ESC Heart Failure最新文献

Introduction: Relationship between changes in cardiac function, functional capacity, and patient-reported health status in heart failure (HF) remains incompletely defined, which may help inform endpoint selection and clarify how distinct clinical domains reflect treatment response.

Methods: This post hoc analysis of the randomized cardiac microcurrent (C-MIC) II trial, which evaluated the efficacy and safety of C-MIC therapy in patients with chronic HF with reduced ejection fraction on optimal guideline-directed medical therapy, included 65 ambulatory patients with non-ischaemic dilated cardiomyopathy, New York Heart Association (NYHA) Class III-IV symptoms, and baseline left ventricular ejection fraction (LVEF) 25-35%. Correlations between changes in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), 6-minute walk distance (6MWD), core lab-assessed LVEF (primary measure) and site-assessed LVEF, and peak oxygen uptake (peak VO2) were evaluated at 4 weeks, 2 months, 3 months, 4 months, and 6 months using Pearson coefficients with 95% confidence intervals (CI).

Results: The mean age was 60.0 ± 9.7 years and baseline LVEF was 29.8 ± 3.3%. Baseline 6MWD was 291.4 ± 61.6 m and KCCQ-OSS was 42.6 ± 22.7. From baseline to 6 months, changes in KCCQ-OSS (n = 63) and 6MWD (n = 61) showed modest correlations with core lab-assessed LVEF (r = 0.39; 95% CI: 0.16-0.58; P = .0015 and r = 0.39; 95% CI: 0.15-0.58; P = .0022, respectively). Changes in KCCQ-OSS and 6MWD correlated strongly (n = 62; r = 0.63; 95% CI: 0.46-0.76; P < .0001). Changes in KCCQ-OSS and 6MWD did not correlate significantly with changes in peak VO2 (P = .06 and P = .30, respectively). Changes in LVEF and peak VO2 (n = 55) demonstrated modest correlation (r = 0.41; 95% CI: 0.16-0.61; P = .002). Baseline correlations with peak VO2 were weak to modest but increased at 6 months for LVEF (n = 59; r = 0.56; 95% CI: 0.35-0.71; P < .0001).

Conclusion: In advanced HF, improvements in health status and submaximal functional capacity associate modestly with LVEF, while LVEF correlates more closely with peak VO2. Cardiac function, functional capacity, and health status represent related but distinct domains, supporting multidimensional assessment in HF trials.

The traditional, hospitalization-centric composite endpoint of cardiovascular (CV) death or time-to-first heart failure (HF) hospitalization is increasingly misaligned with contemporary HF care and, as evidence-based therapies lower event rates over time, requires larger trials with longer follow-up. Improved survival, modern ambulatory pathways mean that a larger share of worsening HF is treated outside the hospital and that patients may experience recurrent worsening HF episodes. Relying on time-to-first hospitalization alone can therefore miss clinically relevant morbidity; recurrent-event approaches can offer additional power mainly when risk heterogeneity is high and treatment discontinuation after a first event is infrequent. To address this gap, we propose a standardized, adjudicated definition of worsening HF events informed by published consensus definitions, expanded to capture ambulatory events across care settings. Building on this definition, we recommend hierarchical primary endpoints that prioritize all-cause death with CV death evaluated as a secondary mortality outcome when prespecified and adjudicated, while robustly measuring morbidity through total adjudicated worsening HF events (first and recurrent), with validated patient-reported outcomes as additional hierarchical levels. We outline operational considerations for event capture and adjudication, including prioritized composite analytic approaches, and highlight safeguards to mitigate ascertainment bias and dilution by more subjectively defined events. Adoption of worsening HF -based hierarchical endpoints can better reflect the total disease burden, improve statistical power, and enhance interpretability across evolving care models.

Background and aims: Long-term real-world effects of sacubitril/valsartan (S/V) and the impact of S/V dose reduction or discontinuation are less defined. We assessed longitudinal changes after S/V initiation and the association of dose changes with major adverse cardiovascular events (MACE).

Methods: Multicentre retrospective study of 592 HFrEF outpatients starting S/V (83% men; age 68 ± 10 years; LVEF 32 ± 7%). NT-proBNP, Kansas City Cardiomyopathy Questionnaire (KCCQ) and echocardiography were collected at baseline, 12 months, and last follow-up. MACE was analysed with Kaplan-Meier and Cox models.

Results: NT-proBNP decreased from 1000 (494-2333) to 751 (304-1726) and 735 (215-1980) pg/ml (P < .001). KCCQ improved from 53 ± 15 to 62 ± 14 and 66 ± 15 (P < .001). LVEF increased from 32 ± 7 to 36 ± 8 and 37 ± 9% (P < .001) and GLS improved from -10.8 ± 3.2 to -12.3 ± 3.1 and -14.0 ± 2.9% (P < .001). During a median follow-up of 3.72 years, 225 patients (38%) experienced MACE (36 deaths; 134 HF hospitalizations). MACE incidence was higher in patients with S/V discontinuation and with dose reduction (log-rank P = .013 and P = .014). In multivariable Cox analysis, S/V discontinuation [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.28-1.97; P = .040], change in GLS (HR 0.81, 95% CI 0.67-0.98; P = .028) and change in KCCQ (HR 0.95, 95% CI 0.92-0.98; P = .001) were independently associated with MACE.

Conclusions: S/V initiation was associated with sustained improvements in NT-proBNP, quality of life, and cardiac remodelling. S/V discontinuation or dose reduction identified patients at higher MACE risk.

