Background: Up to 30 million people in the United States meet criteria for alcohol use disorder. Gabapentin addresses symptoms of protracted withdrawal such as insomnia, irritability, difficulty with attention, dysphoria, and anxiety. It does that by acting on voltage-gated calcium channels and, in turn, influencing GABA and glutamate tone and activity.

A couple of study limitations were a significant noncompletion rate (30% in gabapentin arm and 39% in the placebo arm) and self-reported alcohol withdrawal symptoms prior to entry into the study.

Bottom line: Gabapentin helps in reducing drinking and maintaining alcohol abstinence in individuals with alcohol use disorder, especially those with high–alcohol withdrawal symptoms.

Citation: Anton RF et al. Efficacy of gabapentin for the treatment of alcohol use disorder in patients with alcohol withdrawal symptoms: A randomized clinical trial. JAMA Intern Med. 2020 Mar 9;180(5):728-36.

Dr. Gaddam is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: Up to 30 million people in the United States meet criteria for alcohol use disorder. Gabapentin addresses symptoms of protracted withdrawal such as insomnia, irritability, difficulty with attention, dysphoria, and anxiety. It does that by acting on voltage-gated calcium channels and, in turn, influencing GABA and glutamate tone and activity.

A couple of study limitations were a significant noncompletion rate (30% in gabapentin arm and 39% in the placebo arm) and self-reported alcohol withdrawal symptoms prior to entry into the study.

Bottom line: Gabapentin helps in reducing drinking and maintaining alcohol abstinence in individuals with alcohol use disorder, especially those with high–alcohol withdrawal symptoms.

Citation: Anton RF et al. Efficacy of gabapentin for the treatment of alcohol use disorder in patients with alcohol withdrawal symptoms: A randomized clinical trial. JAMA Intern Med. 2020 Mar 9;180(5):728-36.

Dr. Gaddam is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: Up to 30 million people in the United States meet criteria for alcohol use disorder. Gabapentin addresses symptoms of protracted withdrawal such as insomnia, irritability, difficulty with attention, dysphoria, and anxiety. It does that by acting on voltage-gated calcium channels and, in turn, influencing GABA and glutamate tone and activity.

A couple of study limitations were a significant noncompletion rate (30% in gabapentin arm and 39% in the placebo arm) and self-reported alcohol withdrawal symptoms prior to entry into the study.

Bottom line: Gabapentin helps in reducing drinking and maintaining alcohol abstinence in individuals with alcohol use disorder, especially those with high–alcohol withdrawal symptoms.

Citation: Anton RF et al. Efficacy of gabapentin for the treatment of alcohol use disorder in patients with alcohol withdrawal symptoms: A randomized clinical trial. JAMA Intern Med. 2020 Mar 9;180(5):728-36.

Dr. Gaddam is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

New consensus recommendations address diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), with advice that may also be helpful for patients with lingering symptoms following acute COVID-19 infection.

VioletaStoimenova/Getty Images

The document was published online Aug. 25, 2021, in the Mayo Clinic Proceedings by the 23-member U.S. ME/CFS Clinician Coalition, headed by Lucinda Bateman, MD, of the Bateman Horne Center of Excellence, Salt Lake City. The document is the culmination of work that began with a summit held at the center in March 2018.

The target audience is both generalist and specialist health care providers. While ME/CFS is estimated to affect up to 2.5 million Americans, more than 90% are either undiagnosed or misdiagnosed with other conditions such as depression. And those who are diagnosed often receive inappropriate, outdated treatments such as psychotherapy and exercise prescriptions.

“Despite myalgic encephalomyelitis/chronic fatigue syndrome affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful,” Dr. Bateman and colleagues wrote.

The urgency of appropriate recognition and management of ME/CFS has increased as growing numbers of people are exhibiting signs and symptoms of ME/CFS following acute COVID-19 infection. This isn’t surprising because the illness has long been linked to other infections, including Epstein-Barr virus, the authors noted.

The document covers the epidemiology, impact, and prognosis of ME/CFS, as well as etiology and pathophysiology. “Scientific studies demonstrate multiple dysfunctional organ systems, including neuro, immune, and metabolic, in ME/CFS. These findings are not explained merely by deconditioning,” document coauthor Lily Chu, MD, an independent consultant in Burlingame, Calif., said in an interview.

The document reviews the 2015 U.S. Institute of Medicine (now Academy of Medicine) diagnostic criteria that are now also recommended by the Centers for Disease Control and Prevention. They are based on four main symptoms: substantial reduction or impairment in the ability to engage in preillness levels of occupational, educational, social or personal activities for longer than 6 months; postexertional malaise, a worsening of all current symptoms, that patients often describe as a “crash”; unrefreshing sleep; and cognitive impairment and/or orthostatic intolerance.

“The new diagnostic criteria focusing on the key symptom of postexertional malaise rather than chronic fatigue, which is common in many conditions, may make the diagnostic process quicker and more accurate. Diagnosis now is both an inclusionary and not just exclusionary process, so it’s not necessary to eliminate all causes of fatigue. Diagnose patients who fit the criteria and be alert for it in people with persistent symptoms post COVID,” Dr. Chu said.

The document provides advice for taking a clinical history to obtain the information necessary for making the diagnosis, including use of laboratory testing to rule out other conditions. Physical exams, while they may not reveal specific abnormalities, may help in identifying comorbidities and ruling out alternative diagnoses.

A long list of nonpharmacologic and pharmacologic treatment and management approaches is offered for each of the individual core and common ME/CFS symptoms, including postexertional malaise, orthostatic intolerance, sleep issues, cognitive dysfunction and fatigue, immune dysfunction, pain, and gastrointestinal issues.

The document recommends against using the “outdated standard of care” cognitive-behavioral therapy and graded exercise therapy as primary treatments for the illness. Instead, the authors recommend teaching patients “pacing,” an individualized approach to energy conservation aimed at minimizing the frequency, duration, and severity of postexertional malaise.

Clinicians are also advised to assess patients’ daily living needs and provide support, including acquiring handicap placards, work or school accommodations, and disability benefits.

“There are things clinicians can do now to help patients even without a disease-modifying treatment. These are actions they are already familiar with and carry out for people with other chronic diseases, which often have limited treatment options as well. Don’t underestimate the importance and value of supportive care for patients.” Dr. Chu said.

The recommendations are based primarily on clinical expertise because there are very few randomized trials, and much of the evidence from other types of trials has been flawed, document coauthor Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“The sad reality is there aren’t very many large randomized clinical trials with this illness and so what a group of very experienced clinicians did was to gather their collective experience and report it as that. It’s largely uncontrolled experience, but from people who have seen a lot of patients, for what it’s worth to the medical community.”

Dr. Komaroff also advised that clinicians watch out for ME/CFS in patients with long COVID. “If we find that those called long COVID meet ME/CFS criteria, the reason for knowing that is that there are already some treatments that according to experienced clinicians are helpful for ME/CFS, and it would be perfectly appropriate to try some of them in long COVID, particularly the ones that have minimal adverse reactions.”

