Characteristics and Long-Term Outcome of Echocardiographic Super-Responders to Cardiac Resynchronization Therapy: ‘Real World’ Experience From a Single Tertiary Care Centre

Study Questions:

Do echocardiographic definitions of “super-response” to cardiac resynchronization therapy (CRT) predict outcomes in patients with heart failure (HF)?

Methods:

This was a single-center, nonblinded cohort study of 110 patients undergoing CRT implant. A CRT super-response was defined as: 1) an absolute increase in ejection fraction (EF) of ≥10%, 2) a decrease in indexed left ventricular end-systolic volume (LVESVi) of ≥30%, or 3) a decrease in indexed end-diastolic volume (EDVi) of ≥20%. The primary outcome of interest was a combination of time to death, heart transplant, ventricular assist device implant, or HF hospitalization. Time to implantable cardioverter-defibrillator (ICD) discharge was a secondary outcome.

Results:

The mean ± standard deviation patient (n = 110) age was 63 ± 11 years, 82% were male, and 44% had a history of coronary disease. At baseline, LVEF was 25.8 ± 7.6% and QRS duration was 154 ± 29.2 ms. Mean time to echocardiography follow-up post-implant was 6.4 ± 2.7 months. Over 25 ± 18 months of follow-up, a super-response was found in 47% of patients based on an LVEF increase ≥10%, 40% based on ESVi decrease ≥30%, and 39% based on having an EDVi decrease ≥20%. At baseline, patients with a super-response (using all three definitions) had a shorter time from HF diagnosis to CRT implant. Super-responders based on EDVi and ESVi definitions had larger baseline interventricular mechanical delays than non–super-responders. There were 30 (27%) primary events (15 deaths, 25 HF hospitalizations, 4 transplants, and 3 ventricular assist devices). All three definitions of super-response were associated with a reduced risk of having a primary event (62-64% of super-responders vs. 94-82% of non–super-responders reached the primary endpoint at 3 years). All three definitions of super-response were also associated with fewer HF hospitalizations, but only EDVi and ESVi definitions were significantly associated with mortality. No definition of super-response predicted ICD discharge, which occurred in 23%.

Conclusions:

The authors concluded that all three definitions of super-response predict outcome after CRT implant. However, super-response did not predict ICD discharge.

Perspective:

Favorable cardiac remodeling is associated with improved outcome in patients with HF, and is believed to be one means by which pharmacologic therapies such as renin-angiotensin-aldosterone inhibitors work. CRT therapy is believed to improve outcomes by improving ventricular synchrony and inducing favorable remodeling, thereby reducing the nidus for fatal arrhythmias and reducing HF progression. In this analysis, echocardiographic definitions of ‘super-response’ were associated with increased event-free survival and fewer HF hospitalizations. Since patients who were super-responders had shorter durations of HF prior to device implant, smaller baseline LV volumes, and were less likely to have ischemic cardiac disease, two questions are raised: 1) are CRT benefits time-dependent and should a ‘sooner than later’ approach be undertaken before ‘fixed’ (fibrotic) adverse ventricular remodeling occurs, or 2) does a ‘super-response’ just identify patients with a reversible nonischemic cardiomyopathy that may have recovered devoid of CRT? This study is not powered for detailed multivariable analysis, but controlling for HF duration or requiring a minimal HF duration on maximal medical therapy would help sort out the latter question. Regardless, response to CRT should be assessed by clinical improvement in New York Heart Association and by examining the echocardiographic predictors above. Nonresponders are higher risk for adverse outcome, and may warrant referral to a HF specialist.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Implantable Devices, SCD/Ventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Lipid Metabolism, Novel Agents, Acute Heart Failure, Heart Transplant, Mechanical Circulatory Support, Interventions and Imaging, Echocardiography/Ultrasound

Keywords: Defibrillators, Follow-Up Studies, Tertiary Healthcare, Heart-Assist Devices, Renin, Mineralocorticoid Receptor Antagonists, Referral and Consultation, Coronary Disease, New York, Cardiac Resynchronization Therapy, Heart Transplantation, Heart Diseases, Cardiac Pacing, Artificial, Cardiomyopathies, Ventricular Remodeling, Heart Failure, Stroke Volume, Echocardiography


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