A Medical Device Daily

Biotronik (Berlin), a company that makes wireless remote monitoring technologies for patients with implantable cardiac defibrillators (ICDs) and pacemakers, reported FDA approval to begin an international, prospective, randomized, controlled clinical trial to investigate the use of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with left ventricular systolic dysfunction.

Biotronik said the study, called Echocardiography-guided Cardiac Resynchronization Therapy (EchoCRT), will include more than 1,250 patients with HF, already receiving current standard HF pharmacological therapy, with a narrow QRS width (< 130 ms) and echocardiographic evidence of left ventricular (LV) dyssynchrony.

The study will involve 125 centers worldwide, and is being conducted according to FDA guidelines under an Investigational Device Exemption, the company said.

"The objective of this study is to demonstrate that optimal medical therapy plus CRT reduces all-cause mortality or first hospitalization for worsening heart failure in the study population compared to optimal medical therapy alone," said Frank Ruschitzka, MD, University of Zurich, executive committee co-chairman and international co-principal investigator of EchoCRT. "EchoCRT will provide important scientific evidence for this large group of heart failure patients that currently lack treatment options beyond pharmacological therapy."

"Previous randomized controlled trials with CRT had been limited to patients with a QRS width = 120 ms-130 ms, who represent only 28% of all subjects with chronic heart failure," said William Abraham, MD, from Ohio State University (Columbus), U.S. principal investigator of the study. "Results of recent small studies are encouraging that patients without electrical intraventricular conduction delays but with LV dyssynchrony assessed by echocardiography may benefit from CRT. Thus, withholding CRT treatment from a significant proportion of heart failure patients with a narrow QRS complex (< 120 ms) that have LV dyssynchrony could be unwise. EchoCRT aims to definitively address this question."

Cardiovascular ultrasound equipment used to obtain echocardiograms will be limited to a single manufacturer, who also will provide training and technical support in order to reduce data variability and ensure optimal reliability of the outcomes, Biotronik said. In addition, there will be a single echo core lab, which will independently confirm patient eligibility criteria, the company noted.

In recognition of its substantial clinical benefits, CRT has been recently included in the official guidelines for the management of HF patients. However, these guidelines have limited the recommendation to patients with a QRS width of = 120 ms as a criterion for the prescription of CRT. Pending the outcomes of EchoCRT, the remaining 72% of HF patients with narrow QRS who are still in need could potentially be granted access to this therapy, the company said.

Johannes Holzmeister, MD, of the University of Zurich, executive committee co-chairman and international co-principal investigator of EchoCRT, reconfirmed, "It is established that CRT provides clinical benefit for heart failure patients with wide QRS. Now it is imperative that we understand the effects of CRT in patients with narrow QRS complex (< 130 ms) of whom up to 50% exhibit mechanical dyssynchrony."

The company said EchoCRT was designed by an independent executive committee comprised of internationally renowned cardiology experts from electrophysiology, cardiac imaging and heart failure, and a biostatistician to ensure the clinical validity of the study protocol. A clinical events committee, data safety monitoring board and study statistician are all operationally independent of Biotronik, study sponsor. The University of Zurich Coordination and Data Center will scientifically support study operations and oversight in cooperation with Biotronik, the company said.

Also at the HRS meeting, Cambridge Heart (Tewksbury, Massachusetts) said that Stefan Hohnloser, MD, presented a meta-analysis of Microvolt T-Wave Alternans (MTWA) studies. The study analyzed 14 recent trials, which collectively enrolled about 6,000 patients.

The results showed that MTWA was a highly accurate predictor of arrhythmic events in those studies that used sudden cardiac death or sustained arrhythmias as the primary endpoint. In contrast, results from studies in which "appropriate" ICD discharge was the predominant endpoint, MTWA did not demonstrate similar predictive accuracy, the company said.

Hohnloser, director of electrophysiology at J.W. Goethe University (Frankfurt, Germany), noted that "appropriate" ICD therapy appears to be an unreliable surrogate endpoint for sudden cardiac death and can significantly impact the outcome of risk stratification studies.

"These results demonstrate that MTWA is a consistently accurate predictor of sudden cardiac death and cardiac arrest in patients who do not already have implanted ICDs. These are the patients for whom MTWA testing is intended," Hohnloser said.

Cambridge Heart develops products for the non-invasive diagnosis of cardiac disease, particularly the identification of those at risk of sudden cardiac arrest. The Cambridge Heart Microvolt T-Wave Alternans Test is designed to measure a specific extremely subtle pattern of beat-to-beat fluctuations in a person's electrocardiogram. This pattern of fluctuations is called T-wave alternans. These tiny variations in the electrocardiogram — measured at one millionth of a volt accuracy — are most commonly measured during a sub-maximal exercise stress test in the doctor's office or hospital outpatient setting, the company said. The preparation for the test consists of placing sensors on the patient's chest.