The guidelines project was supported by the Open Medicine Foundation. Dr. Komaroff reported receiving personal fees from Serimmune outside the submitted work. Dr. Chu has no disclosures.

New consensus recommendations address diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), with advice that may also be helpful for patients with lingering symptoms following acute COVID-19 infection.

VioletaStoimenova/Getty Images

The document was published online Aug. 25, 2021, in the Mayo Clinic Proceedings by the 23-member U.S. ME/CFS Clinician Coalition, headed by Lucinda Bateman, MD, of the Bateman Horne Center of Excellence, Salt Lake City. The document is the culmination of work that began with a summit held at the center in March 2018.

The target audience is both generalist and specialist health care providers. While ME/CFS is estimated to affect up to 2.5 million Americans, more than 90% are either undiagnosed or misdiagnosed with other conditions such as depression. And those who are diagnosed often receive inappropriate, outdated treatments such as psychotherapy and exercise prescriptions.

“Despite myalgic encephalomyelitis/chronic fatigue syndrome affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful,” Dr. Bateman and colleagues wrote.

The urgency of appropriate recognition and management of ME/CFS has increased as growing numbers of people are exhibiting signs and symptoms of ME/CFS following acute COVID-19 infection. This isn’t surprising because the illness has long been linked to other infections, including Epstein-Barr virus, the authors noted.

The document covers the epidemiology, impact, and prognosis of ME/CFS, as well as etiology and pathophysiology. “Scientific studies demonstrate multiple dysfunctional organ systems, including neuro, immune, and metabolic, in ME/CFS. These findings are not explained merely by deconditioning,” document coauthor Lily Chu, MD, an independent consultant in Burlingame, Calif., said in an interview.

The document reviews the 2015 U.S. Institute of Medicine (now Academy of Medicine) diagnostic criteria that are now also recommended by the Centers for Disease Control and Prevention. They are based on four main symptoms: substantial reduction or impairment in the ability to engage in preillness levels of occupational, educational, social or personal activities for longer than 6 months; postexertional malaise, a worsening of all current symptoms, that patients often describe as a “crash”; unrefreshing sleep; and cognitive impairment and/or orthostatic intolerance.

“The new diagnostic criteria focusing on the key symptom of postexertional malaise rather than chronic fatigue, which is common in many conditions, may make the diagnostic process quicker and more accurate. Diagnosis now is both an inclusionary and not just exclusionary process, so it’s not necessary to eliminate all causes of fatigue. Diagnose patients who fit the criteria and be alert for it in people with persistent symptoms post COVID,” Dr. Chu said.

The document provides advice for taking a clinical history to obtain the information necessary for making the diagnosis, including use of laboratory testing to rule out other conditions. Physical exams, while they may not reveal specific abnormalities, may help in identifying comorbidities and ruling out alternative diagnoses.

A long list of nonpharmacologic and pharmacologic treatment and management approaches is offered for each of the individual core and common ME/CFS symptoms, including postexertional malaise, orthostatic intolerance, sleep issues, cognitive dysfunction and fatigue, immune dysfunction, pain, and gastrointestinal issues.

The document recommends against using the “outdated standard of care” cognitive-behavioral therapy and graded exercise therapy as primary treatments for the illness. Instead, the authors recommend teaching patients “pacing,” an individualized approach to energy conservation aimed at minimizing the frequency, duration, and severity of postexertional malaise.

Clinicians are also advised to assess patients’ daily living needs and provide support, including acquiring handicap placards, work or school accommodations, and disability benefits.

“There are things clinicians can do now to help patients even without a disease-modifying treatment. These are actions they are already familiar with and carry out for people with other chronic diseases, which often have limited treatment options as well. Don’t underestimate the importance and value of supportive care for patients.” Dr. Chu said.

The recommendations are based primarily on clinical expertise because there are very few randomized trials, and much of the evidence from other types of trials has been flawed, document coauthor Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“The sad reality is there aren’t very many large randomized clinical trials with this illness and so what a group of very experienced clinicians did was to gather their collective experience and report it as that. It’s largely uncontrolled experience, but from people who have seen a lot of patients, for what it’s worth to the medical community.”

Dr. Komaroff also advised that clinicians watch out for ME/CFS in patients with long COVID. “If we find that those called long COVID meet ME/CFS criteria, the reason for knowing that is that there are already some treatments that according to experienced clinicians are helpful for ME/CFS, and it would be perfectly appropriate to try some of them in long COVID, particularly the ones that have minimal adverse reactions.”

The guidelines project was supported by the Open Medicine Foundation. Dr. Komaroff reported receiving personal fees from Serimmune outside the submitted work. Dr. Chu has no disclosures.

New consensus recommendations address diagnosis and management of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), with advice that may also be helpful for patients with lingering symptoms following acute COVID-19 infection.

VioletaStoimenova/Getty Images

The document was published online Aug. 25, 2021, in the Mayo Clinic Proceedings by the 23-member U.S. ME/CFS Clinician Coalition, headed by Lucinda Bateman, MD, of the Bateman Horne Center of Excellence, Salt Lake City. The document is the culmination of work that began with a summit held at the center in March 2018.

The target audience is both generalist and specialist health care providers. While ME/CFS is estimated to affect up to 2.5 million Americans, more than 90% are either undiagnosed or misdiagnosed with other conditions such as depression. And those who are diagnosed often receive inappropriate, outdated treatments such as psychotherapy and exercise prescriptions.

“Despite myalgic encephalomyelitis/chronic fatigue syndrome affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful,” Dr. Bateman and colleagues wrote.

The urgency of appropriate recognition and management of ME/CFS has increased as growing numbers of people are exhibiting signs and symptoms of ME/CFS following acute COVID-19 infection. This isn’t surprising because the illness has long been linked to other infections, including Epstein-Barr virus, the authors noted.

The document covers the epidemiology, impact, and prognosis of ME/CFS, as well as etiology and pathophysiology. “Scientific studies demonstrate multiple dysfunctional organ systems, including neuro, immune, and metabolic, in ME/CFS. These findings are not explained merely by deconditioning,” document coauthor Lily Chu, MD, an independent consultant in Burlingame, Calif., said in an interview.

The document reviews the 2015 U.S. Institute of Medicine (now Academy of Medicine) diagnostic criteria that are now also recommended by the Centers for Disease Control and Prevention. They are based on four main symptoms: substantial reduction or impairment in the ability to engage in preillness levels of occupational, educational, social or personal activities for longer than 6 months; postexertional malaise, a worsening of all current symptoms, that patients often describe as a “crash”; unrefreshing sleep; and cognitive impairment and/or orthostatic intolerance.

“The new diagnostic criteria focusing on the key symptom of postexertional malaise rather than chronic fatigue, which is common in many conditions, may make the diagnostic process quicker and more accurate. Diagnosis now is both an inclusionary and not just exclusionary process, so it’s not necessary to eliminate all causes of fatigue. Diagnose patients who fit the criteria and be alert for it in people with persistent symptoms post COVID,” Dr. Chu said.

