ESC Heart Failure最新文献

Aims: The study aims to investigate the impact of immigration status on short- and long-term outcomes in patients hospitalized with acute decompensated heart failure (ADHF).

Methods: We conducted a retrospective cohort study at a single centre, analysing 7457 patients admitted for ADHF between 2007 and 2017, with follow-up until 2020 (mean 3.7 ± 3.5 years). Patients were categorized as immigrants (born abroad, 78.1%) or natives (born in Israel, 21.9%). Outcomes included in-hospital mortality, 30 day readmissions, 30 day mortality, 1 year mortality and 5 year all-cause mortality. Kaplan-Meier survival curves, a nonparametric analysis, were used to estimate survival probabilities across multiple timeframes while multivariable logistic and Cox regression analyses adjusted for key covariates such as age, sex and comorbidities. A stratified analysis compared outcomes between adulthood and early-life immigrants.

Results: Immigrants were older than natives (79.0 ± 10.1 vs. 70.8 ± 13.8 years, P < 0.001) and more likely to be female (53.2% vs. 45.0%, P < 0.001). Adjusted analyses revealed that immigration status was independently associated with higher 30 day [odds ration (OR) 1.37, 95% CI 1.12-1.67, P = 0.002], 1 year [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.19-1.52, P < 0.001] and 5 year mortality (HR 1.20, 95% CI 1.12-1.29, P < 0.001). No significant associations were found for in-hospital mortality (OR 1.26, 95% CI 0.98-1.63, P = 0.07) or 30 day readmissions (OR 0.93, 95% CI 0.79-1.08, P = 0.31). Stratification by immigration age showed similar 5 year mortality between adulthood and early-life immigrants.

Conclusions: Immigration status independently predicts worse short- and long-term outcomes in ADHF patients. The findings highlight the need for tailored healthcare policies to address disparities and improve outcomes in immigrant populations.

Aims: Pulmonary arterial hypertension (PAH) is often diagnosed in elderly patients with comorbidities. Although initial monotherapy is recommended for these patients, the value of combination therapy remains unclear. Here, we compare the efficacy of initial monotherapy and combination therapy in PAH patients with cardiovascular comorbidities.

Methods and results: Data from adult patients with incident pre-capillary PAH and cardiovascular comorbidities from the COMPERA database (European registry for PH) were analysed. A matched-pair analysis of patients treated with monotherapy versus combination therapy based on age, sex, WHO functional class (FC) and 4-strata risk at baseline was performed. The matching strategy identified 216 pairs of PAH patients with cardiovascular comorbidities, who differed considerably from the enrolled patient population (n = 1871), especially in terms of mean age (mono: matched pairs 62.9 ± 13.5 years vs. 70.6 ± 11.4 years, combination: matched pairs 62.0 ± 13.6 years vs. 60.5 ± 14.9 years). In the matched-pair analysis, the initial combination therapy group showed more pronounced improvements in WHO-FC, N-terminal pro-B-type natriuretic peptide (BNP/NT-proBNP) and risk status than patients treated with initial monotherapy, with no significant differences in 6-min walk distance (6MWD), PAH-related hospitalisations, survival and drug discontinuation.

Conclusions: This analysis suggests that PAH patients with comorbidities may benefit more pronounced from combination therapy regarding WHO-FC, BNP/NT-pro-BNP and risk status without a significant difference in survival. Good tolerability is indicated. However, given the relatively younger patient matched subgroup, these findings may not necessarily apply to older patients with a wider range of comorbidities.

Aims: Electron microscopy reveals microstructural alterations in cardiomyocyte nuclei and myofilaments in non-ischaemic cardiomyopathy (NICM), particularly in dilated cardiomyopathy (DCM). Nevertheless, the correlation between such observations and clinical outcomes, including prognosis and left ventricular reverse remodelling (LVRR), remains unclear. This study aimed to examine the association between electron microscopic findings and outcomes in patients with NICM.

Methods: In this multicentre, prospective, observational study, 170 patients with NICM with reduced ejection fraction (EF) < 40%, scheduled for diagnostic endomyocardial biopsy and optimization of medical therapies, were enrolled. Electron microscopic findings of cardiomyocytes such as discontinuous or continuous nuclear envelopes and injured or preserved myofilaments were evaluated. Data on cardiac events (cardiac death or left ventricular assist device implantation) and LVRR, defined as achieving an EF > 35% with a 10% unit absolute increase, were collected 1 year post-biopsy.

