her height is 170 cm (67 in), and her body mass index (BMI) is 18 kg/m². Vital signs: temperature 35.7°C (96.4°F), blood pressure 92/48 mm Hg, heart rate 73 bpm, respiratory rate 5 breaths per minute, and oxygen saturation 98% on room air.

She appears tired but is alert, conversant, and cooperative. Her skin is normal, and dentition is fair. Her pulse is regular, and respirations are slow. The abdomen is soft, non-tender, and flat. Strength is 4 on a scale of 5 in all extremities. Deep-tendon reflexes are 2+ and symmetric.

Electrocardiography (Figure 1) in the emergency department shows ST-segment depression, a prolonged corrected QT interval of 665 msec, T-wave inversion, PR prolongation, increased P-wave amplitude, and U waves.

1. Which electrolyte abnormality is associated with this electrocardiographic picture?

• Hypercalcemia
• Hyperkalemia
• Hypocalcemia
• Hypokalemia

Hypokalemia is the likely cause of these findings. The finding of U waves is considered significant when they are inverted, merged with the T wave, or have an amplitude greater than the T wave.¹ U waves are best seen in the precordial leads. When severe, hypokalemia can lead to potentially fatal arrhythmias such as high-grade atrioventricular block, ventricular tachycardia, and ventricular fibrillation.²

Hyperkalemia is associated with peaked T waves, a prolonged PR interval, decreased P wave amplitude, and a widened QRS complex.² When acute and severe, hyperkalemia is associated with ventricular arrhythmia.

Hypocalcemia is associated with a prolonged QT interval and ventricular dysrhythmia, but not U waves.²

Hypercalcemia is associated with bradydysrhythmia, as well as with a shortened QT interval.²

LABORATORY TESTING

Laboratory testing shows the following:

• Sodium 126 mmol/L (reference range 135–145)
• Potassium 1.5 mmol/L (3.5–5.1)
• Chloride 58 mmol/L (100–110)
• Bicarbonate 62 mmol/L (20–30)
• Blood urea nitrogen 16 mg/dL (7–18)
• Creatinine 0.8 mg/dL (0.5–1.0)
• Glucose 106 mg/dL (70–110)
• Ionized calcium 4.4 mg/dL (4.5–5.3)
• Magnesium 1.8 mg/dL (1.7–2.3)
• Phosphorus 4.1 mg/dL (2.5–4.5)
• Venous blood gases pH 7.56 (7.35–7.45), Pco₂ 69 mm Hg (35–45).

POTASSIUM HOMEOSTASIS

Ninety-eight percent of potassium is intracellular and only 2% is extracellular.³ The main cellular stores are myocytes and hepatocytes. Patients with decreased muscle mass may be at a higher risk of hypokalemia as a result of decreased skeletal muscle stores.⁴

The acute development of hypokalemia occurs from transcellular shifts. Alkalosis, insulin secretion, and beta-adrenergic stimulation promote the intracellular uptake of potassium. The major hormonal regulator of potassium excretion is aldosterone, which is stimulated by renal hypoperfusion and promotes potassium-ion secretion in the distal convoluted tubule.

Chronic hypokalemia develops in patients with ongoing renal or gastrointestinal potassium loss. If the cause of potassium loss is not elucidated by the history, the physical, and a review of medications, then one of two things is possible: either the patient has renal tubular disease affecting acid-base and potassium regulation, causing excessive mineralocorticoid secretion, which is associated with an abnormal response to aldosterone; or the patient is not being forthcoming in the history.

2. Which is the most likely cause of hypokalemia in this patient?

• Vomiting
• Liddle syndrome
• Bartter syndrome
• Gitelman syndrome
• Diuretic use

Her laboratory tests reveal hypokalemia and hyponatremic-hypochloremic metabolic alkalosis with compensatory respiratory acidosis. In metabolic alkalosis, the expected respiratory compensation is an increase of 0.7 mm Hg in Pco₂ for each 1-mEq/L increase in bicarbonate. Therefore, the expected Pco₂ is 67, close to the patient’s actual value of 69.

Protracted vomiting with loss of gastric acid juices could be a cause of the metabolic disturbances in this young woman, although she did not mention vomiting during the history.

Liddle syndrome, or pseudoaldosteronism, is a rare autosomal dominant disorder characterized by altered renal epithelial sodium channels, excessive sodium retention, and resultant hypertension. Hypokalemia and alkalosis are seen in Liddle syndrome, but the absence of hypertension in our patient makes Liddle syndrome unlikely.