The document provides advice for taking a clinical history to obtain the information necessary for making the diagnosis, including use of laboratory testing to rule out other conditions. Physical exams, while they may not reveal specific abnormalities, may help in identifying comorbidities and ruling out alternative diagnoses.

A long list of nonpharmacologic and pharmacologic treatment and management approaches is offered for each of the individual core and common ME/CFS symptoms, including postexertional malaise, orthostatic intolerance, sleep issues, cognitive dysfunction and fatigue, immune dysfunction, pain, and gastrointestinal issues.

The document recommends against using the “outdated standard of care” cognitive-behavioral therapy and graded exercise therapy as primary treatments for the illness. Instead, the authors recommend teaching patients “pacing,” an individualized approach to energy conservation aimed at minimizing the frequency, duration, and severity of postexertional malaise.

Clinicians are also advised to assess patients’ daily living needs and provide support, including acquiring handicap placards, work or school accommodations, and disability benefits.

“There are things clinicians can do now to help patients even without a disease-modifying treatment. These are actions they are already familiar with and carry out for people with other chronic diseases, which often have limited treatment options as well. Don’t underestimate the importance and value of supportive care for patients.” Dr. Chu said.

The recommendations are based primarily on clinical expertise because there are very few randomized trials, and much of the evidence from other types of trials has been flawed, document coauthor Anthony L. Komaroff, MD, of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

“The sad reality is there aren’t very many large randomized clinical trials with this illness and so what a group of very experienced clinicians did was to gather their collective experience and report it as that. It’s largely uncontrolled experience, but from people who have seen a lot of patients, for what it’s worth to the medical community.”

Dr. Komaroff also advised that clinicians watch out for ME/CFS in patients with long COVID. “If we find that those called long COVID meet ME/CFS criteria, the reason for knowing that is that there are already some treatments that according to experienced clinicians are helpful for ME/CFS, and it would be perfectly appropriate to try some of them in long COVID, particularly the ones that have minimal adverse reactions.”

The guidelines project was supported by the Open Medicine Foundation. Dr. Komaroff reported receiving personal fees from Serimmune outside the submitted work. Dr. Chu has no disclosures.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

There will be so much more to the annual congress of the European Society of Cardiology, which begins Aug. 27 with an all-virtual format, than detailed primary results of EMPEROR-Preserved, a trial that could mark a turning point for heart failure (HF) medical therapy.

Also among the featured Hot Line and Late-Breaking Science sessions are – along with many other studies – explorations of arrhythmia management (ablation or guided by loop recorder); secondary prevention, including by vaccination; oral anticoagulation, notably after transcatheter valve procedures; and colchicine or thrombosis prophylaxis in hospitalized patients with COVID-19.

There will even be a head-to-head comparison of two long-familiar left atrial appendage (LAA) occluders, and a population-based, randomized trial of sodium restriction through wide-scale use of a potassium-based salt substitute.

The congress will also introduce four guideline documents at sessions throughout the Congress, one on each day. They cover new and modified recommendations for heart failure; pacing, including cardiac resynchronization therapy (CRT); cardiovascular (CV) disease prevention; and, with cosponsorship from the European Association for Cardio-Thoracic Surgery, valvular heart disease.
 

The virtues of virtual

That next year’s Congress is slated for Aug. 27-30 in Barcelona should be welcome news for anyone whose “what if” curiosity about all-virtual conferences has already been satisfied. But with experience comes wisdom, as the medical societies have learned that online scientific meetings have some winning qualities that may be worth keeping, as least for a while.

“I think there is no doubt that the digital format will continue, for several reasons. One is that this pandemic is not over,” ESC Congress program committee chair Stephan Windecker, MD, Bern (Switzerland) University Hospital, , told this news organization. “As long as it is not over, the digital format is here to stay.”

But it also appears that people who haven’t been able to attend the congress in person are keen to log in and engage online, Dr. Windecker said. The 2020 all-virtual conference drew a much younger pool of registrants, on average, than did the live conferences before the pandemic.

“I think that’s an indication of people that may be in training, in early stages of their career, or they don’t have the support from departments or from their practice, or other financial means.” But they are able to participate via computer, tablet, or smartphone, he said.

“Another advantage is that the recorded content can be replayed at the convenience of whoever wants to consume it at a later point in time,” he added. “Those are just some examples why the digital format is likely to stay,” on its own or in a new age of hybrid meetings.  
 

New and updated guidelines

Leading off the guideline series is the document on diagnosis and treatment of acute and chronic HF, which leveraged the past few busy years of HF clinical trials to arrive at a number of new recommendations and strengthened level-of-evidence ratings. It covers both drug and device therapy of HF with reduced ejection fraction (HFrEF) and acute decompensated HF, and tweaks and further enshrines the concept of HF with mildly reduced ejection fraction (HFmrEF).

Several updated recommendations for both long-used and novel medications, notably the sodium-glucose cotransporter 2 inhibitors, will be included because of the recently appreciated evidence-based impact in HFrEF, Dr. Windecker noted.

“I think it will be particularly interesting to look for the SGLT2 inhibitors as not a completely new class of drugs, but certainly one where there has been a lot of new evidence, to look at how those drugs will be integrated in the overall care pathway.”

A top-line preview of the new HF guideline limited to drug therapy, presented at July’s Heart Failure Association of the European Society of Cardiology (ESC-HFA), provided a simple answer to a common question in the new, bountiful age of HFrEF medications: Which meds, initiated in what order?

As it happens, the new recommendation for first-line HFrEF drug therapy is not a silver bullet, but a shotgun – prompt initiation of at least four meds, one from each of four drug classes: renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRA), and SGLT2 inhibitors. Each class, as described in the document, is to be started as soon as safely feasible, in a sequence deemed appropriate for each individual patient.
 

Spotlight on EMPEROR-Preserved

The world already knows that the trial, which tested the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) on top of standard therapy, “met” its primary endpoint in almost 6,000 patients with HF with preserved ejection fraction (HFpEF), who included some with HFmrEF by more contemporary definitions.

That means patients in EMPEROR-Preserved assigned to take empagliflozin showed significantly fewer events that made up the study’s primary endpoint, a composite of CV death or HF hospitalization. It appears to be the first clearly significant overall medical therapy benefit for a clinical primary endpoint in a major randomized HFpEF drug trial.

And that, pending fuller presentation of trial results at the Congress on Aug. 27, could be a huge deal for the half of HF patients with left ventricular ejection fractions (LVEF) higher than the HFrEF range.

Those early top-line results weren’t a decisive bombshell for a field now filled with hope for a practice-changing empagliflozin outcome in EMPEROR-Preserved, which isn’t a certainty. They were more like the “boom” of a mortar launching a rocket of fireworks that may explode into a chrysanthemum or green comet or, sometimes, turn out to be no more than a dud. The promise of the early cursory results critically depends on further details.

“Provided there is a compelling benefit, this is what everyone has been waiting for in this condition for decades,” Mikhail N. Kosiborod, MD, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., said.

