Key Points

• This was the first randomized trial to evaluate the safety and efficacy of everolimus and low-dose tacrolimus in pediatric heart transplant recipients.
• The open-label trial demonstrated that this combination is safe compared to standard dose tacrolimus and mycophenolate mofetil but was not associated with a lower burden of coronary allograft vasculopathy, rejection, and chronic kidney disease.
• TEAMMATE was limited by lower event rates than expected and challenges related to protocol adherence due to the COVID19 pandemic.

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Key Points:

• Transthyretin amyloid cardiomyopathy develops because of mis-folded proteins infiltrating the myocardium, leading to clinical heart failure. Currently, tafamidis is the only commercially approved medication and is the most expensive cardiovascular drug on the market.
• Acoramidis is a once-daily medication that stabilizes the transthyretin tetrameric protein, preventing its degradation and subsequent deposition into the myocardium.
• Acoramidis in ATTR-CM resulted in a statistically significant reduction in hospitalization for heart failure and mortality based on a hierarchical analysis of a composite outcome with an overall win ratio of 1.8 (p<0.0001) compared to placebo.

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Key Points:

• Qiliqiangxin is a traditional Chinese herbal medicine extract which has been approved since 2004 for the treatment of HF in China.
• This multicenter, double-blind, placebo-controlled trial compared qiliqiangxin with placebo amongst patients with HFrEF (EF<40%). The primary endpoint was a composite of CV death and HF hospitalizations.
• Over a median follow-up of 18 months, qiliqiangxin use resulted in a reduction in the composite primary endpoint.

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Key Points:

• A high burden of right ventricular pacing among patients with heart failure patients with reduced ejection fraction is known to cause left ventricular dyssynchrony and progressive dysfunction, yet definitive evidence has been lacking to inform the timing of upgrade to CRT devices.
• The BUDAPEST-CRT Upgrade Study randomized 360 patients with LVEF ≤ 35%, NYHA functional classes II–IVa, paced QRS ≥ 150 ms, and RV pacing burden ≥ 20% to either CRT-D (n=215) or traditional ICD (n=145). The primary endpoint was a composite of all-cause mortality, a first HHF event, or <15% reduction in LVESV at 12 months.
• This trial showed a significant reduction in the primary composite endpoint (32.4% in the CRT-D arm versus 78.9% in the ICD arm, aOR = 0.11, 95% CI 0.06-0.19, p-value <0.001), as well as in several individual secondary endpoints. Taken together, these findings support the clinical practice to promptly pursue CRT upgrade among HFrEF patients with intermittent or permanent RV pacing.

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Key Points

• Clinicians estimate heart failure (HF) health status using New York Heart Association (NYHA) class; however, this is often discordant with patient-reported symptom burden.
• The Patient-Reported Outcomes in Heart Failure Clinic (PRO-HF) is a pragmatic, randomized, unblinded trial comparing routine Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) collection prior to outpatient HF clinic visits, which is then shared with the treating clinician, to usual care.
• The primary objectives in this pre-specified sub study were to determine the effect of this intervention on the accuracy of clinician assessment of patient health status and patient experience.
• Provider assessment of NYHA class in the KCCQ-12 arm was more accurate, and patients in the KCCQ-12 arm felt their providers better understood their symptoms.
• Future investigations will determine the effect of routine KCCQ-12 administration on longer term clinical outcomes.

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Key Points:

• ECMO has been used as a salvage strategy in severe cardiogenic shock. However, it is unclear whether immediate ECMO initiation is superior to an initial trial of medical therapy with subsequent MCS utilization as needed if no improvement occurs.
• In the ECMO-CS study, patients presenting with severe cardiogenic shock (SCAI stage D-E) were randomized to either immediate ECMO or medical therapy (with downstream MCS as needed) The primary outcome of interest was a 30-day composite of death from any cause, resuscitated circulatory arrest, and implementation of any other MCS device.
• Immediate ECMO initiation was not associated with a significant reduction in the primary outcome relative to medical therapy with downstream as-needed MCS. There was a 40% crossover in the conservative arm to eventual downstream ECMO.

