heart failure

Grand Rounds October 24, 2025: Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation: The PARACHUTE-HF Trial (Renato Lopes MD, PhD)

Posted on by Sophia Ramirez

Speaker

Renato Lopes MD, PhD
Professor of Medicine, Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute

Keywords

Heart Failure; Chagas Disease; Underserved Population

Key Points

  • Chagas disease is a condition caused by the parasite Trypanosoma cruzi. One of the complications of Chagas is heart failure (HF). Though Latin America has historically borne the brunt of Chagas-related HF, incidence is increasing globally.
  • Chagas-related HF has unique characteristics, with lower prevalence of hypertension and diabetes, worse health-related quality of life, and higher hospitalization and mortality rates when compared to other types of HF. In short, though patients with Chagas-related HF are less likely to have classic HF risk factors, their event rates are higher. Furthermore, there’s a lack of clinical evidence to guide their treatment.
  • Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation (PARACHUTE-HF) was a prospective randomized trial evaluating the effect of sacubitril/valsartan compared with enalapril in improving a hierarchical composite endpoint including cardiovascular (CV) death, HF hospitalization, and reduction in NT-proBNP levels – in that order, on the basis of clinical importance.
  • The study population consisted of 922 patients from 83 sites in 4 Latin American countries: Argentina, Brazil, Colombia, and Mexico. Participants had HF with reduced ejection fraction (HFrEF) and a confirmed diagnosis of Chagas disease.
  • After 12 weeks, the study team found that sacubitril/valsartan was superior to enalapril with respect to the hierarchical composite endpoint. These results were primarily driven by a 32% reduction in average NT-proBNP levels.
  • There were some limitations, including COVID-19-related changes in clinical practice that may have affected HF hospitalization rates and the observed treatment effect.
  • PARACHUTE-HF was the first major randomized trial studying HF treatment in HFrEF patients with Chagas disease. While sacubitril/valsartan has extensive clinical and real-world data supporting its effectiveness for HFrEF, this trial further supports its use in treating this specific population.
  • There is a need for rigorously conducted clinical trials in Chagas disease to better define the cardiovascular benefit/risk profile of new treatment options for this neglected and high-risk population. This trial provides a model for international collaboration among cardiologists and infectious disease physicians with a shared goal.

Discussion Themes

The pathophysiology of Chagas is complex. It includes chronic, low-intensity myocarditis, which can lead to changes in coagulation pathways and thrombotic events; a neurological tropism, which can cause sudden arrythmias; and an autoimmune component.

Dr. Lopes emphasized the impact that an intentional and informed coordinating center; carefully selected sites; deeply invested PIs; and a strong Data and Safety Monitoring Board (DSMB) had on the success of PARACHUTE-HF.

Grand Rounds June 27, 2025: Building Electronic Tools To Enhance and Reinforce CArdiovascular REcommendations for Heart Failure (BETTER CARE-HF) (Amrita Mukhopadhyay, MD, MS)

Posted on by Sophia Ramirez

Speaker

Amrita Mukhopadhyay, MD, MS
Eugene Braunwald, MD Assistant Professor of Cardiology
The Leon H. Charney Division of Cardiology Department of Medicine
Division of Healthcare Delivery Science Department of Population Health
NYU School of Medicine
NYU Langone Health

