ESC Heart Failure最新文献

Cardiac remodelling is a key determinant of worse cardiovascular outcome in patients with heart failure (HF) and reduced ejection fraction (HFrEF). It affects both the left ventricle (LV) structure and function as well as the left atrium (LA) and the right ventricle (RV). Guideline recommended medical therapy for HF, including angiotensin-converting enzyme inhibitors/angiotensin receptors II blockers/angiotensin receptor blocker-neprilysin inhibitors (ACE-I/ARB/ARNI), beta-blockers, mineralocorticoid receptor antagonists (MRA) and sodium-glucose transport protein 2 inhibitors (SGLT2i), have shown to improve morbidity and mortality in patients with HFrEF. By targeting multiple pathophysiological pathways, foundational HF therapies are supposed to drive their beneficial clinical effects by a direct myocardial effect. Simultaneous initiation of guideline directed medical therapy (GDMT) through a synergistic effect promotes a 'reverse remodelling', leading to a full or partial recovered structure and function by enhancing systemic neurohumoral regulation and energy metabolism, reducing cardiomyocyte apoptosis, lowering oxidative stress and inflammation and adverse extracellular matrix deposition. The aim of this review is to describe how these classes of drugs can drive reverse remodelling in the LV, LA and RV and improve prognosis in patients with HFrEF.

Background: Arterial stiffness is a crucial factor in determining an increase in systolic blood pressure and pulse pressure and can also predict the development of cardiovascular disease (CVD). The purpose of this study was to examine the relationship between arterial stiffness and future CVD.

Methods: Out of the original 9704 participants in the Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort study, we randomly selected 363 healthy participants, 226 normal subjects (who reported symptoms of CVD but were not confirmed) and 292 individuals who had experienced a major cardiovascular event. The SphygmoCor XCEL System (AtCor Medical Incorporation) was utilized to measure pulse wave velocity (PWV), central augmentation index (CAI), cardio-ankle vascular index (CAVI) and central aortic pressure (CAP). A multivariate multiple regression model was used to analyse the factors associated with non-invasive arterial stiffness parameters (PWV, CAVI, CAP and CAI) after adjusting for potential confounders. All statistical analyses were conducted using SPSS 21 with a significance level of 0.05.

Results: The mean PWV was significantly higher in patients who had experienced a confirmed CVD event (P < 0.001). The multivariate multiple regression model results, after adjusting for potential confounders, showed a significant association between PWV and the CVD group (normal vs. healthy and event vs. healthy), as well as between hypertension and obesity with PWV and diabetes with CAI (P < 0.05).

Conclusions: PWV was found to be associated with CVD and its related risk factors such as diabetes, obesity and hypertension. It may be more effective than other arterial stiffness parameters in predicting CVD in clinical settings.

Aims: Mortality in cardiogenic shock (CS) remains elevated, with the potential for CS causes to impact prognosis and risk stratification. The aim was to investigate in-hospital prognosis and mortality in CS patients according to aetiology. We also assessed the prognostic accuracy of CardShock and IABP-SHOCK II scores.

Methods: Shock-CAT study was a multicentre, prospective, observational study conducted from December 2018 to November 2019 in eight university hospitals in Catalonia, including non-selected consecutive CS patients. Data on clinical presentation, management, including mechanical circulatory support (MCS) were analysed comparing acute myocardial infarction (AMI) related CS and non-AMI-CS. The accuracy of CardShock and IABP-SHOCK II scores to assess 90 day mortality risk were also compared.

Results: A total of 382 CS patients were included, age 65.3 (SD 13.9) years, 75.1% men. Patients were classified as AMI-CS (n = 232, 60.7%) and non-AMI-CS (n = 150, 39.3%). In the AMI-CS group, 77.6% were STEMI. Main aetiologies for non-AMI-CS were heart failure (36.2%), arrhythmias (22.1%) and valve disease (8.0%). AMI-CS patients required more MCS than non-AMI-CS (43.1% vs. 16.7%, P < 0.001). In-hospital mortality was higher in AMI-CS (37.1 vs. 26.7%, P = 0.035), with a two-fold increased risk after multivariate adjustment (odds ratio 2.24, P = 0.019). The IABP-SHOCK II had superior discrimination for predicting 90 day mortality when compared with CardShock in AMI-CS patients [area under the curve (AUC) 0.74 vs. 0.66, P = 0.047] although both scores performed similarly in non-AMI-CS (AUC 0.64 vs. 0.62, P = 0.693).

Conclusions: In our cohort, AMI-CS mortality was increased by two-fold when compared with non-AMI-CS. IABP-SHOCK II score provides better 90 day mortality risk prediction than CardShock score in AMI-CS, but both scores performed similar in non-AMI-CS patients.

Aims: Cardiac decompensation in cardiorenal syndrome (CRS) results in systemic congestion usually treated with diuretics. When despite high doses of diuretics, response is poor, ultrafiltration (UF) appears to be a useful and safe technique. The aim of the study was to analyse, by means of a systematic review, the efficacy and safety of UF versus conventional diuretic treatment.

