University of Zurich announces worldwide clinical trial of Cardiac Resynchronization Therapy

The University of Zurich announces today an investigator initiated large-scale prospective randomized controlled clinical trial to assess the clinical impact of Cardiac Resynchronization Therapy (CRT) in heart failure patients.

The worldwide study, called "Echocardiography guided Cardiac Resynchronization Therapy (EchoCRT)", is the first prospective randomized clinical trial to evaluate the impact of cardiac resynchronization therapy in patients with advanced heart failure (NYHA Class III) and a narrow QRS complex who show mechanical dyssynchrony as assessed by echocardiography.

"It is established that CRT provides clinical benefit for heart failure patients with wide QRS," said Johannes Holzmeister, MD, University of Zurich, and co-principal investigator of the study. "Now it is imperative that we understand the effects of CRT in patients with narrow QRS complex (<120 ms) of whom more than 30% exhibit echocardiography evidence of dyssynchrony".

"As the majority of heart failure patients present with narrow QRS complex but still suffer from the clinical consequences of dyssynchrony, this trial could potentially expand therapeutic options for a patient population in need", said Frank Ruschitzka, MD, University of Zurich, and co-principal investigator of the study. "We expect the results of EchoCRT to pave the way to better outcomes."

More than 1000 patients with advanced heart failure (NYHA class III) will be randomized to CRT or no CRT and patients in both study arms will receive an implantable cardioverter-defibrillator (ICD) backup to protect against sudden cardiac death. The primary objective of the study is to determine whether CRT will reduce the combined endpoint of all-cause mortality or hospitalization for cardiovascular events.

Heart Failure and Ventricular Dyssynchrony – Implications and Therapy Approaches

Heart failure (HF), with its high morbidity and mortality, remains a major unresolved public health problem worldwide. HF affects nearly 5 million people in the United States, 6 million people in Europe and more than 22 million people worldwide, claiming more than 1.5 million lives annually. In many heart failure patients, the clinical condition and outcome is worsened by poor coordination of the heart chambers in squeezing blood (known as ventricular dyssynchrony) leading to inefficient function of the heart as a pump. This can be helped by a device therapy called CRT. CRT has been proven effective as an adjunct to drug therapies in patients with advanced heart failure and dyssynchrony indirectly assessed by changes in the electrocardiogram or ECG, specifically a wide QRS duration of more than 120 msec. In contrast, an ultrasound of the heart or echocardiogram provides a direct measure of ventricular dyssynchrony and may be particularly helpful in identifying patients without indirect evidence for dyssynchrony (narrow QRS patients) as candidates for CRT. EchoCRT is novel in that it will for the first time select patients who show dyssynchrony directly assessed by echocardiography, but not by ECG.

EchoCRT is supported financially by BIOTRONIK.

"BIOTRONIK is proud to be funding this important trial and to be part of the industry-leading efforts towards medical research and therapy development. This is the largest and highest priority clinical project for our company. With the introduction of the Home Monitoring technology six years ago BIOTRONIK changed the paradigms of the entire area of cardiac rhythm management. Now we set ourselves the goal to expand the indication for CRT in order to provide more patients the way to better therapy", said Dr. Werner Braun, Managing Director at BIOTRONIK GmbH & Co KG.

EchoCRT is governed by an Executive Committee that brings together a world-renowned group of leading cardiology experts from electrophysiology, cardiac imaging and heart failure.

Executive committee members are:

William T. Abraham, MD, Professor of Medicine and Director of the Division of Cardiovascular Medicine at The Ohio State University; Jeroen J. Bax, MD, Dept Cardiology, Leiden University Medical Center, The Netherlands; Jeffrey S. Borer, MD, Professor of Cardiovascular Medicine at Weill Medical College of Cornell University and Chief, Division of Cardiovascular Pathophysiology, at the New York-Presbyterian Hospital, New York; Josep Brugada, MD, Department of Cardiology, Thorax Institute, Hospital Clínic, University of Barcelona, Spain; Kenneth Dickstein, MD PhD, Professor of Medicine, University of Bergen, Norway; Daniel Gras, MD, Department of Cardiology, NCN, Nantes, France; Johannes Holzmeister, MD, Department of Cardiology, University of Zurich; Henry Krum, MD, Professor of medicine, Monash University, Melbourne; Frank Ruschitzka, M.D., Department of Cardiology, University of Zurich.

Perspectives on EchoCRT:

William T. Abraham

"This landmark trial has the potential to expand the indication for CRT to hundreds of thousands of needy heart failure patients", said Dr. William T. Abraham. "These patients have poor quality of life, severe limitation in activity level, and high rates of hospitalization and death. CRT may improve these outcomes, a hypothesis to be tested in EchoCRT."

Joeren John Bax

"More information on the potential use and benefit of CRT in patients with a narrow QRS complex is urgently needed."

Josep Brugada

"So far, patients with heart failure and a narrow QRS complex can not benefit from cardiac resynchronization therapy because so far no evidence has been provided. This study will explore whether these patients might also benefit from CRT."

Kenneth Dickstein

"Measurements of dyssynchrony have been previously based on electrocardiographic criteria and CRT recommendations are restricted to this population. This trial explores efficacy in the large patient population with evidence of mechanical dyssynchrony, the real target for CRT. Additionally, the trial represents an important cooperative effort between electrophysiologists, echocardiographers and heart failure physicians."

Daniel Gras

"Thanks to the positive results of controlled studies, a large number of drug refractory heart failure patients may now benefit from CRT. Thanks to the recent advances achieved in the field of Echocardiography, we may now select an additional subgroup of patients with narrow QRS who could potentially also benefit from CRT. Based on the concept of evidenced based medicine, this hypothesis will, precisely, be investigated in the Echo CRT trial."

Henry Krum

"Positive trial results would add significant validity to the combination of device based therapies with drug regimens in the treatment of heart failure."

Thomas Lüscher, Head of Cardiology, University Zurich comments: "Severe heart failure is an increasing medical need. CRT may provide an effective treatment option for many and an alternative for transplantation in some patients. Zurich is proud to lead this important effort."