Results: A total of 148 patients were finally analysed. Discontinuous nuclear envelopes and myofilament injuries were observed in 17 (11%) and 46 (31%) patients with NICM, respectively. The incidence of cardiac events at 1 year did not differ between groups with discontinuous and continuous nuclear envelopes [12% vs. 6%, odds ratio (OR): 2.05, 95% confidential interval (CI): 0.40-10.6, P = 0.391], whereas the LVRR rate was significantly lower in the discontinuous group than in the continuous group (24% vs. 52%, OR: 0.29, 95% CI: 0.08-0.92, P = 0.036). The incidences of cardiac events and LVRR at 1 year differed between the injured and preserved myofilament groups (15% vs. 3%, OR: 6.64, 95% CI: 1.32-33.5, P = 0.022; 15% vs. 64%, OR: 0.10, 95% CI: 0.04-0.25, P < 0.001, respectively). These associations between electron microscopic findings and clinical outcomes persisted, even in patients who were finally diagnosed with DCM.

Conclusions: Discontinuous nuclear envelopes were associated with a reduced LVRR rate, whereas injured myofilaments were correlated with higher 1 year cardiac events and a decreased LVRR. Evaluation of electron microscopic images in diagnostic endomyocardial biopsy can facilitate risk stratification of NICM or DCM with reduced EF.

Aims: It was recently demonstrated that the intracellular signalling phosphatase calcineurin is subject to cleavage by the protease calpain, resulting in a truncated calcineurin fragment that is a strong inductor of myocardial hypertrophy. We now address the question of whether inhibition of calpain function in cardiomyocytes, and thereby prevention of calcineurin truncation, attenuates development of myocardial hypertrophy.

Methods and results: We generated a transgenic mouse model with conditional cardiac calpastatin overexpression (CAST OE) and compared their cardiac hypertrophic response to angiotensin-II (AngII) with that of non-induced control animals. Angiotensin-II osmotic mini-pumps were removed 3 weeks after implantation and cardiac hypertrophy was re-evaluated 3 weeks after pump removal. Induction of calpastatin overexpression resulted in 88% inhibition of calpain activity and suppressed calcineurin truncation. In CAST OE mice, basal phenotype and AngII-induced myocardial hypertrophy were comparable with non-induced controls (mean heart to body weight ratios ± SD in milligrams per gram: CAST OE, 4.8 ± 0.4; CAST OE + AngII, 7.1 ± 0.5; non-induced, 4.9 ± 0.4; non-induced + AngII, 7.2 ± 0.4). However, CAST OE mice demonstrated a complete reversal of hypertrophy when angiotensin-II was removed, whereas hypertrophy persisted in non-induced controls (CAST OE 5.0 ± 0.5; non-induced 7.0 ± 0.4; P < 0.0001). Persistent hypertrophy in controls was accompanied by nuclear accumulation of truncated calcineurin and elevated activity of the Nuclear Factor of Activated T-cells pathway. Moreover, we found that truncated calcineurin was insufficiently ubiquitinylated compared with its full-length form and thus escaped degradation over several weeks in our in vivo experiments.

Conclusions: Our data demonstrate that calpain-mediated cleavage results in nuclear accumulation of a truncated, constitutively active and degradation-resistant calcineurin isoform that sustains a long-term myocardial hypertrophic response to angiotensin-II beyond withdrawal of the stimulus. Cardiomyocyte specific calpain inhibition by transgenic calpastatin overexpression prevented the post-stimulus myocardial hypertrophic response.

Background: The neutrophil-to-lymphocyte ratio (NLR) may be a useful marker of inflammation, but its associations with clinical characteristics, signs of congestion and outcome in patients with chronic heart failure (HF) are unknown.

Methods and results: We enrolled 4702 ambulatory patients with HF and either left ventricular systolic dysfunction or high N-terminal pro-B-type natriuretic peptide (NTproBNP) (≥125 ng/L). Compared with those in the lowest quartile of NLR (≤2.05), patients in the highest quartile (≥4.10) were older, had higher NTproBNP, and were more likely to have HF with reduced left ventricular ejection fraction (HFrEF), atrial fibrillation and to be treated with loop diuretics. In 813 patients with detailed echocardiographic assessment, lymphocyte count correlated inversely with NTproBNP (r = -0.31) and markers of congestion [left atrial volume index (r = -0.25), inferior vena cava diameter (r = -0.24)]; neutrophil count correlated positively with high-sensitivity C-reactive protein (hsCRP) (r = 0.31, P < 0.001). During a median follow-up of 54 (29-100) months, 3015 (64%) patients died. In models adjusted for NTproBNP and HsCRP, higher NLR [hazard ratio (HR):1.05; 95% confidence interval (CI) 1.03-1.06] and neutrophil count (HR:1.07; 95%CI 1.04-1.10) were associated with higher mortality rates; higher lymphocyte count (HR:0.88; 95%CI 0.82-0.95) was associated with lower risk (all P < 0.001).

