ESC Heart Failure最新文献

Aims: The interstitial space is the major compartment in which the excess fluid is located, forming peripheral congestion in acute decompensated heart failure (ADHF). The lymphatic system is responsible for the constant drainage of the compartment. In ADHF, the inefficiency of this system causes extravascular fluid accumulation, underscoring the crucial role of lymphatic system failure in ADHF's pathophysiology. The eLym™ System is a transcutaneous device designed to facilitate lymph drainage by creating a low-pressure zone in the thoracic duct area, theoretically allowing more efficient decompression of the lymphatic system.

Methods and results: The safety and feasibility of the eLym™ System for the Decongestion of Excess Lymphatic Fluid via the Thoracic Duct in Acute Decompensated Heart Failure: DELTA-HF Study is a prospective, multicentre, single-arm study designed to evaluate the safety and feasibility of the WhiteSwell eLym™ System in the treatment of fluid overload in ADHF. A maximum of 50 subjects may be enrolled and undergo the treatment. Inclusion criteria include the presence of congestion, a home diuretic dose ≥80 mg furosemide (or equivalent) and elevated natriuretic peptides. The key exclusion criteria include anatomical abnormalities and the inability to undergo systemic anticoagulation. The study endpoints include the safety (short- and long-term) and feasibility of the procedure. Several congestion indexes will be prospectively assessed. Descriptive statistics will summarize the study results. The study was registered in clinicaltrial.gov (NCT05747196).

Conclusions: The results of the DELTA-HF study will provide information about the safety and feasibility of the eLym™ System and will provide first-in-human clinical signals of its use in ADHF patients.

Aims: Few data are available regarding the role of tricuspid annulus plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP), a measurement of right ventricular to pulmonary artery coupling, in patients with chronic heart failure and left ventricular systolic dysfunction.

Methods and results: This retrospective single-centre study included outpatients with left ventricular systolic dysfunction (ejection fraction ≤ 50%) evaluated between January 2022 and December 2022. TAPSE/PASP was evaluated as a continuous variable and as tertiles according to its value on the first visit. The primary outcome of the study was a composite of all-cause mortality or heart failure (HF) events at the last available follow-up.

Results: A total of 642 patients were included (mean age 71 ± 13 years, 78% male, mean left ventricular ejection fraction 40% [interquatile range 35-46]). Patients with lower TAPSE/PASP had more co-morbidities (i.e., atrial fibrillation, chronic kidney disease or previous cardiovascular implantable electronic device), an higher New York Heart Association class (P < 0.001), more signs of congestion (P = 0.007), and had more probability to receive intravenous furosemide during the visit (P < 0.001). After a median follow-up of 474 days [interquartile range 392-507 days], a total of 51 patients (8.0%) died (with 24 patients [3.8%] experiencing cardiovascular-related deaths), a total of 179 patients (28.1%) experienced a composite outcome, and 158 patients (24.8%) had HF events. Kaplan-Meier analysis showed that the estimated 1-year rate of the primary outcome was higher in the lowest tertile (38.0%), as compared with the intermediate (19.6%) and highest tertiles (14.9%; P-value log-rank <0.001). TAPSE/PASP ratio as a continuous variable was independently associated with the primary outcome (adjusted hazard ratio for 0.1 mm/mmHg increase 0.91, 95% CI 0.84-0.98, P = 0.009), predominantly driven by a higher risk of HF events during follow-up. Analysing the impact of TAPSE/PASP tertiles on the primary outcome, an independent associated was confirmed at multivariate analisys for the highest versus lowest tertile (adjusted hazard ratio 0.61, 95% CI 0.38-0.99, P = 0.044).

Conclusions: TAPSE/PASP was independently associated with mortality or HF events among ambulatory patients with left ventricular systolic dysfunction.

Aims: Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve health status and outcomes in the setting of heart failure (HF) across the range of ejection fraction (EF). Baseline kidney disease is common in HF, complicates HF management and is strongly linked to worse health status. This study aimed to assess whether the treatment effects of dapagliflozin on health status vary based on estimated glomerular filtration rate (eGFR).

Methods and results: We conducted a pooled participant-level analysis of two double-blind, randomized trials, DEFINE-HF (n = 236) and PRESERVED-HF (n = 324), which evaluated dapagliflozin versus placebo. Both multicentre studies enrolled adults with HF, New York Heart Association Class II or higher, elevated natriuretic peptides, and an EF < 40% in DEFINE-HF or >45% in PRESERVED-HF. The primary exposure was eGFR. The main outcome was the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at 12 weeks. Across both trials, there were 583 (99.3%) participants with a baseline eGFR. The median (25th, 75th) eGFR was 59 (46, 77) mL/min/1.73 m². Dapagliflozin improved KCCQ-CSS at 12 weeks [placebo-adjusted difference, +5.0 points, 95% confidence interval (CI) 2.6-7.5; P < 0.001], and this was consistent in participants with an eGFR ≥ 60 (+6.0 points, 95% CI 2.4-9.7; P = 0.001) and eGFR < 60 (+4.1 points, 95% CI 0.5-7.7; P = 0.025) (P interaction = 0.46). The benefits of dapagliflozin on KCCQ-CSS remained robust across eGFR when modelled as a continuous variable (P interaction = 0.48).

