Redefining Classifications of Response to CRT

Jul 20, 2021
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Authors:
Gold MR, Rickard J, Daubert JC, Zimmerman P, Linde C.
Citation:
Redefining the Classifications of Response to Cardiac Resynchronization Therapy: Results From the REVERSE Study. JACC Clin Electrophysiol 2021;7:871-880.
Summary By:
Eugene H. Chung, MD, MPH, FACC

Quick Takes

  • The benefits of CRT on mortality, hospitalization, functional status, and cardiac function are well established.
  • Identification of the approximately 30% of CRT recipients who do not seem to benefit (i.e., “nonresponders”) remains less clear.
  • Results of this study suggest that the current “nonresponder” classification grouping together stabilized, and worsened CRT response should be reconsidered.

Study Questions:

Does a new classification of response, based on reverse remodeling and the clinical composite score (CCS), better predict survival after cardiac resynchronization therapy (CRT)?

Methods:

This study analyzed patients from the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) study, a randomized trial of CRT with mild heart failure. In REVERSE, patients were randomized in a 2:1 fashion to CRT ON or CRT OFF. Using the CCS, patients were classified as Improved, Stabilized, or Worsened. Using the change in left ventricular end-systolic volume index (LVESVi; Improved = decrease of ≥15% of LVESVi), reverse remodeling was classified as Improved, Stabilized, or Worsened.

Results:

Among the 406 subjects surviving 1 year, 5-year all-cause mortality was significantly lower in the Worsened response group: a 51% increase in mortality compared to the combined Improved or Stabilized subgroup. Similarly, among the 353 subjects with adequate echocardiograms, 5-year all-cause mortality was significantly lower in the Worsened response group compared to the combined Improved or Stabilized subgroup: a 73% reduction in mortality. The Worsened patients were more likely to be male, have ischemic heart disease, non–left bundle branch block QRS morphology, diabetes, and a shorter QRS duration. When combining CCS and LVESVi endpoints, the lowest survival was among subjects who Worsened for both. The highest survival was among those who did not worsen by either. Multivariate analysis showed that independent predictors of survival were worsening LVESVi despite CRT at 6 months, large LVESVi at baseline, and female sex. A Worsened CCS alone was not predictive of mortality.

Conclusions:

Patients who stabilize with CRT by clinical and remodeling measures have a similar survival benefit as those who improve with CRT. Those who worsen despite CRT have a much worse prognosis than other subgroups. The current nonresponder classification that groups together stabilized and worsened CRT response should be modified.

Perspective:

  • The benefits of CRT on mortality, hospitalization, functional status, and cardiac function are well established. Identification of the approximately 30% of CRT recipients who do not seem to benefit (i.e., “nonresponders”) remains less clear, owing to the natural history of heart failure and reversible factors.
  • Using the CCS and LVESVi as endpoints, this study demonstrated that worsening clinical and remodeling measures portend the lowest survival, underscoring the need for early follow-up and evaluation to address potential reversible causes (e.g., atrial fibrillation, lead position). Inactivation of CRT and/or alternative advanced heart failure therapies could also be considered.
  • Moreover, the observation that Stabilized patients have comparable outcomes to Improved patients receiving CRT suggests that the 30% nonresponder rate may indeed be an overestimation; as the authors suggest, classification of CRT response could be revised to Improved, Stabilized, or Worsened.
  • Limitations include the exclusion of moderate and severe heart failure patients and evolution of CRT techniques and tools since the REVERSE trial was published over 12 years ago.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Echocardiography/Ultrasound

Keywords: Arrhythmias, Cardiac, Bundle-Branch Block, Cardiac Resynchronization Therapy, Diabetes Mellitus, Echocardiography, Heart Failure, Myocardial Ischemia, Stroke Volume, Ventricular Dysfunction, Left, Ventricular Remodeling


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