Conclusions: Low lymphocyte count is associated with more congestion and high neutrophil count with more inflammation, which may explain why a greater NLR is associated with a poorer prognosis. For patients with heart failure, NLR or its components could be useful for risk stratification or for monitoring evolving risk, but might also be therapeutic targets.

Aims: Heart failure represents a substantial burden to both patients and healthcare systems worldwide. Nitric oxide (NO) dysregulation may play a key role in patients transitioning from chronic to acute heart failure with a reduced ejection fraction (HFrEF). Plasma nitrite (NO₂ ^-) is highly reflective of local nitric oxide production and has not been studied in acute HFrEF. This study aims to quantify measures of NO biology in patients with acute and chronic HFrEF.

Methods and results: We utilized gas-phase chemiluminescence to determine plasma NO₂ ^- concentrations. Plasma asymmetric dimethylarginine (ADMA) and arterial stiffness were also measured. Plasma concentrations of NO₂ ^- and ADMA, in addition to arterial stiffness, were compared in participants with chronic HFrEF (n = 25) and acute HFrEF (n = 24). We observed lower concentrations of plasma NO₂ ^- in patients with acute HFrEF (P = 0.047). We also observed higher plasma concentrations of ADMA in participants with acute HFrEF (P < 0.001). Plasma NO₂ ^- and ADMA also displayed a significant negative correlation in the total cohort (R_s = -0.38, P = 0.017). There was no significant difference between groups regarding arterial stiffness measures.

Conclusions: We present novel data with regard to plasma NO₂ ^- in both acute and chronic HFrEF. Our results indicate that patients with acute HFrEF have a relative deficiency of plasma NO₂ ^- whilst also displaying a relative increase in ADMA, a modulator of eNOS. Reduced NO bioavailability may therefore relate to impaired NO production in patients with acute decompensation, with implications for both treatment and prevention of episodes.

Aims: H₂FPEF and HFA-PEFF scores have demonstrated prognostic value in heart failure (HF) with preserved ejection fraction. This study aimed to explore the value of the H₂FPEF and HFA-PEFF scores for HF risk stratification in patients with hypertrophic cardiomyopathy (HCM).

Methods and results: In this cohort study, 1068 HCM patients were included. Then the H₂FPEF and HFA-PEFF scores were calculated to categorize patients into low, intermediate, and high score groups. The primary endpoint was a composite of the first HF hospitalization and all-cause death. 594 (55.6%) patients were classified discordantly. After a follow-up period of 3.1 ± 2.1 years, 85 (8.0%) patients were admitted for HF for the first time, and 62 (5.8%) patients died. Rates of first HF hospitalization and all-cause death per 1000 person-years for the low, intermediate, and high H₂FPEF score groups were 25.0 (95% confidence interval [CI]: 14.5-35.4), 52.0 (95% CI: 41.6-62.3), and 148.1 (95% CI: 77.7-218.5), respectively. For the low-intermediate and high HFA-PEFF score groups, rates were 19.3 (95% CI: 11.6-27.0) and 69.3 (95% CI: 56.4-82.1), respectively. Intermediate H₂FPEF score (hazard ratio [HR]: 1.820, 95% CI: 1.135-2.919; P = 0.013), high H₂FPEF score (HR: 3.464, 95% CI: 1.774-6.765; P < 0.001), and high HFA-PEFF score (HR: 2.414, 95% CI: 1.501-3.882; P < 0.001) were each independently associated with an increased risk of the primary endpoint. Intermediate-high H₂FPEF score demonstrated an equal risk for the primary endpoint compared to the high HFA-PEFF score (HR: 0.826, 95% CI: 0.636-1.072; P > 0.05). Obesity (HR: 1.958, 95% CI: 1.140-3.363; P = 0.015), atrial fibrillation (HR: 1.686, 95% CI: 1.071-2.654; P = 0.024), pulmonary hypertension (HR: 1.613, 95% CI: 1.032-2.521; P = 0.036) of the H₂FPEF score, and the morphological major criterion (HR: 1.601, 95% CI: 1.084-2.364; P = 0.018) and functional major criterion (HR: 2.340, 95% CI: 1.442-3.797; P < 0.001) of the HFA-PEFF score were independent predictors of the primary endpoint. A new algorithm was constructed using the independent predictors from both scores, with the functional major criterion weighted as 2 points and the others as 1 point. The H₂FPEF score, HFA-PEFF score, and the new algorithm demonstrated C-indices of 0.594, 0.651, and 0.681, respectively.