Keywords

Heart Failure; Electronic Health Record; Prescribing

Key Points

  • Heart failure is a major public health issue and a leading cause of hospitalization, affecting over 6 million Americans. Mineralocorticoid antagonists (MRA) are a potentially life-saving treatment but are under-prescribed in patients with heart failure with reduced ejection fraction (HFrEF). Closing this treatment gap could save over 20,000 lives in the U.S annually.
  • Electronic Health Record (EHR) tools could be a low-cost, scalable way to improve prescribing. However, there’s wide variability in EHR tool development and design. The optimal delivery and timing of EHR tools is unknown.
  • EHR tools fall into 2 categories: alerts and messages. Alerts apply to a single patient at a time and pop up during a clinical encounter; messages apply to multiple patients at once and are seen between encounters. The BETTER CARE-HF team designed both in accordance with Cognitive Load Theory and Nudge theory, applying the concepts of positioning, the split attention effect, default option, the transient information effect, and social influence.
  • They hypothesized that A) among patients with HFrEF who are evaluated by a cardiologist in the outpatient setting, an alert or a message will improve prescribing of MRA as compared to usual care, and B) the alert would be more effective than the message.
  • The researchers approached the pilot study as a “qualitative phase,” in which they would solicit feedback from participants and refine the intervention. They made several modifications to the EHR alerts and messages in response, and noted that guiding frameworks and pilot-testing were critical to designing an electronic intervention.
  • The pilot study was followed by a pragmatic trial that took place in over 60 practices in the NYU Langone Health System. Patients were cluster-randomized to an alert arm, message arm, or usual care. The primary outcome was new MRA prescription during the study period.
  • In the alert arm, nearly 30% of MRA-eligible patients were newly prescribed MRA – a highly statistically significant increase. The alerts were effective across all practice settings but were especially effective in high-volume settings.
  • In the message arm, 15.6% of MRA-eligible patients were newly prescribed MRA. Compared to 11.7% in the usual care arm, this was still a statistically significant increase, but was less effective than the alerts. Looked at another way, the number of MRA-eligible patients needed to result in one prescription was 25.6 in the message arm, compared to 5.6 in the alert arm.
  • An automated, EHR-embedded, tailored, and selective alert delivered at the time of the visit more than doubled prescribing of MRA as compared to usual care. Well-designed EHR tools could save lives.
  • Despite EHR tool effectiveness, busy physicians may still be hesitant. Too many tools can cause fatigue and burnout; concerns about workload and time costs can hinder uptake. Conversely, EHR tools that save time and reduce cognitive load may be more beneficial in busy practices. A post-trial survey indicated that cardiologist perceptions were generally favorable towards the BETTER CARE-HF tools, with some notable differences when asked about workflow.
  • The research team is conducting a multi-center trial to assess the effectiveness of the alert at other institutions, specifically across 3 high-volume health systems around the country. They are actively seeking other institutions to join the trial and encouraged attendees to reach out if interested.

Discussion Themes

The research team started by compiling EHR data on the current gap in care at NYU Langone. Having that real-time data helped the health system, and the physicians were a part of it, recognize that the intervention was necessary – despite their predisposition that they were delivering high-quality care.

This intervention was targeted to a specific population (cardiologists at NYU Langone) and a specific treatment (MRA) for a specific condition (HFrEF). In a different setting or if there was a different treatment involved, implementation may need to be adjusted.

Dr. Mukhopadhyay noted that folks who saw how the intervention worked were often surprised by how rarely the alert was triggered. She suspects that the selective nature of the intervention helped drive the intervention’s effectiveness by preventing burnout.

Working with a single IRB that understood the intention behind a learning health system helped standardize regulatory expectations across sites and facilitated onboarding.

Grand Rounds May 2, 2025: Fluid REStriction in Heart failure versus liberal fluid UPtake: The FRESH-UP Study (Roland RJ van Kimmenade, MD, PhD)

Posted on by Sophia Ramirez

Speaker

Roland RJ van Kimmenade, MD, PhD
Cardiologist, Radboud University Medical Center
Nijmegen, the Netherlands

Keywords

Heart Failure; Fluids; Cardiology

Key Points

  • We are facing a pandemic of heart failure (HF), with an incidence of 1 – 20 cases of heart failure per 1,000 people. The incidence of HF is stable – if not declining – but mortality remains high, at about 15 – 30% after one year. Attributable health care costs are up, and the prevalence of HF in the general population is increasing.
  • Orthopnea and edema are symptoms of heart failure caused by congestion, or “fluid retention.” This has led to an intuitive assumption that patients should monitor their fluid intake to 1.5 – 2L per day (including beverages, ice cream, soup, and some fruit). Patients are advised to do things like chew gum or suck on frozen grapes to relieve dry mouth and thirst.
  • The literature supporting fluid restriction is limited; as of 2018, the studies supporting it had small sample sizes and heterogeneous populations. They found no differences in mortality and hospitalization. Sets of clinical practice guidelines from 2021 and 2022 also noted that more evidence was needed for fluid restriction, and that existing evidence was low quality.
  • To address this gap in the evidence, the research team used crowdfunding to conduct the Fluid REStriction in Heart failure versus liberal fluid Uptake (FRESH-UP) Study. The randomized, open-label, multicenter clinical trial study took place between May 17, 2021 and June 13, 2024.
  • The primary outcome was health status at 3 months, as assessed by the Kansas City Cardiomyopathy Questionnaire – Overall Summary Score (KCCQ-OSS). The key secondary outcome was thirst distress at 3 months, as assessed by the Thirst Distress Scale for patients with HF (TDS-HF).
  • Participants were randomized to one of two arms: liberal fluid intake (no restriction) or fluid restriction, with a maximum of 1500 mL of fluid per day.
  • After three months, the research team found that the difference in KCCQ-OSS (adjusted for baseline scores) was 2.17, with a p value of 0.06. These findings favor liberal fluid intake, but the primary outcome was not met.
  • Thirst distress was higher in the fluid restriction group. No differences were observed for safety events between groups.
  • The FRESH-UP study questions the benefit of fluid restriction in chronic HF.

