Circulation: Heart Failure最新文献

Background: Despite previous histopathologic evidence for its presence, the role of myocardial inflammation in the development and progression of cardiac transthyretin amyloidosis (ATTR-CA) remains insufficiently understood. Thus, this study sought to characterize the prevalence and potential prognostic implications of myocardial inflammation in ATTR-CA.

Methods: A retrospective observational study including patients with ATTR-CA diagnosed by endomyocardial biopsy was conducted. Myocardial inflammation was diagnosed through a review of routine endomyocardial biopsy reports. Baseline characteristics were compared using the Mann-Whitney U test and the Pearson χ² test. Clinical outcomes were monitored via follow-up visits or telephone calls. Primary outcomes were all-cause death and a composite end point of all-cause death or heart failure hospitalization. Kaplan-Meier analyses, as well as univariable and age- and sex-adjusted multivariable Cox regression analyses, were used to assess differences in overall and composite end point-free survival between patients with ATTR-CA with and without myocardial inflammation.

Results: A total of 103 patients with ATTR-CA (100 wild type; 3 variant) were enrolled. Median follow-up was 18.2 (8.0-31.1) months. Myocardial inflammation was prevalent in 32% (n=33/103) of patients with ATTR-CA. Among evaluable patients with myocardial inflammation, 96% (n=26/27) and 31% (n=9/29) had elevated CD68 (clusters of differentiation 68)-positive macrophage and CD3 (clusters of differentiation 3)-positive T-cell counts, respectively. Overall survival (P=0.017) and composite end point-free survival (P=0.014) were significantly impaired in patients with ATTR-CA with myocardial inflammation (n=33) compared with those without (n=70). Statistical significance for both associations was sustained after adjustment for age and sex, yielding adjusted hazard ratios of 4.72 (95% CI, 1.33-16.71; P=0.016) and 2.30 (95% CI, 1.04-5.11; P=0.041) for all-cause death and the composite end point, respectively.

Conclusions: Our findings affirm previous evidence that myocardial inflammation is present in approximately one-third of all patients with ATTR-CA. Moreover, we provide first data indicating that myocardial inflammation may be associated with a higher risk of death and heart failure hospitalizations in ATTR-CA.

Background: Hypertrophic cardiomyopathy is the most common genetic cardiomyopathy and causes major adverse cardiovascular events (MACE). SVEP1 (Sushi, von Willebrand factor type A, epidermal growth factor, and pentraxin domain containing 1) is a large extracellular matrix protein that is detectable in the plasma. However, it is unknown whether adding plasma SVEP1 levels to clinical predictors including NT-proBNP (N-terminal pro-B-type natriuretic peptide) improves the prognostication in patients with hypertrophic cardiomyopathy.

Methods: We performed a multicenter prospective cohort study of 610 patients with hypertrophic cardiomyopathy. The outcome was MACE defined as heart failure hospitalization or cardiac death. In 4 groups stratified by the median levels of SVEP1 and NT-proBNP, we compared the risk of MACE using the Cox proportional hazards model adjusting for 15 clinical predictors. We also developed a Lasso-regularized Cox proportional hazards model to predict time to first MACE by adding SVEP1 to the 15 clinical predictors with or without NT-proBNP and compared the predictive performance based on C statistics using 10-fold cross-validation.

Results: Even in the low NT-proBNP groups, the high SVEP1 group had higher risks of MACE compared with the low SVEP1 group (adjusted hazard ratio, 4.52 [95% CI, 1.05-19.4]; P=0.042). In predicting time to first MACE, the addition of SVEP1 improved the C statistics of the clinical plus NT-proBNP model (0.87 [0.83-0.91] versus 0.82 [0.78-0.86]; P=0.01). The clinical plus SVEP1 model also outperformed the clinical plus NT-proBNP model (0.86 [0.82-0.91] versus 0.82 [0.78-0.86]; P=0.04).

Conclusions: SVEP1 improved the predictive performance of conventional models, including known clinical parameters with or without NT-proBNP, to predict future MACE in patients with hypertrophic cardiomyopathy.

