Heart of the Matter

The TOPCAT study, reported at the recent American Heart Association meeting in Dallas, examined the murky world of our understanding of heart failure occurring in patients with preserved left ventricular ejection fraction.

That seeming paradox has been the subject of physiologic and therapeutic controversy for some time. The realization that at least half of the patients admitted to the hospital with heart failure have normal or even supernormal left ventricular ejection fraction (HFpEF) has raised the therapeutic importance of this clinical entity. Of even more importance is the fact that patients with HFpEF exhibit morbidity and mortality similar to those heart failure patients with reduced left ventricular ejection fraction (HFrEF).

In an epidemiologic study in Olmsted County, Minnesota (N. Engl. J. Med. 2006;355:251-9), the 1-year mortality was 29% for HFpEF and 32% for HFrEF. Patients with HFpEF were more likely to be female (65.7% vs. 34.6%) and to have hypertension and atrial fibrillation than were those with HFrEF (62.7% vs. 48% and 41.3% vs. 28.5%, respectively).

Although we have significantly impacted mortality in patients who have HFrEF with the use of cardiac resynchronization therapy, implantable cardiac defibrillators, and medical therapy with beta-blockers and renin angiotensin inhibitors, we have failed to modify clinical outcomes in patients with HFpEF.

This has not been for a lack of trying. Several randomized clinical trials have been conducted with all of the drugs currently being used for HFrEF without any definitive results. An important problem in treating this population has been the heterogeneity of patients and multiple comorbidities, including chronic renal and pulmonary disease, acute hypertension, and atrial fibrillation that patients with HFpEF experience with the acute event. In addition, many of these patients are already receiving a multiplicity of concurrent therapies that have been approved for HFrEF for management.

Our understanding of the pathophysiology of HFpEF also remains cloudy. Both left and right ventricular hypertrophy with concomitant decrease in ventricular diastolic relaxation is the common observed echocardiographic abnormality. We have not as yet developed therapy for the treatment of diastolic dysfunction. Aldosterone antagonists, previously shown to be beneficial in patients with HFrEF, have emerged as likely candidates to improve HFpEF. Small clinical studies have shown improvement in diastolic function in elderly patients with hypertension and chronic renal disease. Consequently, the National Heart, Lung, and Blood Institute embarked on the TOPCAT study in 2006.

TOPCAT randomized 3,345 symptomatic heart failure patients who had a heart failure hospitalization in the previous year and with evidence of fluid retention, a left ventricular ejection fraction of more than 45%, controlled systolic blood pressure of less than 140 mm Hg, and elevated brain natriuretic peptide to treatment with placebo or spironolactone at 25 or 50 mg daily. A history of hypertension was present in 91%, coronary artery disease in 57%, atrial fibrillation in 35%, chronic renal disease in 35%, and diabetes in 32%. Patients included in the study had a mean LVEF of 56%; two thirds were in New York Heart Association class II and one third were in NYHA class III.

Over 80% of patients were receiving an ACE inhibitor or angiotensin receptor blocker, beta-blockers, and a diuretic. The mean dose of spironolactone was 25 mg. There was no significant difference in the primary outcome of cardiovascular death, nonfatal hospitalization or resuscitated cardiac arrest in the placebo and treated groups (20.4% and 18.6%, respectively). There was a significant decrease in heart failure hospitalization in the placebo compared to spironolactone patients (14.2% vs. 12.0%; P = .042). Both hyperkalemia greater than 5.5 mmol/L and an increase in serum creatinine were observed in the treated patients.

The striking observation in this trial, as it has been in previous trials, is the disparity between the epidemiologic mortality and the randomized controlled trial experience: 29% annual mortality in Olmsted County, compared with the 10.2% three-year mortality in TOPCAT. It appears that we are studying two separate diseases. And we are. After all the exclusion criteria included in the design of TOPCAT, we are unable to encapsulate the population at risk in this complex heart failure syndrome.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The TOPCAT study, reported at the recent American Heart Association meeting in Dallas, examined the murky world of our understanding of heart failure occurring in patients with preserved left ventricular ejection fraction.

That seeming paradox has been the subject of physiologic and therapeutic controversy for some time. The realization that at least half of the patients admitted to the hospital with heart failure have normal or even supernormal left ventricular ejection fraction (HFpEF) has raised the therapeutic importance of this clinical entity. Of even more importance is the fact that patients with HFpEF exhibit morbidity and mortality similar to those heart failure patients with reduced left ventricular ejection fraction (HFrEF).

In an epidemiologic study in Olmsted County, Minnesota (N. Engl. J. Med. 2006;355:251-9), the 1-year mortality was 29% for HFpEF and 32% for HFrEF. Patients with HFpEF were more likely to be female (65.7% vs. 34.6%) and to have hypertension and atrial fibrillation than were those with HFrEF (62.7% vs. 48% and 41.3% vs. 28.5%, respectively).

Although we have significantly impacted mortality in patients who have HFrEF with the use of cardiac resynchronization therapy, implantable cardiac defibrillators, and medical therapy with beta-blockers and renin angiotensin inhibitors, we have failed to modify clinical outcomes in patients with HFpEF.

This has not been for a lack of trying. Several randomized clinical trials have been conducted with all of the drugs currently being used for HFrEF without any definitive results. An important problem in treating this population has been the heterogeneity of patients and multiple comorbidities, including chronic renal and pulmonary disease, acute hypertension, and atrial fibrillation that patients with HFpEF experience with the acute event. In addition, many of these patients are already receiving a multiplicity of concurrent therapies that have been approved for HFrEF for management.

Our understanding of the pathophysiology of HFpEF also remains cloudy. Both left and right ventricular hypertrophy with concomitant decrease in ventricular diastolic relaxation is the common observed echocardiographic abnormality. We have not as yet developed therapy for the treatment of diastolic dysfunction. Aldosterone antagonists, previously shown to be beneficial in patients with HFrEF, have emerged as likely candidates to improve HFpEF. Small clinical studies have shown improvement in diastolic function in elderly patients with hypertension and chronic renal disease. Consequently, the National Heart, Lung, and Blood Institute embarked on the TOPCAT study in 2006.

TOPCAT randomized 3,345 symptomatic heart failure patients who had a heart failure hospitalization in the previous year and with evidence of fluid retention, a left ventricular ejection fraction of more than 45%, controlled systolic blood pressure of less than 140 mm Hg, and elevated brain natriuretic peptide to treatment with placebo or spironolactone at 25 or 50 mg daily. A history of hypertension was present in 91%, coronary artery disease in 57%, atrial fibrillation in 35%, chronic renal disease in 35%, and diabetes in 32%. Patients included in the study had a mean LVEF of 56%; two thirds were in New York Heart Association class II and one third were in NYHA class III.

Over 80% of patients were receiving an ACE inhibitor or angiotensin receptor blocker, beta-blockers, and a diuretic. The mean dose of spironolactone was 25 mg. There was no significant difference in the primary outcome of cardiovascular death, nonfatal hospitalization or resuscitated cardiac arrest in the placebo and treated groups (20.4% and 18.6%, respectively). There was a significant decrease in heart failure hospitalization in the placebo compared to spironolactone patients (14.2% vs. 12.0%; P = .042). Both hyperkalemia greater than 5.5 mmol/L and an increase in serum creatinine were observed in the treated patients.

The striking observation in this trial, as it has been in previous trials, is the disparity between the epidemiologic mortality and the randomized controlled trial experience: 29% annual mortality in Olmsted County, compared with the 10.2% three-year mortality in TOPCAT. It appears that we are studying two separate diseases. And we are. After all the exclusion criteria included in the design of TOPCAT, we are unable to encapsulate the population at risk in this complex heart failure syndrome.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The TOPCAT study, reported at the recent American Heart Association meeting in Dallas, examined the murky world of our understanding of heart failure occurring in patients with preserved left ventricular ejection fraction.

That seeming paradox has been the subject of physiologic and therapeutic controversy for some time. The realization that at least half of the patients admitted to the hospital with heart failure have normal or even supernormal left ventricular ejection fraction (HFpEF) has raised the therapeutic importance of this clinical entity. Of even more importance is the fact that patients with HFpEF exhibit morbidity and mortality similar to those heart failure patients with reduced left ventricular ejection fraction (HFrEF).

In an epidemiologic study in Olmsted County, Minnesota (N. Engl. J. Med. 2006;355:251-9), the 1-year mortality was 29% for HFpEF and 32% for HFrEF. Patients with HFpEF were more likely to be female (65.7% vs. 34.6%) and to have hypertension and atrial fibrillation than were those with HFrEF (62.7% vs. 48% and 41.3% vs. 28.5%, respectively).

Although we have significantly impacted mortality in patients who have HFrEF with the use of cardiac resynchronization therapy, implantable cardiac defibrillators, and medical therapy with beta-blockers and renin angiotensin inhibitors, we have failed to modify clinical outcomes in patients with HFpEF.

This has not been for a lack of trying. Several randomized clinical trials have been conducted with all of the drugs currently being used for HFrEF without any definitive results. An important problem in treating this population has been the heterogeneity of patients and multiple comorbidities, including chronic renal and pulmonary disease, acute hypertension, and atrial fibrillation that patients with HFpEF experience with the acute event. In addition, many of these patients are already receiving a multiplicity of concurrent therapies that have been approved for HFrEF for management.

Our understanding of the pathophysiology of HFpEF also remains cloudy. Both left and right ventricular hypertrophy with concomitant decrease in ventricular diastolic relaxation is the common observed echocardiographic abnormality. We have not as yet developed therapy for the treatment of diastolic dysfunction. Aldosterone antagonists, previously shown to be beneficial in patients with HFrEF, have emerged as likely candidates to improve HFpEF. Small clinical studies have shown improvement in diastolic function in elderly patients with hypertension and chronic renal disease. Consequently, the National Heart, Lung, and Blood Institute embarked on the TOPCAT study in 2006.

TOPCAT randomized 3,345 symptomatic heart failure patients who had a heart failure hospitalization in the previous year and with evidence of fluid retention, a left ventricular ejection fraction of more than 45%, controlled systolic blood pressure of less than 140 mm Hg, and elevated brain natriuretic peptide to treatment with placebo or spironolactone at 25 or 50 mg daily. A history of hypertension was present in 91%, coronary artery disease in 57%, atrial fibrillation in 35%, chronic renal disease in 35%, and diabetes in 32%. Patients included in the study had a mean LVEF of 56%; two thirds were in New York Heart Association class II and one third were in NYHA class III.

Over 80% of patients were receiving an ACE inhibitor or angiotensin receptor blocker, beta-blockers, and a diuretic. The mean dose of spironolactone was 25 mg. There was no significant difference in the primary outcome of cardiovascular death, nonfatal hospitalization or resuscitated cardiac arrest in the placebo and treated groups (20.4% and 18.6%, respectively). There was a significant decrease in heart failure hospitalization in the placebo compared to spironolactone patients (14.2% vs. 12.0%; P = .042). Both hyperkalemia greater than 5.5 mmol/L and an increase in serum creatinine were observed in the treated patients.

The striking observation in this trial, as it has been in previous trials, is the disparity between the epidemiologic mortality and the randomized controlled trial experience: 29% annual mortality in Olmsted County, compared with the 10.2% three-year mortality in TOPCAT. It appears that we are studying two separate diseases. And we are. After all the exclusion criteria included in the design of TOPCAT, we are unable to encapsulate the population at risk in this complex heart failure syndrome.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Getting the right therapeutic dose of any drug is not always easy. Using antibiotics to treat infection or antihypertensive drugs to lower blood pressure can be measured easily by simple physiologic measurements.