Discussion Themes

Patient-centered research is key in pragmatic trials; this trial came about because a patient voiced their discomfort and questioned the validity of fluid restriction. The researchers took this as a cue to question a key assumption in their field.

The Dutch Heart Foundation facilitated the crowdfunding, from the legal requirements to the website. The money raised from crowdfunding got them far enough to apply for a second grant.

As in clinical practice, the pragmatic nature of the trial made it difficult to guarantee participant fidelity throughout the entire experiment (though they did monitor intake at week six). The research team conducted a survey of participants afterwards to assess adherence. 93% of the patients reported that they adhered well to their regimes.

“Gaps in Evidence” in clinical guidelines is not a summary of failure, but a source of inspiration!

Grand Rounds April 18, 2025: Colchicine and Spironolactone Post-MI — A Review of the Late-Breaking Results of the CLEAR OASIS 9 Trial (Sanjit S. Jolly, MD, MSc, FRCPC)

Posted on by Sophia Ramirez

Speaker

Sanjit S. Jolly, MD, MSc, FRCPC
Interventional Cardiologist, Hamilton Health Sciences
Stuart Connolly Chair in Cardiology
Professor of Medicine, McMaster University

Keywords

Myocardial Infarction; Cardiology; Heart Failure; Colchicine; Spironolactone

Key Points

  • 20 years ago, an article published in Nature hypothesized that if we could find a cardioprotective drug to lower cardio-reactive protein (CRP), we could eliminate heart disease.
  • Over the last 2 decades, there have been successes and failures on that front. The Cardiovascular Inflammation Reduction Trial (CIRT) found that methotrexate did not reduce the rate of major adverse cardiovascular events. The Canakinimab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) found that higher doses of canakinumab reduced cardiovascular (CV) death, myocardial infarction (MI), or stroke by over 15% during follow-up.
  • The CoLchicine and spironolactonE in patients with myocardial infARction/SYNERGY Stent Registry – Organization to Assess Strategies of Ischemic Syndromes 9 (CLEAR SYNERGY OASIS 9) Trial was a large, simple, randomized trial of 7,000 patients with ST-elevation myocardial infarction or large non-ST-elevation myocardial infarction. Participants were randomized in a 2×2 factorial; first to either colchicine or placebo, then to either spironolactone or placebo.
  • The primary outcome in the first factorial was the effect was treatment with colchicine vs placebo on a composite of CV death, MI, stroke, or IDR. The co-primary outcomes in the subsequent factorial were the effects of spironolactone vs a placebo on 1) a composite of CV death or heart failure (HF) and 2) a composite of CV death, HF, stroke, or MI.
  • There have been 2 large trials looking at colchicine in cardiovascular disease: COLCOT and LODOC02. The CLEAR trial started before the results of the COLCOT trial, as the research team believed a larger confirmatory trial with more power was needed and replication of power results were important for Class 1 indications in guidelines. CLEAR is the largest trial of colchicine in acute MI, with substantially more events than prior trials.
  • In the first factorial, they found that while CRP was reduced with colchicine, acute and long-term colchicine did not reduce the composite of CV death, MI, stroke, or ischemia-driven revascularization. Colchicine was also associated with an increase in diarrhea, a known side effect of the drug. The research team believes the role of colchicine post-MI remains uncertain.
  • There have been 2 trials looking at Mineralocorticoid Receptor Antagonists (MRA) post-MI in patients without HF: REMINDER and ALBATROSS. Their results left some questions unanswered.
  • In the second factorial, they found that routine spironolactone post-MI did not reduce either co-primary outcome. There was a reduction in new or worsening heart failure, and on-treatment analysis suggests a potential benefit.

Discussion Themes

Outcomes have improved remarkably over the last 20 years, such that HF event rates in a population with predominantly ST-elevation MI are around 3%; a significant drop from the roughly 20% HF event rate in that population 20 years ago. That makes it more difficult to show treatment effects in this population.

