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

Imaging and Modeling of Myocardial Metabolism

Current imaging methods have focused on evaluation of myocardial anatomy and function. However, since myocardial metabolism and function are interrelated, metabolic myocardial imaging techniques, such as positron emission tomography, single photon emission tomography, and magnetic resonance spectroscopy present novel opportunities for probing myocardial pathology and developing new therapeutic approaches. Potential clinical applications of metabolic imaging include hypertensive and ischemic heart disease, heart failure, cardiac transplantation, as well as cardiomyopathies. Furthermore, response to therapeutic intervention can be monitored using metabolic imaging. Analysis of metabolic data in the past has been limited, focusing primarily on isolated metabolites. Models of myocardial metabolism, however, such as the oxygen transport and cellular energetics model and constraint-based metabolic network modeling, offer opportunities for evaluation interactions between greater numbers of metabolites in the heart. In this review, the roles of metabolic myocardial imaging and analysis of metabolic data using modeling methods for expanding our understanding of cardiac pathology are discussed

Prognostic Significance of Atrial Arrhythmias in a Primary Prevention ICD Population

Introduction: We investigated whether primary prevention implantable cardioverter defibrillator (ICD) patients with atrial arrhythmias are at higher risk for ICD shocks and mortality compared to patients without atrial arrhythmias in a subanalysis of the PREPARE study. Methods and Results: Details of the PREPARE study design and results have been previously reported. We now included 537 of the 700 patients enrolled in PREPARE. These patients had a dual or biventricular device and at least one device follow-up after implantation. Continuously collected device diagnostics data were used to classify patients into two groups during follow-up: with (n = 133) or without (n = 404) atrial tachycardia/atrial fibrillation (AT/AF). The primary outcomes were ICD shocks and mortality. Subjects were followed for a mean of 333 +/- 73 (range 5-365) days. During a follow-up of 1 year, ICD shocks occurred in 44 (8%) patients. Significantly, more patients with AT/AF received a shock (13.0% vs 6.9%, P = 0.03), with inappropriate shocks accounting for the majority of the difference (6.9% vs 2.6%, P = 0.02). There was no difference in prevalence of shocks between patients with and without a history of AF. Mortality was similar in patients with and without AT/AF, whether detected during the study or prior to the study. In addition, the 34 subjects with high average ventricular rate (>= 110 beats per minute) during AT/AF had a higher risk of an inappropriate shock (21.0% vs 2.1%, P <0.01). Conclusion: Primary prevention ICD patients with AT/AF are more likely to receive shocks, especially inappropriate shocks. Mortality was not higher in AT/AF patients. (PACE 2011; 34:1070-1079

Association between implantable cardioverter-defibrillator and survival in patients awaiting heart transplantation: A meta-analysis and systematic review

BackgroundPatients with end-stage heart failure are at high risk for sudden cardiac death. However, implantable cardioverter-defibrillator (ICD) is not routinely implanted given the high competing risk of pump failure. A unique population worth separate consideration are patients with end-stage heart failure awaiting heart transplantation, as prolonged survival improves the chances of receiving transplant.ObjectiveTo compare clinical outcomes of heart failure patients with and without an ICD awaiting heart transplant.MethodsWe performed an extensive literature search and systematic review of studies that compared end-stage heart failure patients with and without an ICD awaiting heart transplantation. We separately assessed the rates of total mortality, sudden cardiac death, nonsudden cardiac death, and heart transplantation. Risk ratio (RR) and 95% confidence intervals were measured using the Mantel-Haenszel method. The random effects model was used owing to heterogeneity across study cohorts.ResultsTen studies with a total of 36,112 patients were included. A total of 62.5% of patients had an ICD implanted. Patients with an ICD had decreased total mortality (RR 0.60, 95% CI 0.51-0.71, P&nbsp;&lt;&nbsp;.00001) and sudden cardiac death (RR 0.27, 95% CI 0.11-0.66, P&nbsp;= .004) and increased rates of heart transplantation (RR 1.09, 95% CI 1.05-1.14, P &lt; .0001). There was no difference in prevalence of nonsudden cardiac death (RR 0.68, 95% CI 0.44-1.04, P = .07).ConclusionICD implantation is associated with improved outcomes in patients awaiting heart transplant, characterized by decreased total mortality and sudden cardiac death as well as higher rates of heart transplantation

Meta-analysis of Effect of Modest (≥10%) Weight Loss in Management of Overweight and Obese Patients With Atrial Fibrillation.