Bartter syndrome is an inherited autosomal recessive disorder of the sodium-potassium-chloride cotransporter in the thick ascending loop of Henle, resulting in impaired reabsorption of chloride and sodium. Bartter syndrome mimics chronic loop-diuretic use and is associated with hypercalciuria. Bartter syndrome is possible in this patient; however, patients with Bartter syndrome are usually diagnosed in infancy or childhood and have evidence of growth impairment.

Gitelman syndrome is an autosomal recessive disorder of the thiazide-sensitive sodium-chloride cotransporter. Although Gitelman syndrome is more common than Bartter syndrome and presents at older ages, it is not usually associated with such profound metabolic alkalosis. Gitelman syndrome mimics chronic use of thiazide diuretics and is associated with hypocalciuria.

Diuretic use could also cause the metabolic disturbances described; however, the patient denied taking diuretics.

The most common cause of hypokalemia in clinical practice is diuretic use.⁴ In this young woman with unexplained hypokalemia, the most likely cause is either undisclosed self-induced vomiting or diuretic abuse. The degree of metabolic alkalosis suggests vomiting, since metabolic alkalosis this severe is usually seen only with protracted vomiting. Bartter and Gitelman syndromes are included in the differential diagnosis, but they are much less common than hypokalemia associated with diuretics or self-induced vomiting.⁵

3. Which test could help elucidate the cause of hypokalemia in this patient?

• Ratio of plasma aldosterone to rennin
• Urine chloride
• Ratio of urinary potassium to creatinine
• Urinary anion gap and urinary pH

APPROACH TO HYPOKALEMIA

Determining the cause of hypokalemia starts with a thorough history and physical examination. The history should focus on drugs such as diuretics and laxatives. Women should be asked about their menstrual history since irregular periods may suggest an eating disorder. The physical examination should focus on signs that suggest self-induced vomiting, such as dry skin, dental erosions, enlarged parotid glands, and calluses or scars on the knuckles.

Patients with an unclear cause of hypokalemia after a thorough history and physical examination can be categorized into one of three groups based on blood pressure and acid-base status:

• Hypokalemia, hypertension, metabolic alkalosis
• Hypokalemia, normal blood pressure, metabolic acidosis
• Hypokalemia, normal blood pressure, metabolic alkalosis.

Hypokalemia, hypertension, metabolic alkalosis

The blood pressure provides an important clue in the evaluation of hypokalemia. The combination of hypertension, hypokalemia, and alkalosis should raise concern for hyperaldosteronism or pseudoaldosteronism. Primary hyperaldosteronism from an adrenal adenoma (Conn syndrome) is characterized by a plasma aldosterone-renin ratio of greater than 20.^6,7 In contrast, patients with secondary hyperaldosteronism due to renovascular disease have a plasma aldosterone-renin ratio of less than 10. Patients with pseudoaldosteronism have low aldosterone and renin levels and hypertension. Since our patient has a normal blood pressure, testing the plasma aldosterone and renin levels would not help determine the cause of her hypokalemia.

Hypokalemia, normal blood pressure, metabolic acidosis

Patients with normal blood pressure, hypokalemia, and normal plasma anion gap acidosis either have renal tubular acidosis or have lost potassium because of diarrhea or laxative abuse. In a patient who denies taking laxatives or denies a history of diarrhea, checking the urinary anion gap and urinary pH may help differentiate the cause of acidosis and hypokalemia.

The urinary anion gap, calculated by the equation sodium + potassium − chloride, is an indirect estimate of hydrogen excretion in the form of ammonium ion⁸; the normal value is 0 to 10 mEq/L. A negative value represents increased hydrogen excretion in response to systemic acidosis from gastrointestinal or renal loss of bicarbonate (proximal renal tubular acidosis). A urinary pH greater than 5.5 in the setting of systemic acidosis suggests impaired ability of the kidneys to acidify urine and raises the possibility of renal tubular acidosis.

This patient has metabolic alkalosis, so calculation of the urinary anion gap would not be helpful.

Hypokalemia, normal blood pressure, metabolic alkalosis

Patients such as ours, with normal blood pressure, hypokalemia, and alkalosis, have been vomiting, have used diuretics, or have an inherited renal tubulopathy such as Bartter or Gitelman syndrome. Usually, differentiating Bartter and Gitelman syndromes from chronic vomiting or diuretic use is done with the history and physical examination. However, in patients with a questionable history and a lack of findings on physical examination, checking the urinary chloride, potassium, calcium, and creatinine may be helpful.

