Clinical data of the REVERSE trial reveals how CRT improves functioning of the heart

Aug 30 2009

Cardiac resynchronization therapy (CRT) is a proven therapy indicated for patients with moderate to severe heart failure. Additional 24-month clinical data presented today on the European cohort of 262 patients in the REVERSE (Resynchronization Reverse Remodeling in Systolic Left Ventricular Dysfunction) trial, sponsored by Medtronic, Inc. (NYSE: MDT), provides a deeper understanding of how CRT improves the function of the heart, including reduction in heart size and improvements in pumping efficiency, in certain heart failure patients with mild symptoms. Currently, CRT is not approved in the United States for use in the mildly symptomatic or asymptomatic patients who were shown to benefit from CRT in this trial.

With 610 patients studied, REVERSE is the first large-scale, global, randomized, double-blind trial to demonstrate the impact of CRT in mild heart failure patients or asymptomatic patients who previously had heart failure symptoms. As previously reported, the trial did not meet statistical significance for its primary endpoint – a heart failure Clinical Composite Score (a measure of both subjective and objective assessments) at 12 months. However, the European cohort, which was followed through 24 months, did demonstrate statistical significance.

Three sessions featuring 24-month REVERSE data were presented today during the European Society of Cardiology congress in Barcelona:

• Clinical Trial Update: “Cardiac Resynchronization Therapy Induces Major Structural and Functional Reverse Remodeling in Mild Heart Failure,” by Dr. Stefano Ghio of Policlinico San Matteo in Pavia, Italy.
• “CRT in Mild Heart Failure: Differences in Outcomes Between NYHA Class I and II Patients Over 24 Months of CRT,” by Prof. Cecilia Linde of Karolinska University Hospital in Stockholm.
• “Relationship of QRS Duration to Reverse Remodeling with CRT in Mild Heart Failure Over Two Years,” by Michael Gold, M.D. of the Medical University of South Carolina in Charleston, S.C.

“The REVERSE 24-month results, presented at ACC 2009, suggest that CRT may improve clinical outcomes and ventricular function,” said Prof. Ghio. “While we’ve already seen improvement in more symptomatic patients with CRT, the additional analyses presented here at ESC give us valuable insights about ventricular structure and how CRT might be used to modify disease progression and help heart failure patients with mild symptoms.”

Patients with systolic heart failure have enlarged hearts, specifically the left ventricle (major pumping chamber), which impairs the heart’s pumping capacity, leading to symptoms such as fatigue, shortness of breath from any type of exertion, and swelling, usually of the feet and ankles. CRT uses an implanted device to resynchronize the heart’s ventricles to help pump blood more effectively through the body. For reference, a healthy heart’s pumping effectiveness (left ventricular ejection fraction, or LVEF) ranges from 50 to 75 percent.

Key Findings

Additional 24-month results from the European cohort of the REVERSE trial indicate that CRT may prevent or slow the progression of disease in asymptomatic or mildly symptomatic heart failure patients.

• CRT reduced the need for heart failure hospitalization in NYHA Class II patients>
• The trial demonstrated a statistically significant reduction in heart size (left ventricular end systolic volume index, or LVESVi), as measured by cardiac ultrasound, improving its function and helping the heart pump more efficiently in patients receiving CRT (p<0.0001). This trend was first seen at 12 months, and continued at 24 months (Ghio).
• There was a statistically significant increase in LVEF: from 28.1 percent to 34.8 percent in patients receiving CRT, compared to 27.8 percent to 29.9 percent in patients not receiving CRT>
• CRT reduced left ventricular volumes throughout the range of QRS duration (the length of time for the heart to contract) (p<0.0001), and CRT effectiveness was greater as QRS duration widened (Gold).

“The REVERSE trial continues to uncover valuable data for the clinical community to inform the treatment of heart failure patients,” said Marshall Stanton, M.D., vice president of clinical research in the Cardiac Rhythm Disease Management business at Medtronic. “Medtronic’s imprint on heart failure treatments, and our support of numerous clinical trials in this space, is unmatched.”

http://www.medtronic.com/