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Cardiac resynchronization therapy induces adaptive metabolic transitions in the metabolomic profile of heart failure.

ABSTRACT: Heart failure (HF) is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT). The aim of this study was to determine the metabolomic signature in HF and its prognostic value regarding the response to CRT.This prospective study consisted of 24 patients undergoing CRT for advanced HF and 10 control patients who underwent catheter ablation for supraventricular arrhythmia but not CRT. Blood samples were collected before and 3 months after CRT. Metabolomic profiling of plasma samples was performed with the use of gas chromatography-mass spectrometry and nuclear magnetic resonance. The plasma metabolomic profile was altered in the HF patients, with a distinct panel of metabolites, including Krebs cycle and lipid, amino acid, and nucleotide metabolism. CRT improved the metabolomic profile. The succinate-glutamate ratio, an index of Krebs cycle activity, improved from 0.58 ± 0.13 to 2.84 ± 0.60 (P < .05). The glucose-palmitate ratio, an indicator of the balance between glycolytic and fatty acid metabolism, increased from 0.96 ± 0.05 to 1.54 ± 0.09 (P < .01). Compared with nonresponders to CRT, responders had a distinct baseline plasma metabolomic profile, including higher isoleucine, phenylalanine, leucine, glucose, and valine levels and lower glutamate levels at baseline (P < .05).CRT improves the plasma metabolomic profile of HF patients, indicating harmonization of myocardial energy substrate metabolism. CRT responders may have a favorable metabolomic profile as a potential biomarker for predicting CRT outcome.

SUBMITTER: Nemutlu E

PROVIDER: S-EPMC4456226 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Cardiac resynchronization therapy induces adaptive metabolic transitions in the metabolomic profile of heart failure.

Nemutlu Emirhan E Zhang Song S Xu Yi-Zhou YZ Terzic Andre A Zhong Li L Dzeja Petras D PD Cha Yong-Mei YM

Journal of cardiac failure 20150422 6

<h4>Background</h4>Heart failure (HF) is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT). The aim of this study was to determine the metabolomic signature in HF and its prognostic value regarding the response to CRT.<h4>Methods and results</h4>This prospective study consisted of 24 patients undergoing CRT for advanced HF and 10 control patients who underwent catheter ablation for supraventricular arrhythmia b ...[more]

PMID: 25911126

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Project description:Approximately 40% of patients with heart failure (HF) who are eligible for cardiac resynchronization therapy (CRT) either fail to respond or are untreatable due to anatomical constraints. To assess the safety and efficacy of a novel, leadless, left ventricular (LV) endocardial pacing system for patients at high risk for a CRT upgrade or whose coronary sinus (CS) lead placement/pacing with a conventional CRT system failed. The SOLVE-CRT study was a prospective multicenter trial, enrolling January 2018 through September 2022, with follow-up in March 2023. Data were analyzed from DATE MONTH, YEAR, through DATE MONTH, YEAR. The trial combined data from an initial randomized, double-blind study (n = 108) and a subsequent single-arm part (n = 75). It took place at 36 centers across Australia, Europe, and the US. Participants were nonresponders, previously untreatable (PU), or high-risk upgrades (HRU). All participants contributed to the safety analysis. The primary efficacy analysis (n = 100) included 75 PU-HRU patients from the single-arm part and 25 PU-HRU patients from the randomized treatment arm. Patients were implanted with the WiSE CRT System (EBR Systems) consisting of a leadless LV endocardial pacing electrode stimulated with ultrasound energy delivered by a subcutaneously implanted transmitter and battery. The primary safety end point was freedom from type I complications. The primary efficacy end point was a reduction in mean LV end systolic volume (LVESV). The study included 183 participants; mean age was 68.1 (SD, 10.3) years and 141 were male (77%). The trial was terminated at an interim analysis for meeting prespecified stopping criteria. In the safety population, patients were either New York Heart Association Class II (34.6%) or III (65.4%). The primary efficacy end point was met with a 16.4% (95% CI, -21.0% to -11.7%) reduction in mean LVESV (P = .003). The primary safety end point was met with an 80.9% rate of freedom from type I complications (P < .001), which included 12 study device system events (6.6%), 5 vascular events (2.7%), 3 strokes (1.6%), and 7 cardiac perforations which mostly occurred early in the study (3.8%). The SOLVE-CRT study has demonstrated that leadless LV endocardial pacing with the WiSE CRT system is associated with a reduction in LVESV in patients with HF. This novel system may represent an alternative to conventional CRT implants in some HF patient populations. ClinicalTrials.gov Identifier: NCT0292203.

Project description:Background Patients with recurring heart failure (HF) following cardiac resynchronization therapy fare poorly. Their management is undecided. We tested remote hemodynamic-guided pharmacotherapy. Methods and Results We evaluated cardiac resynchronization therapy subjects included in the CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in New York Heart Association Class III Heart Failure Patients) trial, which randomized patients with persistent New York Heart Association Class III symptoms and ≥1 HF hospitalization in the previous 12 months to remotely managed pulmonary artery (PA) pressure-guided management (treatment) or usual HF care (control). Diuretics and/or vasodilators were adjusted conventionally in control and included remote PA pressure information in treatment. Annualized HF hospitalization rates, changes in PA pressures over time (analyzed by area under the curve), changes in medications, and quality of life (Minnesota Living with Heart Failure Questionnaire scores) were assessed. Patients who had cardiac resynchronization therapy (n=190, median implant duration 755 days) at enrollment had poor hemodynamic function (cardiac index 2.00±0.59 L/min per m2), high comorbidity burden (67% had secondary pulmonary hypertension, 61% had estimated glomerular filtration rate <60 mL/min per 1.73 m2), and poor Minnesota Living with Heart Failure Questionnaire scores (57±24). During 18 months randomized follow-up, HF hospitalizations were 30% lower in treatment (n=91, 62 events, 0.46 events/patient-year) versus control patients (n=99, 93 events, 0.68 events/patient-year) (hazard ratio, 0.70; 95% CI, 0.51-0.96; P=0.028). Treatment patients had more medication up-/down-titrations (847 versus 346 in control, P<0.001), mean PA pressure reduction (area under the curve -413.2±123.5 versus 60.1±88.0 in control, P=0.002), and quality of life improvement (Minnesota Living with Heart Failure Questionnaire decreased -13.5±23 versus -4.9±24.8 in control, P=0.006). Conclusions Remote hemodynamic-guided adjustment of medical therapies decreased PA pressures and the burden of HF symptoms and hospitalizations in patients with recurring Class III HF and hospitalizations, beyond the effect of cardiac resynchronization therapy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00531661.

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Cardiac resynchronization therapy induces adaptive metabolic transitions in the metabolomic profile of heart failure.

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Cardiac resynchronization therapy induces adaptive metabolic transitions in the metabolomic profile of heart failure.

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