Subgroup Analysis of a Randomized Controlled Trial Evaluating the Safety and Efficacy of Cardiac Contractility Modulation in Advanced Heart Failure

Background: Cardiac contractility modulation (CCM) signals are nonexcitatory electrical signals delivered during the absolute refractory period intended to improve contraction. We previously tested the safety and efficacy of CCM in 428 NYHA functional class III/IV heart failure patients with EF #35% and narrow QRSrandomizedtooptimalmedicaltreatment(OMT)plusCCM(n5215)versusOMTalone(n5213)and found no significant effect on ventilatory anaerobic threshold (VAT), the study’s primary end point. In the present analysis, we sought to identify if there was a subgroup of patients who showed a response to CCM. Methods and Results: The protocol specified that multiregression analysis would be used to determine if baselineEF,NYHAfunctional class,pVO2,oretiologyofheartfailure influencedtheimpactofCCM onAT. Etiology and baseline pVO2 did not affect efficacy. However, baseline NYHA functional class III and EF $25% were significant predictors of increased efficacy. In this subgroup (comprising 97 OMTand 109 CCM patients, w48% of the entire population) VAT increased by 0.10 6 2.36 in CCM versus � 0.54 6 1.83 mL kg � 1 min � 1 in OMT (P 5 .03) and pVO2 increased by 0.34 6 3.11 in CCM versus � 0.97 6 2.31 (P 5 .001) at 24 weeks compared with baseline; 44% of CCM versus 23% of OMT subjects showed improvement of $1 class in NYHA functional class (P 5 .002), and 59% of CCM versus 42% of OMT subjects showed a $10-point reduction in Minnesota Living with Heart Failure Questionnaire (P 5 .01). All of these findings were similar to those seen at 50 weeks. Conclusions: The results of this retrospective hypothesis-generating analysis indicate that CCM significantlyimprovesobjectiveparametersofexercisetoleranceinasubgroupofpatientscharacterizedbynormal QRS duration, NYHA functional class III symptoms, and EF O25%. (J Cardiac Fail 2011;17:710e717)