“Already knowing that the trial met the primary endpoint is obviously very intriguing and encouraging,” he added. “But there are things we don’t know, such as: What is the magnitude of benefit? And whether that benefit, whatever the magnitude, is driven by reductions in both heart failure hospitalizations and cardiovascular death, or only one of the two.”

For example: “If we see an impressive benefit for reduction of hospitalizations, but not a significant reduction in death, that would still be a huge advance. That’s because, to date, we don’t have any drug for HFpEF that has convincingly demonstrated a compelling reduction in heart failure hospitalization or improvement in symptoms, function, or quality of life,” observed Dr. Kosiborod, who wasn’t part of EMPEROR-Preserved.

There have been “suggestions” from HFrEF trials that empagliflozin and dapagliflozin (Farxiga, AstraZeneca) “have very comparable effects on at least the endpoint of cardiovascular death or hospitalization for heart failure,” he said. “So, my expectation would be that whatever is observed in EMPEROR-Preserved is likely a class effect, as well.”

Following EMPEROR-Preserved on the agenda is EMPEROR-Pooled, a patient-level combined analysis of the EMPEROR series of trials that spans the range of HF, regardless of ejection fraction or diabetes status, primarily exploring the effects of empagliflozin on renal function.
 

Other offerings, Friday, Aug. 27

Scheduled immediately after EMPEROR-Preserved is a presentation on the SMART-MI trial, which should clarify whether management guided by continuous ambulatory monitoring is effective in patients considered at especially high arrhythmic risk. Entry called for recent myocardial infarction and an LVEF of 36%-50% with evidence of cardiac autonomic dysfunction.

The trial randomly assigned 400 such patients to be or not be implanted with a Reveal LINQ (Medtronic) loop recorder and followed them for up to 18 months, primarily for detection of potentially serious arrhythmic events. Endpoints that involved mortality, hospitalization or other clinical events were secondary.

In a time slot preceding both SMART-MI and EMPEROR-Preserved, the GUIDE-HF trial is following a projected 3,600 patients with HF implanted with a CardioMEMS HF System (Abbott) pulmonary artery (PA) pressure sensor to explore the its value for guiding management.

The trial’s three cohorts, followed for at least 12 months, include randomized sensor-monitored and control groups of patients with New York Heart Association class 2-4 symptoms, as well as a third observational set of patients in NYHA class 3. That’s the indication for which the CardioMEMS monitor gained approval in the United States in 2014 based on the 2011 CHAMPION trial, and which fared just as well in the 2017 CHAMPION Post-Approval Study.

The Friday Hot Lines also include Dal-GenE, which has entered about 6,000 patients with recent MI to test the once-abandoned cholesterol ester transfer protein (CETP) inhibitor dalcetrapib (DalCor) for any secondary-prevention benefits when used selectively. The trial’s hook: All its patients are confirmed to have the AA genotype of the rs1967309 variant in the ADCY9 gene, which has been associated with a pronounced clinical response to CETP inhibition.

Saturday, Aug. 28

The direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists in patients with nonvalvular atrial fibrillation (AFib). But whether DOACs are similarly preferable in the growing world population of people who have undergone transcatheter aortic valve replacement (TAVR or TAVI), an issue explored with variable results in the ATLANTIS and GALILEO trials, is far from settled.

The ENVISAGE-TAVI AF trial explored the question for the factor X inhibitor edoxaban (Savaysa, Lixiana, Daiichi-Sankyo) in 1,400 patients with AFib and a transfemoral TAVR in the previous 5 days, who were randomly assigned to the DOAC or standard management along with discretionary antiplatelet therapy. They’ve been followed for up to 3 years for a composite endpoint of clinical events – including death, MI, and stroke – and for major bleeding.

The day will also feature MASTER DAPT, a comparison of two dual-antiplatelet therapy (DAPT) regimens in an estimated 4,300 patients considered to be high-risk for bleeding who had received the sirolimus-eluting Ultimaster (Terumo) coronary stent, which has a bioresorbable polymer coating.

Investigators have randomly assigned patients to receive either very-short-duration DAPT, for about a month after stenting, followed by a P2Y12 inhibitor alone for up to a year after the procedure; or a more conventional regimen of a P2Y12 inhibitor for 6-12 months with aspirin maintained for a total of 12 months.

Later that day, investigators from the FIGARO-DKD trial will present their results based on 7,437 patients with type 2 diabetes and chronic kidney disease (CKD), a much fuller version than the top-line findings announced by sponsor Bayer 3 months ago.

Those top-line results suggested that patients assigned to receive the nonsteroidal nonselective mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) on top of standard care benefited with a drop in risk for the primary endpoint of CV death or nonfatal CV events.

Finerenone was recently approved in the United States for treating patients with both type 2 diabetes and CKD based on the published FIDELIO-DKD trial, which had seen less CKD progression and fewer CV events in such patients who took the novel MRA.

Although similar in design to FIGARO-DKD, FIDELIO-DKD had entered fewer patients with early-stage diabetic kidney disease (DKD). That led researchers to pool the two trials’ populations to create a cohort that spans the spectrum of DKD severity. An analysis of the pooled cohort, dubbed FIDELITY, is on the schedule after FIGARO-DKD.

After FIDELITY is the prospective APAF-CRT trial that is following a projected 1,830 patients with permanent, symptomatic AFib and a recent hospitalization for AFib or HF and who were not good candidates for standard ablation. They were assigned to receive either atrioventricular junctional ablation followed by CRT, with or without a defibrillation, on top of optimal meds – a so-called “ablate-and-pace” strategy – or an implantable cardioverter defibrillator with rate-control drug therapy.

The new analysis represents the trial’s second phase in which mortality was followed for 4 years as the primary endpoint, in contrast to the previously reported initial phase that followed the first 102 patients for 2 years for the composite primary endpoint of death, worsening HF, and HF hospitalization. The first phase had halted enrollment before reaching its planned target of 280 patients after an interim analysis showed a significant benefit for ablate and pace. 

Next up: DECAAF 2, a randomized assessment of whether catheter ablation for AFib guided by delayed gadolinium enhancement on MRI, a proxy for scar tissue, can be more effective than standard AFib ablation by pulmonary vein isolation alone. An estimated 900 patients with persistent AFib who had never before undergone ablation for the arrhythmia were randomly assigned to one strategy or the other and followed for AFib recurrence over 18 months.
 

Sunday, Aug. 29

The TOMAHAWK trial aimed to clarify the optimal timing of invasive coronary angiography for resuscitated patients with non–ST-segment elevation out-of-hospital cardiac arrest, a broad population in a setting for which there is little randomized-trial guidance. Investigators randomly assigned 558 such patients to undergo immediate invasive angiography or to direct intensive care unit admission for initial standard care with discretionary delayed angiography. Patients were followed for all-cause mortality, with other clinical events and neurologic outcomes as secondary endpoints.

Next on the schedule, the RIPCORD-2 trial randomly assigned 1,100 patients with stable known or suspected coronary artery disease (CAD) to undergo conventional angiography alone or with added direct pressure-wire measurement of fractional flow reserve to guide management decisions. Primary outcomes include health care costs and patient-reported quality of life at 1 year.

