Dataset Information

Electrophysiological consequences of dyssynchronous heart failure and its restoration by resynchronization therapy.

ABSTRACT: Cardiac resynchronization therapy (CRT) is widely applied in patients with heart failure and dyssynchronous contraction (DHF), but the electrophysiological consequences of CRT in heart failure remain largely unexplored.Adult dogs underwent left bundle-branch ablation and either right atrial pacing (190 to 200 bpm) for 6 weeks (DHF) or 3 weeks of right atrial pacing followed by 3 weeks of resynchronization by biventricular pacing at the same pacing rate (CRT). Isolated left ventricular anterior and lateral myocytes from nonfailing (control), DHF, and CRT dogs were studied with the whole-cell patch clamp. Quantitative polymerase chain reaction and Western blots were performed to measure steady state mRNA and protein levels. DHF significantly reduced the inward rectifier K(+) current (I(K1)), delayed rectifier K(+) current (I(K)), and transient outward K(+) current (I(to)) in both anterior and lateral cells. CRT partially restored the DHF-induced reduction of I(K1) and I(K) but not I(to), consistent with trends in the changes in steady state K(+) channel mRNA and protein levels. DHF reduced the peak inward Ca(2+) current (I(Ca)) density and slowed I(Ca) decay in lateral compared with anterior cells, whereas CRT restored peak I(Ca) amplitude but did not hasten decay in lateral cells. Calcium transient amplitudes were depressed and the decay was slowed in DHF, especially in lateral myocytes. CRT hastened the decay in both regions and increased the calcium transient amplitude in lateral but not anterior cells. No difference was found in Ca(V)1.2 (alpha1C) mRNA or protein expression, but reduced Ca(V)beta2 mRNA was found in DHF cells. DHF reduced phospholamban, ryanodine receptor, and sarcoplasmic reticulum Ca(2+) ATPase and increased Na(+)-Ca(2+) exchanger mRNA and protein. CRT did not restore the DHF-induced molecular remodeling, except for sarcoplasmic reticulum Ca(2+) ATPase. Action potential durations were significantly prolonged in DHF, especially in lateral cells, and CRT abbreviated action potential duration in lateral but not anterior cells. Early afterdepolarizations were more frequent in DHF than in control cells and were reduced with CRT.CRT partially restores DHF-induced ion channel remodeling and abnormal Ca(2+) homeostasis and attenuates the regional heterogeneity of action potential duration. The electrophysiological changes induced by CRT may suppress ventricular arrhythmias, contribute to the survival benefit of this therapy, and improve the mechanical performance of the heart.

SUBMITTER: Aiba T

PROVIDER: S-EPMC2703676 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Electrophysiological consequences of dyssynchronous heart failure and its restoration by resynchronization therapy.

Aiba Takeshi T Hesketh Geoffrey G GG Barth Andreas S AS Liu Ting T Daya Samantapudi S Chakir Khalid K Dimaano Veronica Lea VL Abraham Theodore P TP O'Rourke Brian B Akar Fadi G FG Kass David A DA Tomaselli Gordon F GF

Circulation 20090223 9

<h4>Background</h4>Cardiac resynchronization therapy (CRT) is widely applied in patients with heart failure and dyssynchronous contraction (DHF), but the electrophysiological consequences of CRT in heart failure remain largely unexplored.<h4>Methods and results</h4>Adult dogs underwent left bundle-branch ablation and either right atrial pacing (190 to 200 bpm) for 6 weeks (DHF) or 3 weeks of right atrial pacing followed by 3 weeks of resynchronization by biventricular pacing at the same pacing r ...[more]

PMID: 19237662

Similar Datasets

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.

Dataset Information

Electrophysiological consequences of dyssynchronous heart failure and its restoration by resynchronization therapy.

Publications

Electrophysiological consequences of dyssynchronous heart failure and its restoration by resynchronization therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets