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Reduced T wave alternans in heart failure responders to cardiac resynchronization therapy: Evidence of electrical remodeling.

ABSTRACT: BACKGROUND:T-wave alternans (TWA), a marker of electrical instability, can be modulated by cardiac resynchronization therapy (CRT). The relationship between TWA and heart failure response to CRT has not been clearly defined. METHODS AND RESULTS:In 40-patients (age 65±11 years, left ventricular ejection-fraction [LVEF] 23±7%), TWA was evaluated prospectively at median of 2 months (baseline) and 8 months (follow-up) post-CRT implant. TWA-magnitude (Valt >0?V, k?3), its duration (d), and burden (Valt ·d) were quantified in moving 128-beat segments during incremental atrial (AAI, native-TWA) and atrio-biventricular (DDD-CRT) pacing. The immediate and long-term effect of CRT on TWA was examined. Clinical response to CRT was defined as an increase in LVEF of ?5%. Native-TWA was clinically significant (Valt ?1.9?V, k?3) in 68% of subjects at baseline. Compared to native-TWA at baseline, DDD-CRT pacing at baseline and follow-up reduced the number of positive TWA segments, peak-magnitude, longest-duration and peak-burden of TWA (44±5 to 33±5 to 28±4%, p = 0.02 and 0.002; 5.9±0.8 to 4.1±0.7 to 3.8±0.7?V, p = 0.01 and 0.01; 97±9 to 76±8 to 67±8sec, p = 0.004 and <0.001; and 334±65 to 178±58 to 146±54?V.sec, p = 0.01 and 0.004). In addition, the number of positive segments and longest-duration of native-TWA diminished during follow-up (44±5 to 35±6%, p = 0.044; and 97±9 to 81±9sec, p = 0.02). Clinical response to CRT was observed in 71% of patients; the reduction in DDD-CRT paced TWA both at baseline and follow-up was present only in responders (interaction p-values <0.1). CONCLUSION:Long-term CRT reduces the prevalence and magnitude of TWA. This CRT induced beneficial electrical remodeling is a marker of clinical response after CRT.

SUBMITTER: Nayyar S

PROVIDER: S-EPMC6023131 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Reduced T wave alternans in heart failure responders to cardiac resynchronization therapy: Evidence of electrical remodeling.

Nayyar Sachin S Suszko Adrian A Porta-Sanchez Andreu A Dalvi Rupin R Chauhan Vijay S VS

PloS one 20180628 6

<h4>Background</h4>T-wave alternans (TWA), a marker of electrical instability, can be modulated by cardiac resynchronization therapy (CRT). The relationship between TWA and heart failure response to CRT has not been clearly defined.<h4>Methods and results</h4>In 40-patients (age 65±11 years, left ventricular ejection-fraction [LVEF] 23±7%), TWA was evaluated prospectively at median of 2 months (baseline) and 8 months (follow-up) post-CRT implant. TWA-magnitude (Valt >0μV, k≥3), its duration (d), ...[more]

PMID: 29953465

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Project description:Heart failure (HF) is associated with an increased propensity for atrial fibrillation (AF), causing higher mortality than AF or HF alone. It is hypothesized that HF-induced remodelling of atrial cellular and tissue properties promotes the genesis of atrial action potential (AP) alternans and conduction alternans that perpetuate AF. However, the mechanism underlying the increased susceptibility to atrial alternans in HF remains incompletely elucidated. In this study, we investigated the effects of how HF-induced atrial cellular electrophysiological (with prolonged AP duration) and tissue structural (reduced cell-to-cell coupling caused by atrial fibrosis) remodelling can have an effect on the generation of atrial AP alternans and their conduction at the cellular and one-dimensional (1D) tissue levels. Simulation results showed that HF-induced atrial electrical remodelling prolonged AP duration, which was accompanied by an increased sarcoplasmic reticulum (SR) Ca2+ content and Ca2+ transient amplitude. Further analysis demonstrated that HF-induced atrial electrical remodelling increased susceptibility to atrial alternans mainly due to the increased sarcoplasmic reticulum Ca2+-ATPase (SERCA) Ca2+ reuptake, modulated by increased phospholamban (PLB) phosphorylation, and the decreased transient outward K+ current (Ito). The underlying mechanism has been suggested that the increased SR Ca2+ content and prolonged AP did not fully recover to their previous levels at the end of diastole, resulting in a smaller SR Ca2+ release and AP in the next beat. These produced Ca2+ transient alternans and AP alternans, and further caused AP alternans and Ca2+ transient alternans through Ca2+?AP coupling and AP?Ca2+ coupling, respectively. Simulation of a 1D tissue model showed that the combined action of HF-induced ion channel remodelling and a decrease in cell-to-cell coupling due to fibrosis increased the heart tissue's susceptibility to the formation of spatially discordant alternans, resulting in an increased functional AP propagation dispersion, which is pro-arrhythmic. These findings provide insights into how HF promotes atrial arrhythmia in association with atrial alternans.

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.

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Reduced T wave alternans in heart failure responders to cardiac resynchronization therapy: Evidence of electrical remodeling.

Publications

Reduced T wave alternans in heart failure responders to cardiac resynchronization therapy: Evidence of electrical remodeling.

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