A urinary potassium-creatinine ratio greater than 15 suggests renal loss, whereas a ratio less than 15 suggests extrarenal loss.⁹

Patients who are taking a diuretic or who have Bartter or Gitelman syndrome have a high urinary chloride concentration, ie, greater than 20 mmol/L, whereas patients with hypokalemia and alkalosis from chronic vomiting tend to have a concentration less than 10 mmol/L.¹⁰

Table 1 summarizes an approach to the evaluation of unexplained hypokalemia based on blood pressure and acid-base status.

A HIDDEN HISTORY

On further questioning, the patient admits to an 8-year history of daily self-induced vomiting in an attempt to lose weight, in addition to multiple hospitalizations for hypokalemia and a previous diagnosis of an eating disorder.

INITIAL MANAGEMENT OF HYPOKALEMIA

The initial management of hypokalemia should focus on life-threatening emergencies. While patients with potassium levels greater than 3 mmol/L are usually asymptomatic, those with levels below 3 mmol/L present with muscle weakness and rhabdomyolysis.⁴ An acute drop in serum potassium to less than 2 mmol/L is associated with respiratory muscle weakness and ventricular arrhythmias.⁴ If the patient has cardiac symptoms or hypoventilation due to respiratory muscle weakness, continuous monitoring in the intensive care unit and aggressive therapy are warranted.

4. Which potassium formulation is most appropriate for the treatment of hypokalemia in this patient?

• Potassium chloride
• Potassium phosphate
• Potassium acetate

Oral potassium is preferable in patients with a serum potassium above 2.5 mmol/L.^4,11 Potassium phosphate should be used when supplementation with both potassium and phosphorus is needed. Potassium acetate should be reserved for patients with acidosis and hypokalemia. Otherwise, potassium chloride is typically preferred.^4,12 It comes in liquid and tablet forms. Liquid forms have an unpleasant taste, whereas tablets are usually well tolerated. No more than 20 to 40 mEq of potassium chloride tablets should be given at a time, since higher doses are associated with gastrointestinal mucosal injury.¹²

Potassium chloride is particularly preferred in patients with metabolic alkalosis, since increased chloride intake and delivery to the distal tubule increases the expression of pendrin, a luminal chloride and bicarbonate exchanger in the cortical collecting duct.¹³ With metabolic alkalosis, increased excretion of bicarbonate occurs through up-regulation of pendrin. Potassium depletion down-regulates pendrin.¹³ Additionally, correction of metabolic alkalosis increases serum potassium by movement of potassium from the intracellular to the extracellular space.

Intravenous potassium should be reserved for patients with severe hypokalemia (< 2.5 mmol/L) or significant arrhythmias.¹¹ Oral and intravenous potassium can safely be given simultaneously.¹¹ The intravenous rate should not exceed more than 10 to 20 mEq of potassium chloride per hour unless the patient has a life-threatening arrhythmia, respiratory failure, or severe hypokalemia.^14,15 In life-threatening situations, a femoral line should be placed, and potassium should be given as rapidly as 20 mEq over 15 to 20 minutes.¹⁴ Cannulation of the subclavian and internal jugular veins should be avoided in severe hypokalemia since mechanical irritation from guidewire placement can provoke ventricular arrhythmias.¹⁴

During intravenous administration of potassium, laboratory monitoring after every 20 mEq of potassium chloride is advised because of the possibility of rebound hyperkalemia. In patients with severe hypokalemia, avoidance of factors that can worsen intracellular shift of potassium is also important. Avoid dextrose-containing fluids to prevent insulin-induced shifting of potassium into cells. Restore intravascular volume to blunt hypovolemia-induced renin and aldosterone secretion. If a patient presents with severe hypokalemia and acidosis, correct the hypokalemia before the acidosis to avoid intracellular shift of potassium.

OUR PATIENT’S MANAGEMENT AND FOLLOW-UP PLAN

Given the severity of our patient’s hypokalemia and her complaint of palpitations, she was admitted to the hospital for monitoring. She required 180 mEq of intravenous potassium chloride and 140 mEq of oral potassium chloride during the first 24 hours in order to achieve a serum potassium level above 3 mmol/L. Electrocardiographic U waves resolved once the level was above 2 mmol/L, and ST depressions resolved once it was above 3 mmol/L. The QT interval normalized after 24 hours of hospitalization.

On discharge, she was prescribed oral potassium chloride 40 mEq daily and magnesium sulfate 400 mg twice daily, with plans for a followup visit with her outpatient therapy team, which includes a psychiatrist, a social worker, and her primary care provider. She declined a referral for inpatient therapy but agreed to a goal of decreasing the frequency of induced vomiting and outpatient visits. She was also educated on how and when to access emergency medical care.¹⁶

A 20-year-old woman presents to the emergency department with fatigue and the sudden onset of palpitations. She reports no history of significant illness or surgery. She says she is not currently taking prescription or over-the-counter medications. She does not smoke, drink alcohol, or use illicit drugs.

