8 research outputs found
Assessment of Metabolic Phenotypes in Patients with Non-ischemic Dilated Cardiomyopathy Undergoing Cardiac Resynchronization Therapy
Studies of myocardial metabolism have reported that contractile performance at a given myocardial oxygen consumption (MVO2) can be lower when the heart is oxidizing fatty acids rather than glucose or lactate. The objective of this study is to assess the prognostic value of myocardial metabolic phenotypes in identifying non-responders among non-ischemic dilated cardiomyopathy (NIDCM) patients undergoing cardiac resynchronization therapy (CRT). Arterial and coronary sinus plasma concentrations of oxygen, glucose, lactate, pyruvate, free fatty acids (FFA), and 22 amino acids were obtained from 19 male and 2 female patients (mean age 56 ± 16) with NIDCM undergoing CRT. Metabolite fluxes/MVO2 and extraction fractions were calculated. Flux balance analysis (FBA) was performed with MetaFluxNet 1.8 on a metabolic network of the cardiac mitochondria (189 reactions, 230 metabolites) reconstructed from mitochondrial proteomic data (615 proteins) from human heart tissue. Non-responders based on left ventricular ejection fraction (LVEF) demonstrated a greater mean FFA extraction fraction (35% ± 17%) than responders [18 ± 10%, p = 0.0098, area under the estimated ROC curve (AUC) was 0.8238, S.E. 0.1115]. Calculated adenosine triphosphate (ATP)/MVO2 using FBA correlated with change in New York Heart Association (NYHA) class (rho = 0.63, p = 0.0298; AUC = 0.8381, S.E. 0.1316). Non-responders based on both LVEF and NYHA demonstrated a greater mean FFA uptake/MVO2 (0.115 ± 0.112) than responders (0.034 ± 0.030, p = 0.0171; AUC = 0.8593, S.E. 0.0965). Myocardial FFA flux and calculated maximal ATP synthesis flux using FBA may be helpful as biomarkers in identifying non-responders among NIDCM patients undergoing CRT
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Renal dialysis as a risk factor for appropriate therapies and mortality in implantable cardioverter-defibrillator recipients
Patients with end-stage renal disease are at increased risk for sudden cardiac death, although the utility of implantable cardioverter-defibrillators (ICDs) in these patients is unknown.
The purpose of this study was to evaluate whether end-stage renal disease is an independent risk factor for appropriate ICD therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) and to compare the long-term survival of ICD recipients with and without end-stage renal disease.
A retrospective cohort study was performed on ICD recipients at a single center. The primary endpoint was first appropriate ICD therapy for VT/VF. The secondary endpoint was survival.
The study included 585 patients, 19 (3.2%) of whom had end-stage renal disease prior to device implantation. Average follow-up time was 2.2 ± 2.4 years, during which time 156 patients (26.7%) received appropriate ICD therapy. End-stage renal disease was strongly associated with appropriate ICD therapy (hazard ratio 2.30, 95% confidence interval 1.17–4.54) and remained a significant predictor following adjustment for implant indication, ejection fraction, diabetes, hypertension, and beta-blocker use. Survival was significantly shorter in the end-stage renal disease patients, with a median survival time of 3.2 ± 0.6 (SEM) years in the dialysis cohort and 7.4 ± 0.5 (SEM) years in those without end-stage renal disease (log rank
P = .009). The majority of deaths in the end-stage renal disease cohort were due to non–device-related infection.
In this cohort, end-stage renal disease was the single greatest predictor of ICD therapies for VT/VF. The survival rate was significantly shorter than that of ICD recipients without end-stage renal disease, suggesting that comorbidities in end-stage renal disease patients meeting current implant indications may reduce the survival benefit of ICD placement in this population
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Acute flaccid myelitis: cause, diagnosis, and management
Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population