Jolie Bruno

Acute heart failure (AHF) is a leading cause of hospitalisation worldwide, with the majority of cases triggered by an identifiable precipitant. Recognition of these precipitants is important for both acute management and long-term prevention, as they are frequently reversible, carry prognostic significance and directly inform targeted therapy. The epidemiology of precipitants varies across settings, and patterns are evolving as the prevalence of heart failure with preserved ejection fraction rises. In this review, we summarise the epidemiology, diagnostic evaluation and management of the most common precipitants of AHF. Globally, the leading precipitants of AHF are ischaemia/acute coronary syndrome, infection, arrhythmias, uncontrolled hypertension, nonadherence and renal dysfunction, although their relative distribution varies by geography and heart failure phenotype. Optimal medical management necessitates initial haemodynamic stabilisation, identification of the underlying precipitant and delivery of targeted therapy. Importantly, successful identification and treatment of a reversible precipitant should not preclude initiation or optimisation of guideline-directed medical therapy, which remain essential for long-term outcomes.

Heart failure (HF) continues to challenge clinicians worldwide, not only because of its high morbidity and mortality but also due to the persistent difficulty in translating therapeutic advances into routine care. Despite the availability of effective treatments, data show striking gaps in the optimal use of guideline-directed medical therapy. Among the four pillars of guideline-directed medical therapy, mineralocorticoid receptor antagonists (MRAs) remain the least prescribed. This underuse is concerning considering the evidence demonstrating consistent benefits of MRAs across different HF phenotypes. In this review, we revisit the role of MRAs across the spectrum of HF. We summarise the supporting evidence, discuss their mechanisms of action and provide practical guidance on patient eligibility and initiation strategies. In addition, we address common barriers that often limit their use. By combining mechanistic insights, trial evidence and pragmatic recommendations, this review aims to facilitate broader and earlier use of MRAs, thereby helping to close a major gap in the implementation of evidence-based HF care.

Aims: Recent clinical trials have underscored the importance of early initiation of heart failure (HF) guideline-directed medical therapy (GDMT), with growing emphasis on rapid sequencing, particularly after hospitalization for acute HF (AHF). Despite the proven short-term benefit of this approach, few patients receive this therapy at discharge. In patients with AHF, we evaluated whether treatment at discharge with dual sodium–glucose co-transporter-2 inhibitors (SGLT2i)–mineralocorticoid receptor antagonist (MRA) therapy or four-class GDMT was associated with short-term mortality and incremental risk reduction. Methods: We analysed two prospective registries of AHF: the China HF-CAP (n = 441 320; main cohort) and the Swedish HF Registry (SwedeHF) (n = 2367; external validation cohort). We assessed the association between discharge prescription of dual therapy SGLT2i and MRA versus neither, and four-class GDMT vs none, with 90-day cardiovascular (CV) and all-cause mortalities, further stratified by baseline serum potassium levels and left ventricular ejection fraction (LVEF) categories. Results: In the main cohort, for dual SGLT2i and MRA therapy (n = 71 154) vs neither (n = 81 793) therapy, adjusted odds of 90-day CV and all-cause death were 0.320 [0.283–0.361] and 0.504 [0.472–0.539], respectively. In the external validation cohort, results were directionally consistent. Association between dual SGLT2i and MRA therapy and short-term survival was consistent irrespective of hyperkalaemia and across HF phenotypes. Further, in the main cohort, adjusted odds of 90-day CV death of four-class GDMT (n = 36 301) were 0.122 (0.106–0.14) vs no therapy (n = 18 374). Conclusion: After AHF, early initiation of dual SGLT2i and MRA therapy was associated with lower short-term mortality, irrespective of LVEF or potassium levels. Four-class GDMT conferred the lowest risk, emphasizing the importance of timely implementation after AHF.

