JACC. Heart failure最新文献

Background: Younger patients (18-49 years of age) with advanced heart failure (HF) face unique challenges in decision-making for advanced HF therapies. Although heart transplantation (HT) offers excellent survival, it is associated with finite graft longevity. The HeartMate 3 (HM3) left ventricular assist device (LVAD) has demonstrated promising outcomes, but direct comparisons with those listed for or undergoing HT in this age group remain limited.

Objectives: This study sought to compare survival and adverse event (AE) outcomes between younger patients receiving HM3 LVAD support and those listed for or undergoing HT.

Methods: The authors analyzed patients 18-49 years of age from the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) portfolio (HM3 cohort; n = 420) and the UNOS (United Network for Organ Sharing) registry (HT listing cohort; n = 1,955) (HT recipients; n = 1,176) from 2014-2018. Propensity score matching was performed to adjust for baseline differences. Outcomes included 2-year survival from time of treatment or time of listing, freedom from death or delisting for deterioration, and 1-year incidence of major AEs (ie, stroke, renal dysfunction, infection).

Results: After propensity score matching, 2-year survival from treatment was similar for HM3 and HT (88.7% vs 90.2%; HR: 1.18; P = 0.53). When comparing outcomes from time of transplant listing vs LVAD implantation, HM3 was associated with higher freedom from death compared with freedom from death or delisting due to deterioration in UNOS (90.1% vs 76.7%; HR: 0.38; P < 0.0001). AE analysis showed lower 1-year rates of renal dysfunction requiring dialysis (5.0% vs 10.4%; P = 0.016) and fewer infection-related hospitalizations (24.8% vs 34.2%; P = 0.012) in HM3 recipients, but a higher incidence of debilitating stroke (3.4% vs 0.3%; P = 0.027).

Conclusions: Contemporary data suggest that durable LVAD therapy may offer survival outcomes comparable to HT in adults <50 years of age. These findings support the consideration of an LVAD-first strategy as a viable initial approach to heart replacement therapy in appropriately selected patients. (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 Investigational Device Exemption [MOMENTUM 3 IDE]; NCT02224755) (MOMENTUM 3 Continued Access Protocol [MOMENTUM 3 CAP]; NCT02892955).

Background: Given that mineralocorticoid receptor antagonists have the potential to impair renal function and induce hyperkalemia, close monitoring of estimated glomerular filtration rate (eGFR) and serum potassium levels is essential to ensure the safe administration of this therapy.

Objectives: In this prespecified analysis, the authors evaluated the efficacy and safety of the kidney function-based finerenone dosing strategy used in the FINEARTS-HF trial.

Methods: In FINEARTS-HF, patients with an eGFR of 25 to 60 mL/min/1.73 m² at baseline were stratified at randomization to the low-dose group and started on 10 mg of finerenone once daily (titrated to a maximum 20 mg/d) or matching placebo, whereas those with an eGFR >60 mL/min/1.73 m² at baseline were stratified to the high-dose group and started on 20 mg of finerenone once daily (titrated to a maximum 40 mg/d) or matching placebo. The primary outcome was the composite of total (first and recurrent) heart failure events and cardiovascular death.

Results: Among 5,986 (99.8%) analyzable patients, 3,159 were assigned to the higher eGFR/high-dose stratum and 2,827 to the lower eGFR/low-dose stratum group. The mean ± SD achieved dose was 32.3 ± 9.1 mg (finerenone) and 34.4 ± 7.8 mg (placebo) in the higher eGFR/high-dose stratum, and 15.6 ± 4.3 mg (finerenone) and 16.7 ± 4.0 mg (placebo) in the lower eGFR/low-dose stratum. The effect of finerenone on the primary outcome was consistent across the 2 dosing strata (higher eGFR/high-dose stratum: rate ratio: 0.77 [95% CI: 0.63-0.94] vs lower eGFR/low-dose stratum: rate ratio: 0.87 [95% CI: 0.74-1.03]; P for interaction = 0.34). Consistent benefits were observed for the components of the primary outcome and all-cause death. Safety was also consistent between dosing strata, except for hypokalemia, where the reduction in the odds of hypokalemia with finerenone compared to placebo was greater in the higher eGFR/high-dose stratum (P-interaction < 0.01).

Conclusions: In FINEARTS-HF, an eGFR-based dosing strategy allowed effective and safe use of finerenone in patients with heart failure with mildly reduced ejection fraction/ heart failure with preserved ejection fraction with a baseline eGFR as low as 25 mL/min/1.73 m². We recommend that clinicians implement the trial-validated dosing strategy and incorporate appropriate uptitration to the target dose to ensure optimal therapeutic outcomes. (FINEARTS-HF [Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40%; NCT04435626).