Conclusions: Dapagliflozin led to early and clinically meaningful improvements in health status in HF patients, regardless of EF or baseline eGFR.

Aims: Sacubitril/valsartan (Sac/Val) is used for treatment of heart failure. The effect of Sac/Val on regional dysfunction following myocardial infarction (MI) remains uncertain. This study aimed at understanding the effects of Sac/Val on regional function after MI.

Methods and results: MI or sham surgery was performed in Sprague-Dawley rats. Animals were randomized to treatment with Sac/Val, valsartan (Val) or vehicle (Veh). Magnetic resonance imaging was used to acquire left ventricular volumes and strain. Left ventricular tissue was obtained for wesern blotting, PCR and Masson's trichrome staining. Isolated cardiac fibroblasts were cultured with Veh, atrial natriuretic peptide (ANP), adrenomedullin (ADM) and sacubitrilat, and collagen expression assessed with droplet digital PCR.

Results: Sac/Val reduced ventricular end-diastolic volume by 18% compared with Veh, and preserved circumferential systolic strain in the zone proximal to infarction compared with sham after 42 days of treatment (peak strain ± SEM: sham: -0.19 ± 0.01%; Sac/Val: -0.14 ± 0.02%; Val: -0.10 ± 0.02%; Veh: -0.10 ± 0.02%). Masson's trichrome staining demonstrated lower fibrotic deposition in the intermediate zone with Sac/Val treatment than Veh (sham: 2.29 ± 0.17%; Sac/Val: 2.31 ± 0.27%; Val: 3.22 ± 0.60%; Veh: 4.14 ± 0.48%). The amounts of the pro-apoptotic caspase 3 cleavage fragments p19/17 were 89% higher in Val than sham, with Sac/Val showing no significant increase compared with sham. Collagen expression in human fibroblast culture was lower in cells co-treated with sacubitrilat and ANP, an effect not observed with sacubitrilat/ADM co-treatment.

Conclusions: Sac/Val preserves in vivo myocardial function in the region most proximal to MI in rats and reduces left ventricular dilatation. These effects may be related to a reduction in both fibrosis and pro-apoptotic signalling.

Aims: Blood levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) may be modified by low renal clearance and anaemia. The aim of this study was to investigate the impact of the blood NT-proBNP level on cardiovascular and renal outcomes in patients with these two manifestations.

Methods: This post hoc analysis stemmed from the oBservational clinical Research In chronic kidney disease patients with renal anemia: renal proGnosis in patients with Hyporesponsive anemia To Erythropoiesis-stimulating agents, darbepoetiN alfa (BRIGHTEN) trial, a large prospective study involving patients with non-dialysis kidney disease experiencing anaemia. The Pearson correlation coefficient was employed to examine the association of baseline NT-proBNP level with renal function or anaemia. Longitudinal assessment of the association of baseline blood NT-proBNP levels with cardiovascular outcomes (cardiac death, acute coronary syndrome, hospitalization due to heart failure or fatal arrhythmia) and renal outcomes [the initiation of maintenance dialysis, kidney transplantation, a 50% decrease in the estimated glomerular filtration rate (eGFR) or an eGFR of ≤6 mL/min/1.73 m²] was conducted by using restricted cubic spline analysis and Cox proportional hazard model analysis.

Results: In total, this study included 1484 patients [mean age, 70.2 ± 11.8 years; women, 40.6%; eGFR, 20.3 ± 9.6 mL/min/1.73 m²; haemoglobin (Hb) level, 9.8 ± 0.9 g/dL]. Baseline NT-proBNP levels were a median of 496.0 pg/mL [inter-quartile range: 235.0-1090.0 pg/mL]. A weak association existed between NT-proBNP levels, on a logarithmic scale, and eGFR (r = -0.131, P < 0.001) or Hb levels (r = -0.182, P < 0.001) at baseline. During 2.29 ± 0.89 years, 92 cardiovascular and 573 renal events were recorded. After adjusting for potential confounders such as eGFR and blood Hb level, a nonlinear relationship existed between blood NT-proBNP levels and cardiorenal outcomes. Patients with a baseline NT-proBNP level ≥1000 and 500-1000 pg/mL exhibited a greater risk for cardiovascular outcomes than did patients with an NT-proBNP level <250 pg/mL {hazard ratio [HR] = 8.10 [95% confidence interval (CI), 2.80-23.40] and 3.35 [95% CI, 1.10-10.18], respectively}. These patients also exhibited a moderate risk for renal outcomes [HR = 1.77 (95% CI, 1.36-2.31) and 1.54 (95% CI, 1.19-2.00), respectively].

