ESC Heart Failure最新文献

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: Multicenter 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 analyzed with Kaplan-Meier and Cox models.

Results: NT-proBNP decreased from 1,000 (494-2,333) to 751 (304-1,726) and 735 (215-1,980) pg/mL (p<0.001). KCCQ improved from 53±15 to 62±14 and 66±15 (p<0.001). LVEF increased from 32±7 to 36±8 and 37±9% (p<0.001) and GLS improved from -10.8±3.2 to -12.3±3.1 and -14.0±2.9% (p<0.001). 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=0.013 and p=0.014). In multivariable Cox analysis, S/V discontinuation (HR 1.52, 95% CI 1.28-1.97; p=0.040), change in GLS (HR 0.81, 95% CI 0.67-0.98; p=0.028) and change in KCCQ (HR 0.95, 95% CI 0.92-0.98; p=0.001) were independently associated with MACE.

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

Background: Left ventricular reverse remodeling (LVRR) is a key objective of contemporary heart failure (HF) therapies and is characterized by reversal of left ventricular (LV) dilation and dysfunction.

Objectives: To report the incidence and clinical impact of early (30-day) LVRR patients with primary (PMR) and secondary mitral regurgitation (SMR) treated with mitral transcatheter edge-to-edge repair (M-TEER), and to identify independent associations with early LVRR.

Methods: The EXPANDed cohort includes 2205 patients treated with M-TEER from the EXPAND and EXPAND G4 studies. Patients were classified as having early LVRR if they demonstrated a >10% reduction in LV dimension or volume from baseline to 30 days. All LV measurements were assessed by independent echocardiographic core laboratories.

Results: Among 527 SMR patients, 338 patients (64.1%) experienced early LVRR after M-TEER. At 1 year, SMR patients with early LVRR had significantly lower rates of death or HF hospitalizations compared to those without (early LVRR: 24.7% vs no early LVRR: 35.9%, p=0.009), despite similar MR reduction (both ≥93% in both groups) and comparable improvements in functional status (NYHA≤II ≥78%) and quality of life (∼20-points improvement per KCCQ-OS). Independent associations with early LVRR included hypertension (OR=1.96, p=0.004), absence of prior cardiac surgeries (OR=0.51, p=0.002), and smaller LV end-systolic volume (OR=0.81, p=0.002).Among 536 PMR patients, 391 (73.0%) experienced early LVRR at 30 days. At 1 year, PMR patients with early LVRR group had similar clinical (composite all-cause mortality or HF hospitalization: early LVRR: 14.5% vs no early LVRR: 17.1%, p=0.47) and symptomatic outcomes (≥83% NYHA≤II; ∼19-point improvement per KCCQ-OS) compared to those without. However, among PMR patients with dilated ventricles, early LVRR group was associated with significantly lower all-cause mortality (early LVRR: 3.8%, no Early LVRR: 14.0%, p=0.028).

Conclusions: Regardless of etiology, most patients experienced early LVRR after M-TEER with significant MR reduction and symptom relief. In SMR patients, early LVRR was associated with lower rates of HF hospitalization and death.

Aims: 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: Analysis 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 < 0.0001), more frequently female (47.7% vs. 35.8%, p = 0.0013) and Black (42.8% vs. 14.4%, p < 0.0001), with lower NT-proBNP concentrations (p<0.0001). 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=0.078). Changes in cDPP3 were not associated with NT-proBNP reduction (continuous p=0.797; ≥30% responder p=0.990). In pooled multivariable analysis, MRA use was independently associated with cDPP3 ≥40 ng/mL (OR 3.83; 95% CI 1.47-9.96; p = 0.006), whereas non-Black ethnicity was associated with lower odds (OR 0.43; 95% CI 0.29-0.64; p < 0.0001).

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.

Aims: 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 = 0.009) and NT-proBNP (-35%, p < 0.001). During the acute protocol, both BNP and NT-proBNP increased significantly over time (timepoint effect p < 0.001), with parallel trajectories before and after S/V initiation and no visit-by-time interaction (p = 0.17 for BNP; p = 0.95 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: Glucagon-like peptide-1 receptor (GLP1R) agonists reduce cardiovascular events in patients with obesity and diabetes, and recent trials demonstrate symptomatic and functional benefits in heart failure with preserved ejection fraction (HFpEF). Whether these benefits reflect glycaemic control, weight reduction, or additional mechanisms remains uncertain.