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Key Points:

• Iron deficiency is common and a poor prognostic feature in patients with heart failure. However, while iron infusion has improved symptoms in patients with HFrEF, there has been no association with improved “hard” outcomes such as hospitalization or CV death.
• In the IRONMAN study, patients with HFrEF and iron deficiency were randomized to Intravenous Ferric Derisomaltose (IV FDI) or placebo. The primary outcome of interest was a composite of recurrent HF hospitalizations and CV death.
• The observed reduction in primary endpoint with Intravenous Ferric Derisomaltose did not reach statistical significance compared to usual care.

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Key Points:

• HF patients frequently present to the ED for acute exacerbations, and the decision whether to discharge, observe, or admit these patients can be complex.
• The COACH trial randomized acute HF patients presenting to the ED to either a standardized clinical risk stratification algorithm (based on the EHMRG30-ST score) with associated rapid outpatient HF clinic or to standard of care.
• Patients receiving the intervention had reduced 30-day and 20-month composite death and non-elective cardiovascular hospitalizations.

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Key Points:

• Transthyretin Amyloidosis (ATTR) is a highly morbid and often fatal cause of cardiomyopathy. Existing therapies targeting TTR protein reduction have been effective, but have not managed to achieved complete or sustained knockdown of TTR levels.
• This was a Phase I study of a novel in vivo Crisp/Cas9 editing system (NTLA-2001) to reduce TTR. The primary objective was to assess safety, tolerability and PK and PD, and the secondary objective was to evaluate efficacy on clinical measures of cardiac disease.
• NTLA-2001 was generally well tolerated, with largely mild-moderate adverse events reported. Patients receiving NTLA-2001 achieved sustained, >90% reduction in TTR up to 4-6 months after infusion.

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Key points:

• Loop diuretics are routinely used to manage congestion in heart failure (HF) but have never been directly compared in a large-scale randomized trial.
• The TRANSFORM-HF trial compared torsemide vs. furosemide for long-term clinical outcomes among patients hospitalized with HF.
• At median follow up of 17.4 months, there was no significant difference in clinical outcomes (all-cause mortality) between torsemide and furosemide in HF patients.
• The pragmatic nature of the TRANSFORM-HF study allowed for diverse patient recruitment, high site engagement and clinically generalizable results.

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KEY POINTS:

• An experimental new therapeutic for heart failure, omecamtiv mecarbil is a novel, selective cardiac myosin activator that was previously shown in the GALACTIC-HF trial to improve heart failure (HF) outcomes amongst patients with heart failure with reduced ejection fraction (HFrEF)
• This extended analysis of the GALACTIC-HF trial showed that omecamtiv mecarbil exerts a greater relative and absolute therapeutic benefit in patients with worsening ejection fraction (EF), in keeping with the drug’s mechanism of selectively improving cardiac function
• The relative and absolute benefits from omecamtiv mecarbil significantly improved with progressively lower EF
• No clear benefit of omecamtiv mecarbil among patients with EF >30% was shown, with more research into this subgroup forthcoming
• The potential role for omecamtiv mecarbil is to be additive to other guideline-directed medical therapies (GDMT) for all patients with LVEF <35% and 1+ heart failure hospitalization in the prior year

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Key Points:

• CONNECT-HF, one of the largest heart failure (HF) implementation science trials performed to date, was performed to evaluate how the principles of audit and feedback with personalized feedback by HF and quality improvement experts might impact HF outcomes
• Results showed that this hospital-level intervention did not meaningfully improve clinical outcomes or quality of care delivery at 12 months compared to usual care
• According to the investigators, new approaches are needed to improve care above current quality improvement efforts for patients with HFrEF and next steps include finding alternative QI systems that do improve HF outcomes and rigorously studying those practices

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Key Points:

Myocardial fibrosis has previously been associated with death and repeat hospitalization in patients with heart failure with preserved ejection fraction.

