https://orcid.org/0000-0002-9341-117X
The year in cardiovascular medicine 2024: The top 10 papers in heart failure Left: Studies in heart failure with preserved/mildly reduced ejection fraction (HFpEF/mrEF). Right: Studies in heart failure with reduced ejection fraction (HFrEF). 6MWD, 6-minute walking distance; CSS, clinical summary score; CV, cardiovascular; GRMT, guideline-recommended medical therapy; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFmrEF, heart failure with mildly reduced ejection fraction; HFrEF, heart failure with reduced ejection fraction; KCCQ, Kansas City Cardiomyopathy Questionnaire; LVAD, left ventricular assist device; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; M-TEER, mitral valve transcatheter edge-to edge repair; NYHA, New York Heart Association; OS score, overall summary score; PA, pulmonary artery pressure; PH, pulmonary hypertension; PPCM, peripartum cardiomyopathy; SOC, standard of care; T2DM, type 2 diabetes mellitus; VKA, vitamin K antagonists.
Due to its high prevalence and incidence, heart failure (HF) continues to be a major threat to patients and health care professionals. Here, we have compiled 10 impactful papers published in 2024.
For patients with HF with preserved ejection fraction (HFpEF), there is no guideline-recommended medical therapy (GRMT) with the exception of diuretics and SGLT2 inhibition (based on the EMPEROR-Preserved/DELIVER studies). The FINEARTS-HF trial reported the effect of the novel nonsteroidal mineralocorticoid receptor antagonist finerenone on the composite of total worsening HF events (first/recurrent unplanned hospitalization or urgent visit for HF) and cardiovascular (CV) death in >6000 patients with HFpEF/mrEF.1 Finerenone reduced primary-outcome events (rate ratio, 0.84; 95% confidence interval [CI], 0.74–0.95; P = .007), mainly driven by reduction of worsening HF events (rate ratio, 0.82; 95% CI, 0.71–0.94; P = .006). Cardiovascular death occurred in 8.1% and 8.7%, respectively (hazard ratio, 0.93; 95% CI, 0.78–1.11). Finerenone was associated with an increased risk of hyperkalaemia and a reduced risk of hypokalaemia. Thus, finerenone appears to be a promising novel treatment modality in patients with HFpEF/mrEF.
Heart failure with preserved ejection fraction is often related to obesity and type 2 diabetes mellitus (T2DM). Although physical training and weight loss improves symptoms, only a minority of patients is able to implement durable life style changes. The STEP HFpEF-DM trial randomized >600 patients with HFpEF, obesity (body mass index of ≥30) and T2DM to once-weekly semaglutide (2.4 mg) or placebo.2 Primary endpoints were change in body weight and the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS). Semaglutide treatment significantly reduced body weight (mean change −9.8% vs. −3.4%; estimated difference, −6.4% points; 95% CI −7.6 to −5.2; P < .001), and improved KCCQ-CSS (mean change +13.7 semaglutide vs. +6.4 placebo; estimated difference, 7.3 points; 95% CI 4.1–10.4; P < .001). Also, the secondary endpoints (e.g. change in 6 min walk distance and change in C-reactive protein level) showed benefits for semaglutide. Although the STEP HFpEF-DM study was not powered for HF endpoints such as HF hospitalization, there was a numerical trend favouring semaglutide (at a low HF hospitalization rate).
In SUMMIT, the first trial with incretin mimetics powered for HF outcomes in HFpEF and obesity,3 tirzepatide (up to 15 mg subcutaneously once per week) significantly improved both primary endpoints: the composite of CV death or a first worsening HF event (hazard ratio, 0.62; 95% CI, 0.41–0.95; P = .026) and second, the change from baseline to 52 weeks in KCCQ-CSS (19.5 ± 1.2 vs. 12.7 ± 1.3; between-group difference, 6.9; 95% CI, 3.3–10.6; P < .001). Also, the secondary endpoints (e.g. change in 6 min walk distance and change in C-reactive protein level) showed benefits. Adverse events (mainly gastrointestinal) that led to drug discontinuation occurred in 23 tirzepatide-treated patients (6.3%) vs. 5 (1.4%) on placebo.
Heart failure with preserved ejection fraction patients often suffer from pulmonary hypertension, prompting the question whether phosphodiesterase (PDE)-5 inhibitors would improve symptoms and outcome. Before such a treatment, detailed diagnostic work-up is necessary typically with right heart catheterization to differentiate forms of pulmonary hypertension. The PASSION study randomized HFpEF patients with combined postcapillary and precapillary pulmonary hypertension to receive tadalafil (40 mg) or placebo.4 Unfortunately, the study was terminated early because of disruption in study medication supply. The primary endpoint (time to first composite event of adjudicated HF hospitalization or all-cause death) occurred in 32% on placebo and 27% on tadalafil (HR, 1.02 [95% CI, 0.52–2.01]; P = .95). There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10 [95% CI, 1.10–23.69]; P = .04). PDE-5 inhibitors should not be used broadly in HFpEF patients with pulmonary hypertension, but only after implementation of sufficient diuretic therapy and detailed assessment in a dedicated centre.