The integrative physiology of the left ventricle and systemic circulation is fundamental to our understanding of advanced heart failure and cardiogenic shock. In simplest terms, any increase in aortic stiffness increases the vascular afterload presented to the failing left ventricle. The net effect is increased myocardial oxygen demand and reduced coronary perfusion pressure, thereby further deteriorating contractile function. Although mechanical circulatory support devices should theoretically work in concert with guideline-directed medical therapy, cardiac resynchronization and inotropic and vasopressor agents designed to support myocardial performance and enhance left ventricle recovery, this does not always occur. Each therapy and intervention may result in vastly different and sometimes deleterious effects on vascular afterload. Although best described by a combination of both steady-state and pulsatile components, the latter is frequently overlooked when mean arterial pressure or systemic vascular resistance alone is used to quantify vascular afterload in advanced heart failure and cardiogenic shock. In this state-of-the-art review, we examine what is known about vascular afterload in advanced heart failure and cardiogenic shock, including the use of temporary and permanent mechanical circulatory support systems. Importantly, we outline 4 key components for a more complete assessment of vascular afterload. Unlike previous discussions on this topic, we set aside considerations of venous return and ventricular preload, as important as they are, to focus exclusively on the hydraulic load within the systemic circulation against which the impaired left ventricle must contract.

Background: Objective indices of functional capacity in patients with diabetic cardiomyopathy and stage B heart failure (HF) have not been comprehensively defined. We sought to characterize the cardiopulmonary exercise characteristics of individuals with diabetic cardiomyopathy at high risk for overt HF.

Methods: The relationships from cardiopulmonary exercise testing with clinical and laboratory characteristics of participants with diabetic cardiomyopathy were evaluated using baseline data from the ARISE-HF trial (Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure). Cluster phenogroups with different comorbidities and their corresponding functional capacity profiles were identified.

Results: Among study participants (n=689), the median (Q1, Q3) peak oxygen uptake and ventilatory efficiency (slope of the ratio of minute ventilation/carbon dioxide production) were 15.7 (interquartile range, 13.0-18.0) mL/kg per minute and 31.2 (interquartile range, 27.2-34.1), respectively. Lower peak oxygen uptake was associated with older age, female sex, higher body mass index, higher N-terminal pro-B-type natriuretic peptide, and an increasing burden of noncardiac comorbid conditions but was not associated with cardiac troponin T or echocardiogram-derived strain, left atrial volume index, E/e', or right ventricular systolic pressure. Elevated left ventricular mass index was the only echocardiographic abnormality associated with lower peak oxygen uptake. Multivariable analysis revealed that female sex, higher body mass index, and no history of dyslipidemia were independently associated with lower baseline peak oxygen uptake. Cluster analysis revealed 3 clusters with profiles of different cardiovascular/exercise parameters and health status profiles.

Conclusions: Baseline cardiopulmonary exercise testing data from the ARISE-HF trial highlight predominant associations of extracardiac clinical and demographic variables with significant impairment in exercise capacity despite strict fulfillment of diagnostic criteria for stage B HF.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04083339.

Background: The therapeutic armamentarium for heart failure with preserved ejection fraction (HFpEF) remains notably constrained. A factor contributing to this problem could be the scarcity of in vitro models for HFpEF, which hinders progress in developing new therapeutic strategies. Here, we aimed at developing a novel, comorbidity-inspired, human, in vitro model for HFpEF.

Methods: Human induced pluripotent stem cells-derived cardiomyocytes were used to produce cardiac organoids. The generated organoids were then subjected to HFpEF-associated, comorbidity-inspired conditions, such as hypertension, diabetes, and obesity-related inflammation. To assess the development of HFpEF pathophysiological features, organoids were thoroughly evaluated for their structural, functional, electrophysiological, and metabolic properties.

Results: Exposure to the combination of all comorbidity-mimicking conditions resulted in the largest cellular volume of 1692±52 versus 1346±84 µm³ in RPMI (Roswell Park Memorial Institute medium) control group (P=0.003), while lower in obesity, hypertension, and diabetes groups: 1059±40 µm³ (P=0.014), 1276±35 µm³ (P=0.940), and 1575±70 µm³ (P=0.146), respectively. Similarly, ultrastructural fibrosis was most significantly observed after exposure to the combination of all HFpEF-inducing conditions 14.6±1.2% compared with single condition exposure 5.2±1.3% (obesity), 6.7±3.5% (hypertension), and 9.0±1.1% (diabetes; P<0.001). Moreover, HFpEF-related conditions led to an increase in passive force compared with control (7.52±1.08 versus 2.33±0.46 mN/mm, P<0.001), whereas no significant alterations were noted in active contractile forces. Relaxation constant τ was significantly prolonged after exposure to HFpEF conditions showing a prolongation of 95.9 ms (36.4-106.4; P=0.028) compared with a shortening of 35.6 ms (43.3-67.3; P=0.80) in the control. Finally, organoid exposure to HFpEF conditions led to a significant increase in oxidative stress levels and a significant decline in oxygen consumption rate.

Conclusions: We established a novel, human, in vitro model for HFpEF, based on comorbidity-inspired conditions. The model faithfully recapitulated the structural, functional, and mechanistic features of HFpEF. This model holds the potential to provide mechanistic insights and facilitate the identification of novel therapeutic targets.