September 26, 2011

September 23, 2011 (Boston, Massachusetts) — While casting a net around a poorly functioning, enlarged heart may seem a quaint approach to treating heart failure (HF), it was associated with improved echocardiographic measures of left ventricular (LV) mass and size in a previously reported study that tested the strategy in patients not responding well to guidelines-recommended HF therapy.

Now a subanalysis of that trial, the Prospective Evaluation of Elastic Restraint to Lessen the Effects of Heart Failure (PEERLESS-HF) study, suggests that use of the HeartNet (Paracor Medical), a mesh ventricular restraining device, may boost the effectiveness of cardiac resynchronization therapy (CRT) in patients who had previously been CRT nonresponders [1].

"When you put the HeartNet on, you reduce wall stress, you improve [ventricular] function regionally, and you also reduce dyssynchrony mechanically, which we think leads to improved pacing," Dr Russell J Ivanhoe, Vice President of Medical Affairs at Paracor, told heartwire . "So in a sense, HeartNet and CRT seem synergistic." Russell presented the analysis in poster form here at the Heart Failure Society of America 2011 Scientific Meeting.

In PEERLESS-HF, 217 patients were randomized at 29 US and six Canadian sites who had stage C ischemic or nonischemic HF and left ventricular ejection fraction (LVEF) <35% despite guidelines-based therapy--meds and, for those with the approved indications, CRT--to also receive or not receive a HeartNet. The device is put in place via minithoracotomy.

As previously reported by heartwire , the trial was halted early when no significant difference was seen in peak VO2 after six months. Quality-of-life scores and some echo parameters had significantly improved, but there were only trends of a benefit with HeartNet for survival, six-minute-walk distance, and New York Heart Association (NYHA) class.

The current analysis focused on the trial's 104 patients whose existing treatment at study entry had included CRT for at least three months previously (mean 1.5 years). Of that subgroup, 44 patients had been randomized to receive a HeartNet and 60 patients simply remained on meds and CRT as controls.

At six months, the HeartNet group showed significantly greater improvements in scores on two widely used quality-of-life assessments, the Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire. There was also evidence of significant reverse remodeling in the HeartNet group, including improved LV end-diastolic volume at six months and LV mass at 12 months.

Change in Quality of Life and Echocardiographic Measures in the PEERLESS-HF CRT Substudy

Parameter HeartNet (n=44) Control (n=60) p
Six months      
KCCQ +12 +4 0.01
MLHFQ –13 –7 0.05
LVEDV (mL) –11 +17 0.03
LVESV (mL) –11 +9 0.06
12 months      
LV mass (g) –37 +8 0.04

KCCQ = Kansas City Cardiomyopathy Questionnaire (greater change in scores mean greater improvement) LVEDV=left ventricular end-diastolic volume

LVESV=left ventricular end-systolic volume

MLHFQ = Minnesota Living with Heart Failure Questionnaire (lower scores mean greater improvement)

And several clinical end points improved over the mean 22-month follow-up, including hospitalizations for HF.

Ivanhoe pointed out the preliminary, hypothesis-generating nature of the overall trial, which had been prematurely stopped, and especially of the CRT subanalysis. Although the latter was not officially prespecified, he noted, it had always been planned, and investigators even intentionally "overenrolled" patients with CRT, such that they made up about half the randomized population (compared with the approximately one-third seen in clinical practice).

Hazard Ratio (HR) for Clinical Outcomes in PEERLESS-HF CRT Subanalysis, Heartnet Patients vs Controls (Mean Follow-Up, 22 Months)

Endpoint HR p
Major cardiac procedures 0.53 0.02
HF hospitalization 0.42 0.02
Death, major cardiac procedures, or HF hospitalization 0.53 0.06

According to Ivanhoe, HeartNet may improve CRT pacing efficiency because dyssynchrony tends to vary in a heart by myocardial segment, and pacing may "capture" some of the dysfunctioning segments, but not all. There is some evidence that dyssynchrony raises epicardial pressure in segments relative to those contracting normally. Applying a HeartNet, he explained, appears to mechanically restrain those segments that remain dysfunctional despite pacing, relieving the epicardial pressure.

It's all hypothesis, Ivanhoe cautioned, but the result seems to be a more consistently global ventricular resynchronization where CRT alone had previously resynchronized the ventricles only partially or not at all.

There's a confirmatory study in the works, he said, in which CRT nonresponders who meet certain functional criteria--similar to those in PEERLESS-HF--will be randomized to get a HeartNet or not and followed for a minimum of 18 months.

Ivanhoe is an employee and shareholder of Paracor Medical.