In a phase II clinical trial, Pirfenidone, an oral antifibrotic agent used in the treatment of idiopathic pulmonary fibrosis, was found to significantly decrease myocardial fibrosis when compared to placebo. Dr. Christopher Miller of the University of Manchester presented the results of the PIROUETTE trial (NCT02932566) at a Late Breaking Clinical Trial session at the 2021 American College of Cardiology Scientific Sessions meeting. Given its effect in reducing pulmonary fibrosis, investigators hypothesized that the TGF-B1 antagonist would work similarly in the myocardium and hoped for a clinical benefit in volume status and quality of life as well.
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Key Points:

• This is the first study to assess the effects of Sacubitril/Valsartan in patients with advanced heart failure with reduced ejection fraction.
• No difference was found between Valsartan and Sacubitril/Valsartan when assessing the change in NT-proBNP levels from baseline in this sicker population.
• The two drugs had similar efficacy and tolerability profiles, with the exception of higher rates of hyperkalemia in the Sacubitril/Valsartan arm.

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Key Points:

• Elderly frail patients with acute decompensated heart failure hospitalizations benefit from cardiac rehabilitation
• Tailored rehabilitation led to a large, significant improvement in Short Physical Performance Battery (SPPB) score which was relatively uniform across pre-specified subgroups
• Rehabilitation intervention patients saw large, significant, clinically meaningful improvements in 6-minute walk distance, quality-of-life, Fried Frailty score, and depression

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New results were presented from the Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA) trial at ACC 2021 on May 16 and published concurrently in Circulation .  The authors found that medications administered in addition to surgery, adjuvant breast cancer (BC) therapy with anthracylines with or without anti-human epidermal growth factor receptor 2 (HER2) therapy, and radiotherapy may not significantly attenuate the reduction in left ventricular ejection fraction (LVEF), nor improve cardiac troponins in early-stage BC patients.
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Adjuvant breast cancer therapy, while beneficial in prolonging survival, has been shown to have harmful effects on the heart, prompting some providers to prescribe neurohormonal blocking agents to attenuate the myocardial damage. The original PRADA trial showed that candesartan and metoprolol helped prevent a decline in LVEF in patients on adjuvant therapy. To date, however, smaller studies have not shown a similar benefit to neurohormonal blockade. In a late breaking clinical trial session on May 16 at the 2021 American College of Cardiology Scientific Sessions meeting, Dr. Siri Lagethon Heck of Akershush University Hospital in Oslo, Norway, presented the long-term follow up results of the PRADA trial. Continue reading →

Transcatheter tricuspid valve replacement has become a feasible alternative to surgery in patients deemed to be at high risk of adverse events, and in the past decade, various devices have been designed to meet this clinical need. In his Focused Clinical Research session on the opening day of the American College of Cardiology 2021 Scientific Sessions, Dr. Susheel Kodali, director of the Structural Heart & Valve Center at New York-Presbyterian/ Columbia University Medical Center presented the 30-day results from the implantation of the EVOQUE valve, as part of the TRISCEND study. Continue reading →

KEY POINTS

• Sacubitril/valsartan did not provide a lower rate of cardiovascular death, heart failure hospitalization, or outpatient development of heart failure when compared to active treatment with ramipril in patients after high-risk myocardial infarction.
• When examining total adjudicated events and investigator reported primary endpoints, there was a trend toward clinical benefit in patients randomized to sacubitril/valsartan.

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EXPLORER-HCM presented at the American College of Cardiology 2021 meeting by John A. Spertus, MD, MPH, and simultaneously published in The Lancet, demonstrated that the use of mavacamten, a first-in-class cardiac myosin inhibitor, was associated with a highly significant improvement in patients’ health status. 1 out of 5 patients treated with mavacamten tended to experience a significant improvement in health status. Continue reading →