Slated for later that day, the Asymptomatic Carotid Surgery Trial-2 (ACST-2) has entered an estimated 3600 patients with a substantial carotid artery narrowing not associated with symptoms but for which either carotid endarterectomy (CEA) or carotid artery stenting (CAS) was considered anatomically feasible. There also must have been “substantial uncertainty” regarding the optimal procedure choice.

The trial, conducted in 40 countries primarily in Europe and North America and launched in 2008, randomly assigned the patients to undergo either CEA or CAS, in both cases with appropriate medical therapy, and followed them for periprocedural events and up to 10 years for strokes and stroke-related events.

The LOOP study, which is to directly follow ACST-2, has explored whether screening for AFib using the Medtronic Reveal LINQ monitor in older patients with non-AFib stroke risk factors – with oral anticoagulation prescribed for those who test positive – can lower their risk for stroke or systemic embolism. It randomly assigned 6,000 such patients to care guided by the loop recorder or to standard care.

On a somewhat larger scale, the Salt Substitute and Stroke Study (SSaSS) randomly assigned a total of 20,996 people in about 600 villages across northern China and Tibet to sodium-restriction intervention and control groups by village. All participants had a history of stroke or were aged at least 60 years with uncontrolled hypertension.

As described by the trial’s online portal, participants in villages assigned to the intervention group were given a supply of a low-sodium, potassium-supplementing salt substitute to replace their own salt supplies, along with education on the health benefits of sodium restriction. Participants in control villages continued their normal diets and, at the trial’s beginning, received “advice to reduce their salt intake.” All were required to own a telephone.

Clinical events, including strokes and hospitalizations throughout a 5-year follow-up, were tracked by phone calls made to all participants every 6 months and were documented at follow-up home visits.

Sunday is also to feature a Late-Breaking Trials session with a focus on COVID-19, which leads off with COLCOVID, a test of colchicine in patients hospitalized for suspected SARS-CoV-2 infection and in acute respiratory distress.

The 1,279 participants in Argentina were randomly assigned to receive or not receive the potent anti-inflammatory agent on top of antivirals and other standard management and followed for death or new need for mechanical ventilation. A successful outcome would contrast with the RECOVERY trial, which terminated a colchicine group of patients hospitalized with COVID-19 because of a lack of efficacy earlier this year.

COLCOVID is to be followed by the MICHELLE trial of rivaroxaban (Xarelto, Bayer/Janssen) prophylaxis, compared with no preventive oral anticoagulant, in 320 patients who, when hospitalized with COVID-19, had been on parenteral anticoagulants because of an elevated risk for venous thromboembolism. The trial, conducted in Brazil, called for postdischarge rivaroxaban at a once-daily dosage of 10 mg for about 1 month.

The session also includes a presentation called “Insights into the Effects of the COVID-19 Pandemic: Comprehensive Analysis from the GUIDE-HF Trial,” the primary outcomes of which will be reported on the first day of the Congress.

Following is a presentation on the PREPARE-IT study of icosapent ethyl (Vascepa, Amarin), given at high dosages intended to be anti-inflammatory, compared with placebo, in an estimated 4,000 adults. The trial has two groups: A prevention group of adults living and circulating in the community; and a treatment group of patients aged at least 40 years with confirmed symptomatic SARS-CoV-2 infection for whom the need for hospitalization isn’t clear.
 

Monday, Aug. 30

The final day of the Congress features a trial called Influenza Vaccination after Myocardial Infarction (IAMI), which has tested the secondary preventive effect of influenza vaccination by randomly assigning 2,571 patients to receive a standard vaccine or a saline placebo injection on one occasion.

Entry to the international trial called for a diagnosis of MI with or without ST-segment elevation, or stable CAD and age at least 75 years with other risk factors. The patients were followed for death, MI, stent thrombosis, and a slew of secondary endpoints over 12 months.

Monday offerings continue later in a time block leading off with the STEP trial, which has randomly assigned an estimated 8,000 patients at 40 centers in China who are 60 to 80 years of age with a systolic blood pressure of 140 to <190 mm Hg to be on standard guideline-based therapy or an intensive drug-management strategy.

The systolic BP goals are 130 to <150 mm Hg for standard care and 110 to <130 mm Hg for the intensive regimen. The composite primary endpoint includes death and clinical events related to acute coronary syndromes, HF, revascularization, and stroke.

Following on heels of STEP, the Amulet IDE trial – the first major randomized comparison of two transcatheter LAA closure devices – entered 1,878 patients with nonvalvular AFib who were considered high-risk for bleeding and stroke or systemic embolism.

They were randomly assigned in the noninferiority trial to receive either the AMPLATZER Amulet (Abbott Medical Devices) or the WATCHMAN (Boston Scientific) closure devices and were followed for safety and efficacy for up to 5 years.

Both LAA closure devices, intended to make patients with AFib less reliant on oral anticoagulation, are now available on both sides of the Atlantic – as well as many other countries – after the Amulet’s United States market approval on Aug. 16, based largely on the Amulet IDE trial.

Rounding out the final Hot Line set is one of the latest efforts to show the efficacy and safety of a very short DAPT period after coronary stenting in patients with acute coronary syndromes, the STOPDAPT-2 ACS trial.

The study assigned 3,008 patients in Japan to receive aspirin and clopidogrel for either 1 month or 1 year after implantation with an everolimus-eluting cobalt-chromium stent and followed them for up to 5 years for a composite of MI, CV death, stent thrombosis, stroke, and bleeding.

The trial follows the published STOPDAPT-2 trial that showed superiority for the 1-month DAPT regimen in a predominantly stable-CAD population treated with the same kind of stent.
 

Program structure and format

A total of 15 online channels are to be available in the morning, European time, their schedules running in parallel. Presentations often are prerecorded, but also include live sessions at 8:00 a.m. Central time and 12 p.m. CET (2:00 a.m. and 6:00 a.m. Eastern time) to liven up the channel offerings, Dr. Windecker observed, and to make them more immediate and potentially interactive.

Many of the parallel channels are devoted throughout the Congress to particular silos of cardiology; for example, arrhythmias and device therapy is on channel 3; CAD and acute care is on 5; HF is on 6; and preventive cardiology is on 9.

Other channels swing across different topics from day to day, such as channel 1, which covers COVID-19 topics on the first and third day of the meeting, “advances in science” on day 2, and “digital health, public health, health economics” on day 4.

The focus each day, starting at 2:00 p.m. CET (8:00 a.m. ET) and continuing into the evening in Europe, shifts over to the Prime Time live program, which features the Hot Line and guideline presentations and many of the live abstract presentations.

Dr. Kosiborod, not a researcher with the EMPEROR trials, is chair of the Dapagliflozin in Preserved Ejection Fraction Heart Failure ( PRESERVED-HF ) trial, which is scheduled for presentation at the September 2021 Heart Failure Society of American meeting.

A version of this article first appeared on Medscape.com.