Conclusions: NT-proBNP provides prognostic insights into cardiovascular and renal outcomes among patients with advanced chronic kidney disease experiencing anaemia.

Aims: The extent of irreversible cardiomyocyte necrosis after acute myocardial infarction (AMI) is a major determinant of residual left ventricular (LV) function and clinical outcome. Cell therapy based on CD34+ cells has emerged as an option to help repair the myocardium and to improve outcomes. The dose of CD34+ cells and the route of administration are two important factors that will determine the clinical effectiveness of the approach, provided it is robust and feasible. Here, we describe the rationale and design of the multicentre open-label randomized controlled phase I/IIb trial evaluating the safety and the likelihood of efficacy of transendocardial expanded CD34+ cell administration in patients presenting with AMI and a reduced LV ejection fraction.

Methods: Patients with a large AMI and LV ejection fraction <50% are randomized 3:1 to transendocardial expanded CD34+ cell injection plus standard of care or standard of care alone. Patients randomized to intervention are treated with lenograstim for 5 days before 220 ± 10 mL blood cell harvest from which autologous CD34+ cells are purified and expanded for 9 days using an automated good manufacturing practice compliant platform. The primary endpoint is the incidence of major adverse cardiac events over 6 months. The main secondary endpoints are LV end systolic volume index and the viability of the infarcted segments.

Conclusions: Autologous CD34+ cell therapy is currently limited by technological constraints. This is the first trial to evaluate the feasibility and potential effect of CD34+ cells after automated expansion and transendocardial administration in patients with large AMI.

Aims: This study aimed to evaluate the change of the main electrocardiographic (ECG) characteristics and their prognostic role across the main subtypes of cardiac amyloidosis [light-chain amyloidosis (AL) and hereditary (ATTRv) and wild-type transthyretin amyloidosis (ATTRwt)].

Methods and results: This multicentre, retrospective study was performed in six referral centres for cardiac amyloidosis. Clinical and ECG data were collected at the first and last evaluations. Three hundred fifty-six patients were included (AL, n = 105; ATTRv, n = 50; ATTRwt, n = 201). The median age was 76 (67-81) years, and 271 (74%) were men. At baseline, patients with ATTRwt showed a higher prevalence of conduction abnormalities compared with those with AL [first-degree atrioventricular block, n = 51 (40%) vs. n = 13 (34%), P < 0.01; left bundle branch block, n = 23 (11%) vs. n = 2 (2%), P < 0.01], and patients with AL more often had low QRS voltage [n = 58 (55%); in ATTRv, n = 17 (34%); in ATTRwt, n = 67 (33%), P value < 0.01] and T wave inversion compared with those with ATTR [n = 39 (37%); in ATTRv, n = 9 (18%); in ATTRwt, n = 37 (18%)]. After a median follow-up of 15 (8-26) months, the adjusted differences in mean PR, QRS interval, total, peripheral, and precordial QRS scores were similar across subtypes of amyloidosis (P value for linear regression > 0.05). The adjusted odds ratios for the development of right bundle branch block were higher in AL compared with ATTRwt [odds ratio 4.7 (95% confidence interval 1.5-15), P < 0.05]. QRS duration at baseline remained independently associated with patient survival in the overall population even after adjustment for relevant clinical variables [hazard ratio 1.78 (95% confidence interval 1.13-2.8), P < 0.01].

Conclusions: The progression of the ECG abnormalities seems similar across amyloidosis subtypes. QRS duration could be a marker of more advanced disease.

Aims: ZSF1 obese rats harbouring two mutant leptin receptor alleles (Lepr^cp and Lepr^fa) develop metabolic syndrome and heart failure with preserved ejection fraction (HFpEF), making them a widely used animal model in cardiometabolic research. Studies using ZSF1 rats have contributed significantly to the elucidation of pathophysiological mechanisms underlying HFpEF and therapeutic strategies against this multi-organ syndrome. In contrast, hybrid, lean ZSF1 rats (L-ZSF1) do not develop HFpEF and generally serve as controls, disregarding the possibility that the presence of one mutant Lepr allele might affect left ventricular ejection fraction (LVEF), diastolic dysfunction and other relevant HFpEF parameters, such as N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and cardiac inflammation, which could increase during disease manifestation.

