LAS VEGAS – Percutaneous ventricular restoration using the Parachute device in patients with ischemic dilated cardiomyopathy had a promisingly low 26% combined rate of all-cause mortality and heart failure hospitalization at 1 year in the PARACHUTE III trial, according to Dr. William T. Abraham

PARACHUTE III was a European postmarketing study. And while the composite endpoint of all-cause mortality and heart failure hospitalization was a prespecified secondary outcome in that study, it’s the primary endpoint in the ongoing pivotal U.S. phase III PARACHUTE IV trial headed by Dr. Abraham.

The Parachute device may slow or reverse progression of heart failure in patients with ischemic dilated cardiomyopathy.

What’s encouraging about the PARACHUTE III result is that the 26% rate of the combined endpoint is in line with the PARACHUTE IV investigators’ assumption for outcomes in the ongoing U.S. trial, which will randomize roughly 500 patients to device therapy plus optimal medical therapy or optimal medical therapy alone, he reported at the annual meeting of the Heart Failure Society of America.

“The PARACHUTE III results are reassuring. In historical controls, the expected rate [of all-cause mortality and heart failure hospitalization] in this kind of population at 1 year is about 35%,” according to Dr. Abraham, professor of internal medicine, physiology, and cell biology and director of the division of cardiovascular medicine at Ohio State University, Columbus.

Plus, technical improvements in device design and percutaneous implantation technique have been made since PARACHUTE III and are incorporated in PARACHUTE IV. These improvements could drive the composite endpoint rate in the ongoing U.S. trial even lower, he continued. For example, while the 1-year major complication rate in the European postmarketing study was 11%, thus far it’s less than 8% in the U.S. experience.

The proprietary Parachute device is so named because, when deployed, it looks like an upside-down parachute. It is intended for patients with ischemic dilated cardiomyopathy secondary to anteroapical MI. The goal of this device therapy is to attenuate or reverse progression of heart failure in this high-risk population.

The Parachute device has two proposed mechanisms of action, the cardiologist explained. One involves ventricular restoration via ventricular partitioning to reduce wall stress in the upper chamber as well as fostering a return to a more normal, elliptical shape to the heart. Dr. Abraham termed the other mechanism a trampoline effect, in which the compliant device encourages replacement of eccentric apical wall motion with more synchronized wall motion throughout the cardiac cycle.

The device, comprised mainly of a fluoropolymer membrane and a nitinol frame, is implanted percutaneously retrograde across the aortic valve. It is placed in the apex of the left ventricle.

The European Union PARACHUTE III postmarketing study was a single-arm study including 100 consecutive symptomatic patients in 10 countries. Their baseline left ventricular ejection fraction was 28%. Device implantation was accomplished in 97 of the 100 patients, with a mean 94-minute procedure duration and 23 minutes of fluoroscopy time.

The primary study endpoint was a safety outcome: the 1-year rate of procedure- and/or device-related adverse events. The 7% rate included several cases of left ventricular perforation as well as aortic or mitral valve damage.

“The rates and distribution of these events are comparable to other structural heart disease interventions, such as transcatheter aortic valve replacement, and might be considered an acceptable postmarketing result,” Dr. Abraham commented.

There was a 3.2% stroke rate through 1 year and a 9.5% mortality rate.

Hemodynamic improvements were seen in both systolic and diastolic function. The left atrial volume index improved from 42.5 to 38.3 mL/m², indicative of favorable remodeling. The improvement in systolic function was expressed in an increased contractility index.

Moreover, left ventricular end-systolic volume index improved over the course of the year from 84 to 70.5 mL/m², while left ventricular end-diastolic volume index also improved, from 117.3 to 99.1 mL/m².

Eighty percent of patients maintained or improved their 6-minute walk distance. On average, patients improved their walk distance by 25 m from a mean baseline of 372 m. Similarly, 80% of patients maintained or improved their baseline New York Heart Association functional class.

Discussant Dr. James C. Fang called the Parachute device “an important investigational therapeutic option. ” He urged cardiologists to enroll patients in PARACHUTE IV in order to learn whether the percutaneous device therapy will indeed enable patients to live longer and/or avoid hospitalizations for heart failure.

The improvements in myocardial contractility and left atrial volume documented in PARACHUTE III are particularly encouraging, added Dr. Fang, professor of internal medicine and chief of the division of cardiovascular medicine at the University of Utah, Salt Lake City.

Dr. Abraham reported serving as a consultant to CardioKinetix, which sponsors the PARACHUTE IV trial.

bjancin@frontlinemedcom.com

Heart failure device shown safe in PARACHUTE III