PRO-HF Sub-Study: Routine KCCQ-12 assessments in HF improves accuracy of provider assessment of patient health status.
- 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.
ECMO-CS: Early ECMO Does not Improve Outcomes in Severe Cardiogenic Shock
- 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.
IRONMAN: Intravenous Ferric Derisomaltose did not not meet primary endpoint in HFrEF
- 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.
COACH – A Patient-Risk Based Health System Intervention for Acute Heart Failure Care: The Comparison of Outcomes and Access to Care for Heart Failure (COACH) Trial
- 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.
First-in-Human in vivo Crispr/Cas9 Editing of the TTR Gene by NTLA-2001 in patients with Transthyretin Amyloid Cardiomyopathy
- 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.
Does Loop Diuretic Type Affect Clinical Outcomes in Heart Failure? Furosemide vs. Torsemide Compared in the TRANSFORM-HF Trial
- 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.
Role for Omecamtiv Mecarbil in Pts with EF <35%
- 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
Hospital-level Intervention Did Not Improve Outcomes or Quality in HFrEF
- 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
Pirfenidone Shown to Decrease Fibrosis in Patients with HFpEF
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.
Sacubitril/Valsartan Not More Effective Than Valsartan alone in Advanced HF: LIFE trial
- 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.
REHAB-HF: A Novel Physical Rehabilitation Intervention For Older Patients With ADHF
- 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
Are ACE Inhibitors or Beta-Blockers Cardioprotective During Adjuvant Treatment for Early-Stage Breast Cancer?
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.
PRADA: Cardioprotective Agents May Not Be Required During Breast Cancer Tx
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
Tricuspid Valve Replacement with the Transcatheter Evoque Valve is Safe and Effective at 30 days
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
Prospective ARNI Versus Ace Inhibitor Trial to Determine Superiority In Reducing Heart Failure Events After Myocardial Infarction (PARADISE-MI)
- 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.
EXPLORER-HCM Trial: Mavacamten Associated With Significant Improvement in Patients’ Health Status in Patients With Symptomatic LV Outflow Tract Obstruction
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
Post-Hoc Analysis of DAPA-HF: Dapagliflozin Use Is Associated With Rapid Reduction of Cardiovascular Death Among Patients With Heart Failure With Reduced Ejection Fraction
A recent study by Dr. David D. Berg, published in JAMA Cardiology, found that the use of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was associated with reducing the risk of cardiovascular death and heart failure hospitalization, emerging very early after randomization. Of note, patients with a recent history of hospitalization due to heart failure worsening tend to benefit more and experienced greater relative and absolute risk reductions when treated with dapagliflozin. Continue reading
REPLACE COVID Trial: Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers Can Be Safely Continued in Patients Admitted to Hospital With COVID-19
A recent trial by Dr. Jordana B Cohen, published in The LANCET, indicated that consistent with international society recommendations, patients admitted to the hospital with COVID-19 can safely continue treatment with renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB)) unless there is a distinct medical contraindication to ongoing therapy.
EMPEROR-Reduced Trial: Empagliflozin Use Was Associated With a Better Clinical Outcomes Among Patients With Heart Failure and a Reduced Ejection Fraction
A recent study by Dr. Milton Packer, published in Circulation, demonstrated that empagliflozin use has been associated with a reduction in the total number of inpatient and outpatient visits in patients with heart failure and a reduced ejection fraction. These benefits were observed within 12-28 days of treatment initiation and were persisted over the duration of the trial. Continue reading
DAPA Trial: Prophylactic Defibrillator Implantation After Primary Percutaneous Coronary Intervention Lowers Long Term Mortality in Patients at High Risk of Death
Results of the DAPA trial, published in Circulation: Arrhythmia and Electrophysiology, demonstrated that the use of early prophylactic implantable cardioverter defibrillator (ICD) in high-risk post-primary percutaneous coronary intervention (PCI) patients was associated with lower all-cause and cardiac mortality rates. However, the results of this trial should be interpreted with caution, since the trial was stopped prematurely.
The optimal timing of ICD implantation in STEMI patients treated with primary angioplasty is not identified yet. Previous clinical trials have failed to show the benefit of early ICD implantation (4-60 days) in post-MI patients with a low left ventricular ejection fraction (≤35-40%). The risk of sudden cardiac death (SCD) is high within the post STEMI period. However, ICD implantation after 40 days may not be indicated due to left ventricular remodeling and a potential increase in LVEF post-primary PCI. The Defibrillator After Primary Angioplasty (DAPA) trial evaluated all-cause and cardiac mortality of patients undergoing early prophylactic ICD implantation after PCI for STEMI. Following a recommendation from the data safety board, the trial was terminated early after just 38% of the planned sample size was enrolled due to slow enrollment.
This multicenter, randomized, controlled trial included patients with STEMI who had undergone primary PCI and met at least one of the following criteria: LVEF<30% within 4 days after admission, primary ventricular fibrillation (VF) within 24 hours (during PCI excluded), signs of heart failure on admission (Killip class ≥ 2), and/or thrombolysis in myocardial infarction (TIMI) flow post PCI < 3. The participants were randomized in a 1:1 ratio to receive either ICD implantation or conventional therapy within 30 to 60 days of the STEMI event. The primary endpoint was all-cause mortality at 3 and 9-years. The secondary endpoints of the study included the incidence of sudden cardiac death (SCD) and hospital admission for sustained ventricular tachyarrhythmias or appropriate ICD therapy.
A total of 266 patients with primary PCI for STEMI were included in the study with 131 patients allocated to the ICD arm and 135 patients assigned to the conventional therapy arm. After 3-years of follow-up, the primary outcome of interest was significantly lower among patients who received ICD implantation (5%) compared to the conventional therapy group (13%) (Hazard ratio (HR):0.37; [95% CI: 0.15-0.95]; p=0.04). This result remained similar at a median of 9-years follow-up (HR: 0.58; [95% CI: 0.37-0.91]; p=0.02). In terms of cardiac mortality, ICD implantation was associated with fewer deaths (11%) compared to the control group (22%) (HR: 0.52; [95% CI: 0.28-0.99]; p=0.04). Although not statistically significant, the incidence of SCD was also lower in the ICD group (3.1%) compared to the control group (5.9%) (HR 0.45; [95% CI 0.14–1.50]; p=0.19).
The results of this study should be interpreted with consideration of the following limitations. First, the premature termination of the study makes it underpowered for analysis. Second, the study used more than one inclusion criteria, so results should be interpreted with consideration of the patient characteristics. The high treatment crossovers (10.2%) within the first 3 years of the study and the lack of information on treatment crossovers between 3 and 9 years are additional limitations of the trial. Furthermore, while pharmacotherapy of the participants was similar at baseline, there is a lack of data regarding the follow-up medical therapy which may have impacted the mortality rates.
In conclusion, this prematurely terminated trial suggests that early prophylactic ICD implantation may be associated with a better survival rate in patients at high risk of death after primary PCI for STEMI. The results of this trial should be confirmed in future studies.