To the Editor:

Protothecosis infections are caused by an achlorophyllic algae of the species Prototheca. Prototheca organisms are found mostly in soil and water.¹ Human infections are rare and involve 2 species, Prototheca wickerhamii and Prototheca zopfii. The former most commonly is responsible for human infections, though P zopfii results in more serious systemic infections with a poor prognosis. There are various types of Prototheca infection presentations, with a 2007 review of 117 cases reporting that cutaneous infections are most common (66%), followed by systemic infections (19%), and olecranon bursitis (15%).² Skin lesions most commonly occur on the extremities and face, and they present as vesiculobullous and ulcerative lesions with purulent drainage. The skin lesions also may appear as erythematous plaques or nodules, subcutaneous papules, verrucous or herpetiformis lesions, or pyogenic granuloma–like lesions.³ Protothecosis typically affects immunocompromised individuals, especially those with a history of chronic corticosteroid use, malignancy, diabetes mellitus, AIDS, and/or organ transplant.¹ We present a case of cutaneous protothecosis on the dorsal distal extremity of a 94-year-old woman. History of exposure to soil while gardening was elicited from the patient, and no immunosuppressive history was present aside from the patient’s age. This case may prompt workup for malignancy or immunosuppression in this patient subset.

A 94-year-old woman with a medical history of cutaneous squamous cell carcinoma (SCC) presented with a growing lesion on the dorsal surface of the left fourth digit of 2 months’ duration. The patient reported the lesion was painful, and she noted preceding trauma to the area that was suspected to have occurred while gardening. Physical examination revealed an ulcerated, hypertrophic, erythematous nodule on the dorsal surface of the left fourth metacarpophalangeal joint. The differential diagnosis included SCC, inflamed cyst, verruca vulgaris, and orf virus due to the clinical presentation. A shave biopsy was performed, and the lesion subsequently was treated with electrodesiccation and curettage.

Histopathologic evaluation revealed pseudoepitheliomatous hyperplasia with a mixed inflammatory infiltrate including lymphocytes and histiocytes. A morula within the dermis was characteristic of a protothecosis infection (Figure 1). On follow-up visit 6 weeks later, the lesion had grown back to its original size and morphology (Figure 2). At this time, the lesion was again treated with shave removal, followed by electrodesiccation and curettage, and the patient was placed on oral fluconazole 200 mg daily for 1 month. When the lesion did not resolve with fluconazole, she was referred to infectious disease as well as general surgery for surgical removal and debridement of the lesion. Unfortunately, the patient was lost to follow-up.

Protothecosis is an infectious disease comprised of achlorophyllic algae found in soil and water that rarely affects humans. When it does affect humans, cutaneous infections are most common. All human cases in which organisms were identified to species level have been caused by P wickerhamii or P zopfii species.² Inoculation is suspected to occur through trauma to affected skin, especially when in the context of contaminated water. Our patient reported history of trauma to the hand, with soil from gardening as the potential aquagenic source of the infection.

The clinical presentation of protothecosis ranges from localized cutaneous to disseminated systemic infections, with most reported cases of systemic disease occurring in immunocompromised individuals. The cutaneous lesions of protothecosis vary greatly in clinical appearance including ulcerative nodules (as in our case), papules, plaques, pustules, and vesicles with erosion or crusting.⁴

Cutaneous protothecosis has the potential to mimic many other skin diseases and lesions, and, given its rarity, it may not be on the radar of dermatologists. Our patient’s lesion was presumed to be a skin cancer and was treated as such because of the history of SCC and clinical presentation. Although excision of individual lesions of protothecosis can be curative, electrodesiccation and curettage does not appear to be an adequate treatment, as the lesion subsequently recurred. It also is possible that this case represents P zopfii infection, as it did not respond to treatment with oral fluconazole, though in vitro studies with fluconazole to both P zopfii and P wickerhamii had variable treatment success.² Also, the histopathologic findings were most consistent with P wickerhamii, revealing small, round, symmetrical morula, compared to P zopfii, which typically will display oval or cylindrical, asymmetrical, random internal segmentation.⁵ This case may warrant determination of species, which can be accomplished by a culture on Sabouraud dextrose agar, carbohydrate and alcohol assimilation test, yeast biochemical card, serological typing by immunoblotting, immunofluorescence study using species-specific antibodies, or amplification by polymerase chain reaction for small subunit ribosomal DNA sequences.^2,6-8

The natural history of isolated skin disease is an indolent progressive course; however, reports do exist noting spontaneous resolution.^4,9 Treatment options for Prototheca infections can be disappointing and consist of both surgical and medical management, or a combination of the 2 approaches. Reports in the literature support the use of antifungals including ketoconazole, voriconazole, itraconazole, fluconazole, and amphotericin B, with the latter displaying the best activity against Prototheca species.² Tetracycline has been used in combination with oral or topical amphotericin B and was found to be synergistic in vitro and in case reports at successfully treating cutaneous protothecosis infections. It is possible that our patient was not treated with fluconazole long enough for it to become therapeutic, as most reported treatment regimens are weeks to months in length. Conversely, it may have been of benefit to transition the patient to topical amphotericin B and tetracycline, as fluconazole failed in this patient. However, treatment successes and failures are limited to case reports/case series and in vitro studies, with prospective studies lacking. Due to the variability with in vitro susceptibility profiles for Prototheca species, it generally is not recommended to pursue in vitro susceptibility testing in the management of Prototheca skin infections due to the inconsistency demonstrated between in vitro activity and clinical response to therapy.²

To the Editor:

Protothecosis infections are caused by an achlorophyllic algae of the species Prototheca. Prototheca organisms are found mostly in soil and water.¹ Human infections are rare and involve 2 species, Prototheca wickerhamii and Prototheca zopfii. The former most commonly is responsible for human infections, though P zopfii results in more serious systemic infections with a poor prognosis. There are various types of Prototheca infection presentations, with a 2007 review of 117 cases reporting that cutaneous infections are most common (66%), followed by systemic infections (19%), and olecranon bursitis (15%).² Skin lesions most commonly occur on the extremities and face, and they present as vesiculobullous and ulcerative lesions with purulent drainage. The skin lesions also may appear as erythematous plaques or nodules, subcutaneous papules, verrucous or herpetiformis lesions, or pyogenic granuloma–like lesions.³ Protothecosis typically affects immunocompromised individuals, especially those with a history of chronic corticosteroid use, malignancy, diabetes mellitus, AIDS, and/or organ transplant.¹ We present a case of cutaneous protothecosis on the dorsal distal extremity of a 94-year-old woman. History of exposure to soil while gardening was elicited from the patient, and no immunosuppressive history was present aside from the patient’s age. This case may prompt workup for malignancy or immunosuppression in this patient subset.

A 94-year-old woman with a medical history of cutaneous squamous cell carcinoma (SCC) presented with a growing lesion on the dorsal surface of the left fourth digit of 2 months’ duration. The patient reported the lesion was painful, and she noted preceding trauma to the area that was suspected to have occurred while gardening. Physical examination revealed an ulcerated, hypertrophic, erythematous nodule on the dorsal surface of the left fourth metacarpophalangeal joint. The differential diagnosis included SCC, inflamed cyst, verruca vulgaris, and orf virus due to the clinical presentation. A shave biopsy was performed, and the lesion subsequently was treated with electrodesiccation and curettage.