The treatment of heart failure with beta-blockers or ACE inhibitors, however, has been largely defined by clinical trials, which by their nature use one dosage and usually provide the clinician with limited information about the range of the best and most effective dosages. The rigor of choosing the correct dosage in clinical trials is often limited to small, underpowered phase II studies carried out well before the major phase III trials, which are designed to support efficacy and safety, usually at that one dosage. And still, physicians usually pick the lowest dose, following Hippocrates’ dictum to "do no harm." This dilemma has particular importance in picking the best dose of a beta-blocker in heart failure.

A recent presentation at the annual congress of the European Society of Cardiology by Dr. L. Brent Mitchell ("Full-dose beta-blockers still show benefit," October 2013, p. 26) sheds some important light on the benefit of maximum dosing with beta-blockers in heart failure patients treated with cardiac resynchronization therapy (CRT) or implantable cardiac defibrillators (ICDs) in whom bradycardia escape pacing was present.

Although all patients received standard drug therapy, patients receiving less than 50% of the full recommended dose of beta-blocker had a worse outcome in regard to mortality and rehospitalization when compared with patients receiving the full recommended dose, regardless of the beta-blocker used. Roughly one-half of these heart failure ICD/CRT patients were receiving less than half of the recommended dose for heart failure therapy. Older patients and those with more advance heart failure tended to receive the lower dose. In this patient population with pacemaker-controlled low heart rate, the issue of beta-blocker–induced bradycardia is no longer an issue: the higher the better.

In patients with atrial-controlled heart rates with sinus rhythm or atrial fibrillation, however, the induction of bradycardia has been an issue as physicians up-titrate dosages. The effect on morbidity and mortality of varying doses of metoprolol succinate (Toprol) was examined in the MERIT-HF trial (J. Am. Coll. Cardiol. 2002;40:491-8), in which physicians were encouraged to up-titrate to the highest dose. The limitation of up-titration was bradycardia. The high-dose (greater than 100 mg/day) and low-dose (100 mg/day or less) patients received 192 mg and 76 mg/day, respectively. Despite the different maximal doses, the final heart rate achieved with the up-titration was 68 beats/min. Patients receiving the high dose and low dose achieved the same relative benefit of therapy. The low-dose patient group was older and had a higher New York Heart Association functional class.

These observations suggest that there was a significant variability in the patient’s sensitivity to beta-blocker therapy, but the achievement of a low heart rate, regardless of dose, was effective in achieving the best therapeutic benefit. In a small dose-ranging study, patients were randomized to receive 50 or 200 mg/day of Toprol. The patients receiving 200 mg demonstrated an increase in ejection fraction and a decrease in end systolic volume, compared with the 50 mg–dose patients, who failed to evidence any hemodynamic improvement (Circulation 2007;116:49-56).

These observations emphasize the uncertainties of drug dosing in heart failure with our standard therapy. The benefit of high doses of beta-blockers in the ICD/CRT trial in patients whose heart rate was controlled with bradycardia pacing provides important support for the use of high doses in these individuals. In patients whose heart rate was controlled by atrial rhythms in the MERIT-HF trial, heart rate became the major limitation of drug therapy. In these patients, up-titration to maximal heart rate expressed the presence of a variable sensitivity to beta-blockade. The achievement of a slow heart rate, regardless of dose, appeared to achieve a similar benefit on heart failure outcomes.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies, and was the co-principal investigator of the MERIT-HF trial.

Getting the right therapeutic dose of any drug is not always easy. Using antibiotics to treat infection or antihypertensive drugs to lower blood pressure can be measured easily by simple physiologic measurements.

The treatment of heart failure with beta-blockers or ACE inhibitors, however, has been largely defined by clinical trials, which by their nature use one dosage and usually provide the clinician with limited information about the range of the best and most effective dosages. The rigor of choosing the correct dosage in clinical trials is often limited to small, underpowered phase II studies carried out well before the major phase III trials, which are designed to support efficacy and safety, usually at that one dosage. And still, physicians usually pick the lowest dose, following Hippocrates’ dictum to "do no harm." This dilemma has particular importance in picking the best dose of a beta-blocker in heart failure.

A recent presentation at the annual congress of the European Society of Cardiology by Dr. L. Brent Mitchell ("Full-dose beta-blockers still show benefit," October 2013, p. 26) sheds some important light on the benefit of maximum dosing with beta-blockers in heart failure patients treated with cardiac resynchronization therapy (CRT) or implantable cardiac defibrillators (ICDs) in whom bradycardia escape pacing was present.

Although all patients received standard drug therapy, patients receiving less than 50% of the full recommended dose of beta-blocker had a worse outcome in regard to mortality and rehospitalization when compared with patients receiving the full recommended dose, regardless of the beta-blocker used. Roughly one-half of these heart failure ICD/CRT patients were receiving less than half of the recommended dose for heart failure therapy. Older patients and those with more advance heart failure tended to receive the lower dose. In this patient population with pacemaker-controlled low heart rate, the issue of beta-blocker–induced bradycardia is no longer an issue: the higher the better.

In patients with atrial-controlled heart rates with sinus rhythm or atrial fibrillation, however, the induction of bradycardia has been an issue as physicians up-titrate dosages. The effect on morbidity and mortality of varying doses of metoprolol succinate (Toprol) was examined in the MERIT-HF trial (J. Am. Coll. Cardiol. 2002;40:491-8), in which physicians were encouraged to up-titrate to the highest dose. The limitation of up-titration was bradycardia. The high-dose (greater than 100 mg/day) and low-dose (100 mg/day or less) patients received 192 mg and 76 mg/day, respectively. Despite the different maximal doses, the final heart rate achieved with the up-titration was 68 beats/min. Patients receiving the high dose and low dose achieved the same relative benefit of therapy. The low-dose patient group was older and had a higher New York Heart Association functional class.

These observations suggest that there was a significant variability in the patient’s sensitivity to beta-blocker therapy, but the achievement of a low heart rate, regardless of dose, was effective in achieving the best therapeutic benefit. In a small dose-ranging study, patients were randomized to receive 50 or 200 mg/day of Toprol. The patients receiving 200 mg demonstrated an increase in ejection fraction and a decrease in end systolic volume, compared with the 50 mg–dose patients, who failed to evidence any hemodynamic improvement (Circulation 2007;116:49-56).

These observations emphasize the uncertainties of drug dosing in heart failure with our standard therapy. The benefit of high doses of beta-blockers in the ICD/CRT trial in patients whose heart rate was controlled with bradycardia pacing provides important support for the use of high doses in these individuals. In patients whose heart rate was controlled by atrial rhythms in the MERIT-HF trial, heart rate became the major limitation of drug therapy. In these patients, up-titration to maximal heart rate expressed the presence of a variable sensitivity to beta-blockade. The achievement of a slow heart rate, regardless of dose, appeared to achieve a similar benefit on heart failure outcomes.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies, and was the co-principal investigator of the MERIT-HF trial.

Getting the right therapeutic dose of any drug is not always easy. Using antibiotics to treat infection or antihypertensive drugs to lower blood pressure can be measured easily by simple physiologic measurements.

The treatment of heart failure with beta-blockers or ACE inhibitors, however, has been largely defined by clinical trials, which by their nature use one dosage and usually provide the clinician with limited information about the range of the best and most effective dosages. The rigor of choosing the correct dosage in clinical trials is often limited to small, underpowered phase II studies carried out well before the major phase III trials, which are designed to support efficacy and safety, usually at that one dosage. And still, physicians usually pick the lowest dose, following Hippocrates’ dictum to "do no harm." This dilemma has particular importance in picking the best dose of a beta-blocker in heart failure.

A recent presentation at the annual congress of the European Society of Cardiology by Dr. L. Brent Mitchell ("Full-dose beta-blockers still show benefit," October 2013, p. 26) sheds some important light on the benefit of maximum dosing with beta-blockers in heart failure patients treated with cardiac resynchronization therapy (CRT) or implantable cardiac defibrillators (ICDs) in whom bradycardia escape pacing was present.

Although all patients received standard drug therapy, patients receiving less than 50% of the full recommended dose of beta-blocker had a worse outcome in regard to mortality and rehospitalization when compared with patients receiving the full recommended dose, regardless of the beta-blocker used. Roughly one-half of these heart failure ICD/CRT patients were receiving less than half of the recommended dose for heart failure therapy. Older patients and those with more advance heart failure tended to receive the lower dose. In this patient population with pacemaker-controlled low heart rate, the issue of beta-blocker–induced bradycardia is no longer an issue: the higher the better.

In patients with atrial-controlled heart rates with sinus rhythm or atrial fibrillation, however, the induction of bradycardia has been an issue as physicians up-titrate dosages. The effect on morbidity and mortality of varying doses of metoprolol succinate (Toprol) was examined in the MERIT-HF trial (J. Am. Coll. Cardiol. 2002;40:491-8), in which physicians were encouraged to up-titrate to the highest dose. The limitation of up-titration was bradycardia. The high-dose (greater than 100 mg/day) and low-dose (100 mg/day or less) patients received 192 mg and 76 mg/day, respectively. Despite the different maximal doses, the final heart rate achieved with the up-titration was 68 beats/min. Patients receiving the high dose and low dose achieved the same relative benefit of therapy. The low-dose patient group was older and had a higher New York Heart Association functional class.

These observations suggest that there was a significant variability in the patient’s sensitivity to beta-blocker therapy, but the achievement of a low heart rate, regardless of dose, was effective in achieving the best therapeutic benefit. In a small dose-ranging study, patients were randomized to receive 50 or 200 mg/day of Toprol. The patients receiving 200 mg demonstrated an increase in ejection fraction and a decrease in end systolic volume, compared with the 50 mg–dose patients, who failed to evidence any hemodynamic improvement (Circulation 2007;116:49-56).

These observations emphasize the uncertainties of drug dosing in heart failure with our standard therapy. The benefit of high doses of beta-blockers in the ICD/CRT trial in patients whose heart rate was controlled with bradycardia pacing provides important support for the use of high doses in these individuals. In patients whose heart rate was controlled by atrial rhythms in the MERIT-HF trial, heart rate became the major limitation of drug therapy. In these patients, up-titration to maximal heart rate expressed the presence of a variable sensitivity to beta-blockade. The achievement of a slow heart rate, regardless of dose, appeared to achieve a similar benefit on heart failure outcomes.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies, and was the co-principal investigator of the MERIT-HF trial.

For over a half a century, the vitamin K antagonists coumarin and warfarin have been the only anticoagulants available to prevent clot formation in a variety of cardiovascular clinical settings. They are now about to be replaced with direct thrombin and factor Xa inhibitors. Vitamin K antagonists have not only dominated anticoagulant therapy, they have created an entire industry within the cardiovascular domain for the monitoring and control of its dose administration.

The story began in 1933 when Karl Paul Link, Ph.D., working in a laboratory at the University of Wisconsin School of Agriculture, was asked to examine the blood of cows dying of hemorrhage thought to be due to the ingestion of spoiled sweet clover. After years of research, Link was able to isolate an anticoagulant from the clover feed, called dicumarol, and he initially patented it in 1941 as rat poison. The marketed drug was called warfarin, after the Wisconsin Agricultural Research Foundation (WARF). Based on that patent, billions of dollars were generated for future research at the WARF.

Warfarin began to be used in the 1950s by a number of clinical investigators to prevent pulmonary embolism in the setting of an acute myocardial infarction (Lancet 1954;266:92-5). At that time, 1 month of complete bed rest was standard therapy for an AMI, and thrombophlebitis together with pulmonary and systemic embolism were the main causes of mortality. When early ambulation became acceptable for AMI patients, warfarin use tapered off. As clinicians became more focused on the prevention of intravascular thrombus formation after prosthetic valve surgery, and to prevent thromboembolism in patients with atrial fibrillation, warfarin therapy became more widely used, and the definition of the therapeutic dose of warfarin became important.