Obesity and atrial fibrillation (AF) are growing epidemics with significant overlap in co-morbidities. Multiple smaller studies have evaluated the effects of weight loss and risk factor modification on recurrence of AF, reduction in AF burden and improvement in AF symptom severity. The objective of this study was to determine if a modest weight loss of ≥10% of initial body weight is enough to improve outcomes in overweight or obese patients with established AF. We performed an extensive literature search and systematic review of studies that compared weight loss of ≥10% versus weight loss of less than 10% or weight gain and assessed outcomes including recurrence of AF as determined through a Holter monitor, AF burden and improvement in AF symptom severity. Risk ratio 95% confidence intervals (CI) were measured for dichotomous variables and mean difference (MD) 95% CI were measured for continuous variables, where MD &gt;0 favors the group with ≥10% weight loss. Five studies with a total of 548 patients were included. Patients who lost ≥10% of their initial body weight experienced less recurrence of AF (risk ratio 0.29; 95% CI 0.19 to 0.44) and a larger reduction in reported event frequency (MD 1.74; 95% CI 0.70 to 2.79), episode duration (MD 2.14; 95% CI 0.04 to 4.23), global episode severity (MD 1.89; 95% CI 1.34 to 2.45), and symptom severity (MD 5.36; 95% CI 3.75 to 6.97). In conclusion, weight loss is associated with less risk of recurrent AF, reduction in AF burden, and improvement in AF symptom severity

Meta-analysis of Effect of Modest (≥10%) Weight Loss in Management of Overweight and Obese Patients With Atrial Fibrillation.

Obesity and atrial fibrillation (AF) are growing epidemics with significant overlap in co-morbidities. Multiple smaller studies have evaluated the effects of weight loss and risk factor modification on recurrence of AF, reduction in AF burden and improvement in AF symptom severity. The objective of this study was to determine if a modest weight loss of ≥10% of initial body weight is enough to improve outcomes in overweight or obese patients with established AF. We performed an extensive literature search and systematic review of studies that compared weight loss of ≥10% versus weight loss of less than 10% or weight gain and assessed outcomes including recurrence of AF as determined through a Holter monitor, AF burden and improvement in AF symptom severity. Risk ratio 95% confidence intervals (CI) were measured for dichotomous variables and mean difference (MD) 95% CI were measured for continuous variables, where MD &gt;0 favors the group with ≥10% weight loss. Five studies with a total of 548 patients were included. Patients who lost ≥10% of their initial body weight experienced less recurrence of AF (risk ratio 0.29; 95% CI 0.19 to 0.44) and a larger reduction in reported event frequency (MD 1.74; 95% CI 0.70 to 2.79), episode duration (MD 2.14; 95% CI 0.04 to 4.23), global episode severity (MD 1.89; 95% CI 1.34 to 2.45), and symptom severity (MD 5.36; 95% CI 3.75 to 6.97). In conclusion, weight loss is associated with less risk of recurrent AF, reduction in AF burden, and improvement in AF symptom severity

Defibrillation effectiveness and safety of the shock waveform used in a contemporary wearable cardioverter defibrillator: Results from animal and human studies.

IntroductionThe wearable cardioverter defibrillator (WCD) is used to protect patients at risk for sudden cardiac arrest. We examined defibrillation efficacy and safety of a biphasic truncated exponential waveform designed for use in a contemporary WCD in three animal studies and a human study.MethodsAnimal (swine) studies: #1: Efficacy comparison of a 170J BTE waveform (SHOCK A) to a 150J BTE waveform (SHOCK B) that approximates another commercially available waveform. Primary endpoint first shock success rate. #2: Efficacy comparison of the two waveforms at attenuated charge voltages in swine at three prespecified impedances. Primary endpoint first shock success rate. #3: Safety comparison of SHOCK A and SHOCK B in swine. Primary endpoint cardiac biomarker level changes baseline to 6 and 24 hours post-shock. Human Study: Efficacy comparison of SHOCK A to prespecified goal and safety evaluation. Primary endpoint cumulative first and second shock success rate. Safety endpoint adverse events.ResultsAnimal Studies #1: 120 VF episodes in six swine. First shock success rates for SHOCK A and SHOCK B were 100%; SHOCK A non-inferior to SHOCK B (entire 95% CI of rate difference above -10% margin, p ConclusionsThe BTE waveform effectively and safely terminated induced VF in swine and a small sample in humans.Trial registrationHuman study clinical trial registration: URL: https://clinicaltrials.gov; Unique identifier: NCT04132466