Histopathologic evaluation revealed pseudoepitheliomatous hyperplasia with a mixed inflammatory infiltrate including lymphocytes and histiocytes. A morula within the dermis was characteristic of a protothecosis infection (Figure 1). On follow-up visit 6 weeks later, the lesion had grown back to its original size and morphology (Figure 2). At this time, the lesion was again treated with shave removal, followed by electrodesiccation and curettage, and the patient was placed on oral fluconazole 200 mg daily for 1 month. When the lesion did not resolve with fluconazole, she was referred to infectious disease as well as general surgery for surgical removal and debridement of the lesion. Unfortunately, the patient was lost to follow-up.

Protothecosis is an infectious disease comprised of achlorophyllic algae found in soil and water that rarely affects humans. When it does affect humans, cutaneous infections are most common. All human cases in which organisms were identified to species level have been caused by P wickerhamii or P zopfii species.² Inoculation is suspected to occur through trauma to affected skin, especially when in the context of contaminated water. Our patient reported history of trauma to the hand, with soil from gardening as the potential aquagenic source of the infection.

The clinical presentation of protothecosis ranges from localized cutaneous to disseminated systemic infections, with most reported cases of systemic disease occurring in immunocompromised individuals. The cutaneous lesions of protothecosis vary greatly in clinical appearance including ulcerative nodules (as in our case), papules, plaques, pustules, and vesicles with erosion or crusting.⁴

Cutaneous protothecosis has the potential to mimic many other skin diseases and lesions, and, given its rarity, it may not be on the radar of dermatologists. Our patient’s lesion was presumed to be a skin cancer and was treated as such because of the history of SCC and clinical presentation. Although excision of individual lesions of protothecosis can be curative, electrodesiccation and curettage does not appear to be an adequate treatment, as the lesion subsequently recurred. It also is possible that this case represents P zopfii infection, as it did not respond to treatment with oral fluconazole, though in vitro studies with fluconazole to both P zopfii and P wickerhamii had variable treatment success.² Also, the histopathologic findings were most consistent with P wickerhamii, revealing small, round, symmetrical morula, compared to P zopfii, which typically will display oval or cylindrical, asymmetrical, random internal segmentation.⁵ This case may warrant determination of species, which can be accomplished by a culture on Sabouraud dextrose agar, carbohydrate and alcohol assimilation test, yeast biochemical card, serological typing by immunoblotting, immunofluorescence study using species-specific antibodies, or amplification by polymerase chain reaction for small subunit ribosomal DNA sequences.^2,6-8

The natural history of isolated skin disease is an indolent progressive course; however, reports do exist noting spontaneous resolution.^4,9 Treatment options for Prototheca infections can be disappointing and consist of both surgical and medical management, or a combination of the 2 approaches. Reports in the literature support the use of antifungals including ketoconazole, voriconazole, itraconazole, fluconazole, and amphotericin B, with the latter displaying the best activity against Prototheca species.² Tetracycline has been used in combination with oral or topical amphotericin B and was found to be synergistic in vitro and in case reports at successfully treating cutaneous protothecosis infections. It is possible that our patient was not treated with fluconazole long enough for it to become therapeutic, as most reported treatment regimens are weeks to months in length. Conversely, it may have been of benefit to transition the patient to topical amphotericin B and tetracycline, as fluconazole failed in this patient. However, treatment successes and failures are limited to case reports/case series and in vitro studies, with prospective studies lacking. Due to the variability with in vitro susceptibility profiles for Prototheca species, it generally is not recommended to pursue in vitro susceptibility testing in the management of Prototheca skin infections due to the inconsistency demonstrated between in vitro activity and clinical response to therapy.²

To the Editor:

Protothecosis infections are caused by an achlorophyllic algae of the species Prototheca. Prototheca organisms are found mostly in soil and water.¹ Human infections are rare and involve 2 species, Prototheca wickerhamii and Prototheca zopfii. The former most commonly is responsible for human infections, though P zopfii results in more serious systemic infections with a poor prognosis. There are various types of Prototheca infection presentations, with a 2007 review of 117 cases reporting that cutaneous infections are most common (66%), followed by systemic infections (19%), and olecranon bursitis (15%).² Skin lesions most commonly occur on the extremities and face, and they present as vesiculobullous and ulcerative lesions with purulent drainage. The skin lesions also may appear as erythematous plaques or nodules, subcutaneous papules, verrucous or herpetiformis lesions, or pyogenic granuloma–like lesions.³ Protothecosis typically affects immunocompromised individuals, especially those with a history of chronic corticosteroid use, malignancy, diabetes mellitus, AIDS, and/or organ transplant.¹ We present a case of cutaneous protothecosis on the dorsal distal extremity of a 94-year-old woman. History of exposure to soil while gardening was elicited from the patient, and no immunosuppressive history was present aside from the patient’s age. This case may prompt workup for malignancy or immunosuppression in this patient subset.

A 94-year-old woman with a medical history of cutaneous squamous cell carcinoma (SCC) presented with a growing lesion on the dorsal surface of the left fourth digit of 2 months’ duration. The patient reported the lesion was painful, and she noted preceding trauma to the area that was suspected to have occurred while gardening. Physical examination revealed an ulcerated, hypertrophic, erythematous nodule on the dorsal surface of the left fourth metacarpophalangeal joint. The differential diagnosis included SCC, inflamed cyst, verruca vulgaris, and orf virus due to the clinical presentation. A shave biopsy was performed, and the lesion subsequently was treated with electrodesiccation and curettage.

Histopathologic evaluation revealed pseudoepitheliomatous hyperplasia with a mixed inflammatory infiltrate including lymphocytes and histiocytes. A morula within the dermis was characteristic of a protothecosis infection (Figure 1). On follow-up visit 6 weeks later, the lesion had grown back to its original size and morphology (Figure 2). At this time, the lesion was again treated with shave removal, followed by electrodesiccation and curettage, and the patient was placed on oral fluconazole 200 mg daily for 1 month. When the lesion did not resolve with fluconazole, she was referred to infectious disease as well as general surgery for surgical removal and debridement of the lesion. Unfortunately, the patient was lost to follow-up.

Protothecosis is an infectious disease comprised of achlorophyllic algae found in soil and water that rarely affects humans. When it does affect humans, cutaneous infections are most common. All human cases in which organisms were identified to species level have been caused by P wickerhamii or P zopfii species.² Inoculation is suspected to occur through trauma to affected skin, especially when in the context of contaminated water. Our patient reported history of trauma to the hand, with soil from gardening as the potential aquagenic source of the infection.