It soon became evident that vitamin K antagonists had a very narrow therapeutic window, framed by excessive bleeding at high doses and inefficacy at lower dose. As a result, the need for closer dose monitoring became important, and this led to the establishment of anticoagulant clinics. However, even with the establishment of these clinics, it became obvious that the clinical status of patients and dietary variability played major roles in dosing. The need for frequent blood sampling and the logistics of dose management were frustrations for both the patient and physician for decades.

As the need for better anticoagulant therapy became evident, drugs were developed that had a wider therapeutic range and that could be administered orally without the need of blood monitoring. The development of direct-acting thrombin and factor Xa inhibitors have led to major advances in anticoagulant therapy, resulting in safer oral fixed-dose drugs with therapeutic efficacy comparable to or better than vitamin K antagonists. In addition, they appear to be free from the effects of dietary variation. The factor Xa inhibitors apixaban and rivaroxaban have been approved by the Food and Drug Administration for the prevention of systemic emboli in patients with atrial fibrillation. Rivaroxaban is also indicated for preventing and treating deep vein thrombosis and pulmonary embolism. The direct thrombin inhibitor dabigatran has also been approved for the prevention of thromboembolism in patients with atrial fibrillation. The only settings for which the new anticoagulants have not been approved are acute coronary syndrome and prevention of thromboembolism with prosthetic valves.

The development of new anticoagulants provides an opportunity to improve therapy and witness the retirement of a ponderous and complicated dosing program that has been inconvenient to both patients and doctors. The retirement of warfarin and the death of the anticoagulant clinic will be appreciated by all.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

For over a half a century, the vitamin K antagonists coumarin and warfarin have been the only anticoagulants available to prevent clot formation in a variety of cardiovascular clinical settings. They are now about to be replaced with direct thrombin and factor Xa inhibitors. Vitamin K antagonists have not only dominated anticoagulant therapy, they have created an entire industry within the cardiovascular domain for the monitoring and control of its dose administration.

The story began in 1933 when Karl Paul Link, Ph.D., working in a laboratory at the University of Wisconsin School of Agriculture, was asked to examine the blood of cows dying of hemorrhage thought to be due to the ingestion of spoiled sweet clover. After years of research, Link was able to isolate an anticoagulant from the clover feed, called dicumarol, and he initially patented it in 1941 as rat poison. The marketed drug was called warfarin, after the Wisconsin Agricultural Research Foundation (WARF). Based on that patent, billions of dollars were generated for future research at the WARF.

Warfarin began to be used in the 1950s by a number of clinical investigators to prevent pulmonary embolism in the setting of an acute myocardial infarction (Lancet 1954;266:92-5). At that time, 1 month of complete bed rest was standard therapy for an AMI, and thrombophlebitis together with pulmonary and systemic embolism were the main causes of mortality. When early ambulation became acceptable for AMI patients, warfarin use tapered off. As clinicians became more focused on the prevention of intravascular thrombus formation after prosthetic valve surgery, and to prevent thromboembolism in patients with atrial fibrillation, warfarin therapy became more widely used, and the definition of the therapeutic dose of warfarin became important.

It soon became evident that vitamin K antagonists had a very narrow therapeutic window, framed by excessive bleeding at high doses and inefficacy at lower dose. As a result, the need for closer dose monitoring became important, and this led to the establishment of anticoagulant clinics. However, even with the establishment of these clinics, it became obvious that the clinical status of patients and dietary variability played major roles in dosing. The need for frequent blood sampling and the logistics of dose management were frustrations for both the patient and physician for decades.

As the need for better anticoagulant therapy became evident, drugs were developed that had a wider therapeutic range and that could be administered orally without the need of blood monitoring. The development of direct-acting thrombin and factor Xa inhibitors have led to major advances in anticoagulant therapy, resulting in safer oral fixed-dose drugs with therapeutic efficacy comparable to or better than vitamin K antagonists. In addition, they appear to be free from the effects of dietary variation. The factor Xa inhibitors apixaban and rivaroxaban have been approved by the Food and Drug Administration for the prevention of systemic emboli in patients with atrial fibrillation. Rivaroxaban is also indicated for preventing and treating deep vein thrombosis and pulmonary embolism. The direct thrombin inhibitor dabigatran has also been approved for the prevention of thromboembolism in patients with atrial fibrillation. The only settings for which the new anticoagulants have not been approved are acute coronary syndrome and prevention of thromboembolism with prosthetic valves.

The development of new anticoagulants provides an opportunity to improve therapy and witness the retirement of a ponderous and complicated dosing program that has been inconvenient to both patients and doctors. The retirement of warfarin and the death of the anticoagulant clinic will be appreciated by all.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

For over a half a century, the vitamin K antagonists coumarin and warfarin have been the only anticoagulants available to prevent clot formation in a variety of cardiovascular clinical settings. They are now about to be replaced with direct thrombin and factor Xa inhibitors. Vitamin K antagonists have not only dominated anticoagulant therapy, they have created an entire industry within the cardiovascular domain for the monitoring and control of its dose administration.

The story began in 1933 when Karl Paul Link, Ph.D., working in a laboratory at the University of Wisconsin School of Agriculture, was asked to examine the blood of cows dying of hemorrhage thought to be due to the ingestion of spoiled sweet clover. After years of research, Link was able to isolate an anticoagulant from the clover feed, called dicumarol, and he initially patented it in 1941 as rat poison. The marketed drug was called warfarin, after the Wisconsin Agricultural Research Foundation (WARF). Based on that patent, billions of dollars were generated for future research at the WARF.

Warfarin began to be used in the 1950s by a number of clinical investigators to prevent pulmonary embolism in the setting of an acute myocardial infarction (Lancet 1954;266:92-5). At that time, 1 month of complete bed rest was standard therapy for an AMI, and thrombophlebitis together with pulmonary and systemic embolism were the main causes of mortality. When early ambulation became acceptable for AMI patients, warfarin use tapered off. As clinicians became more focused on the prevention of intravascular thrombus formation after prosthetic valve surgery, and to prevent thromboembolism in patients with atrial fibrillation, warfarin therapy became more widely used, and the definition of the therapeutic dose of warfarin became important.

It soon became evident that vitamin K antagonists had a very narrow therapeutic window, framed by excessive bleeding at high doses and inefficacy at lower dose. As a result, the need for closer dose monitoring became important, and this led to the establishment of anticoagulant clinics. However, even with the establishment of these clinics, it became obvious that the clinical status of patients and dietary variability played major roles in dosing. The need for frequent blood sampling and the logistics of dose management were frustrations for both the patient and physician for decades.

As the need for better anticoagulant therapy became evident, drugs were developed that had a wider therapeutic range and that could be administered orally without the need of blood monitoring. The development of direct-acting thrombin and factor Xa inhibitors have led to major advances in anticoagulant therapy, resulting in safer oral fixed-dose drugs with therapeutic efficacy comparable to or better than vitamin K antagonists. In addition, they appear to be free from the effects of dietary variation. The factor Xa inhibitors apixaban and rivaroxaban have been approved by the Food and Drug Administration for the prevention of systemic emboli in patients with atrial fibrillation. Rivaroxaban is also indicated for preventing and treating deep vein thrombosis and pulmonary embolism. The direct thrombin inhibitor dabigatran has also been approved for the prevention of thromboembolism in patients with atrial fibrillation. The only settings for which the new anticoagulants have not been approved are acute coronary syndrome and prevention of thromboembolism with prosthetic valves.

The development of new anticoagulants provides an opportunity to improve therapy and witness the retirement of a ponderous and complicated dosing program that has been inconvenient to both patients and doctors. The retirement of warfarin and the death of the anticoagulant clinic will be appreciated by all.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

A recent report at the American College of Cardiology annual meeting concluded that handheld ultrasound was superior to a group of trained cardiologists in the determination of cardiac pathology and function (J. Am. Coll. Cardiol. 2013;61:E1442).

This sort of information immediately raised my hackles. I am all for technological advances, but this proclamation struck close to my heart. I have progressed from cardiac catheterization using "red glass" accommodation for fluoroscopy to high-intensity multiplane angiography. I have even participated in the development of biventricular pacemakers for the treatment of heart failure and defibrillation. But the suggestion that a cardiologist can be replaced by a toy activated my Luddite receptors.

For those of you who are unaware of who or what a Luddite is, I refer you to England in the year 1811, when Edward (Ned) Ludd protested the replacement of hand-loom workers with a mechanized knitting process that threw thousands of English weavers out of work. He started a protest movement by Luddites that led to attacks on weaving mills and ultimately the hanging of some of his followers as terrorists in 1817. At about that time, in 1816, Rene Laennec developed the stethoscope by using a "quire" of paper rolled into a cylinder to listen to an obese young lady’s heart rather than his naked ear placed on her chest, which was the practice at that time.

From that paper tube has evolved the stethoscope as we know it today. Occasionally it is used to listen to the heart and lungs of patients, but it is seen mostly as a professional "necktie" in TV dramas. The fact that cardiologists and the stethoscope were to be replaced by the handheld ultrasound just as the loom weavers were replaced by the knitting machine led me to respond to the challenge.

I believe that the author, Dr. Manish Mehta of Oregon Health and Science University, Portland, spoke to an important issue. I would agree that many cardiologists are more comfortable using an echocardiogram than a stethoscope. The value of auscultation skills can be judged by the fact that cardiology board examinations do not include testing of auscultation skills but provide numerous questions on the interpretation of echocardiograms. Of course, there are the economic benefits of performing an echocardiogram compared with auscultation, which does not come up on my charge sheet.

I would grant that a handheld ultrasound can identify whether a pericardial effusion is present, a physical diagnostic challenge that I have frequently failed, particularly in thick-chested individuals. But give me a thin, young guy and I’ll get it every time. But does the presence of a leaking or stenotic valve or an enlarged heart, both easily identified by the handheld ultrasound, indicate heart failure? Give me an S3 gallop or distended neck veins and I can make the diagnosis of heart failure without a B-type natriuretic peptide level. The problem is that no one – well, very few of us – teaches how to examine the heart.

There is also the importance of the physician actually touching the patient as part of the examination. Not only examining the heart; but how about the abdomen? If we followed the path led by the BS echo, we could take the nurse’s recorded chief complaint and send the patient directly to radiology for a CT or an MRI. The fact that this is what the patient really wants does not escape this skeptic. But is this what medicine is really about? Much has been written about physician-patient interaction, but has it come to doctors being only a triage to the radiology department?

I am not going to break up the nearest echo machine with my stethoscope and end up on the hospital director’s "scaffolds" like the 18th century Luddites did. Echocardiography clearly provides a wonderful view of the heart and its valves, and can guide us to the surgical correction of valvular and muscular defects. Some technology, such as Doppler imaging, actually does provide information about physiologic phenomena including myocardial function and ischemia. But if the cardiologists lose in a contest with handheld ultrasound, it is because we have lost our bedside skills as a result of our overreliance on technology and have been blinded to its limitations.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

A recent report at the American College of Cardiology annual meeting concluded that handheld ultrasound was superior to a group of trained cardiologists in the determination of cardiac pathology and function (J. Am. Coll. Cardiol. 2013;61:E1442).

This sort of information immediately raised my hackles. I am all for technological advances, but this proclamation struck close to my heart. I have progressed from cardiac catheterization using "red glass" accommodation for fluoroscopy to high-intensity multiplane angiography. I have even participated in the development of biventricular pacemakers for the treatment of heart failure and defibrillation. But the suggestion that a cardiologist can be replaced by a toy activated my Luddite receptors.

For those of you who are unaware of who or what a Luddite is, I refer you to England in the year 1811, when Edward (Ned) Ludd protested the replacement of hand-loom workers with a mechanized knitting process that threw thousands of English weavers out of work. He started a protest movement by Luddites that led to attacks on weaving mills and ultimately the hanging of some of his followers as terrorists in 1817. At about that time, in 1816, Rene Laennec developed the stethoscope by using a "quire" of paper rolled into a cylinder to listen to an obese young lady’s heart rather than his naked ear placed on her chest, which was the practice at that time.