Meta-analysis of the Usefulness of Catheter Ablation of Atrial Fibrillation in Patients With Heart Failure With Preserved Ejection Fraction.

Catheter ablation improves clinical outcomes in atrial fibrillation (AF) patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, the role of catheter ablation in HF with a preserved ejection fraction (HFpEF) is less clear. We performed a literature search and systematic review of studies that compared AF recurrence at one year after catheter ablation of AF in patients with HFpEF versus those with HFrEF. Risk ratio (RR; where a RR &lt;1.0 favors the HFpEF group) and mean difference (MD; where MD &lt;0 favors the HFpEF group) 95% confidence intervals (CI) were measured for dichotomous and continuous variables, respectively. Six studies with a total of 1,505 patients were included, of which 764 (51%) had HFpEF and 741 (49%) had HFrEF. Patients with HFpEF experienced similar recurrence of AF 1 year after ablation on or off antiarrhythmic drugs compared with those with HFrEF (RR 1.01; 95% CI 0.76, 1.35). Fluoroscopy time was significantly shorter in the HFpEF group (MD -5.42; 95% CI -8.51, -2.34), but there was no significant difference in procedure time (MD 1.74; 95% CI -11.89, 15.37) or periprocedural adverse events between groups (RR 0.84; 95% CI 0.54,1.32). There was no significant difference in hospitalizations between groups (MD 1.18; 95% CI 0.90, 1.55), but HFpEF patients experienced significantly less mortality (MD 0.41; 95% CI 0.18, 0.94). In conclusion, based on the results of this meta-analysis, catheter ablation of AF in patients with HFpEF appears as safe and efficacious in maintaining sinus rhythm as in those with HFrEF

Strategic programming of detection and therapy parameters in implantable cardioverter-defibrillators reduces shocks in primary prevention patients - Results from the PREPARE (Primary Prevention Parameters Evaluation) study

Objectives Our purpose was to demonstrate that strategically chosen implantable cardioverter-defibrillator (ICD) ventricular tachycardia (VT) or ventricular fibrillation (VF) detection and therapy parameters can reduce the combined incidence of device-delivered shocks, arrhythmic syncope, and untreated sustained symptomatic VT/VF (morbidity index). Background Strategically chosen ICD VT/VF detection and therapy parameters have been shown in previous studies to reduce the number of shocked episodes. In the PREPARE (Primary Prevention Parameters Evaluation) study, these prior strategies were combined with additional strategies specific to primary prevention patients. Methods The PREPARE study was a prospective, cohort-controlled study that analyzed 700 patients (biventricular [Bi-V] ICD and non-Bi-V ICD) with primary prevention indications for an ICD from 38 centers followed for 1 year. VT/VF was detected for rates >= 182 beats/min that were maintained for at least 30 of 40 beats. Antitachycardia pacing was programmed as the first therapy for regular rhythms with rates of 182 to 250 beats/min, and supraventricular tachycardia discriminators were used for rhythms Results The PREPARE programming significantly reduced the morbidity index incidence density (0.26 events/patient-year for PREPARE study patients vs. 0.69 control cohort, p = 0.003). The PREPARE study patients were less likely to receive a shock in the first year compared with control patients (9% vs. 17%, p <0.01). The incidence of untreated VT and arrhythmic syncope was similar between the PREPARE study patients and the control cohort. Conclusions Strategically chosen VT/VF detection and therapy parameters can safely reduce shocks and other morbidities associated with ICD therapy in patients receiving an ICD for primary prevention indications. (PREPARE-Primary Prevention Parameters Evaluation; NCT00279279