Her weight is 52 kg (115 lb), her height is 170 cm (67 in), and her body mass index (BMI) is 18 kg/m². Vital signs: temperature 35.7°C (96.4°F), blood pressure 92/48 mm Hg, heart rate 73 bpm, respiratory rate 5 breaths per minute, and oxygen saturation 98% on room air.

She appears tired but is alert, conversant, and cooperative. Her skin is normal, and dentition is fair. Her pulse is regular, and respirations are slow. The abdomen is soft, non-tender, and flat. Strength is 4 on a scale of 5 in all extremities. Deep-tendon reflexes are 2+ and symmetric.

Electrocardiography (Figure 1) in the emergency department shows ST-segment depression, a prolonged corrected QT interval of 665 msec, T-wave inversion, PR prolongation, increased P-wave amplitude, and U waves.

1. Which electrolyte abnormality is associated with this electrocardiographic picture?

• Hypercalcemia
• Hyperkalemia
• Hypocalcemia
• Hypokalemia

Hypokalemia is the likely cause of these findings. The finding of U waves is considered significant when they are inverted, merged with the T wave, or have an amplitude greater than the T wave.¹ U waves are best seen in the precordial leads. When severe, hypokalemia can lead to potentially fatal arrhythmias such as high-grade atrioventricular block, ventricular tachycardia, and ventricular fibrillation.²

Hyperkalemia is associated with peaked T waves, a prolonged PR interval, decreased P wave amplitude, and a widened QRS complex.² When acute and severe, hyperkalemia is associated with ventricular arrhythmia.

Hypocalcemia is associated with a prolonged QT interval and ventricular dysrhythmia, but not U waves.²

Hypercalcemia is associated with bradydysrhythmia, as well as with a shortened QT interval.²

LABORATORY TESTING

Laboratory testing shows the following:

• Sodium 126 mmol/L (reference range 135–145)
• Potassium 1.5 mmol/L (3.5–5.1)
• Chloride 58 mmol/L (100–110)
• Bicarbonate 62 mmol/L (20–30)
• Blood urea nitrogen 16 mg/dL (7–18)
• Creatinine 0.8 mg/dL (0.5–1.0)
• Glucose 106 mg/dL (70–110)
• Ionized calcium 4.4 mg/dL (4.5–5.3)
• Magnesium 1.8 mg/dL (1.7–2.3)
• Phosphorus 4.1 mg/dL (2.5–4.5)
• Venous blood gases pH 7.56 (7.35–7.45), Pco₂ 69 mm Hg (35–45).

POTASSIUM HOMEOSTASIS

Ninety-eight percent of potassium is intracellular and only 2% is extracellular.³ The main cellular stores are myocytes and hepatocytes. Patients with decreased muscle mass may be at a higher risk of hypokalemia as a result of decreased skeletal muscle stores.⁴

The acute development of hypokalemia occurs from transcellular shifts. Alkalosis, insulin secretion, and beta-adrenergic stimulation promote the intracellular uptake of potassium. The major hormonal regulator of potassium excretion is aldosterone, which is stimulated by renal hypoperfusion and promotes potassium-ion secretion in the distal convoluted tubule.

Chronic hypokalemia develops in patients with ongoing renal or gastrointestinal potassium loss. If the cause of potassium loss is not elucidated by the history, the physical, and a review of medications, then one of two things is possible: either the patient has renal tubular disease affecting acid-base and potassium regulation, causing excessive mineralocorticoid secretion, which is associated with an abnormal response to aldosterone; or the patient is not being forthcoming in the history.

2. Which is the most likely cause of hypokalemia in this patient?

• Vomiting
• Liddle syndrome
• Bartter syndrome
• Gitelman syndrome
• Diuretic use

Her laboratory tests reveal hypokalemia and hyponatremic-hypochloremic metabolic alkalosis with compensatory respiratory acidosis. In metabolic alkalosis, the expected respiratory compensation is an increase of 0.7 mm Hg in Pco₂ for each 1-mEq/L increase in bicarbonate. Therefore, the expected Pco₂ is 67, close to the patient’s actual value of 69.

Protracted vomiting with loss of gastric acid juices could be a cause of the metabolic disturbances in this young woman, although she did not mention vomiting during the history.

Liddle syndrome, or pseudoaldosteronism, is a rare autosomal dominant disorder characterized by altered renal epithelial sodium channels, excessive sodium retention, and resultant hypertension. Hypokalemia and alkalosis are seen in Liddle syndrome, but the absence of hypertension in our patient makes Liddle syndrome unlikely.

Bartter syndrome is an inherited autosomal recessive disorder of the sodium-potassium-chloride cotransporter in the thick ascending loop of Henle, resulting in impaired reabsorption of chloride and sodium. Bartter syndrome mimics chronic loop-diuretic use and is associated with hypercalciuria. Bartter syndrome is possible in this patient; however, patients with Bartter syndrome are usually diagnosed in infancy or childhood and have evidence of growth impairment.

Gitelman syndrome is an autosomal recessive disorder of the thiazide-sensitive sodium-chloride cotransporter. Although Gitelman syndrome is more common than Bartter syndrome and presents at older ages, it is not usually associated with such profound metabolic alkalosis. Gitelman syndrome mimics chronic use of thiazide diuretics and is associated with hypocalciuria.

Diuretic use could also cause the metabolic disturbances described; however, the patient denied taking diuretics.

The most common cause of hypokalemia in clinical practice is diuretic use.⁴ In this young woman with unexplained hypokalemia, the most likely cause is either undisclosed self-induced vomiting or diuretic abuse. The degree of metabolic alkalosis suggests vomiting, since metabolic alkalosis this severe is usually seen only with protracted vomiting. Bartter and Gitelman syndromes are included in the differential diagnosis, but they are much less common than hypokalemia associated with diuretics or self-induced vomiting.⁵

3. Which test could help elucidate the cause of hypokalemia in this patient?

• Ratio of plasma aldosterone to rennin
• Urine chloride
• Ratio of urinary potassium to creatinine
• Urinary anion gap and urinary pH

APPROACH TO HYPOKALEMIA

Determining the cause of hypokalemia starts with a thorough history and physical examination. The history should focus on drugs such as diuretics and laxatives. Women should be asked about their menstrual history since irregular periods may suggest an eating disorder. The physical examination should focus on signs that suggest self-induced vomiting, such as dry skin, dental erosions, enlarged parotid glands, and calluses or scars on the knuckles.

Patients with an unclear cause of hypokalemia after a thorough history and physical examination can be categorized into one of three groups based on blood pressure and acid-base status:

• Hypokalemia, hypertension, metabolic alkalosis
• Hypokalemia, normal blood pressure, metabolic acidosis
• Hypokalemia, normal blood pressure, metabolic alkalosis.

Hypokalemia, hypertension, metabolic alkalosis

The blood pressure provides an important clue in the evaluation of hypokalemia. The combination of hypertension, hypokalemia, and alkalosis should raise concern for hyperaldosteronism or pseudoaldosteronism. Primary hyperaldosteronism from an adrenal adenoma (Conn syndrome) is characterized by a plasma aldosterone-renin ratio of greater than 20.^6,7 In contrast, patients with secondary hyperaldosteronism due to renovascular disease have a plasma aldosterone-renin ratio of less than 10. Patients with pseudoaldosteronism have low aldosterone and renin levels and hypertension. Since our patient has a normal blood pressure, testing the plasma aldosterone and renin levels would not help determine the cause of her hypokalemia.

Hypokalemia, normal blood pressure, metabolic acidosis

Patients with normal blood pressure, hypokalemia, and normal plasma anion gap acidosis either have renal tubular acidosis or have lost potassium because of diarrhea or laxative abuse. In a patient who denies taking laxatives or denies a history of diarrhea, checking the urinary anion gap and urinary pH may help differentiate the cause of acidosis and hypokalemia.

The urinary anion gap, calculated by the equation sodium + potassium − chloride, is an indirect estimate of hydrogen excretion in the form of ammonium ion⁸; the normal value is 0 to 10 mEq/L. A negative value represents increased hydrogen excretion in response to systemic acidosis from gastrointestinal or renal loss of bicarbonate (proximal renal tubular acidosis). A urinary pH greater than 5.5 in the setting of systemic acidosis suggests impaired ability of the kidneys to acidify urine and raises the possibility of renal tubular acidosis.

This patient has metabolic alkalosis, so calculation of the urinary anion gap would not be helpful.

Hypokalemia, normal blood pressure, metabolic alkalosis

Patients such as ours, with normal blood pressure, hypokalemia, and alkalosis, have been vomiting, have used diuretics, or have an inherited renal tubulopathy such as Bartter or Gitelman syndrome. Usually, differentiating Bartter and Gitelman syndromes from chronic vomiting or diuretic use is done with the history and physical examination. However, in patients with a questionable history and a lack of findings on physical examination, checking the urinary chloride, potassium, calcium, and creatinine may be helpful.