From that paper tube has evolved the stethoscope as we know it today. Occasionally it is used to listen to the heart and lungs of patients, but it is seen mostly as a professional "necktie" in TV dramas. The fact that cardiologists and the stethoscope were to be replaced by the handheld ultrasound just as the loom weavers were replaced by the knitting machine led me to respond to the challenge.

I believe that the author, Dr. Manish Mehta of Oregon Health and Science University, Portland, spoke to an important issue. I would agree that many cardiologists are more comfortable using an echocardiogram than a stethoscope. The value of auscultation skills can be judged by the fact that cardiology board examinations do not include testing of auscultation skills but provide numerous questions on the interpretation of echocardiograms. Of course, there are the economic benefits of performing an echocardiogram compared with auscultation, which does not come up on my charge sheet.

I would grant that a handheld ultrasound can identify whether a pericardial effusion is present, a physical diagnostic challenge that I have frequently failed, particularly in thick-chested individuals. But give me a thin, young guy and I’ll get it every time. But does the presence of a leaking or stenotic valve or an enlarged heart, both easily identified by the handheld ultrasound, indicate heart failure? Give me an S3 gallop or distended neck veins and I can make the diagnosis of heart failure without a B-type natriuretic peptide level. The problem is that no one – well, very few of us – teaches how to examine the heart.

There is also the importance of the physician actually touching the patient as part of the examination. Not only examining the heart; but how about the abdomen? If we followed the path led by the BS echo, we could take the nurse’s recorded chief complaint and send the patient directly to radiology for a CT or an MRI. The fact that this is what the patient really wants does not escape this skeptic. But is this what medicine is really about? Much has been written about physician-patient interaction, but has it come to doctors being only a triage to the radiology department?

I am not going to break up the nearest echo machine with my stethoscope and end up on the hospital director’s "scaffolds" like the 18th century Luddites did. Echocardiography clearly provides a wonderful view of the heart and its valves, and can guide us to the surgical correction of valvular and muscular defects. Some technology, such as Doppler imaging, actually does provide information about physiologic phenomena including myocardial function and ischemia. But if the cardiologists lose in a contest with handheld ultrasound, it is because we have lost our bedside skills as a result of our overreliance on technology and have been blinded to its limitations.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

A recent report at the American College of Cardiology annual meeting concluded that handheld ultrasound was superior to a group of trained cardiologists in the determination of cardiac pathology and function (J. Am. Coll. Cardiol. 2013;61:E1442).

This sort of information immediately raised my hackles. I am all for technological advances, but this proclamation struck close to my heart. I have progressed from cardiac catheterization using "red glass" accommodation for fluoroscopy to high-intensity multiplane angiography. I have even participated in the development of biventricular pacemakers for the treatment of heart failure and defibrillation. But the suggestion that a cardiologist can be replaced by a toy activated my Luddite receptors.

For those of you who are unaware of who or what a Luddite is, I refer you to England in the year 1811, when Edward (Ned) Ludd protested the replacement of hand-loom workers with a mechanized knitting process that threw thousands of English weavers out of work. He started a protest movement by Luddites that led to attacks on weaving mills and ultimately the hanging of some of his followers as terrorists in 1817. At about that time, in 1816, Rene Laennec developed the stethoscope by using a "quire" of paper rolled into a cylinder to listen to an obese young lady’s heart rather than his naked ear placed on her chest, which was the practice at that time.

From that paper tube has evolved the stethoscope as we know it today. Occasionally it is used to listen to the heart and lungs of patients, but it is seen mostly as a professional "necktie" in TV dramas. The fact that cardiologists and the stethoscope were to be replaced by the handheld ultrasound just as the loom weavers were replaced by the knitting machine led me to respond to the challenge.

I believe that the author, Dr. Manish Mehta of Oregon Health and Science University, Portland, spoke to an important issue. I would agree that many cardiologists are more comfortable using an echocardiogram than a stethoscope. The value of auscultation skills can be judged by the fact that cardiology board examinations do not include testing of auscultation skills but provide numerous questions on the interpretation of echocardiograms. Of course, there are the economic benefits of performing an echocardiogram compared with auscultation, which does not come up on my charge sheet.

I would grant that a handheld ultrasound can identify whether a pericardial effusion is present, a physical diagnostic challenge that I have frequently failed, particularly in thick-chested individuals. But give me a thin, young guy and I’ll get it every time. But does the presence of a leaking or stenotic valve or an enlarged heart, both easily identified by the handheld ultrasound, indicate heart failure? Give me an S3 gallop or distended neck veins and I can make the diagnosis of heart failure without a B-type natriuretic peptide level. The problem is that no one – well, very few of us – teaches how to examine the heart.

There is also the importance of the physician actually touching the patient as part of the examination. Not only examining the heart; but how about the abdomen? If we followed the path led by the BS echo, we could take the nurse’s recorded chief complaint and send the patient directly to radiology for a CT or an MRI. The fact that this is what the patient really wants does not escape this skeptic. But is this what medicine is really about? Much has been written about physician-patient interaction, but has it come to doctors being only a triage to the radiology department?

I am not going to break up the nearest echo machine with my stethoscope and end up on the hospital director’s "scaffolds" like the 18th century Luddites did. Echocardiography clearly provides a wonderful view of the heart and its valves, and can guide us to the surgical correction of valvular and muscular defects. Some technology, such as Doppler imaging, actually does provide information about physiologic phenomena including myocardial function and ischemia. But if the cardiologists lose in a contest with handheld ultrasound, it is because we have lost our bedside skills as a result of our overreliance on technology and have been blinded to its limitations.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The successful treatment of cancer with chemotherapeutic agents has led to a new set of cardiac problems related to their acute and chronic cardiac toxicity. It should not be surprising that drugs that impact so potently on intrinsic cell function and energy production to cause tumor cell death also impact on other systems, including the heart. An unfortunate by-product of the success of adjuvant therapy has been development of cardiomyocyte dysfunction and death and the development of heart failure.

Current estimates indicate that cardiovascular disease has become a competing comortality risk in women undergoing cancer chemotherapy. Cohort studies indicate that breast cancer patients who have undergone chemotherapy are at an increased cardiovascular mortality risk, compared with age matched controls. The National Cancer Institute and the Centers for Disease Control and Prevention estimate that there are more than 10 million cancer survivors in the United States and that 60% of adults newly diagnosed with cancer will be alive 5 or more years later. Many of these survivors will have significant heart failure as a result of their "successful" chemotherapy (J. Clin. Oncol. 2007;25:3991-4008).

Most of these survivors will have been treated either acutely or chronically with anthracycline drugs (such as doxorubicin), drugs directed at HER2 monoclonal antibodies (trastuzumab), or endocrine-like drugs (tamoxifen). Treatment protocols vary widely and have focused primarily on the acute, chronic, and recurrent therapy for tumor eradication with limited regard – until recently – for the acute or chronic cardiotoxic effects of the drugs. The precise incidence of cardiac toxicity is poorly understood since there are very few long-term follow-up data regarding cardiac morbidity and mortality. In these long-term survivors, cardiovascular mortality will be the predominant cause of death in women over age 60 treated for breast cancer (Circulation 2012;126:2749-63). It is estimated that half of the patients treated with anthracyclines will exhibit some cardiac dysfunction within 10-20 years and 5% will develop overt heart failure.

The mechanism by which cardiac dysfunction occurs varies depending upon the drug used. Anthracycline drugs cause ultrastructural cell changes, vacuolar degeneration, myofibrillar loss, and apoptosis. This change can be observed during early administration but may manifest years later, seemingly without any early evidence of dysfunction. Trastuzumab causes cardiac function as a result of deletion of HER2, which is essential for cardiomyocyte survival and stress adaptation. Tamoxifen-like drugs can lead to the acceleration of typical cardiac risk factors. Interaction of any of these classes of drugs when used in combination for recurrent or resistant disease can accelerate the occurrence of cardiac pathology.

The degree of adverse acute and chronic cardiac effects is related to the dose and duration of therapy. Early recognition of cardiac toxicity appears to be critical in order to mitigate the toxic drug effects. Clinical data suggest that early administration of ACE inhibitors or beta-blockers may limit or reverse cardiac dysfunction (Circulation 2006;114:2474-81). The measurement of LVEF has been used to identify early cardiac dysfunction. A symptomatic decrease in LVEF from 5% to 55% or an asymptomatic decrease of 10% is considered to be diagnostic of cardiac toxicity. Serum troponin I of greater than 0.08% also has been reported to increase the occurrence of cardiac toxicity 24-fold. Recent studies suggest that measurement of myocardial contractile velocity and strain and rate of strain by tissue Doppler imaging may provide earlier identification of myocardial dysfunction than that achieved with LVEF alone (Circulation 2012;126:2749-63).

The increased development of heart failure as a result of cancer chemotherapy has largely slipped under the cardiologist’s radar. The recent awareness of the adverse cardiac effect of these agents has generated investigation into the development of early and more sensitive biological markers and methods of mitigating cell dysfunction with concomitant medical therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The successful treatment of cancer with chemotherapeutic agents has led to a new set of cardiac problems related to their acute and chronic cardiac toxicity. It should not be surprising that drugs that impact so potently on intrinsic cell function and energy production to cause tumor cell death also impact on other systems, including the heart. An unfortunate by-product of the success of adjuvant therapy has been development of cardiomyocyte dysfunction and death and the development of heart failure.

Current estimates indicate that cardiovascular disease has become a competing comortality risk in women undergoing cancer chemotherapy. Cohort studies indicate that breast cancer patients who have undergone chemotherapy are at an increased cardiovascular mortality risk, compared with age matched controls. The National Cancer Institute and the Centers for Disease Control and Prevention estimate that there are more than 10 million cancer survivors in the United States and that 60% of adults newly diagnosed with cancer will be alive 5 or more years later. Many of these survivors will have significant heart failure as a result of their "successful" chemotherapy (J. Clin. Oncol. 2007;25:3991-4008).

Most of these survivors will have been treated either acutely or chronically with anthracycline drugs (such as doxorubicin), drugs directed at HER2 monoclonal antibodies (trastuzumab), or endocrine-like drugs (tamoxifen). Treatment protocols vary widely and have focused primarily on the acute, chronic, and recurrent therapy for tumor eradication with limited regard – until recently – for the acute or chronic cardiotoxic effects of the drugs. The precise incidence of cardiac toxicity is poorly understood since there are very few long-term follow-up data regarding cardiac morbidity and mortality. In these long-term survivors, cardiovascular mortality will be the predominant cause of death in women over age 60 treated for breast cancer (Circulation 2012;126:2749-63). It is estimated that half of the patients treated with anthracyclines will exhibit some cardiac dysfunction within 10-20 years and 5% will develop overt heart failure.

The mechanism by which cardiac dysfunction occurs varies depending upon the drug used. Anthracycline drugs cause ultrastructural cell changes, vacuolar degeneration, myofibrillar loss, and apoptosis. This change can be observed during early administration but may manifest years later, seemingly without any early evidence of dysfunction. Trastuzumab causes cardiac function as a result of deletion of HER2, which is essential for cardiomyocyte survival and stress adaptation. Tamoxifen-like drugs can lead to the acceleration of typical cardiac risk factors. Interaction of any of these classes of drugs when used in combination for recurrent or resistant disease can accelerate the occurrence of cardiac pathology.

The degree of adverse acute and chronic cardiac effects is related to the dose and duration of therapy. Early recognition of cardiac toxicity appears to be critical in order to mitigate the toxic drug effects. Clinical data suggest that early administration of ACE inhibitors or beta-blockers may limit or reverse cardiac dysfunction (Circulation 2006;114:2474-81). The measurement of LVEF has been used to identify early cardiac dysfunction. A symptomatic decrease in LVEF from 5% to 55% or an asymptomatic decrease of 10% is considered to be diagnostic of cardiac toxicity. Serum troponin I of greater than 0.08% also has been reported to increase the occurrence of cardiac toxicity 24-fold. Recent studies suggest that measurement of myocardial contractile velocity and strain and rate of strain by tissue Doppler imaging may provide earlier identification of myocardial dysfunction than that achieved with LVEF alone (Circulation 2012;126:2749-63).

The increased development of heart failure as a result of cancer chemotherapy has largely slipped under the cardiologist’s radar. The recent awareness of the adverse cardiac effect of these agents has generated investigation into the development of early and more sensitive biological markers and methods of mitigating cell dysfunction with concomitant medical therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The successful treatment of cancer with chemotherapeutic agents has led to a new set of cardiac problems related to their acute and chronic cardiac toxicity. It should not be surprising that drugs that impact so potently on intrinsic cell function and energy production to cause tumor cell death also impact on other systems, including the heart. An unfortunate by-product of the success of adjuvant therapy has been development of cardiomyocyte dysfunction and death and the development of heart failure.

Current estimates indicate that cardiovascular disease has become a competing comortality risk in women undergoing cancer chemotherapy. Cohort studies indicate that breast cancer patients who have undergone chemotherapy are at an increased cardiovascular mortality risk, compared with age matched controls. The National Cancer Institute and the Centers for Disease Control and Prevention estimate that there are more than 10 million cancer survivors in the United States and that 60% of adults newly diagnosed with cancer will be alive 5 or more years later. Many of these survivors will have significant heart failure as a result of their "successful" chemotherapy (J. Clin. Oncol. 2007;25:3991-4008).

Most of these survivors will have been treated either acutely or chronically with anthracycline drugs (such as doxorubicin), drugs directed at HER2 monoclonal antibodies (trastuzumab), or endocrine-like drugs (tamoxifen). Treatment protocols vary widely and have focused primarily on the acute, chronic, and recurrent therapy for tumor eradication with limited regard – until recently – for the acute or chronic cardiotoxic effects of the drugs. The precise incidence of cardiac toxicity is poorly understood since there are very few long-term follow-up data regarding cardiac morbidity and mortality. In these long-term survivors, cardiovascular mortality will be the predominant cause of death in women over age 60 treated for breast cancer (Circulation 2012;126:2749-63). It is estimated that half of the patients treated with anthracyclines will exhibit some cardiac dysfunction within 10-20 years and 5% will develop overt heart failure.

The mechanism by which cardiac dysfunction occurs varies depending upon the drug used. Anthracycline drugs cause ultrastructural cell changes, vacuolar degeneration, myofibrillar loss, and apoptosis. This change can be observed during early administration but may manifest years later, seemingly without any early evidence of dysfunction. Trastuzumab causes cardiac function as a result of deletion of HER2, which is essential for cardiomyocyte survival and stress adaptation. Tamoxifen-like drugs can lead to the acceleration of typical cardiac risk factors. Interaction of any of these classes of drugs when used in combination for recurrent or resistant disease can accelerate the occurrence of cardiac pathology.

The degree of adverse acute and chronic cardiac effects is related to the dose and duration of therapy. Early recognition of cardiac toxicity appears to be critical in order to mitigate the toxic drug effects. Clinical data suggest that early administration of ACE inhibitors or beta-blockers may limit or reverse cardiac dysfunction (Circulation 2006;114:2474-81). The measurement of LVEF has been used to identify early cardiac dysfunction. A symptomatic decrease in LVEF from 5% to 55% or an asymptomatic decrease of 10% is considered to be diagnostic of cardiac toxicity. Serum troponin I of greater than 0.08% also has been reported to increase the occurrence of cardiac toxicity 24-fold. Recent studies suggest that measurement of myocardial contractile velocity and strain and rate of strain by tissue Doppler imaging may provide earlier identification of myocardial dysfunction than that achieved with LVEF alone (Circulation 2012;126:2749-63).

The increased development of heart failure as a result of cancer chemotherapy has largely slipped under the cardiologist’s radar. The recent awareness of the adverse cardiac effect of these agents has generated investigation into the development of early and more sensitive biological markers and methods of mitigating cell dysfunction with concomitant medical therapy.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

We have recently been informed by an American Heart Association committee that owning a pet decreases your cardiovascular risk. Since I am of the age when a coronary event is almost inevitable, the opinion of the committee caught my attention.

I am not much into pets, and I am not what you would call a dog lover; but I have had a dog that I really loved. Her name was Cassiopeia, "Cassie" for short, named after my then–10-year-old son’s favorite constellation. She was a warm and attentive golden retriever who jumped up on my car to greet me every evening when I came home from the hospital. My wife, who dutifully walked her every day, rarely got so much as a tail wag. She was clearly "my" dog and, like any person or animal that comes up to you at the end of the day with a lick or a kiss, was someone to be cherished.

In her 10th year, Cassie’s kidneys failed. After several weeks of daily administration of intravenous fluids, I gave up and took her to the vet to be euthanized. I freely admit that I was mildly depressed for a few weeks after she died. We never got another dog because my wife refused to continue to take care of an animal that never showed any appreciation.

The American Heart Association’s position on the benefit of pet ownership in the reduction of cardiovascular risk is one of at least three scientific statements that the organization makes each month. It did bring to mind the effect of Cassie on my psyche and the potentially beneficial effect that she had on my coronary arteries. However, I would have to admit I have failed to pay much attention to previous proclamations by well-meaning scientific bodies like the AHA committees. I have ignored the advice about my large coffee intake, my lack of daily exercise, and the amount of salt I put on my steak.

This particular statement by the AHA, however, was cautious about the justification of the canine-human interaction and indicated that there are scant randomized data to support the claim, and what existed related to cats, a species to which my wife is allergic. The recent dog–heart disease statement had come about as a result of a "growing number of news reports and medical studies" that purported to show a beneficial relationship between pet ownership and heart disease. It is amazing how one fails to notice a brouhaha right in our own midst. According to the New York Times account, the public uproar had reached such a "point that it would be reasonable to formally investigate" the issue.

But how would you ever try to design a trial testing the hypothesis that owning a dog was a panacea for cardiovascular disease? It is not clear what mechanism of action could be attributed to the presence of the dog. Was it exercise or depression? Of course, members of the committee jumped to the obvious relationship between exercising the dog and exercising the human. The particular species of dog certainly could have importance. Should it be a big friendly golden lab, a huge Great Dane, or a little Pekingese? Did its weight or disposition have any importance? How could you ever get rid of all of the variables? Forget the idea of a randomized trial; let’s just deal with the science of the matter.

I still could not forget Cassie and I tried to see how a new dog could help me. I thought about how my wife would take this, but I decided that her unhappiness would tip the balance against getting another dog. Another Cassie to bolster my psyche just doesn’t seem to be in the cards. In my own situation I wasn’t going to exercise the dog anyway. I had already assigned that responsibility to my wife, and I am not prepared to take that from her, even though she was willing to pass it on to someone else. I think that I will do without a dog and just try to carry on.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

We have recently been informed by an American Heart Association committee that owning a pet decreases your cardiovascular risk. Since I am of the age when a coronary event is almost inevitable, the opinion of the committee caught my attention.

I am not much into pets, and I am not what you would call a dog lover; but I have had a dog that I really loved. Her name was Cassiopeia, "Cassie" for short, named after my then–10-year-old son’s favorite constellation. She was a warm and attentive golden retriever who jumped up on my car to greet me every evening when I came home from the hospital. My wife, who dutifully walked her every day, rarely got so much as a tail wag. She was clearly "my" dog and, like any person or animal that comes up to you at the end of the day with a lick or a kiss, was someone to be cherished.

In her 10th year, Cassie’s kidneys failed. After several weeks of daily administration of intravenous fluids, I gave up and took her to the vet to be euthanized. I freely admit that I was mildly depressed for a few weeks after she died. We never got another dog because my wife refused to continue to take care of an animal that never showed any appreciation.

The American Heart Association’s position on the benefit of pet ownership in the reduction of cardiovascular risk is one of at least three scientific statements that the organization makes each month. It did bring to mind the effect of Cassie on my psyche and the potentially beneficial effect that she had on my coronary arteries. However, I would have to admit I have failed to pay much attention to previous proclamations by well-meaning scientific bodies like the AHA committees. I have ignored the advice about my large coffee intake, my lack of daily exercise, and the amount of salt I put on my steak.

This particular statement by the AHA, however, was cautious about the justification of the canine-human interaction and indicated that there are scant randomized data to support the claim, and what existed related to cats, a species to which my wife is allergic. The recent dog–heart disease statement had come about as a result of a "growing number of news reports and medical studies" that purported to show a beneficial relationship between pet ownership and heart disease. It is amazing how one fails to notice a brouhaha right in our own midst. According to the New York Times account, the public uproar had reached such a "point that it would be reasonable to formally investigate" the issue.

But how would you ever try to design a trial testing the hypothesis that owning a dog was a panacea for cardiovascular disease? It is not clear what mechanism of action could be attributed to the presence of the dog. Was it exercise or depression? Of course, members of the committee jumped to the obvious relationship between exercising the dog and exercising the human. The particular species of dog certainly could have importance. Should it be a big friendly golden lab, a huge Great Dane, or a little Pekingese? Did its weight or disposition have any importance? How could you ever get rid of all of the variables? Forget the idea of a randomized trial; let’s just deal with the science of the matter.

I still could not forget Cassie and I tried to see how a new dog could help me. I thought about how my wife would take this, but I decided that her unhappiness would tip the balance against getting another dog. Another Cassie to bolster my psyche just doesn’t seem to be in the cards. In my own situation I wasn’t going to exercise the dog anyway. I had already assigned that responsibility to my wife, and I am not prepared to take that from her, even though she was willing to pass it on to someone else. I think that I will do without a dog and just try to carry on.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

We have recently been informed by an American Heart Association committee that owning a pet decreases your cardiovascular risk. Since I am of the age when a coronary event is almost inevitable, the opinion of the committee caught my attention.

I am not much into pets, and I am not what you would call a dog lover; but I have had a dog that I really loved. Her name was Cassiopeia, "Cassie" for short, named after my then–10-year-old son’s favorite constellation. She was a warm and attentive golden retriever who jumped up on my car to greet me every evening when I came home from the hospital. My wife, who dutifully walked her every day, rarely got so much as a tail wag. She was clearly "my" dog and, like any person or animal that comes up to you at the end of the day with a lick or a kiss, was someone to be cherished.

In her 10th year, Cassie’s kidneys failed. After several weeks of daily administration of intravenous fluids, I gave up and took her to the vet to be euthanized. I freely admit that I was mildly depressed for a few weeks after she died. We never got another dog because my wife refused to continue to take care of an animal that never showed any appreciation.

The American Heart Association’s position on the benefit of pet ownership in the reduction of cardiovascular risk is one of at least three scientific statements that the organization makes each month. It did bring to mind the effect of Cassie on my psyche and the potentially beneficial effect that she had on my coronary arteries. However, I would have to admit I have failed to pay much attention to previous proclamations by well-meaning scientific bodies like the AHA committees. I have ignored the advice about my large coffee intake, my lack of daily exercise, and the amount of salt I put on my steak.

This particular statement by the AHA, however, was cautious about the justification of the canine-human interaction and indicated that there are scant randomized data to support the claim, and what existed related to cats, a species to which my wife is allergic. The recent dog–heart disease statement had come about as a result of a "growing number of news reports and medical studies" that purported to show a beneficial relationship between pet ownership and heart disease. It is amazing how one fails to notice a brouhaha right in our own midst. According to the New York Times account, the public uproar had reached such a "point that it would be reasonable to formally investigate" the issue.

