SNOWMASS, COLO. – The indication for primary prophylactic implantable cardioverter-defibrillator therapy in patients with nonischemic heart failure is likely to be downgraded in the next iteration of the ACC/AHA heart failure guidelines as a consequence of the negative results of the DANISH trial, William T. Abraham, MD, predicted at the Annual Cardiovascular Conference at Snowmass.

In addition to outlining where the guideline recommendations for implantable cardioverter-defibrillator (ICD) therapy stand today, and how they’re likely to change in response to the DANISH findings, he highlighted the latest patient selection criteria for cardiac resynchronization therapy (CRT), which have grown considerably more complicated over time.

Dr. William T. Abraham is professor of medicine, physiology, and cell biology and director of the division of cardiovascular medicine at Ohio State University in Columbus. — Dr. William T. Abraham

During the past 15 or so years, CRT and ICDs have had a remarkable impact on the treatment of heart failure, observed Dr. Abraham, professor of medicine, physiology, and cell biology and director of the division of cardiovascular medicine at Ohio State University in Columbus.

“Following the success of neurohormonal inhibitors and antagonists, our only other breakthroughs for the management of heart failure have been CRT and ICDs,” he noted.

The two device therapies are complementary, and indeed are often employed in combination.

“CRT makes patients feel better and saves lives, while ICDs prolong survival without an effect on improving heart failure per se,” the cardiologist explained.

To put the quality of life benefits of CRT into perspective, studies show that the device therapy results in a placebo-subtracted improvement on the Minnesota Living With Heart Failure Questionnaire of 9-10 points.

“This is a large and clinically meaningful improvement in quality of life. Our best drugs for heart failure – beta blockers and ACE inhibitors – improve this same measure by 4 or 5 points,” Dr. Abraham said.

Current American College of Cardiology/American Heart Association heart failure guidelines give a class I, level of evidence: A, recommendation for prophylactic ICD therapy in patients with an left ventricular ejection fraction (LVEF) of 35% or less and New York Heart Association functional class II or III symptoms despite optimal medical therapy, regardless of whether their heart failure is attributable to ischemic heart disease or nonischemic dilated cardiomyopathy.

The DANISH trial investigators looked at the evidence base for primary prevention ICDs in nonischemic heart failure and concluded it needed shoring up. The recommendation relied mainly on subgroup analyses of larger landmark trials done about 15 years ago, before major improvements in medical therapy had occurred. These reservations were the impetus for the DANISH trial, in which more than 1,100 patients with symptomatic systolic heart failure were randomized to an ICD or usual care.

The primary outcome in the DANISH trial – all-cause mortality – occurred in 21.6% of patients in the ICD group and 23.4% of controls during a median follow-up of 68 months, a nonsignificant difference (N Engl J Med. 2016 Sep 29;375[13]:1221-30).

Turning to the CRT guidelines, Dr. Abraham noted that the simple, broad, class I recommendation for this form of device therapy in patients with cardiac dyssynchrony as defined by a QRS duration greater than 120 msec contained in the 2005 ACC/AHA heart failure guidelines has been whittled down over time as new evidence has unfolded. The only class I recommendation in the current guidelines is in patients with an LVEF of 35% or less, sinus rhythm, left bundle branch block with a QRS duration of 150 msec or longer, and NYHA class II, III, or ambulatory IV symptoms while on guideline-directed medical therapy (Circulation. 2012 Oct 1;126:1784-800). “That’s the money group right there. That’s the group for whom we have the greatest confidence of producing the greatest benefit with the application of cardiac resynchronization therapy,” he explained.

Studies examining the use of CRT in heart failure patients with a non–left bundle branch morphology and a QRS duration of less than 150 msec have yielded negative findings. So have attempts to utilize echocardiographic evidence of mechanical dyssynchrony rather than ECG measurement of QRS duration to guide patient selection for CRT.

“In our practice, any patient with a left bundle branch block gets a CRT device. Our confidence in its efficacy is greater in patients with a QRS of at least 150 msec, but the studies demonstrate clear benefit for patients with left bundle branch block and a QRS of 120-149 msec as well,” according to the cardiologist.

Studies also show that patients who are dependent upon ventricular pacing benefit from CRT.

“If you have a patient who requires at least 40% or more ventricular pacing and also has reduced ejection fraction heart failure, that patient should have a CRT device rather than a dual chamber ICD or standard right-sided right ventricular pacemaker,” he said.

All of this presupposes that first and foremost the patient is already on optimized guideline-directed medical therapy.

“With optimal medical therapy, some of these patients may improve their left ventricular ejection fraction above 35%, or they may become asymptomatic and no longer have an indication for CRT,” Dr. Abraham added.

The rationale for utilizing CRT in combination with an ICD is a bit shaky, resting on a single older landmark study, the COMPANION trial (N Engl J Med. 2004; 350:2140-50).

“That study wasn’t powered to answer the question of whether CRT-D [a combined CRT/ICD device] is better than CRT. Really, this remains somewhat of an unanswered question. So where are we today? Essentially, if a patient has an indication for CRT and an indication for an ICD, we implant a combined device,” he said.

Dr. Abraham reported serving as a consultant to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical.

bjancin@frontlinemedcom.com

Trials refine device therapy options for heart failure