Prognostic Significance of Heart Rate Variability Among Patients Treated With Cardiac Resynchronization Therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy)

Saadia Sherazi; Valentina Kutyifa; Scott McNitt; Mehmet K Aktas; Jean-Philippe Couderc; Benjamin Peterson; Poul Erik Bloch Thomsen; Joseph Kautzner; Arthur J Moss; Wojciech Zareba

doi:10.1016/j.jacep.2015.03.004

Prognostic Significance of Heart Rate Variability Among Patients Treated With Cardiac Resynchronization Therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy)

JACC Clin Electrophysiol. 2015 Mar-Apr;1(1-2):74-80. doi: 10.1016/j.jacep.2015.03.004. Epub 2015 Apr 20.

Affiliations

¹ Cardiology Division, Heart Research Follow-up Program, University of Rochester Medical Center, Rochester, New York. Electronic address: saadia_sherazi@urmc.rochester.edu.
² Cardiology Division, Heart Research Follow-up Program, University of Rochester Medical Center, Rochester, New York.
³ Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
⁴ Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

PMID: 29759342
DOI: 10.1016/j.jacep.2015.03.004

Abstract

Objectives: This study sought to evaluate the prognostic value of heart rate variability (HRV) for death or heart failure in patients with mildly symptomatic heart failure undergoing cardiac resynchronization therapy with a defibrillator (CRT-D).

Background: There are limited data regarding the prognostic value of HRV as a means of identifying high-risk patients treated with CRT-D.

Methods: We analyzed the relationship between pre-implant time-domain (SD of all normal-to-normal RR intervals [SDNN], SDs of averaged 5-min normal-to-normal RR intervals, root mean square of successive differences, and mean of the SDs of all normal-to-normal RR intervals for all 5-min segments of the entire recording), and frequency-domain (low-frequency power, very-low-frequency power [VLF], high-frequency power, low-frequency power/low-frequency power ratio) HRV parameters, and the end point of death or heart failure and death alone. Study subjects include 719 patients in normal sinus rhythm enrolled in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy); outcomes of CRT-D patients with low HRV (lower tertile) were compared with CRT-D patients with preserved HRV (2 upper tertiles) and with patients receiving implantable cardioverter-defibrillators only.

Results: During a mean 3.4 ± 0.9 years of follow-up, 124 patients reached the primary end point of death or heart failure, and 47 died. In multivariate analysis, low SDNN (≤93 ms) was associated with significantly higher risk of death or heart failure (hazard ratio [HR] 1.63 [95% confidence interval (CI): 1.12 to 2.36]; p = 0.010) and mortality (HR 2.10 [95% CI: 1.14 to 3.87]; p = 0.017) compared with higher SDNN (>93 ms). Similarly, low VLF (≤179 ms²) was associated with an increased risk of death or heart failure (HR 2.14 [95% CI: 1.46 to 3.13]; p < 0.001) and death alone (HR 2.49 [95% CI: 1.35 to 4.57]; p = 0.003). There was no significant difference in outcome between low HRV patients treated with CRT-D and patients receiving an implantable cardioverter-defibrillator only.

Conclusions: Our findings indicate that autonomic dysfunction (quantified by low SDNN and low VLF) identified patients with no benefit or limited benefit from cardiac resynchronization therapy. Pre-implant HRV analysis might help in optimizing qualifications for this treatment.

Keywords: autonomic dysfunction; cardiac resynchronization therapy; heart rate variability.