Methods and results: We collected specimens and echocardiography data of male and female L-ZSF1 rats (n = 165; ZSF1-Lepr^faLepr^cp/Crl) at the age of 6-32 weeks from four independent research groups and performed genotyping as well as the genotype-phenotype analyses. The genotype distribution within L-ZSF1 was in line with the Hardy-Weinberg equilibrium. Genotypes were not associated with CD68 counts (n = 52, P = 0.886), E/e' ratio (n = 125, P > 0.250) and NT-proBNP (n = 126, P = 0.874). LVEF significantly decreased from 25 weeks of age (P = 0.021) but was independent of the genotype (P = 0.768 at <25 weeks of age and P = 0.069 at ≥25 weeks of age, n = 128).

Conclusions: In conclusion, validation of the genotype distribution in L-ZSF1 rats revealed no associations between the genotype and HFpEF-relevant measures, namely, NT-proBNP, CD68 count, LVEF or E/e'.

Aims: Understanding heart failure (HF) characteristics is essential to improve patient outcomes. Categorizing HF beyond left ventricular ejection fraction (LVEF) is challenging due to heterogeneous clinical presentation and aetiologies. Despite global studies on HF, the role of LVEF on mortality remains controversial. We explored the association of LVEF with mortality, considering sex differences and comorbidities in a cohort from the largest tertiary cardiovascular centre in Switzerland.

Methods: HF patients admitted to the University Hospital of Bern from January 2015 to December 2019 were evaluated. LVEF was used to classify patients into HF with preserved ejection fraction (HFpEF), HF with mid-range ejection fraction (HFmrEF) and HF with reduced preserved ejection fraction (HFrEF) categories. Cox proportional hazard models and time-stratified analyses adjusted for potential confounders were employed.

Results: A total of 5824 HF patients were included, and 2912 died over a median follow-up time of 3.39 years. Mortality rates across LVEF categories showed no significant differences, while overall, women showed significantly higher mortality; 30 day mortality was lower in the HFpEF category [hazard ratio (HR) 0.67, 95% confidence interval (CI): 0.52-0.88, P = 0.003], with persistent effects upon stratification in males (HR 0.59, 95% CI: 0.42-0.81, P < 0.001) and non-diabetics (HR 0.62, 95% CI: 0.44-0.87, P = 0.005). An isolated reduction in HFpEF mortality was observed in females after 1 year (HR 0.72, 95% CI: 0.53-0.98, P = 0.035).

Conclusions: The prognostic role of LVEF on all-cause mortality remains unclear, while differences in mortality rate distribution between women and men mirror established HF pathophysiological sex differences. Future HF studies should focus on HF aetiology and include measures beyond LVEF for comprehensive characterization.

Aims: Renin-angiotensin-aldosterone system inhibitors (RAASi) are foundational in the management of heart failure (HF) and chronic kidney disease (CKD) but increase the risk of hyperkalaemia. To facilitate continuation of RAASi therapy, guidelines suggest managing hyperkalaemia using newer potassium binders such as sodium zirconium cyclosilicate (SZC). This observational study describes the likelihood of continued RAASi therapy by duration of SZC treatment.

Methods: The study population included non-dialysis-dependent adults diagnosed with HF and/or CKD who initiated outpatient SZC treatment while receiving RAASi therapy. Patients were identified using healthcare registers and claims data from the United States, Japan and Spain. SZC treatment duration was described using the Kaplan-Meier method. Hernán's clone-censor-weight (CCW) approach, using principles of trial emulation, was applied to evaluate the likelihood of continued RAASi therapy at specific time points by distinct SZC treatment durations, using a weighted Kaplan-Meier method and Z-tests.

Results: The study included 7980 patients, from the United States (n = 4849), Japan (n = 2759) and Spain (n = 372). Across the three countries, mean patient age was 73.1-75.0 years, 53.2%-66.4% of patients were male, 39.0%-75.0% had HF and 76.9%-95.3% had CKD. Between Days 30 and 120, the percentage of patients remaining on SZC treatment decreased from 36.5% to 12.8% in the United States, from 63.8% to 33.7% in Japan, and from 81.9% to 65.0% in Spain. In the United States, patients who continued SZC treatment beyond 30 days had a higher likelihood of continuing RAASi therapy for up to 90 days (P < 0.001), and continuing SZC treatment beyond 60 days was superior for continuing RAASi therapy for up to 6 months (P < 0.001), versus earlier SZC discontinuation. At 120 days, the likelihood of remaining on RAASi therapy was 69%-70% for SZC treatment durations exceeding 60 days, versus 59% for shorter durations (1-30 days) (P < 0.001). Similar patterns were observed in Japan. At 120 days, the likelihood of remaining on RAASi therapy was 86%-87% for SZC treatment durations exceeding 90 days, versus 82% for shorter SZC treatment durations (1-30 days) (P < 0.05). The CCW analyses were not deemed feasible in the Spanish dataset due to the smaller initial sample size and few patients having a relatively short SZC treatment duration.

Conclusions: Patients with longer SZC treatment experience sustained protection against RAASi discontinuation, and the risk of RAASi discontinuation resumes once SZC is discontinued.