Methods and results: Search of the main databases (Pubmed, Embase and Cochrane Central Register of Controlled Trials) identifying comparative studies of UF versus diuretic therapy, from 2000 to the present. After screening the studies, 13 studies were analysed; 1100 patients (UF: 532, diuretic treatment: 568). Renal function: UF showed a trend to lower creatinine at discharge (SME = -0.68; 95% CI -1.50 to 0.13; I² = 97%) with no difference in glomerular filtration rate (SME = 0.05; 95% CI -0.17 to 0.27; I² = 0%). Diuretic response: With UF, there was a trend towards greater weight loss (SME = 1.82; 95% CI -0.79 to 4.42; I² = 99.7%) and greater volume removed (SME = 3.04; 95% CI -2.13 to 8.20; I² = 99.8%). Morbidity and mortality: No difference in days of hospital stay (LogOR = -0.14; 95% CI -0.52 to 0.23; I² = 66.9%) and mortality at 1 month (LogOR = -0.04; 95% CI -0.34 to 0.44; I² = 0%) but reduction in readmissions in patients with UF (LogOR = -0.60; 95% CI -0.94 to -0.26; I² = 40.5%).

Conclusions: In decompensated HF and CRS with inadequate diuretic response, UF versus diuretic intensification is an effective and safe option; it reduces readmissions with a tendency to decrease weight, creatinine levels and increase volume depletion without affecting mortality. Prospective randomised studies with a sufficient number of patients are needed to corroborate these results.

Aims: No curative treatment is available for RASopathy-associated childhood-onset hypertrophic cardiomyopathy (RAS-CM). Preclinical data and individual reports suggest a beneficial effect of small molecules targeting the RAS-mitogen-activated protein (MAP) kinase (MAPK) pathway in severely affected RAS-CM patients. The aim of this study was to evaluate the biophysical effects of trametinib, rapamycin and dasatinib on cultivated myocardial tissue slices of a paediatric RAS-CM patient using biomimetic cultivation chambers (BMCCs) and to correlate the findings with clinical data.

Methods: Contracting right ventricular (RV) tissue slices were prepared from resected myocardium, cultivated in BMCCs and treated with distinct molecules directly and indirectly targeting the RAS-MAPK pathway (trametinib, rapamycin and dasatinib) or dimethyl sulfoxide (DMSO). Tissue biophysical properties were assessed using electrical stimulation protocols. Contractile function, force-frequency relationship and post-pause potentiation were compared before and after treatment. These parameters correlated to L-type Ca²⁺ channel function and sarcoplasmic Ca²⁺ loading.

Results: In vivo, off-label treatment with MAPK kinase (MEK) inhibitor trametinib of a child with severe RAS-CM resulted in a modest reduction of RV outflow tract (RVOT) obstruction (RVOT 151 to 122 mmHg after 11 weeks) and improved diastolic function (E/A 0.68 to 1.09 after 11 weeks) and myocardial strain [RV global radial strain (RV-GRS) 25.94 to 42.76; RV global circumferential strain (RV-GCS) -15.26 to -18.61; and RV global longitudinal strain (RV-GLS) -10.31 to -16.78 at 11 weeks], as determined by echocardiography and cardiac magnetic resonance tomography. In cultivated RV myocardial tissue slices, contraction force decreased after addition of trametinib and rapamycin but not after addition of DMSO and dasatinib. Improvement of Ca²⁺ handling, as depicted by a more positive force-frequency relationship and enhanced post-pause potentiation (31.2%), was noted in the trametinib-treated slice. The increase in post-pause potentiation was less pronounced in rapamycin-treated (26%) and absent in dasatinib-treated (<1%) slices.

Conclusions: Ex vivo analysis of cultivated and electrically stimulated RV myocardial tissue slices of a patient with RAS-CM showed decreased contractility and improved sarcoplasmic reticulum function after addition of trametinib and in part after addition of rapamycin, but not after addition of dasatinib.

Aims: Sodium-glucose co-transporter inhibitors (SGLTis) have cardiovascular protective effects. We aimed to assess the effects of SGLTis on individual hard clinical endpoints and quality of life (QoL) in patients with cardiovascular risk factors.