Introduction: Single-pill combinations (SPC, polypills) have proven effective in cardiovascular areas, yet no such therapy exists for patients with heart failure (HF) despite substantial polypharmacy and pill burden in this population. Simplifying treatment through an HF-specific SPC containing key guideline-directed medical therapy (GDMT) components could improve adherence and outcomes.

Methods: Two prospective, electronic surveys were conducted between June and October 2025 to assess real-world attitudes towards a polypill in HF with ejection fraction ≤50%. The physician-oriented survey (22 questions) was distributed internationally and explored GDMT practices, perceived needs, barriers, and potential preferred composition of an HF dedicated SPC. The patient-oriented survey (11 questions) explored medication burden, adherence, and perceptions of a potential polypill use.

Results: A total of 250 physicians and 126 patients participated. Among physicians, 77% reported a clear need for strategies to simplify GDMT optimisation in HFrEF, with cost (66%) and polypharmacy (54%) being selected as the most frequent barriers. Nearly all physicians (95%) recognized a real clinical need for an HF-specific SPC, and most perceived it as clinically useful (88%), logistically feasible (76%), and acceptable to patients (94%). Approximately 48% of physicians declared that they would use it regularly, and another 49% would use it in selected patients. The preferred composition of HF-specific SPC included a beta-blocker, mineralocorticoid receptor antagonist (MRA), and SGLT2 inhibitor (61.2%).Among patients, polypharmacy was common (70% taking ≥6 drugs daily), and 75% admitted to occasional non-adherence. Most responders (82%) would support a solution that reduces the pill burden, and 83% would take an HF-specific SCP if offered, particularly if there is no extra cost.

Conclusion: Both physicians and patients showed strong openness and willingness towards an HF-specific SPC, supporting further development and evaluation of HF-specific polypill strategies.

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.

Background and aims: Patients with heart failure and preserved ejection fraction (HFpEF) experience significant exercise intolerance, yet its underlying mechanisms remain poorly defined and are multifactorial. Iron deficiency (ID) occurs frequently in HFpEF and may contribute to exercise impairment. This study evaluated mitochondrial oxidative muscle metabolism in HFpEF using in vivo  31phosphorus magnetic resonance spectroscopy (31P-MRS) employing two exercise protocols, and assessed whether ID influences exercise energetics.

Methods: In this parallel analysis of prospective studies at two sites, patients with HFpEF and control individuals performed either isometric exercise (isolated leg protocol) or dynamic exercise (cardiopulmonary protocol) with concomitant phosphocreatine recovery assessment using in vivo  31P-MRS. Associations between clinical factors and oxidative metabolism were evaluated. ID was defined as ferritin <100 µg/L, or ferritin 100-299 µg/L with transferrin saturation <20%.

Results: Fifty-eight patients with HFpEF and 16 controls performed isometric exercise (n = 46 HFpEF; n = 16 control) or cardiopulmonary exercise (n = 12 HFpEF). Phosphocreatine recovery halftime after isometric exercise was prolonged in patients versus controls [27 (23-32) vs 24 (19-28) seconds, respectively; P = .03]. Phosphocreatine recovery halftime after dynamic exercise in patients was 39 (27-57) seconds. Both cohorts consisted of patients with and without ID (n = 19 and 27, and n = 6 and 6, respectively), who had comparable exercise and oxidative muscle capacity (all P > .42). High-sensitive C-reactive protein was associated with prolonged phosphocreatine recovery halftime (P =. 01).

Conclusions: Patients with HFpEF exhibit impaired whole-muscle oxidative capacity of skeletal muscle, as shown by two different 31P-MRS protocols with upper leg measurements, independent of ID status.

Study registration: NTR6605, NTR7297 (https://onderzoekmetmensen.nl/nl/trial/55673); NCT05750940 (https://clinicaltrials.gov/study/NCT05750940).

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) improve outcomes in patients with heart failure (HF) and are recommended to be initiated in the 6 weeks following an HF hospitalization. We aimed to explore prescription rates and clinical benefits of SGLT2is among patients with newly diagnosed HF and reduced ejection fraction (HFrEF) in real-world practice.

Methods: We conducted a retrospective analysis using the TriNetX Global Collaborative research network. Patients with HFrEF who experienced their first HF hospitalization between September 2021 and December 2023 were identified and were categorized into two groups based on the initiation of SGLT2is within 6 weeks following HF hospitalization. After using propensity score matching to baseline characteristics, Cox hazard ratios (HRs) were calculated to compare outcomes over a 1-year period.

Results: Among the identified 70 042 patients with HFrEF, 21.3% were initiated on SGLT2is within 6 weeks following their first HF hospitalization. Sodium-glucose cotransporter-2 inhibitor users were younger, more likely to be male, and had a higher prevalence of diabetes, compared with SGLT2i non-users. After matching, 14 670 matched pairs were created (mean age 64 ± 17 years; 41.6% female; 20% Black). Sodium-glucose cotransporter-2 inhibitor users vs non-users had a lower risk of 1-year all-cause mortality [HR, 95% confidence interval (CI) = 0.75, 0.69-0.83], all-cause hospitalizations (HR, 95% CI = 0.86, 0.83-0.91), and emergency department visits (HR, 95% CI = 0.91, 0.86-0.96).

Conclusion: In this large multinational real-world data of patients with HFrEF, the prescription rate for SGLT2is within 6 weeks after the first HF hospitalization remained low. However, SGLT2i initiation was associated with improved outcomes, underscoring the importance of guideline-recommended early use.