SAN DIEGO – Beefing up a sick left ventricle via a set of injections of an inert alginate hydrogel resulted in significantly improved functional capacity, compared with optimal medical therapy through 6 months of follow-up in patients with advanced heart failure in the randomized AUGMENT-HF trial.
Investigators also noted “an interesting and striking reduction” in hospitalizations for worsening heart failure in the group that received left ventricular (LV) augmentation with the material, known as Algisyl-LVR, Dr. Stefan D. Anker reported at the annual meeting of the American College of Cardiology.
Bruce Jancin/Frontline Medical News
Dr. Stefan D. Anker
Indeed, among 78 patients with advanced heart failure randomized to hydrogel injections plus optimal medical therapy or to optimal medical therapy alone, there were 14 hospitalizations for worsening heart failure in eight controls, compared with 5 hospitalizations in four patients in the LV augmentation group. The between-group difference is large, but the number of hospitalizations is still small. AUGMENT-HF will continue for 2 years of follow-up.
“This gives us hope for the future,” said Dr. Anker, professor of cardiology and cachexia research at Charité Medical School, Berlin.
In addition, based upon the favorable 6-month study results, planning is underway for a larger, pivotal phase III U.S. trial of Algisyl-LVR, classified as a medical device, to start later this year.
At present, surgeons implant the hydrogel through a minithoracotomy. The procedure involves 10-20 injections totaling 4-5 mL of the inert, permanent material, which is placed as a ring of beads along a circumferential line at the left ventricular midwall.
“We make the wall thicker and the cavity of the ventricle a little smaller, thereby reducing wall stress. We basically try to change the physics of the pump action of the heart to improve patient status and perhaps patient outcome,” Dr. Anker explained.
Surgeons say it’s an easily learned procedure. The surgical morbidity and mortality seen in AUGMENT-HF were deemed acceptable by investigators and the study sponsor, so this new therapy will initially be developed as a surgical procedure. But it’s certainly a treatment that lends itself to delivery by percutaneous catheter in the future, according to the cardiologist.
Study participants had moderate to severe heart failure, with an average LV ejection fraction of 25%. Most were New York Heart Association (NYHA) functional class III.
The primary study endpoint was change in peak oxygen uptake (VO2) at 6 months from a baseline of 12.2 mL/kg/min. The value improved to 13.5 mL/kg/min in the LV augmentation group, compared with 12.4 mL/kg/min in controls, a between-group difference that Dr. Anker characterized as clinically relevant. He noted that one of the study’s strengths was that each peak VO2 result was the average of two tests performed on the same occasion, a method that markedly improves test reproducibility.
Also, 6-minute walk distance improved in the LV augmentation group by a mean of 84.7 meters from a baseline 280 meters, while decreasing by 15.4 meters in controls.
“This is quite a positive result rarely seen with other therapies. For everybody involved, this was a very positive finding,” Dr. Anker said.
Among controls, NYHC class stayed steady over the course of 6 months while showing a 0.9-class improvement in the LV augmentation group.
Heart failure etiology – ischemic versus nonischemic – had no bearing on LV augmentation’s effectiveness. Baseline 6-minute walk distance did, though. Patients with a baseline walk distance of less than 287 meters experienced a much larger treatment effect: a mean 2.42 mL/kg/min greater improvement from baseline to 6 months with LV augmentation than in controls, as compared with a nonsignificant 0.4 mL/kg/min advantage among patients who covered more than 287 meters at baseline.
The mean procedure time was 80 minutes, with 190 minutes of anesthesia time. Patients spent an average of 2 days in the ICU.
Three deaths occurred in the surgical group within the first 30 days. Excluding the index hospitalization, there were 22 major adverse cardiovascular events in the control group and 9 in the LV augmentation group. Among these were three cardiovascular deaths in each study arm, for a total of six deaths through 6 months in the LV augmentation patients. However, with additional study follow-up beyond the 6 months presented at ACC 15, mortality has evened out in the two groups, according to Dr. Anker. Sustained ventricular tachycardia occurred in four controls and one patient who received LV augmentation. Several audience members expressed surprise at the low arrhythmia rate in the LV augmentation group, but Dr. Anker’s coinvestigator Dr. Douglas L. Mann explained that the implantation doesn’t create an isthmus, thus there is no nidus for arrhythmia formation.