AIMS
This report describes the design and baseline characteristics of the SPIRIT-HF trial and compares them with prior heart failure with mildly reduced or preserved ejection fraction (HFpEF/HFmrEF) trials.
METHODS AND RESULTS
In this multicenter, double-blind, placebo-controlled phase III trial, 730 patients aged ≥50 years with left ventricular ejection fraction (LVEF) ≥40%, New York Heart Association (NYHA) class II-IV symptoms, and either elevated N-terminal-pro-B-type natriuretic peptide (NT-proBNP) or HF hospitalization within 12 months were randomized 1:1 to spironolactone or placebo. The primary endpoint is a composite of rate of total (first and recurrent) HF hospitalizations and cardiovascular death within 24 months from randomization, which will be analyzed using the LWYY model. Secondary endpoints in a hierarchical order include total HF hospitalizations, CV hospitalizations, all hospitalizations, and cardiovascular death within 24 months from randomization. Results will first be analyzed based on the SPIRIT-HF dataset only. Then, a pre-specified individual participant data meta-analysis combining SPIRIT-HF and TOPCAT Americas will be conducted to refine treatment effect estimates. The median age of the patients enrolled in the SPIRIT-HF was 77.8 years, and 52% were women. The median LVEF was 55% (50-60), with 18% of patients having a LVEF between 40-49%. In SPIRIT-HF, prior HF hospitalization was similarly frequent (46.4% vs. 55%), but NT-proBNP was slightly higher (970 vs. 900 pg/ml) compared to TOPCAT Americas. However, the proportion of patients with NYHA class III (33% vs. 35%), patients with comorbidities such as atrial fibrillation at baseline electrocardiogram (25% vs. 25%) and chronic kidney disease (50% vs. 48%); and background therapy, such as beta-blockers (76% vs. 79%), and diuretics (83% vs. 89%), including loop diuretics (69% vs. 78%), were similar between SPIRIT-HF and TOPCAT Americas. Compared with prior HFpEF/HFmrEF trials, SPIRIT-HF patients demonstrated a higher risk with a similar proportion of patients with recent HF hospitalization (46.4%) and slightly higher NT-proBNP concentrations (970 pg/ml) at baseline.
CONCLUSION
SPIRIT-HF addresses key evidence gaps for spironolactone in high-risk HFpEF/HFmrEF, and could inform guideline recommendations on MRA use in this cohort.
D. Zurkan, B. Pieske, J. Petutschnigg et al.· European Journal of Heart Fa...· 1 citation
Heart failure (HF) remains a major cause of morbidity, mortality, impaired quality of life and healthcare expenditure worldwide. The global burden of HF continues to increase due to population aging, improved survival, and the growing prevalence of cardiovascular, renal, and metabolic comorbidities. Simultaneously, the pace of scientific progress in HF has accelerated considerably. Recent advances have refined our understanding of HF epidemiology, prognosis, and disease trajectories, including emerging concepts of HF improvement, remission, and recovery. The Second Universal Definition of HF has also updated the classification framework, moving beyond the traditional ejection fraction-based categories. HF is now broadly classified into two major phenotypes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Novel mechanistic insights highlight the role of inflammation, immune activation, metabolic dysfunction, mitochondrial biology, and multisystem interactions in HF progression. There has also been significant progress in the characterization and management of major comorbidities, including chronic kidney disease (CKD), diabetes, obesity, atrial fibrillation (AF), pulmonary hypertension, frailty, malnutrition, and cancer. Diagnostic innovations include novel biomarkers, multi-omics technologies, artificial intelligence-based approaches, advanced imaging techniques, congestion assessment tools, and emerging digital health solutions. Important advances have occurred in specific HF aetiologies, including cardiomyopathies, cardiac amyloidosis (CA), myocarditis, arrhythmia-induced cardiomyopathy (AiCM), and Chagas cardiomyopathy. Therapeutic developments continue to reshape HF management across the spectrum of left ventricular ejection fraction. Recent evidence has focused on optimization of guideline-directed medical therapy in HFrEF, expansion of evidence-based therapies in HFpEF, and growing roles for sodium-glucose cotransporter-2 inhibitors, finerenone, incretin-based therapies, and transcatheter valve interventions. Collectively, these advances support the transition from a predominantly phenotype-based approach towards a more personalized and biologically informed model of HF care, with the potential to further improve outcomes across the entire HF spectrum.
Valentino Liguori, Angelica Rizzello, M. Adamo et al.· ESC Heart Failure· 0 citations
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