But how would you ever try to design a trial testing the hypothesis that owning a dog was a panacea for cardiovascular disease? It is not clear what mechanism of action could be attributed to the presence of the dog. Was it exercise or depression? Of course, members of the committee jumped to the obvious relationship between exercising the dog and exercising the human. The particular species of dog certainly could have importance. Should it be a big friendly golden lab, a huge Great Dane, or a little Pekingese? Did its weight or disposition have any importance? How could you ever get rid of all of the variables? Forget the idea of a randomized trial; let’s just deal with the science of the matter.

I still could not forget Cassie and I tried to see how a new dog could help me. I thought about how my wife would take this, but I decided that her unhappiness would tip the balance against getting another dog. Another Cassie to bolster my psyche just doesn’t seem to be in the cards. In my own situation I wasn’t going to exercise the dog anyway. I had already assigned that responsibility to my wife, and I am not prepared to take that from her, even though she was willing to pass it on to someone else. I think that I will do without a dog and just try to carry on.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

In bygone days, your community hospital was a place where babies were born and gallbladders were removed. They were often run by city governments or local religious organizations. Of course, a lot has changed since then. Now your hospital advertises on television and extols the viewer about the medical miracles that are performed inside its walls. They also are getting bigger and merging with smaller and occasionally coequal institutions in the name of efficiency and in the effort to expand their patient catchment.

In an even larger sense, hospitals have been gobbled up by insurance companies and by for-profit networks in an attempt to maximize profits and minimize overhead. Some prestigious hospitals like the Mayo Clinic, the Cleveland Clinic, and MD Anderson Cancer Center have even established affiliations with community hospitals thousands of miles away seemingly to improve local care and at the same time to expand their referral network. Where local hospitals are not adequate and the market beckons, some have even built their own facilities not only in the United States, but also in countries around the globe.

The intent of these network affiliations is not only to improve their image but to impart some of their prestige to the local entities as well. As a result of these mergers and consolidations, they are positioning themselves to be more competitive in the new world of health care. Some would profess the altruism of providing better care either locally or at a distance, but in the long run, economics and market share are the driving force. They have not been concerned with delivering babies or taking out gallbladders for a long time.

Few can predict what the new world will look like, but it is quite certain that the Affordable Care Act will re-create or substantially modify American health care as we know it. The potential of attracting thousands of previously uninsured patients, who – with the help of the federal government – can come in the front door for care rather that using the back door of the emergency department for treatment, will be an important target.

In this environment, the practicing physician is caught in the changing tide. Many who are not in the swim will be washed up on the beach. Cardiology, along with oncology and gastroenterology, are the prime targets for the anticipated efficiencies evolving from the hospital system expansions and mergers. Although there is a well-recognized need for primary care health care professionals, much of this need is already being filled by nonphysician professionals. It is possible that cardiology, which has been one of the star profit centers, could become a target for consolidation and economy in the future. We may be seeing some of this, as the opportunities for finishing trainees appear to be diminishing.

It is obvious that there has been a major shift in the setting cardiology practices in the last few years. Since 2007, the proportion of physician-owned practices has decreased substantially. While the number of cardiologists employed by hospitals has grown from 11% to 35%, physician-owned practices have decreased from 59% to 36%. This migration of private practice to hospital-based practice is sure to continue. Cardiology practice will soon be directed by managers representing corporate health care who will be intent on putting in place programs that will establish protocol-driven therapy in the name of "quality" and "cost." Many of the changes will lead to better outcomes. Patient "satisfaction" will be measured by metrics already operational in the corporate environment. As the era of cardiology entrepreneurism faces institutional controls, such profit centers as imaging already are facing significant obstacles. The "down side" of this process will be the death of medical care as we knew it. It was not all bad. That mode of physician-driven, patient-centered care will not be easily transferred into the corporate care environment. The physician will need to ensure that at least that vestige of old-style medical care will not be entirely lost.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

In bygone days, your community hospital was a place where babies were born and gallbladders were removed. They were often run by city governments or local religious organizations. Of course, a lot has changed since then. Now your hospital advertises on television and extols the viewer about the medical miracles that are performed inside its walls. They also are getting bigger and merging with smaller and occasionally coequal institutions in the name of efficiency and in the effort to expand their patient catchment.

In an even larger sense, hospitals have been gobbled up by insurance companies and by for-profit networks in an attempt to maximize profits and minimize overhead. Some prestigious hospitals like the Mayo Clinic, the Cleveland Clinic, and MD Anderson Cancer Center have even established affiliations with community hospitals thousands of miles away seemingly to improve local care and at the same time to expand their referral network. Where local hospitals are not adequate and the market beckons, some have even built their own facilities not only in the United States, but also in countries around the globe.

The intent of these network affiliations is not only to improve their image but to impart some of their prestige to the local entities as well. As a result of these mergers and consolidations, they are positioning themselves to be more competitive in the new world of health care. Some would profess the altruism of providing better care either locally or at a distance, but in the long run, economics and market share are the driving force. They have not been concerned with delivering babies or taking out gallbladders for a long time.

Few can predict what the new world will look like, but it is quite certain that the Affordable Care Act will re-create or substantially modify American health care as we know it. The potential of attracting thousands of previously uninsured patients, who – with the help of the federal government – can come in the front door for care rather that using the back door of the emergency department for treatment, will be an important target.

In this environment, the practicing physician is caught in the changing tide. Many who are not in the swim will be washed up on the beach. Cardiology, along with oncology and gastroenterology, are the prime targets for the anticipated efficiencies evolving from the hospital system expansions and mergers. Although there is a well-recognized need for primary care health care professionals, much of this need is already being filled by nonphysician professionals. It is possible that cardiology, which has been one of the star profit centers, could become a target for consolidation and economy in the future. We may be seeing some of this, as the opportunities for finishing trainees appear to be diminishing.

It is obvious that there has been a major shift in the setting cardiology practices in the last few years. Since 2007, the proportion of physician-owned practices has decreased substantially. While the number of cardiologists employed by hospitals has grown from 11% to 35%, physician-owned practices have decreased from 59% to 36%. This migration of private practice to hospital-based practice is sure to continue. Cardiology practice will soon be directed by managers representing corporate health care who will be intent on putting in place programs that will establish protocol-driven therapy in the name of "quality" and "cost." Many of the changes will lead to better outcomes. Patient "satisfaction" will be measured by metrics already operational in the corporate environment. As the era of cardiology entrepreneurism faces institutional controls, such profit centers as imaging already are facing significant obstacles. The "down side" of this process will be the death of medical care as we knew it. It was not all bad. That mode of physician-driven, patient-centered care will not be easily transferred into the corporate care environment. The physician will need to ensure that at least that vestige of old-style medical care will not be entirely lost.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

In bygone days, your community hospital was a place where babies were born and gallbladders were removed. They were often run by city governments or local religious organizations. Of course, a lot has changed since then. Now your hospital advertises on television and extols the viewer about the medical miracles that are performed inside its walls. They also are getting bigger and merging with smaller and occasionally coequal institutions in the name of efficiency and in the effort to expand their patient catchment.

In an even larger sense, hospitals have been gobbled up by insurance companies and by for-profit networks in an attempt to maximize profits and minimize overhead. Some prestigious hospitals like the Mayo Clinic, the Cleveland Clinic, and MD Anderson Cancer Center have even established affiliations with community hospitals thousands of miles away seemingly to improve local care and at the same time to expand their referral network. Where local hospitals are not adequate and the market beckons, some have even built their own facilities not only in the United States, but also in countries around the globe.

The intent of these network affiliations is not only to improve their image but to impart some of their prestige to the local entities as well. As a result of these mergers and consolidations, they are positioning themselves to be more competitive in the new world of health care. Some would profess the altruism of providing better care either locally or at a distance, but in the long run, economics and market share are the driving force. They have not been concerned with delivering babies or taking out gallbladders for a long time.

Few can predict what the new world will look like, but it is quite certain that the Affordable Care Act will re-create or substantially modify American health care as we know it. The potential of attracting thousands of previously uninsured patients, who – with the help of the federal government – can come in the front door for care rather that using the back door of the emergency department for treatment, will be an important target.

In this environment, the practicing physician is caught in the changing tide. Many who are not in the swim will be washed up on the beach. Cardiology, along with oncology and gastroenterology, are the prime targets for the anticipated efficiencies evolving from the hospital system expansions and mergers. Although there is a well-recognized need for primary care health care professionals, much of this need is already being filled by nonphysician professionals. It is possible that cardiology, which has been one of the star profit centers, could become a target for consolidation and economy in the future. We may be seeing some of this, as the opportunities for finishing trainees appear to be diminishing.

It is obvious that there has been a major shift in the setting cardiology practices in the last few years. Since 2007, the proportion of physician-owned practices has decreased substantially. While the number of cardiologists employed by hospitals has grown from 11% to 35%, physician-owned practices have decreased from 59% to 36%. This migration of private practice to hospital-based practice is sure to continue. Cardiology practice will soon be directed by managers representing corporate health care who will be intent on putting in place programs that will establish protocol-driven therapy in the name of "quality" and "cost." Many of the changes will lead to better outcomes. Patient "satisfaction" will be measured by metrics already operational in the corporate environment. As the era of cardiology entrepreneurism faces institutional controls, such profit centers as imaging already are facing significant obstacles. The "down side" of this process will be the death of medical care as we knew it. It was not all bad. That mode of physician-driven, patient-centered care will not be easily transferred into the corporate care environment. The physician will need to ensure that at least that vestige of old-style medical care will not be entirely lost.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

A recent spate of observational or registry analyses have challenged conventional wisdom derived from randomized clinical trials (RCTs). Both RCTs and registries have inherent flaws, but both provide important information in regard to drug efficacy in the search for "truth."

RCTs examine therapeutic effects in highly selected patient populations by focusing on one clinical entity, thereby excluding many patients with comorbidities that could influence or blunt the effect of the intervention. In a sense, RCTs do not represent the real-world expression of disease, since diseases rarely exists in isolation.

Registry trials collect large numbers of patients with a particular diagnosis within a large database. They include unselected patients and examine the effect of therapy in one disease regardless of comorbidities and are subject to both doctor and patient bias and confounding by comorbidities like chronic renal and pulmonary disease and, above all, are not randomized. Using a contemporary analogy, RCTs are a rifle shot whereas registries are more of a shotgun blast.

There have been two recent important targets for clinical research in heart failure. One is the search for better therapy for heart failure patients with preserved ejection fraction (HFPEF). The other is a search for drugs or devices that can provide added benefit to contemporary therapy for heart failure with reduced ejection fraction (HFREF)

The observation that many HFPEF patients develop heart failure despite current therapy with renin angiotensin aldosterone system (RAAS) antagonists and beta-blockers has led to a search for better therapy. RCTs with newer agents. including focused therapy with new RAAS antagonists, have failed to affect mortality in HFPEF (Lancet 2003;362:759-66). In contrast, a recent publication using the Swedish Heart Failure Registry (JAMA 2012;308:2108-17) found that patients treated with RAAS antagonists benefited compared with patients not taking them. The failure of the newer drugs to reach significance was attributed to flawed patient selection in RCTs that led to lower mortality rates and rendered the trials underpowered.

Similar discordance was observed between RCT and registry data in patients with HFREF who were treated with aldosterone antagonist (AA) in addition to contemporary RAAS antagonists and beta-blocker therapy. Using the Medicare database (JAMA 2012;308:2097-107), the investigators failed to observe any treatment benefit of AA on mortality that had previously been reported (N. Engl. J. Med. 1999;341:709-17). They did observe a decrease in rehospitalization for heart failure associated with an increase in rehospitalization for hyperkalemia. The authors attributed the reported benefit in the RCT to the exclusion of older and diabetic patients in addition to those with renal impairment, who were included in the registry analysis and reflected the real world of HFREF.

One registry study examining the benefit of ICDs in heart failure patients (JAMA 2013;309:55-62) from the analysis by the National Cardiovascular Registry did support the mortality benefit observed in the RCT (N. Engl. J. Med. 2002; 346:877-83).

As RCTs have developed over the last half-century, they have changed from investigations of therapeutic concepts to assessments of the efficacy of new and, often, expensive drugs. Much of this search has been supported by the pharmaceutical and device industries, which are intent on more focused research because of their concern about the "noise" generated by comorbidities that could obscure the benefit of their product. As a result, RCTs have identified lower-risk, homogeneous patient populations that may not reflect the real-world experience. Nevertheless, registry studies suffer from the major effect of bias, which is influenced by the physicians’ therapeutic choices and can distort the observed outcome. Unfortunately, the search for "truth" in clinical research remains often out of our reach.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

A recent spate of observational or registry analyses have challenged conventional wisdom derived from randomized clinical trials (RCTs). Both RCTs and registries have inherent flaws, but both provide important information in regard to drug efficacy in the search for "truth."

RCTs examine therapeutic effects in highly selected patient populations by focusing on one clinical entity, thereby excluding many patients with comorbidities that could influence or blunt the effect of the intervention. In a sense, RCTs do not represent the real-world expression of disease, since diseases rarely exists in isolation.

Registry trials collect large numbers of patients with a particular diagnosis within a large database. They include unselected patients and examine the effect of therapy in one disease regardless of comorbidities and are subject to both doctor and patient bias and confounding by comorbidities like chronic renal and pulmonary disease and, above all, are not randomized. Using a contemporary analogy, RCTs are a rifle shot whereas registries are more of a shotgun blast.

There have been two recent important targets for clinical research in heart failure. One is the search for better therapy for heart failure patients with preserved ejection fraction (HFPEF). The other is a search for drugs or devices that can provide added benefit to contemporary therapy for heart failure with reduced ejection fraction (HFREF)

The observation that many HFPEF patients develop heart failure despite current therapy with renin angiotensin aldosterone system (RAAS) antagonists and beta-blockers has led to a search for better therapy. RCTs with newer agents. including focused therapy with new RAAS antagonists, have failed to affect mortality in HFPEF (Lancet 2003;362:759-66). In contrast, a recent publication using the Swedish Heart Failure Registry (JAMA 2012;308:2108-17) found that patients treated with RAAS antagonists benefited compared with patients not taking them. The failure of the newer drugs to reach significance was attributed to flawed patient selection in RCTs that led to lower mortality rates and rendered the trials underpowered.

Similar discordance was observed between RCT and registry data in patients with HFREF who were treated with aldosterone antagonist (AA) in addition to contemporary RAAS antagonists and beta-blocker therapy. Using the Medicare database (JAMA 2012;308:2097-107), the investigators failed to observe any treatment benefit of AA on mortality that had previously been reported (N. Engl. J. Med. 1999;341:709-17). They did observe a decrease in rehospitalization for heart failure associated with an increase in rehospitalization for hyperkalemia. The authors attributed the reported benefit in the RCT to the exclusion of older and diabetic patients in addition to those with renal impairment, who were included in the registry analysis and reflected the real world of HFREF.

One registry study examining the benefit of ICDs in heart failure patients (JAMA 2013;309:55-62) from the analysis by the National Cardiovascular Registry did support the mortality benefit observed in the RCT (N. Engl. J. Med. 2002; 346:877-83).

As RCTs have developed over the last half-century, they have changed from investigations of therapeutic concepts to assessments of the efficacy of new and, often, expensive drugs. Much of this search has been supported by the pharmaceutical and device industries, which are intent on more focused research because of their concern about the "noise" generated by comorbidities that could obscure the benefit of their product. As a result, RCTs have identified lower-risk, homogeneous patient populations that may not reflect the real-world experience. Nevertheless, registry studies suffer from the major effect of bias, which is influenced by the physicians’ therapeutic choices and can distort the observed outcome. Unfortunately, the search for "truth" in clinical research remains often out of our reach.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

A recent spate of observational or registry analyses have challenged conventional wisdom derived from randomized clinical trials (RCTs). Both RCTs and registries have inherent flaws, but both provide important information in regard to drug efficacy in the search for "truth."

RCTs examine therapeutic effects in highly selected patient populations by focusing on one clinical entity, thereby excluding many patients with comorbidities that could influence or blunt the effect of the intervention. In a sense, RCTs do not represent the real-world expression of disease, since diseases rarely exists in isolation.

Registry trials collect large numbers of patients with a particular diagnosis within a large database. They include unselected patients and examine the effect of therapy in one disease regardless of comorbidities and are subject to both doctor and patient bias and confounding by comorbidities like chronic renal and pulmonary disease and, above all, are not randomized. Using a contemporary analogy, RCTs are a rifle shot whereas registries are more of a shotgun blast.

There have been two recent important targets for clinical research in heart failure. One is the search for better therapy for heart failure patients with preserved ejection fraction (HFPEF). The other is a search for drugs or devices that can provide added benefit to contemporary therapy for heart failure with reduced ejection fraction (HFREF)

The observation that many HFPEF patients develop heart failure despite current therapy with renin angiotensin aldosterone system (RAAS) antagonists and beta-blockers has led to a search for better therapy. RCTs with newer agents. including focused therapy with new RAAS antagonists, have failed to affect mortality in HFPEF (Lancet 2003;362:759-66). In contrast, a recent publication using the Swedish Heart Failure Registry (JAMA 2012;308:2108-17) found that patients treated with RAAS antagonists benefited compared with patients not taking them. The failure of the newer drugs to reach significance was attributed to flawed patient selection in RCTs that led to lower mortality rates and rendered the trials underpowered.

Similar discordance was observed between RCT and registry data in patients with HFREF who were treated with aldosterone antagonist (AA) in addition to contemporary RAAS antagonists and beta-blocker therapy. Using the Medicare database (JAMA 2012;308:2097-107), the investigators failed to observe any treatment benefit of AA on mortality that had previously been reported (N. Engl. J. Med. 1999;341:709-17). They did observe a decrease in rehospitalization for heart failure associated with an increase in rehospitalization for hyperkalemia. The authors attributed the reported benefit in the RCT to the exclusion of older and diabetic patients in addition to those with renal impairment, who were included in the registry analysis and reflected the real world of HFREF.

One registry study examining the benefit of ICDs in heart failure patients (JAMA 2013;309:55-62) from the analysis by the National Cardiovascular Registry did support the mortality benefit observed in the RCT (N. Engl. J. Med. 2002; 346:877-83).

As RCTs have developed over the last half-century, they have changed from investigations of therapeutic concepts to assessments of the efficacy of new and, often, expensive drugs. Much of this search has been supported by the pharmaceutical and device industries, which are intent on more focused research because of their concern about the "noise" generated by comorbidities that could obscure the benefit of their product. As a result, RCTs have identified lower-risk, homogeneous patient populations that may not reflect the real-world experience. Nevertheless, registry studies suffer from the major effect of bias, which is influenced by the physicians’ therapeutic choices and can distort the observed outcome. Unfortunately, the search for "truth" in clinical research remains often out of our reach.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Although to many, the concept of Heart Teams, as examined in Mitchel L. Zoler’s article, "Heart teams inch into routine cardiac practice," seem novel, such collaborations were the norm at the dawn of cardiac surgery.

Beginning with the surgical approach to valvular and, later, coronary vascular surgery, the interaction between cardiac physiologists (as they were called then), coronary angiographers, and cardiac surgeons in deciding where and when to operate was often difficult and contentious. Cardiac surgery was a high-risk procedure, and the outcomes were uncertain. Over the last 50 years we have come a long way and much of what we do is almost commonplace, as frequently performed as a cholecystectomy or appendectomy and with similar risks. Over time, we have become casual with our decision-making process. Both cardiologists and cardiac surgeons have staked out their own therapeutic parameters. Specialty society guidelines have provided important boundaries within which we can and should operate.

At the same time, we continue to push the envelope to identify therapeutic targets and technologies. We have developed complex interventional and surgical procedures and have applied them to older and sicker patient populations. New technology has opened avenues of therapy that we could not have imagined at the inception of interventional cardiology and cardiac surgery.

The advanced interventional surgical approach now requires even greater interaction with more special players in both cardiology and surgery. Although the modern cardiology practice is built on everyday procedures that provide the platform on which we treat a variety of cardiac issues that commonly do not require ongoing group interactions, the new treatment options require a more interactive and collegial environment. It is in this domain that the Heart Team has an important role and has found success. It was re-initiated as a result of the development of the transcatheter aortic valve implantation, which requires close cardiology and surgical interaction. It has expanded as a team approach to the treatment choices in the care of patients with structural heart disease.

Definitions of the boundaries of the new therapies raise important economic and professional challenges. The Heart Team as currently organized provides the framework of that discourse. To some, it will represent an inconvenience and an obstruction to their individual professional performance: The requirement to participate in a structured interaction is just one more barrier to the daily performance of their skills. To others, it will provide an important process that will improve performance: It is an opportunity to coordinate the different skills required for the advance treatments and, more importantly, it represents a forum to educate not only the current participants but also the physician, nurses, and technicians for the future. The discussion and planning for the surgical approach for a particular patient provides a dynamic discussion of the therapeutic options and the important decisions about appropriateness of the procedure. This interactive learning process is critical to the interdisciplinary training of all present and future players.

The growth of cardiovascular therapy has led to the construction of large stand-alone units or sections within hospitals identified as heart centers or institutes. The creation of these facilities provides the professional structure and financial environment to create the Heart Team and answer some of the issues raised in the article in this issue. Initially devised as a combination of marketing and professional associations, they now can provide the educational and scientific structure of the Heart Team.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Although to many, the concept of Heart Teams, as examined in Mitchel L. Zoler’s article, "Heart teams inch into routine cardiac practice," seem novel, such collaborations were the norm at the dawn of cardiac surgery.

Beginning with the surgical approach to valvular and, later, coronary vascular surgery, the interaction between cardiac physiologists (as they were called then), coronary angiographers, and cardiac surgeons in deciding where and when to operate was often difficult and contentious. Cardiac surgery was a high-risk procedure, and the outcomes were uncertain. Over the last 50 years we have come a long way and much of what we do is almost commonplace, as frequently performed as a cholecystectomy or appendectomy and with similar risks. Over time, we have become casual with our decision-making process. Both cardiologists and cardiac surgeons have staked out their own therapeutic parameters. Specialty society guidelines have provided important boundaries within which we can and should operate.

At the same time, we continue to push the envelope to identify therapeutic targets and technologies. We have developed complex interventional and surgical procedures and have applied them to older and sicker patient populations. New technology has opened avenues of therapy that we could not have imagined at the inception of interventional cardiology and cardiac surgery.

The advanced interventional surgical approach now requires even greater interaction with more special players in both cardiology and surgery. Although the modern cardiology practice is built on everyday procedures that provide the platform on which we treat a variety of cardiac issues that commonly do not require ongoing group interactions, the new treatment options require a more interactive and collegial environment. It is in this domain that the Heart Team has an important role and has found success. It was re-initiated as a result of the development of the transcatheter aortic valve implantation, which requires close cardiology and surgical interaction. It has expanded as a team approach to the treatment choices in the care of patients with structural heart disease.

Definitions of the boundaries of the new therapies raise important economic and professional challenges. The Heart Team as currently organized provides the framework of that discourse. To some, it will represent an inconvenience and an obstruction to their individual professional performance: The requirement to participate in a structured interaction is just one more barrier to the daily performance of their skills. To others, it will provide an important process that will improve performance: It is an opportunity to coordinate the different skills required for the advance treatments and, more importantly, it represents a forum to educate not only the current participants but also the physician, nurses, and technicians for the future. The discussion and planning for the surgical approach for a particular patient provides a dynamic discussion of the therapeutic options and the important decisions about appropriateness of the procedure. This interactive learning process is critical to the interdisciplinary training of all present and future players.