The clinical presentation of protothecosis ranges from localized cutaneous to disseminated systemic infections, with most reported cases of systemic disease occurring in immunocompromised individuals. The cutaneous lesions of protothecosis vary greatly in clinical appearance including ulcerative nodules (as in our case), papules, plaques, pustules, and vesicles with erosion or crusting.⁴

Cutaneous protothecosis has the potential to mimic many other skin diseases and lesions, and, given its rarity, it may not be on the radar of dermatologists. Our patient’s lesion was presumed to be a skin cancer and was treated as such because of the history of SCC and clinical presentation. Although excision of individual lesions of protothecosis can be curative, electrodesiccation and curettage does not appear to be an adequate treatment, as the lesion subsequently recurred. It also is possible that this case represents P zopfii infection, as it did not respond to treatment with oral fluconazole, though in vitro studies with fluconazole to both P zopfii and P wickerhamii had variable treatment success.² Also, the histopathologic findings were most consistent with P wickerhamii, revealing small, round, symmetrical morula, compared to P zopfii, which typically will display oval or cylindrical, asymmetrical, random internal segmentation.⁵ This case may warrant determination of species, which can be accomplished by a culture on Sabouraud dextrose agar, carbohydrate and alcohol assimilation test, yeast biochemical card, serological typing by immunoblotting, immunofluorescence study using species-specific antibodies, or amplification by polymerase chain reaction for small subunit ribosomal DNA sequences.^2,6-8

The natural history of isolated skin disease is an indolent progressive course; however, reports do exist noting spontaneous resolution.^4,9 Treatment options for Prototheca infections can be disappointing and consist of both surgical and medical management, or a combination of the 2 approaches. Reports in the literature support the use of antifungals including ketoconazole, voriconazole, itraconazole, fluconazole, and amphotericin B, with the latter displaying the best activity against Prototheca species.² Tetracycline has been used in combination with oral or topical amphotericin B and was found to be synergistic in vitro and in case reports at successfully treating cutaneous protothecosis infections. It is possible that our patient was not treated with fluconazole long enough for it to become therapeutic, as most reported treatment regimens are weeks to months in length. Conversely, it may have been of benefit to transition the patient to topical amphotericin B and tetracycline, as fluconazole failed in this patient. However, treatment successes and failures are limited to case reports/case series and in vitro studies, with prospective studies lacking. Due to the variability with in vitro susceptibility profiles for Prototheca species, it generally is not recommended to pursue in vitro susceptibility testing in the management of Prototheca skin infections due to the inconsistency demonstrated between in vitro activity and clinical response to therapy.²

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

Bimekizumab has been approved by the European Commission for the treatment of moderate to severe plaque psoriasis in adults, according to a statement from the manufacturer.

Bimekizumab (Bimzelx), a humanized IgG1 monoclonal antibody, is the first approved treatment for moderate to severe plaque psoriasis that selectively inhibits interleukin (IL)–17A and IL-17F, the statement from UCB said.

In the United States, the Food and Drug Administration is expected to make a decision on approval of bimekizumab for treating psoriasis on Oct. 15.

Approval in the EU was based on data from three phase 3 trials including a total of 1,480 adult patients with moderate to severe psoriasis, which found that those treated with bimekizumab experienced significantly greater skin clearance, compared with placebo, ustekinumab, and adalimumab, with a favorable safety profile, according to the company.

In all three studies (BE VIVID, BE READY, and BE SURE), more than 80% of patients treated with bimekizumab showed improved skin clearance after 16 weeks, significantly more than those treated with ustekinumab, placebo, or adalimumab, based on an improvement of at least 90% in the Psoriasis Area & Severity Index (PASI 90) and an Investigator’s Global Assessment (IGA) response of clear or almost clear skin (IGA 0/1). In all three studies, these clinical responses persisted after 1 year.

The recommended dose of bimekizumab is 320 mg, given in two subcutaneous injections every 4 weeks to week 16, then every 8 weeks. However, for “some patients” weighing 120 kg or more who have not achieved complete skin clearance at 16 weeks, 320 mg every 4 weeks after that time may improve response to treatment, according to the company statement.

The most common treatment-related adverse events in the studies were upper respiratory tract infections (a majority of which were nasopharyngitis), reported by 14.5% of patients, followed by oral candidiasis, reported by 7.3%.

Results of BE READY and BE VIVID were published in The Lancet. Results of the BE SURE study were published in The New England Journal of Medicine.

Bimekizumab is contraindicated for individuals with clinically important active infections such as tuberculosis, and for individuals with any hypersensitivity to the active substance. More details on bimekizumab are available on the website of the European Medicines Agency.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.

Parkinson’s disease patients who develop anxiety early in their disease are at risk for reduced physical activity, which promotes further anxiety and cognitive decline, data from nearly 500 individuals show.

Anxiety occurs in 20%-60% of Parkinson’s disease (PD) patients but often goes undiagnosed, wrote Jacob D. Jones, PhD, of California State University, San Bernardino, and colleagues.

“Anxiety can attenuate motivation to engage in physical activity leading to more anxiety and other negative cognitive outcomes,” although physical activity has been shown to improve cognitive function in PD patients, they said. However, physical activity as a mediator between anxiety and cognitive function in PD has not been well studied, they noted.

In a study published in Mental Health and Physical Activity the researchers identified 487 adults with newly diagnosed PD within the past 2 years who were enrolled in the Parkinson’s Progression Markers Initiative. Participants were followed for up to 5 years and completed neuropsychological tests, tests of motor severity, and self-reports on anxiety and physical activity. Anxiety was assessed using the State-Trait Anxiety Inventory-Trait (STAI-T) subscale. Physical activity was assessed using the Physical Activity Scale for the Elderly (PASE). Motor severity was assessed using the Unified Parkinson’s Disease Rating Scale-Part III (UPDRS). The average age of the participants was 61 years, 65% were men, and 96% were White.

Using a direct-effect model, the researchers found that individuals whose anxiety increased during the study period also showed signs of cognitive decline. A significant between-person effect showed that individuals who were generally more anxious also scored lower on cognitive tests over the 5-year study period.

In a mediation model computed with structural equation modeling, physical activity mediated the link between anxiety and cognition, most notably household activity.

“There was a significant within-person association between anxiety and household activities, meaning that individuals who became more anxious over the 5-year study also became less active in the home,” reported Dr. Jones and colleagues.

However, no significant indirect effect was noted regarding the between-person findings of the impact of physical activity on anxiety and cognitive decline. Although more severe anxiety was associated with less activity, cognitive performance was not associated with either type of physical activity.

The presence of a within-person effect “suggests that reductions in physical activity, specifically within the first 5 years of disease onset, may be detrimental to mental health,” the researchers emphasized. Given that the study population was newly diagnosed with PD “it is likely the within-person terms are more sensitive to changes in anxiety, physical activity, and cognition that are more directly the result of the PD process, as opposed to lifestyle/preexisting traits,” they said.

The study findings were limited by several factors, including the use of self-reports to measure physical activity, and the lack of granular information about the details of physical activity, the researchers noted. Another limitation was the inclusion of only newly diagnosed PD patients, which might limit generalizability.

“Future research is warranted to understand if other modes, intensities, or complexities of physical activity impact individuals with PD in a different manner in relation to cognition,” they said.

Dr. Jones and colleagues had no disclosures. The PPMI is supported by the Michael J. Fox Foundation for Parkinson’s Research and funding partners, including numerous pharmaceutical companies.