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Background— Impaired bioenergetics is a prominent feature of the failing heart, but the underlying metabolic perturbations are poorly understood. Methods and Results— We compared metabolomic, gene transcript, and protein data from 6 paired samples of failing human left ventricular tissue obtained during left ventricular assist device insertion (heart failure samples) and at heart transplant (post-left ventricular assist device samples). Nonfailing left ventricular wall samples procured from explanted hearts of patients with right heart failure served as novel comparison samples. Metabolomic analyses uncovered a distinct pattern in heart failure tissue: 2.6-fold increased pyruvate concentrations coupled with reduced Krebs cycle intermediates and short-chain acylcarnitines, suggesting a global reduction in substrate oxidation. These findings were associated with decreased transcript levels for enzymes that catalyze fatty acid oxidation and pyruvate metabolism and for key transcriptional regulators of mitochondrial metabolism and biogenesis, peroxisome proliferator-activated receptor γ coactivator 1α ( PGC1A , 1.3-fold) and estrogen-related receptor α ( ERRA , 1.2-fold) and γ ( ERRG , 2.2-fold). Thus, parallel decreases in key transcription factors and their target metabolic enzyme genes can explain the decreases in associated metabolic intermediates. Mechanical support with left ventricular assist device improved all of these metabolic and transcriptional defects. Conclusions— These observations underscore an important pathophysiologic role for severely defective metabolism in heart failure, while the reversibility of these defects by left ventricular assist device suggests metabolic resilience of the human heart.

Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease. Although regional functional heterogeneity in HCM is well-known, cellular and molecular regional heterogeneity in human HCM remain unrecognized. We evaluated the molecular and histological heterogeneity as well as mitochondrial function in HCM and their relation to functional heterogeneity in 16 left ventricular segments from a patient with HCM with normal ejection fraction who underwent heart transplantation for advanced heart failure. The patient was a 61-year-old man who had a long-standing history of HCM with asymmetrical septal hypertrophy and maximum wall thickness of 26 mm. He underwent myectomy because of severe dyspnea and left ventricular outflow tract dynamic obstruction but was in New York Heart Association functional class IV heart failure despite successful surgery. He received an implantable cardioverter-defibrillator because of risk factors for sudden cardiac death. There was no evidence of epicardial coronary artery disease by angiography. The patient underwent cardiac transplantation because of persistent symptoms, …

Introduction: Pump thrombosis is a potentially life-threatening event that currently presents a diagnostic challenge. We therefore sought to explore the diagnostic utility and the association of measured cardiac computed tomography (CT) parameters in patients with LVAD malfunction due to pump thrombosis. Methods: From 2009 to 2013, 150 patients underwent placement of Heart Mate II continuous flow pump at our institution. Of these 52 patients, underwent cardiac CT with contrast either as part of a prospective protocol or for suspected malfunction. 14 patients had pump thrombosis per the INTERMACS criteria and the remaining were used as controls. Rigorous linear and area measurements for the inflow and outflow tracts of LVADs were performed. Results: The mean age of the population was 55 ± 11, 36 were male, and 28 had ischemic cardiomyopathy. Results are shown in table 1. For inflow cannula, measurement of axial area shown in figure 1, was significantly higher in the pump thrombosis group compared to the control group 31±16 cm2 vs 20 ± 12 cm2 (p=.02). Although, the difference in the acute angle for the inflow cannula relative to the perpendicular axis between the midpoint of the mitral annulus and tip of inflow cannulas was not significantly different between the two groups, there was a trend towards greater angulation in the pump thrombosis group (60 ± 6 vs 53 ± 15) and there was a positive correlation between both measurements r=0.513, p-value= 0.003. Conclusions: Area in the axial view of the ventricle at the site of the inflow cannula tip may be a surrogate for off axis placement of the cannula. This area may be helpful in predicting pump thrombosis in patients.