Cardiac Electrical and Mechanical Synchrony of Super-Responders to Cardiac Resynchronization Therapy
Cardiac resynchronization therapy (CRT) has become a cornerstone in the management of heart failure (HF), significantly reducing morbidity and mortality by correcting cardiac electrical and mechanical dyssynchrony. Among CRT recipients, a subset of patients, termed super-responders (SRs), exhibit remarkable improvements, often regaining near-normal or normal cardiac function. Despite the well-documented benefits of CRT, the extent to which SRs regain cardiac synchrony and whether they require continued biventricular (BIV) pacing remains unclear. This study aims to evaluate the cardiac electrical and mechanical synchrony of SRs, focusing on their intrinsic rhythm after achieving super-response.
The study retrospectively analyzed data from CRT recipients between 2008 and 2016 at two centers. SRs were identified based on an increase in left ventricular ejection fraction (LVEF) to ≥50% at follow-up. Cardiac synchrony was assessed in both intrinsic and BIV-paced rhythms. Electrical synchrony was estimated by QRS duration, while left ventricular (LV) mechanical synchrony was evaluated using single-photon emission computed tomography (SPECT) myocardial perfusion imaging.
Seventeen SRs were included in the study, with LVEF increasing from 33.0 ± 4.6% to 59.3 ± 6.3%. The intrinsic QRS duration after super-response was 148.8 ± 30.0 ms, significantly shorter than the baseline duration of 174.8 ± 11.9 ms but longer than the BIV-paced duration of 135.5 ± 16.7 ms. Intrinsic LV mechanical synchrony also showed significant improvement after super-response, with phase standard deviation (PSD) decreasing from 51.1 ± 16.5° to 19.8 ± 8.1° and phase histogram bandwidth (PHB) decreasing from 171.7 ± 64.2° to 60.5 ± 22.9°. However, these values were still inferior to those observed during BIV-paced rhythm (PSD: 15.2 ± 6.4°; PHB: 46.0 ± 16.3°).
The study further categorized SRs based on changes in intrinsic QRS duration after super-response. Two patients (11.8%) exhibited complete electrical reverse remodeling, with QRS morphology changing from left bundle branch block (LBBB) to normal, and a mean QRS duration of 85 ms. Twelve patients (70.6%) showed partial electrical remodeling, with shortened QRS duration but unchanged morphology, and a mean QRS duration of 152.5 ± 18.2 ms. Three patients (17.6%) had no change in QRS duration or morphology, maintaining a QRS duration of 176.7 ± 5.8 ms.
LV mechanical synchrony was evaluated in 13 of the 17 SRs. Those with shortened intrinsic QRS duration experienced greater improvements in LV mechanical synchrony compared to those with unchanged QRS duration. Specifically, SRs with complete electrical remodeling achieved normalization of LV mechanical synchrony in the intrinsic rhythm (PSD: 12.2 ± 1.8°; PHB: 39.5 ± 7.8°). SRs with partial electrical remodeling showed significant improvements in PSD and PHB, while those without electrical remodeling exhibited minimal changes in LV mechanical synchrony.
The findings of this study highlight the significant improvements in cardiac electrical and mechanical synchrony among SRs following CRT. However, the intrinsic synchrony of SRs remains inferior to that achieved with BIV pacing, indicating the necessity of continued BIV pacing to maintain long-term cardiac synchrony. This is particularly important given that SRs often exhibit better prognosis and survival rates comparable to the normal population.
The mechanism underlying the improvement in intrinsic QRS duration and LV mechanical synchrony in SRs is not fully understood. It is hypothesized that CRT-induced reductions in heart size and improvements in the conduction system contribute to these changes. The reversal of molecular alterations associated with dyssynchronous HF, such as correction of cardiac gap junction proteins and ion channel remodeling, may also play a role.
Previous studies have demonstrated that cessation of BIV pacing in SRs leads to deterioration in clinical and echocardiographic parameters. This study supports those findings by showing that SRs still exhibit inferior cardiac synchrony in their intrinsic rhythm, even when they achieve normal LVEF. Therefore, continued BIV pacing is essential to maintain optimal electrical and mechanical synchrony in SRs.
The study has some limitations, including its small sample size and retrospective design. The highly selective super-response criteria and the inability to obtain all cardiac synchrony measurements may have influenced the results. Future large-scale prospective trials are needed to confirm these findings and further explore the mechanisms underlying the improvements in cardiac synchrony in SRs.
In conclusion, CRT super-responders experience significant improvements in cardiac electrical and mechanical synchrony. However, their intrinsic synchrony remains inferior to that achieved with BIV pacing, necessitating continued BIV pacing to maintain long-term cardiac synchrony. This study provides valuable insights into the management of SRs and underscores the importance of ongoing BIV pacing in this population.
doi.org/10.1097/CM9.0000000000000600
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