The growth of cardiovascular therapy has led to the construction of large stand-alone units or sections within hospitals identified as heart centers or institutes. The creation of these facilities provides the professional structure and financial environment to create the Heart Team and answer some of the issues raised in the article in this issue. Initially devised as a combination of marketing and professional associations, they now can provide the educational and scientific structure of the Heart Team.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

Although to many, the concept of Heart Teams, as examined in Mitchel L. Zoler’s article, "Heart teams inch into routine cardiac practice," seem novel, such collaborations were the norm at the dawn of cardiac surgery.

Beginning with the surgical approach to valvular and, later, coronary vascular surgery, the interaction between cardiac physiologists (as they were called then), coronary angiographers, and cardiac surgeons in deciding where and when to operate was often difficult and contentious. Cardiac surgery was a high-risk procedure, and the outcomes were uncertain. Over the last 50 years we have come a long way and much of what we do is almost commonplace, as frequently performed as a cholecystectomy or appendectomy and with similar risks. Over time, we have become casual with our decision-making process. Both cardiologists and cardiac surgeons have staked out their own therapeutic parameters. Specialty society guidelines have provided important boundaries within which we can and should operate.

At the same time, we continue to push the envelope to identify therapeutic targets and technologies. We have developed complex interventional and surgical procedures and have applied them to older and sicker patient populations. New technology has opened avenues of therapy that we could not have imagined at the inception of interventional cardiology and cardiac surgery.

The advanced interventional surgical approach now requires even greater interaction with more special players in both cardiology and surgery. Although the modern cardiology practice is built on everyday procedures that provide the platform on which we treat a variety of cardiac issues that commonly do not require ongoing group interactions, the new treatment options require a more interactive and collegial environment. It is in this domain that the Heart Team has an important role and has found success. It was re-initiated as a result of the development of the transcatheter aortic valve implantation, which requires close cardiology and surgical interaction. It has expanded as a team approach to the treatment choices in the care of patients with structural heart disease.

Definitions of the boundaries of the new therapies raise important economic and professional challenges. The Heart Team as currently organized provides the framework of that discourse. To some, it will represent an inconvenience and an obstruction to their individual professional performance: The requirement to participate in a structured interaction is just one more barrier to the daily performance of their skills. To others, it will provide an important process that will improve performance: It is an opportunity to coordinate the different skills required for the advance treatments and, more importantly, it represents a forum to educate not only the current participants but also the physician, nurses, and technicians for the future. The discussion and planning for the surgical approach for a particular patient provides a dynamic discussion of the therapeutic options and the important decisions about appropriateness of the procedure. This interactive learning process is critical to the interdisciplinary training of all present and future players.

The growth of cardiovascular therapy has led to the construction of large stand-alone units or sections within hospitals identified as heart centers or institutes. The creation of these facilities provides the professional structure and financial environment to create the Heart Team and answer some of the issues raised in the article in this issue. Initially devised as a combination of marketing and professional associations, they now can provide the educational and scientific structure of the Heart Team.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The increased frequency in recent years of what has been termed "ad hoc" percutaneous coronary intervention is of concern to both interventional cardiologists and third-party payers.

The definition of ad hoc PCI that accompanied recent guidelines on that subject in a statement by the Society of Cardiovascular Angiography and Interventions (SCAI) is a "diagnostic catheterization followed in the same session or same sitting by PCI." Much of this increase has occurred in patients without symptoms and with minimal if any evidence of ischemia. Convenience and economics also play a role. As a result, cardiologists presume that they can do no harm without asking the question of whether they are doing any good.

A recent report on 144,737 nonacute PCIs using the National Cardiovascular Data Registry indicated that almost 30,000 PCIs (24.4%) were performed in patients without symptoms or class I angina and 30% were at low risk by noninvasive testing. In these nonacute patients, 67% were considered either inappropriate or uncertain (JAMA 2011;306:53-61). The rate of performing inappropriate PCI in hospitals varied between 6% and 16%. A number of hospitals had inappropriate rates exceeding 25%, and some had rates as high as 48%. The registry does not provide the number of ad hoc procedures performed, but one might presume that many of these patients would have fit the criteria for entry into the COURAGE trial (N. Engl. J. Med. 2007;356:1503-16), in which patients with stable coronary disease, 43% of whom had either no angina or class I angina, did as well with medical treatment as with PCI.

Angiographers have admitted having difficulty assessing the severity of stenosis, and therefore often proceeding to ad hoc PCI. The recent FAME study suggests that the measure of fractional flow reserve (FFR) is able to define coronary lesions that are clinically significant (N. Engl. J. Med. 2009;360;213-24). However, the conclusions of FAME have been challenged in regard to the clinical importance of FFR measurement.

Included in the recent SCAI guidelines is the requirement that before ad hoc PCI is performed, patients should be given information about the appropriateness, relative risk, and benefit of the procedure as well as therapeutic alternatives to PCI. For patients with ongoing symptoms and positive diagnostic tests for ischemia, this is easily obtained prior to intervention. But patients without symptoms and without evidence by stress testing may not be given the real story before the procedure. For these patients, SCAI advises that "time-out" be called and that they be given time to consider the alternatives for treatment of their disease (Catheter. Cardiovasc. Interv. 2012 Nov. 29 [doi: 10.1002/ccd.24701]).

Unfortunately for all of us, the federal government is also concerned about the issue of appropriateness. A recent whistleblower lawsuit in Ohio was resolved with a payment of fines of $3 million by the hospital and more than $500,000 by the physician group involved in the lawsuit. According to press reports, the physicians defended their "high rates as a result of their aggressive style of medicine." The physicians defended the medical care that they provided although they "might not have met the government’s guidelines of reimbursement" (New York Times, Jan. 5, 2013, sec. B1).

Unless we adhere to good practice guidelines, the federal government will force our adherence, whether we like it or not.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies. This column, "Heart of the Matter," appears regularly in Cardiology News.

The increased frequency in recent years of what has been termed "ad hoc" percutaneous coronary intervention is of concern to both interventional cardiologists and third-party payers.

The definition of ad hoc PCI that accompanied recent guidelines on that subject in a statement by the Society of Cardiovascular Angiography and Interventions (SCAI) is a "diagnostic catheterization followed in the same session or same sitting by PCI." Much of this increase has occurred in patients without symptoms and with minimal if any evidence of ischemia. Convenience and economics also play a role. As a result, cardiologists presume that they can do no harm without asking the question of whether they are doing any good.

A recent report on 144,737 nonacute PCIs using the National Cardiovascular Data Registry indicated that almost 30,000 PCIs (24.4%) were performed in patients without symptoms or class I angina and 30% were at low risk by noninvasive testing. In these nonacute patients, 67% were considered either inappropriate or uncertain (JAMA 2011;306:53-61). The rate of performing inappropriate PCI in hospitals varied between 6% and 16%. A number of hospitals had inappropriate rates exceeding 25%, and some had rates as high as 48%. The registry does not provide the number of ad hoc procedures performed, but one might presume that many of these patients would have fit the criteria for entry into the COURAGE trial (N. Engl. J. Med. 2007;356:1503-16), in which patients with stable coronary disease, 43% of whom had either no angina or class I angina, did as well with medical treatment as with PCI.

Angiographers have admitted having difficulty assessing the severity of stenosis, and therefore often proceeding to ad hoc PCI. The recent FAME study suggests that the measure of fractional flow reserve (FFR) is able to define coronary lesions that are clinically significant (N. Engl. J. Med. 2009;360;213-24). However, the conclusions of FAME have been challenged in regard to the clinical importance of FFR measurement.

Included in the recent SCAI guidelines is the requirement that before ad hoc PCI is performed, patients should be given information about the appropriateness, relative risk, and benefit of the procedure as well as therapeutic alternatives to PCI. For patients with ongoing symptoms and positive diagnostic tests for ischemia, this is easily obtained prior to intervention. But patients without symptoms and without evidence by stress testing may not be given the real story before the procedure. For these patients, SCAI advises that "time-out" be called and that they be given time to consider the alternatives for treatment of their disease (Catheter. Cardiovasc. Interv. 2012 Nov. 29 [doi: 10.1002/ccd.24701]).

Unfortunately for all of us, the federal government is also concerned about the issue of appropriateness. A recent whistleblower lawsuit in Ohio was resolved with a payment of fines of $3 million by the hospital and more than $500,000 by the physician group involved in the lawsuit. According to press reports, the physicians defended their "high rates as a result of their aggressive style of medicine." The physicians defended the medical care that they provided although they "might not have met the government’s guidelines of reimbursement" (New York Times, Jan. 5, 2013, sec. B1).

Unless we adhere to good practice guidelines, the federal government will force our adherence, whether we like it or not.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies. This column, "Heart of the Matter," appears regularly in Cardiology News.

The increased frequency in recent years of what has been termed "ad hoc" percutaneous coronary intervention is of concern to both interventional cardiologists and third-party payers.

The definition of ad hoc PCI that accompanied recent guidelines on that subject in a statement by the Society of Cardiovascular Angiography and Interventions (SCAI) is a "diagnostic catheterization followed in the same session or same sitting by PCI." Much of this increase has occurred in patients without symptoms and with minimal if any evidence of ischemia. Convenience and economics also play a role. As a result, cardiologists presume that they can do no harm without asking the question of whether they are doing any good.

A recent report on 144,737 nonacute PCIs using the National Cardiovascular Data Registry indicated that almost 30,000 PCIs (24.4%) were performed in patients without symptoms or class I angina and 30% were at low risk by noninvasive testing. In these nonacute patients, 67% were considered either inappropriate or uncertain (JAMA 2011;306:53-61). The rate of performing inappropriate PCI in hospitals varied between 6% and 16%. A number of hospitals had inappropriate rates exceeding 25%, and some had rates as high as 48%. The registry does not provide the number of ad hoc procedures performed, but one might presume that many of these patients would have fit the criteria for entry into the COURAGE trial (N. Engl. J. Med. 2007;356:1503-16), in which patients with stable coronary disease, 43% of whom had either no angina or class I angina, did as well with medical treatment as with PCI.

Angiographers have admitted having difficulty assessing the severity of stenosis, and therefore often proceeding to ad hoc PCI. The recent FAME study suggests that the measure of fractional flow reserve (FFR) is able to define coronary lesions that are clinically significant (N. Engl. J. Med. 2009;360;213-24). However, the conclusions of FAME have been challenged in regard to the clinical importance of FFR measurement.

Included in the recent SCAI guidelines is the requirement that before ad hoc PCI is performed, patients should be given information about the appropriateness, relative risk, and benefit of the procedure as well as therapeutic alternatives to PCI. For patients with ongoing symptoms and positive diagnostic tests for ischemia, this is easily obtained prior to intervention. But patients without symptoms and without evidence by stress testing may not be given the real story before the procedure. For these patients, SCAI advises that "time-out" be called and that they be given time to consider the alternatives for treatment of their disease (Catheter. Cardiovasc. Interv. 2012 Nov. 29 [doi: 10.1002/ccd.24701]).

Unfortunately for all of us, the federal government is also concerned about the issue of appropriateness. A recent whistleblower lawsuit in Ohio was resolved with a payment of fines of $3 million by the hospital and more than $500,000 by the physician group involved in the lawsuit. According to press reports, the physicians defended their "high rates as a result of their aggressive style of medicine." The physicians defended the medical care that they provided although they "might not have met the government’s guidelines of reimbursement" (New York Times, Jan. 5, 2013, sec. B1).

Unless we adhere to good practice guidelines, the federal government will force our adherence, whether we like it or not.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies. This column, "Heart of the Matter," appears regularly in Cardiology News.