Conclusions: There is discordance in the classification of patients with HCM using the H₂FPEF and HFA-PEFF scores. Both scores demonstrated prognostic value in risk stratification for HF hospitalization and all-cause death in HCM patients. Future studies should develop and validate a new algorithm integrating both scores.

Aims: Understanding sex-related cardiovascular differences in those with pre-HFpEF (asymptomatic with normal ejection fraction, elevated natriuretic peptides and structural or functional heart disease) could help explain why females are more likely to develop symptomatic HFpEF compared with males. This study analyses sex-related cardiovascular differences in pre-HFpEF, including measures of cardiovascular stiffness and vascular resistance derived from cardiac magnetic resonance imaging (CMR) and Doppler echocardiography.

Methods and results: This post hoc analysis of the PARABLE trial enrolled 250 patients with pre-HFpEF. CMR and Doppler echocardiography were used to estimate baseline markers of cardiovascular stiffness and resistance, including effective arterial elastance (EAE), systemic vascular resistance (SVR), total arterial compliance (TAC), left ventricular end diastolic pressure (LVEDP) and left ventricular end diastolic chamber stiffness index (LVSId). The population median age was 72.0 [IQR 68.0; 77.0] years and 38.4% were female. Both sexes had a similar age, blood pressure, HbA1c, renal function and H2FPEF score. Fewer female participants had a diagnosis of diabetes and coronary artery disease. When adjusted for age, hypertension, diabetes, obesity and vascular disease, female participants had higher pulse pressures (62.1 (SD 15.3) vs. 60.1 (SD 12.5) mmHg, P < 0.001) as well as higher median [IQR] levels of LDL-cholesterol (2.50 [2.10; 3.25] vs. 2.00 [1.60; 2.40] mmol/L, P < 0.001), EAE (1.55 [1.26; 1.84] vs. 1.26 [1.05; 1.51] mmHg/mL/m², P < 0.001), SVR (1609 [1288; 1887] vs. 1336 [1132; 1734] mmHg/mL/min², P = 0.001), LVEDP (18.5 [17.2; 20.1] vs. 18.0 [16.9; 19.3] mmHg, P < 0.001) and LVSId (0.28 [0.24; 0.31] vs 0.24 [0.20; 0.29] mmHg/mL/m², P < 0.001) than males. Females had higher median [IQR] NT-proBNP (176 [95.8; 286] vs. 127 [81.5; 242] pg/mL, P < 0.001) and lower median [IQR] TAC (1.24 [0.99; 1.58] vs. 1.55 [1.18; 1.91] mL/mmHg, P < 0.001) than male participants.

Conclusions: Markers of elevated cardiovascular stiffness and vascular resistance are seen in female versus male participants with pre-HFpEF, suggesting that sex-related pathophysiological mechanisms are present before symptoms of HF develop.

Aims: This study aimed to evaluate the effects of various exercise modalities on physical function and quality of life in individuals with heart failure and to identify the most effective approaches.

Methods and results: A network meta-analysis was conducted by searching PubMed, Embase and the Cochrane Library databases. Random-effects meta-analyses were performed to estimate mean differences (MD) and 95% confidence intervals (CI). A total of 60 randomized controlled trials, comprising 3261 participants, were included in the analysis. Yoga was associated with the greatest improvement in left ventricular ejection fraction (P-score = 0.91, MD: 0.90; 95% CI: 0.42 to 1.38) and the most significant reduction in serum natriuretic peptide levels (P-score = 0.965, MD: -1.46; 95% CI: -1.88 to -1.04). Interval training demonstrated superior effectiveness in increasing the 6-min walk distance (6MWD) (P-score = 0.873, MD: 113.01; 95% CI: 28.55 to 197.47). Combined aerobic and resistance training (AT + RT) showed the greatest benefits in enhancing peak oxygen uptake (VO_2peak) (P-score = 0.829, MD: 3.68; 95% CI: 2.23 to 5.13). High-intensity interval training combined with inspiratory muscle training (HIIT + IMT) yielded the most significant improvements in quality of life (P-score = 0.871, MD: -19.28; 95% CI: -26.42 to -12.14) and the greatest reduction in dyspnea (P-score = 0.804, MD: -1.58; 95% CI: -2.64 to -0.52).

Conclusions: Current evidence suggests that yoga, interval training, AT + RT, and HIIT + IMT significantly enhance physical function and quality of life in individuals with heart failure, with each modality exhibiting distinct advantages. Further high-quality studies are warranted to confirm these findings and refine exercise prescriptions for this population.