Assessment of permanent dual-chamber pacing as a treatment for drug-refractory symptomatic patients with obstructive hypertrophic cardiomyopathy. A randomized, double-blind, crossover study (M-PATHY). Doppler evaluation of the descending aorta in patients with hypertrophic cardiomyopathy: potential for assessing the functional significance of outflow tract gradients and for optimizing pacemaker function. Dual-chamber pacing for hypertrophic cardiomyopathy: a randomized, double-blind, crossover trial.
Dual-chamber pacing (DDD) has been proposed as a treatment alternative to surgery for severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), based largely on uncontrolled studies.
                This prospective, multicenter trial assessed pacing in 48 symptomatic HCM patients with >/=50 mm Hg basal gradient, refractory to drug therapy. Patients were randomized to 3 months each of DDD pacing and pacing backup (AAI-30) in a double-blind, crossover study design, followed by an uncontrolled and unblinded 6-month pacing trial. With randomization, no significant differences were evident between pacing and no pacing for subjective or objective measures of symptoms or exercise capacity, including NYHA functional class, quality of life score, treadmill exercise time or peak oxygen consumption. After 6 additional months of unblinded pacing, functional class and quality of life score were improved compared with baseline (P<0.01), but peak oxygen consumption was unchanged. Outflow gradient decreased 40%, 82+/-32 mm Hg to 48+/-32 mm Hg (P<0. 001), and was reduced in 57% of patients but showed no change or an increase in 43%. At 12 months, 6 individual patients (12%) showed improved functional capacity; each was 65 to 75 years of age. Left ventricular wall thicknesses in the overall study group showed no remodeling between baseline (22+/-5 mm) and 12 months (21+/-5 mm; P=NS).
                (1) Pacing cannot be regarded as a primary treatment for obstructive HCM; (2) with randomization, perceived symptomatic improvement was most consistent with a substantial placebo effect; (3) longer, uncontrolled pacing periods were associated with some subjective benefit but unaccompanied by objective improvement in cardiovascular performance and should be interpreted cautiously; (4) modest reduction in outflow gradient was achieved in most patients; and (5) a small subset (12%) >/= 65 years of age showed a clinical response, suggesting that DDD pacing could be a therapeutic option for some elderly patients. We evaluated whether analysis of aortic flow could be useful for determining the functional significance of left ventricular outflow gradients and for optimizing pacing therapy in patients with hypertrophic cardiomyopathy (HOCM).
                Doppler echocardiography was performed in 32 patients with HOCM. Eleven patients with pacemakers (PPM) also underwent treadmill and quality-of-life (QOL) testing in a randomized crossover trial (1 month of backup pacing (AAI at 30 beats per minute), 1 month with an atrioventricular interval (AVI) of 30 ms (DDD30), and 1 month with an "optimized" AVI (DDDop) that maximized the descending aortic Doppler velocity time integral.
                Patients with HOCM displayed a notch in the aortic Doppler flow profile. The location of the notch in systole corresponded with the development of the peak left ventricular outflow gradient. Aortic flow after the notch was variable ranging from 6-48% of the total flow. In patients with pacemakers, improved response to pacing was noted in those patients that developed the notch early in systole and had subsequent attenuation of aortic flow. Optimizing the AVI was associated with improved exercise tolerance (AAI: 4.6 +/- 2.3 min., DDD30: 5.5 +/- 2.2 min., and DDDop: 7.7 +/- 2.5 min.; p < 0.05) and improved QOL.
                Patients with HOCM have a notch in their aortic Doppler flow profile. The location of the notch correlates with the development of the peak left ventricular outflow gradient and flow after the notch is variable. Patients with an early notch and attenuated flow after the notch appear to have the greatest response to pacing therapy. In a double-blind, randomized, crossover trial we sought to evaluate the effect of dual-chamber pacing in patients with severe symptoms of hypertrophic obstructive cardiomyopathy.
                Recently, several cohort trials showed that implantation of a dual-chamber pacemaker in patients with severely symptomatic hypertrophic obstructive cardiomyopathy can relieve symptoms and decrease the severity of the left ventricular outflow tract gradient. However, the outcome of dual-chamber pacing has not been compared with that of standard therapy in a randomized, double-blind trial.
                Twenty-one patients with severely symptomatic hypertrophic obstructive cardiomyopathy were entered into this trial after baseline studies consisting of Minnesota quality-of-life assessment, two-dimensional and Doppler echocardiography and cardiopulmonary exercise tests. Nineteen patients completed the protocol and underwent double-blind randomization to either DDD pacing for 3 months followed by backup AAI pacing for 3 months, or the same study arms in reverse order.
                Left ventricular outflow tract gradient decreased significantly to 55 +/- 38 mm Hg after DDD pacing compared with the baseline gradient of 76 +/- 61 mm Hg (p < 0.05) and the gradient of 83 +/- 59 mm Hg after AAI pacing (p < 0.05). Quality-of-life score and exercise duration were significantly improved from the baseline state after the DDD arm but were not significantly different between the DDD arm and the backup AAI arm. Peak oxygen consumption did not significantly differ among the three periods. Overall, 63% of patients had symptomatic improvement during the DDD arm, but 42% also had symptomatic improvement during the AAI backup arm. In addition, 31% had no change and 5% had deterioration of symptoms during the DDD pacing arm.
                Dual-chamber pacing may relieve symptoms and decrease gradient in patients with hypertrophic obstructive cardiomyopathy. In some patients, however, symptoms do not change or even become worse with dual-chamber pacing. Subjective symptomatic improvement can also occur from implantation of the pacemaker without its hemodynamic benefit, suggesting the role of a placebo effect. Long-term follow-up of a large number of patients in randomized trials is necessary before dual-chamber pacing can be recommended for all patients with severely symptomatic hypertrophic obstructive cardiomyopathy.
Trials published to date lack information on clinically relevant end-points. Existing data is derived from small trials at high risk of bias, which concentrate on physiological measures. Their results are inconclusive. Further large and high quality trials with more appropriate outcomes are warranted.