Introduction: Circulating dipeptidyl peptidase 3 (cDPP3) is implicated in cardiocirculatory failure and elevated concentrations predict poor outcomes in shock states. Its role in acute heart failure (AHF) is unexplored. We assessed the clinical relevance of cDPP3 in AHF. Methods: Analyses were performed using two prospective AHF trials: STRONG-HF and CORTAHF. cDPP3 was measured at baseline and follow-up (day 90 in STRONG-HF; day 30 in CORTAHF). Associations with 180-day (STRONG-HF) and 90-day (CORTAHF) outcomes were evaluated according to baseline concentrations. Longitudinal changes during guideline-directed medical therapy (GDMT) optimization and predictors of elevated cDPP3 were analysed. Results: In STRONG-HF, 222/973 patients (23%) had cDPP3 ≥ 40 ng/mL. These patients were younger (58 ± 15 vs. 65 ± 13 years, P < .0001), more frequently female (47.7% vs. 35.8%, P = .0013) and Black (42.8% vs. 14.4%, P < .0001), with lower NT-proBNP concentrations (P < .0001). Baseline cDPP3 ≥ 40 ng/mL was not associated with 180-day outcomes. Over 90 days, cDPP3 decreased by −15% with high-intensity care and −8% with usual care (P = .078). Changes in cDPP3 were not associated with NT-proBNP reduction (continuous P = .797; ≥30% responder P = .990). In pooled multivariable analysis, MRA use was independently associated with cDPP3 ≥ 40 ng/mL (OR 3.83; 95% CI 1.47–9.96; P = .006), whereas non-Black ethnicity was associated with lower odds (OR 0.43; 95% CI 0.29–0.64; P < .0001). Conclusion: In AHF, cDPP3 was mildly elevated and was not associated with clinical outcomes or congestion relief during GDMT optimization. Elevated cDPP3 identified a distinct clinical phenotype but did not confer adverse prognosis.

Introduction: Natriuretic peptides (NPs) are central to the diagnostic and therapeutic management of heart failure (HF), yet their short-term dynamics under sacubitril/valsartan (S/V) therapy and during acute volume changes remain incompletely characterized. We aimed to assess changes in circulating biomarkers and response to standardized acute intravascular volume expansion and diuretic treatment before and after S/V initiation. Methods: We studied 229 ambulatory patients with HF with reduced ejection fraction receiving guideline-directed medical therapy who initiated S/V. Patients were evaluated at three outpatient visits: before S/V initiation and after 2 and 3 months of treatment. At each visit, participants underwent a standardized 9-hour protocol including volume infusion followed by diuretic administration. BNP, NT-proBNP, MR-proANP, and neprilysin activity were measured serially alongside clinical assessment and natriuresis. Results: Across visits, initiation of S/V was associated with lower concentrations of BNP (−8%, P = .009) and NT-proBNP (−35%, P < .001). During the acute protocol, both BNP and NT-proBNP increased significantly over time (timepoint effect P < .001), with parallel trajectories before and after S/V initiation and no visit-by-time interaction (P = .17 for BNP; P = .95 for NT-proBNP). Despite marked natriuresis and improvement in clinical signs following diuretic administration, BNP and NT-proBNP continued to rise during the 9-hour observation period. Conclusion: In a controlled acute volume overload setting, BNP and NT-proBNP provide comparable information, but their short-term dynamics lag behind clinical decongestion. Routine serial NP measurements at very short time intervals are unlikely to add incremental clinical value in the early phase of acute HF.

Jolie Bruno, M.D., Aziz Daghmouri, M.D., Ayu Asakage, M.D., Camille Gobeaux, M.D., Kamilė Čerlinskaitė-Bajorė, M.D., Jelena Čelutkienė, M.D., Ph.D., Naoki Sato, M.D., Ph.D., Koji Takagi, M.D., Alexandre Mebazaa, M.D., Ph.D., Benjamin Deniau, M.D., Ph.D., and Shiro Ishihara, M.D., Ph.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2025.0232