Methods and results: Data was searched in PubMed, Embase, Cochrane Library and clinicaltrials.gov databases up to February 2024. Randomized controlled trials (RCTs) comparing SGLTis with placebo were included. The primary outcomes were individual hard clinical endpoints (Subset A) and QoL (Subset B). For Subset A, 13 RCTs including 90 413 patients were enrolled (age 66 ± 10.1 years, 35.7% female, follow-up 2.4 ± 0.3 years); as compared with placebo, SGLTis were associated with significantly lower risk of all-cause mortality [risk ratio (RR): 0.90, 95% confidence interval (CI): 0.86-0.94, P < 0.01], cardiovascular mortality (RR: 0.87, 95% CI: 0.82-0.92, P < 0.01), hospitalization for heart failure (HF) (RR: 0.72, 95% CI: 0.68-0.76, P < 0.01), HF events (RR: 0.72, 95% CI: 0.68-0.75, P < 0.01), hospitalization for any cause (RR: 0.91, 95% CI: 0.88-0.93, P < 0.01) and myocardial infarction (MI) (RR: 0.92, 95% CI: 0.85-0.99, P = 0.03). Notably, the favourable effect of SGLTis on all-cause mortality was more pronounced in younger (<65 years) patients (RR: 0.86, 95% CI: 0.81-0.92) and in studies with less female (RR: 0.84, 95% CI: 0.79-0.90). The favourable effect of SGLTis on MI was only observed in patients who received sotagliflozin (RR: 0.47, 95% CI: 0.31-0.73). For Subset B, nine RCTs including 2552 HF patients were enrolled (age 67.8 ± 12.4 years, 36.4% female, follow-up 3.4 ± 1.9 months); SGLTis were associated with significant improvement in QoL as compared with placebo.

Conclusions: In patients with a broad spectrum of cardiovascular risk factors, SGLTis substantially improve individual hard clinical outcomes and QoL.

Aims: Natriuretic peptide-based pre-heart failure screening has been proposed in recent guidelines. However, an effective strategy to identify screening targets from the general population, more than half of which are at risk for heart failure or pre-heart failure, has not been well established. This study evaluated the performance of machine learning prediction models for predicting elevated N terminal pro brain natriuretic peptide (NT-proBNP) levels in the US general population.

Methods and results: Individuals aged 20-79 years without cardiovascular disease from the nationally representative National Health and Nutrition Examination Survey 1999-2004 were included. Six prediction models (two conventional regression models and four machine learning models) were trained with the 1999-2002 cohort to predict elevated NT-proBNP levels (>125 pg/mL) using demographic, lifestyle, and commonly measured biochemical data. The model performance was tested using the 2003-2004 cohort. Of the 10 237 individuals, 1510 (14.8%) had NT-proBNP levels >125 pg/mL. The highest area under the receiver operating characteristic curve (AUC) was observed in SuperLearner (AUC [95% CI] = 0.862 [0.847-0.878], P < 0.001 compared with the logistic regression model). The logistic regression model with splines showed a comparable performance (AUC [95% CI] = 0.857 [0.841-0.874], P = 0.08). Age, albumin level, haemoglobin level, sex, estimated glomerular filtration rate, and systolic blood pressure were the most important predictors. We found a similar prediction performance even after excluding socio-economic information (marital status, family income, and education status) from the prediction models. When we used different thresholds for elevated NT-proBNP, the AUC (95% CI) in the SuperLearner models 0.846 (0.830-0.861) for NT-proBNP > 100 pg/mL and 0.866 (0.849-0.884) for NT-proBNP > 150 pg/mL.

Conclusions: Using nationally representative data from the United States, both logistic regression and machine learning models well predicted elevated NT-proBNP. The predictive performance remained consistent even when the models incorporated only commonly available variables in daily clinical practice. Prediction models using regularly measured information would serve as a potentially useful tools for clinicians to effectively identify targets of natriuretic-peptide screening.

Background and aims: Patients with heart failure with preserved ejection fraction (HFpEF) tend to have low resting and exercise heart rates. Phosphodiesterase-3 (PDE-3) inhibitors improve heart rates, haemodynamics and symptoms in patients with HFpEF. Cilostazol is an oral PDE-3 inhibitor used in peripheral artery disease. This study thought to evaluate the short-term effects of cilostazol on health status, N-terminal brain natriuretic peptide (NT-proBNP) levels and mechanisms of action.

Methods: The effect of cilostazol was evaluated in 23 patients with HFpEF in a randomized placebo controlled multiple crossover trial (CLIP-HFpEF). Participants received placebo or cilostazol for 1 week followed by three crossovers to the alternate assignment at weeks 2, 3 and 4. The primary endpoint was the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) overall summary score obtained at the end of each treatment period. NT-proBNP was the secondary endpoint. In an exploratory mechanistic analysis, pulmonary artery (PA) pressures and heart rates were followed amongst the five participants with implanted pressure monitors.

Results: Cilostazol improved the KCCQ score by 4.8 points (95% confidence interval, 2.0-7.7, P = 0.003). NT-proBNP levels were 448 (154-1056) pg/mL on placebo and 375 (68-974) pg/mL on cilostazol (P = 0.006). In patients with PA pressure monitors, diastolic pressure was 20.5 (18.7-23.0) mmHg on placebo and 18.0 (17.0-20.0) mmHg on cilostazol, an effect linked to higher heart rates (P < 0.001).

Conclusions: Amongst patients with HFpEF, short-term treatment with cilostazol leads to improvements in health status and NT-proBNP when compared with placebo. These effects are likely conveyed by a heart rate-dependent reduction in cardiac filling pressures.

Trial registration: ClinicalTrials.gov Identifier: NCT05126836.