Patients with de novo HF with reduced ejection fraction (HFrEF) should receive an optimized GRMT for at least 3 months, before considering implantable cardioverter defibrillator (ICD) implantation. There is clinical experience that several HFrEF patients improve with their left ventricular ejection fraction (LVEF) beyond 3 months, however, it is unclear how long improvement may occur during GRMT optimization. In the HF-OPT study, newly diagnosed HFrEF patients with LVEF ≤ 35% prescribed a wearable cardioverter-defibrillator (WCD) entered a 3-month registry phase followed by a study phase up to 1 year.5 A total of 46% of patients with persistently low LVEF at Day 90 had LVEF improvement > 35% by Day 180, increasing the total rate of improvement > 35% to 68%. Sustained ventricular tachyarrhythmias were observed in 24 WCD carriers (1.8%) until Day 90, thereafter no sustained ventricular tachyarrhythmia occurred. Thus, optimization of GRMT in newly diagnosed HFrEF beyond 3 months leads to additional LVEF improvement > 35%, and may prevent unnecessary preventive ICD implantations.
Pulmonary artery pressure (PA)-guided HF therapy appears useful in patients with moderate-to-severe HF (NYHA class III) after a recent hospitalisation. Controversy remains what HF population is best treated with a PA monitor. Therefore, a subanalysis of the MONITOR-HF trial, among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, LVEF, HF aetiology, and presence or absence of cardiac resynchronization therapy, and presence or absence of an ICD, evaluated if specific subgroups conferred more clinical benefit from PA-guided HF management.6The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in all predefined subgroups, without any clinically relevant heterogeneity. Therefore, classic assessment based on functional impairment after admission appears to adequately identify patients eligible for this therapy.
Another remaining controversy was if transcatheter mitral-valve repair improves outcomes in patients with HF and functional mitral regurgitation (MR). The RESHAPE-2 study7 assigned 505 patients with HF and moderate-to-severe functional MR to either transcatheter mitral-valve repair and GRMT (device group) or GRMT alone (control group). There were three primary endpoints: (i) the composite of total hospitalization for HF or CV death during 24 months; (ii) the rate of total HF hospitalization during 24 months; and (iii) the change from baseline to 12 months in KCCQ-OS scores. The rate of total HF hospitalizations or CV death was 37.0/100 patient-years in the device group and 58.9/100 patient-years in the control group (rate ratio, 0.64 [95% CI 0.48–0.85], P = .002). Total HF hospitalizations were also reduced (rate ratio, 0.59 [95% CI, 0.42–0.82]; P = .002), while KCCQ-OS score increased by 21.6 ± 26.9 points in the device group vs. 8.0 ± 24.5 in the control group (mean difference, 10.9 [95% CI, 6.8–15.0]; P < .001). These results, together with the earlier data from COAPT and MITRA-FR, provide a clear foundation to consider transcatheter mitral-valve repair in HF patients with moderate-to-severe functional MR.
The HeartMate 3 (HM3) is a fully magnetically continuous flow left ventricular assist device (LVAD) in use since almost 10 years. The ELEVATE Registry collected real-world outcomes in 463 subjects who were implanted an HM3.8 Patients were 56 years old, and 89% were male. The majority received an LVAD as bridge to transplant (66%). The overall survival at 5 years was 63.3% and survival free of stroke 58.1%. Patients experienced substantial improvements in functional capacity and quality of life maintained for 5 years. These real-world data show good survival rates with acceptable stroke rate, and suggest that the current LVAD generation may extend life in terminally ill HF patients for many years, with good quality of life.
Even better outcomes for LVAD patients may be achieved with omission of aspirin and long-term oral anticoagulant therapy based on vitamin K antagonists without additional antiplatelet therapy. ARIES randomized >600 patients implanted with a HM3-LVAD to placebo or aspirin.9 The composite primary endpoint, assessed for noninferiority of placebo, was survival free of a major nonsurgical (>14 days after implant) haemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. Noninferiority of placebo was demonstrated (74% on placebo, 68% on aspirin free of haemocompatibility events; absolute difference, 6.0% improvement in event-free survival with placebo [lower one-sided 97.5% CI, −1.6%]; P < .001). Thus, in patients implanted with a HM3-LVAD on vitamin K antagonists, avoidance of aspirin reduces bleeding, and does not increase thrombo-embolic risk. These data are of major importance for LVAD patients and will further improve long-term outcomes.
The dopamine agonist bromocriptine by limiting the release of prolactin constitutes a promising pathophysiology-based treatment for peripartum cardiomyopathy (PPCM), however, given the lack of large randomized controlled studies, the evidence regarding its efficacy remains limited. A non-randomized analysis from the EORP-PPCM registry investigated maternal outcome in relation to bromocriptine treatment among 552 PPCM patients, 85 treated with bromocriptine (15%).10 The composite maternal outcome (death or hospital readmission, or persistently severely reduced LVEF [<35%] after 6 months) occurred in 22% treated with bromocriptine and in 33% treated with standard of care (P = .044). This association remained after applying multiple imputation and methods to correct for confounding by indication (inverse probability weighted model on imputed data OR 0.39, 95% CI 0.19–0.81, P = .011). Thrombo-embolic events occurred in 5.9% in the bromocriptine group vs. 5.6% in the standard of care group (P = .900). These data provide further support for use of bromocriptine at least in patients with moderate–severe PPCM.
Declarations
Disclosure of Interest
J.B. received honoraria for lectures/consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, Corvia, Norgine, Edwards, and Roche not related to this article; and research support for the department from Zoll, CVRx, Abiomed, Norgine, and Roche, not related to this article. R.A.d.B. has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, Novo Nordisk, and Roche; and has had speaker engagements with and/or received fees from Abbott, AstraZeneca, Bristol Myers Squibb, Cardior Pharmaceuticals GmbH, Novartis, and Roche. S.Z. received research grant support, served on advisory boards for, or speaker engagements with AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Janssen, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer, Roche, Servier, and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, and Pfizer.