Methods: We performed drug-target Mendelian randomization (MR) using genetic variants in the GLP1R locus to proxy GLP1R activation. MR estimates for GLP1R agonism were scaled to per 0.1 log-odds lower liability to type 2 diabetes (T2DM) and compared with general type 2 diabetes (T2DM) or body mass index (BMI) lowering effects. Summary statistics were obtained from the largest available GWAS of HF, non-ischaemic HF (ni-HF), ni-HFpEF, ni-HFrEF, and atrial fibrillation (AF). Primary inverse-variance weighted analysis was adjusted for multiple testing and validated via weighted median and MR-Egger sensitivity analyses.

Results: Genetically proxied GLP1R activation was associated with lower risk of overall HF (OR 0.96 [95% CI 0.95-0.98], p=0.0002), ni-HF (0.94 [0.91-0.96], p=0.0001), and ni-HFpEF (0.82 [0.74-0.90], p=0.0001) per 0.1 log-odds lower T2DM liability. The GLP1R-proxied effects were greater than those expected from glycaemic lowering alone and were of comparable magnitude to those from BMI reduction. Associations for ni-HFrEF were directionally adverse but not significant. AF showed a nominal, exploratory association consistent with BMI lowering and driven by a single cis-BMI variant.

Conclusions: This study provides genetic support for a protective association between GLP1R activation and HF, particularly ni-HFpEF, with effects beyond glycaemia. The magnitude and subtype specificity are consistent with contemporary trial evidence and support further evaluation of GLP1R agonism in cardiometabolic HFpEF.

Aims: Greater sodium avidity in acute heart failure (AHF) is associated with worse outcomes, but whether kidney tubule injury is associated with sodium avidity and impaired diuretic responsiveness remains underexplored.

Methods: We evaluated 339 participants from the ROSE-AHF trial, which enrolled patients hospitalized for AHF with kidney dysfunction and randomized them to the dopamine, nesiritide or placebo group. Urinary kidney injury molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) were measured at enrollment. Associations between these biomarkers and urinary sodium (uNa) concentration at baseline, fractional excretion of sodium (FeNa), as well as total uNa output and urine output over 72-hours were assessed using multivariable regression models.

Results: Higher KIM-1 and NAG values at baseline were associated with lower uNa concentration at baseline (-6.1% [-8.5%, -3.7%], p < 0.001 and -5.9% [-9.2%, -2.6%], p = 0.001, respectively, per two-fold increase in each biomarker). Higher baseline KIM-1 and NAG were also associated with lower FeNa (-6.1% [-8.5%, -3.6%], p < 0.001 and -5.2% [-8.6%, -3.6%], p = 0.001, respectively, per two-fold increase in each biomarker). Higher baseline KIM-1 was associated with lower total uNa excretion over 72-hours (-3.6% [-6.8%, -0.2%], p = 0.037 per two-fold increase). None of the biomarkers were associated with urine output over 72-hours.

Conclusion: Kidney tubular injury, as assessed by urine KIM-1 and NAG, is associated with greater sodium avidity and higher KIM-1 is associated with impaired diuretic responsiveness in AHF.

Background and aims: We have previously shown an association between metabolic syndrome (MS) and heart failure (HF) outcomes in patients with implanted defibrillators (ICD) or cardiac resynchronization therapy (CRT-D). However, the role of MS in predicting outcomes was not assessed in non-obese patients. We aimed to examine how the presence of MS and its components predicts the risk of HF/death in non-obese ICD or CRT-D patients.

Methods: We included obese and non-obese patients, enrolled in Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT). Patients needed at least 2 of the 3 criteria, dyslipidemia, diabetes, or hypertension, to be considered for having MS. Kaplan-Meier analyses were used to assess the rate of HF/death by MS. Multivariate Cox-proportional analyses were performed to assess the risk of HF/death by MS.

Results: From 1,180 (65%) non-obese patients in MADIT-CRT, 672 (57%) presented with MS. Among non-obese patients with MS, 284 (42%) had diabetes mellitus. Non-obese MS patients had a significantly higher, 34% cumulative probability of HF/death at 3 years, as compared to the 20% of non-obese patients without MS (log-rank p<0.001) (Hazard Ratio: 1.64, 95% CI: 1.15-2.32, p=0.006). Within non-obese MS patients, those with diabetes had a significantly higher rate of HF/death with 28% vs. 20% in non-diabetics at 2.5 years (log-rank p<0.001). Reverse remodeling was similar in all subgroups.

Conclusions: Metabolic syndrome in non-obese ICD or CRT-D patients is associated with a higher risk of HF/Death, most prominent in those with diabetes, necessitating early intervention.