The study team developed their inclusion criteria to select for a study population that would be applicable in standard clinical practice. The trial became more pragmatic as the study went on as a result of pivots they made in response to the COVID-19 pandemic.

Key challenges were driven by the COVID-19 pandemic. These included shipping expenses, which spiked significantly; shifting logistics, regarding who would receive the materials; and a pause in recruitment. The study team also came up against varying drug approvals in different locations; this was a global trial, taking place over roughly 70 sites in 11 countries.

Grand Rounds July 26, 2024: Interventions for Optimization of Guideline-Directed Medical Therapy for Heart Failure (Gregg C. Fonarow, MD, FACC, FAHA, FHFSA)

Posted on by Sophia Ramirez

Speaker

Gregg C. Fonarow, MD, FACC, FAHA, FHFSA
Eliot Corday Professor of Cardiovascular Medicine and Science
Director, Ahmanson-UCLA Cardiomyopathy Center
Codirector, UCLA Preventative Cardiology Program
UCLA Division of Cardiology

Keywords

Heart failure; HFrEF; guideline-directed medical therapy; implementation; systematic review

Key Points

  • Despite the availability of effective therapies for heart failure (HF), a large number of eligible patients are not receiving one or more evidence-based, guideline-recommended therapies. This implementation gap has stymied improvements in morbidity and mortality.
  • The benefits of evidence-based heart failure medications are cumulative. If all therapies are used, there is a relative risk reduction of 74.0% and an absolute risk reduction of 25.9%. Simultaneous or rapid initiation of therapies reduces HF hospitalizations, rehospitalizations, and mortality.
  • Reasons for underutilization of Guideline-Directed Medical Therapy (GDMT) for heart failure include a lack of systems to reliably implement therapies; gaps in knowledge and awareness of guidelines; therapeutic inertia; and insufficient urgency.
  • Dr. Fonarow’s team conducted a systematic review of interventions for the optimization of GDMT, including 28 randomized clinical trials with an aggregate sample of over 19,000 patients. They found that the initiatives that used interdisciplinary teams, largely comprised of nurses and pharmacists, most consistently led to improvements in GDMT. Clinician education, electronic health record initiatives, and patient interventions, on the other hand, resulted in no or modest improvements in GDMT.
  • Implementation of GDMT needs to improve in all clinical settings. Programs that successfully implement GDMT often have access to current and accurate data on treatment outcomes; administrative and clinician support; use care maps and pathways; and use data to provide feedback. There is also a need for further implementation science innovation and testing.

 

Discussion Themes

– Do you still see lack of education as a major problem that needs to be approached differently, or should we really be focusing on something else? I do think it need to be further studied. I think our educational efforts around the clinician need to center on the really practical aspects, on what the common pitfalls are in trying to apply and uptitrate these medications. Interdisciplinary teams and cross-discipline education are critically important. [The study results] don’t mean that education shouldn’t be part of further interventions, but I think we need to look at what’s truly going to see a meaningful increase in medication titration and persistence of GDMT.

– The polypill could address some of the clinical inertia issues and patient resistance. Patients hate it when you keep adding on four different medications and you’re increasing the doses. Is it being studied in this context? There is work going on, editorials have been written about it, the concept has been laid out. There are small pilot studies that have been done. There are challenges; is titration necessary? You’ll need a series of polypills to uptitrate, or you’ll get the therapy started and then you’ll bring them together as a polypill. One thing I do want to highlight, though, is that starting medications simultaneously defeats that patient question of, “Why are you adding this extra medication? Are the prior medications not working?” It’s a different mindset upfront: “Here are these four medications you’re going to be on.”

 

 

Tags

#pctGR, @Collaboratory1

June 8, 2022: PCT Grand Rounds Asks, ‘Do We Really Need So Many Heart Failure Clinicians?’

Posted on by Damon Seils

Headshot of Dr. Tariq AhmadIn this Friday’s PCT Grand Rounds, Dr. Tariq Ahmad of Yale University will present “Do We Really Need So Many Heart Failure Clinicians?” The Grand Rounds session will be held on Friday, June 10, 2022, at 1:00 pm eastern.

Dr. Ahmad is the medical director of heart transplantation and mechanical circulatory support and chief of heart failure in the Yale School of Medicine. His work focuses on the care of patients with end-stage heart failure, left ventricular assist devices, and cardiac transplantation.

Join the online meeting.