REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction - REVERSE

May 06, 2013
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Medtronic, Inc.
Date Presented:
08/27/2012
Date Published:
05/02/2013
Date Updated:
05/06/2013
Original Posted Date:
05/06/2013
References

Description:

The goal of this trial was to evaluate cardiac resynchronization therapy (CRT) compared with optimal medical therapy among patients with New York Heart Association (NYHA) class I-II heart failure (left ventricular ejection fraction [LVEF] <40%) and ventricular dyssynchrony.

Hypothesis:

CRT would improve LV remodeling among patients with mild heart failure symptoms.

Study Design

  • Parallel
  • Blinded
  • Randomized

Patients Enrolled: 610
NYHA Class: Class I: 18%, class II: 82%
Mean Follow Up: 12 months, 5 years
Mean Patient Age: 63 years
Mean Ejection Fraction: 27%

Patient Populations:

  • LV dysfunction (≤40%)
  • Prolonged QRS duration (≥120 ms)
  • NYHA class I-II
  • Optimal medical therapy
  • No indication for permanent pacing
  • LVEDD ≥55 mm

Primary Endpoints:

  • Heart failure clinical composite response
  • Clinical composite response was defined as the percentage of patients worsened with CRT ON versus CRT OFF. Composite includes all-cause mortality, heart failure hospitalization, crossover due to worsening heart failure, NYHA class, and patient global assessment.

Secondary Endpoints:

  • LVESVi comparing CRT ON versus CRT OFF

Drug/Procedures Used:

Patients with LV dysfunction and NYHA class I-II underwent CRT implant and were randomized to CRT ON (n = 419) or CRT OFF with optimal medical therapy (n = 191). In the CRT OFF group, the device was turned on at 1-year for United States enrollees and at 2 years for European enrollees.

Concomitant Medications:

Angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (>97%), beta-blockers (95%)

Principal Findings:

There was a 97% device implant success rate with a 9.5% LV-related complication.

The primary endpoint, the percentage of patients who clinically worsened, was 16% with CRT ON versus 21% for those with CRT OFF (p = 0.1). The LV end-systolic volume index (LVESVi) decreased 18.4 ml/m2 for CRT compared with a decrease of 1.3 ml/m2 for medical therapy (p < 0.0001). This effect on LV remodeling was greatest among patients with ischemic heart failure. The risk of heart failure hospitalization was reduced with CRT ON (hazard ratio 0.47, p = 0.03). Overall mortality was similar (2% vs. 2%, p = NS).

In substudy analysis of the European cohort with a longer duration of follow-up (18 months), there was a significant progressive reduction in LVESVi (-27 vs. -7 ml/m2, p < 0.0001) and LV end-diastolic volume index (LVEDVi) (-28 vs. -6 ml/m2, p < 0.0001) in those with CRT ON compared with CRT OFF.

At 5 years, total mortality was 13.5%, mortality or first heart failure hospitalization was 28.1%, and LV lead-related complications occurred in 12.5% in the CRT ON group. LV dimensions and LVEF remained stable to 5 years. Initial improvements in walk distance and heart failure symptoms diminished after 3-4 years.

Interpretation:

The use of CRT in patients with mildly symptomatic heart failure did not reduce the proportion of patients who clinically worsened at 12 months, but it did delay the time to first hospitalization for heart failure. There was no difference in mortality. This therapy resulted in significant reverse LV remodeling, which remained stable to 5 years. The role of this therapy among patients with mildly symptomatic heart failure remains unknown.

References:

Linde C, Gold MR, Abraham WT, et al., on behalf of the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) Study Group. Long-term impact of cardiac resynchronization therapy in mild heart failure: 5-year results from the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study. Eur Heart J 2013;34:2592-9.

Linde C, Abraham WT, Gold MR, St. John Sutton M, Ghio S, Daubert C, on behalf of the REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) Study Group. Randomized Trial of Cardiac Resynchronization in Mildly Symptomatic Heart Failure Patients and in Asymptomatic Patients With Left Ventricular Dysfunction and Previous Heart Failure Symptoms. J Am Coll Cardiol 2008;52:1834-1843.

CRT Produces Long-Term Improvements in Disease Progression in Mildly Symptomatic Heart Failure Patients: Five-Year Results From the REsynchronization ReVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study. Presented by Dr. Cecilia Linde at the European Society of Cardiology Congress, Munich, Germany, August 27, 2012.

Progressive Reverse Remodeling in Patients With Mild or Asymptomatic Heart Failure With Previous Symptoms: Results From the REVERSE Trial. Presented by Dr. Cecilia Linde at the European Society of Cardiology Congress, Munich, Germany, August/September 2008.

12-Month Results of the REVERSE Study. Presented by Dr. Cecilia Linde at the SCAI-ACC i2 Summit/American College of Cardiology Annual Scientific Session, Chicago, IL, March/April 2008.

Keywords: Follow-Up Studies, Ventricular Function, Left, Heart Failure, Stroke Volume, Heart Ventricles, Cardiac Resynchronization Therapy


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