Circulation: Heart Failure最新文献

Background: Changes in the phenotype and genotype in hypertrophic cardiomyopathy (HCM) are thought to involve the myocardium as well as extracardiac tissues. Here, we describe the structural and functional changes in the ascending aorta of obstructive patients with HCM.

Methods: Changes in the aortic wall were studied in a cohort of 101 consecutive patients with HCM undergoing myectomy and 9 normal controls. Biopsies were examined histologically, immunohistochemically, and by electron microscopy. Changes in protein expression were quantified using morphometry and Western blotting. Pulse wave velocity was measured using cardiac magnetic resonance in 85 patients with HCM and compared with 117 age-matched normal controls.

Results: In HCM, the number of medial lamellar units was significantly decreased, associated with an increase in interlamellar distance and aortic wall thickness, as compared with controls. Electron microscopy showed an altered lamellar structure with disorientation of elastin fibers from the circumferential direction. There was a significant decrease in collagen content, α-smooth muscle actin, smooth muscle myosin, smooth muscle 22 and integrin β1, as well as a significant increase in calponin and caspase-3. Fibulins 1, 2, and 5 showed reduced expression in HCM-aortic biopsies. Functionally, pulse wave velocity was significantly higher in patients with HCM compared with healthy controls, with an association between higher pulse wave velocity and more severe molecular and clinical parameters.

Conclusions: The increased wall stiffness observed in the aortas of obstructive patients with HCM is associated with structural alterations in the medial lamellar unit, including changes in smooth muscle cells and the extracellular matrix, indicating potential arterial dysfunction.

Background: Consensus regarding on-support evaluation and weaning concepts from Impella 5.5 support is scarce. The derived left ventricular end-diastolic pressure (dLVEDP), estimated by device algorithms, is a rarely reported tool for monitoring the weaning process. Its validation and clinical accuracy have not been studied in patients. We assess dLVEDP's accuracy in predicting pulmonary capillary wedge pressure (PCWP) and propose a corrective equation.

Methods: We included 29 consecutive patients treated with Impella 5.5: 12 in a generation cohort and 17 in a validation cohort. dLVEDP and PCWP were measured 5-fold every 8 hours during support, totaling 698 series with 3490 measurements. Variables such as Impella 5.5 performance level, heart rhythm, pacemaker settings, sex, mechanical ventilation, and body mass index were recorded. Linear regression was used to correct dLVEDP-PCWP discrepancies. Analysis included Bland-Altman plots, linear regression, histograms, and violin plots.

Results: The raw dLVEDP and PCWP data did not coincide satisfactorily. The Impella 5.5 dLVEDP overestimation was 3.5±1.5 mm Hg (mean±SD), increasing with higher pressures and unaffected by cardiac rhythm, mechanical ventilation, and performance levels. Statistical correction using the formula modified dLVEDP=-0.457+(1-sex[1=male, 0=female])×0.719-0.0496× body mass index+1.015×body surface area+0.811×dLVEDP significantly reduced the overestimation (P<0.01) to 0.0±1.2 mm Hg.

Conclusion: dLVEDP, calculated by the Impella 5.5 Smart Algorithm, is a feasible and effective tool for continuously monitoring PCWP at performance levels 3 to 9. Correction of dLVEDP by using the described equation further enhances its accuracy. Hence, hemodynamic surveillance via dLVEDP may aid in managing and weaning temporary microaxial support, potentially reducing the need for continuous monitoring with a Swan-Ganz catheter.

Background: Iron deficiency (ID) is currently defined as a serum ferritin level <100 or 100 to 299 ng/mL with transferrin saturation (TSAT) <20%. Serum ferritin and TSAT are currently used to define absolute and functional ID. However, individual markers of iron metabolism may be more informative than current arbitrary definitions of ID.

Methods: We assessed prognostic associations of ferritin, serum iron, and TSAT among 2050 participants with heart failure (HF) with reduced/mid-range (n=1821) or preserved (n=229) left ventricular ejection fraction enrolled in the PHFS (Penn HF Study), a prospective cohort study. We measured 4928 plasma proteins using an aptamer-based assay (SOMAScanv4) and assessed prognostic and proteomic associations of markers of iron metabolism.

Results: Ferritin concentrations were not associated with outcomes, whereas low TSAT and serum iron were associated with the risk of all-cause death (TSAT: standardized hazard ratio, 0.84 [95% CI, 0.76-0.93]; P=0.001; serum iron: standardized hazard ratio, 0.87 [95% CI, 0.79-0.96]; P=0.007). Similarly, TSAT was associated with the risk of death or HF-related admission (standardized hazard ratio, 0.89 [95% CI, 0.83-0.95]; P=0.0006). Significant interactions between TSAT and HF with preserved ejection fraction status were found such that TSAT was more strongly associated with the risk of death and death or HF-related admission in HF with preserved ejection fraction. We identified 359 proteins associated with TSAT, including TFRC (transferrin receptor protein; β, -0.455; P<0.0001) and CRP (C-reactive protein; β, -0.355; P<0.0001). Pathway analyses demonstrated associations with lipid metabolism, complement activation, and inflammation. In contrast to the robust associations between TSAT and outcomes, ID and absolute ID defined by current criteria were not associated with death or death or HF-related admission. TSAT was associated with outcomes regardless of the presence of functional versus absolute ID.

Conclusions: Low TSAT, but not ferritin concentrations, is significantly associated with adverse outcomes in HF. Low TSAT is more strongly associated with outcomes in HF with preserved ejection fraction. Pathways related to inflammation and lipid metabolism are associated with low TSAT in HF.

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.