Pacemaker-based cardiac neuromodulation therapy in patients with hypertension: A pilot study

BACKGROUND: In prior unblinded studies, cardiac neuromodulation therapy (CNT) employing a sequence of variably timed short and longer atrioventricular intervals yielded sustained reductions of systolic blood pressure (SBP) in patients with hyperten-sion. The effects of CNT on SBP were investigated in this double-blind randomized pilot study. METHODS AND RESULTS: Eligible patients had daytime ambulatory SBP (aSBP) ≥130 mm Hg and office SBP ≥140 mm Hg despite taking ≥1 antihypertensive medication, and an indication for a dual-chamber pacemaker. Patients underwent Moderato device implantation, which was programmed as a standard pacemaker during a 1-month run-in phase. Patients whose daytime aSBP was ≥125 mm Hg at the end of this period were randomized (1:1, double blind) to treatment (CNT) or control (CNT inactive). The primary efficacy end point was the between-group difference of the change in 24-hour aSBP at 6 months. Of 68 patients initially enrolled and who underwent implantation with the Moderato system, 47 met criteria for study continuation and were randomized (26 treatment, 21 control). The mean age was 74.0±8.7 years, 64% were men, left ventricular ejection fraction was 59.2%±5.7%, and aSBP averaged 141.0±10.8 mm Hg despite the use of 3.3±1.5 antihypertensive medications; 81% had isolated systolic hypertension. Six months after randomization, aSBP was 11.1±10.5 mm Hg (95% CI, −15.2 to −8.1 mm Hg) lower than prerand-omization in the treatment group compared with 3.1±9.5 mm Hg (−7.4 to 1.2 mm Hg) lower in controls, yielding a net treatment effect of 8.1±10.1 mm Hg (−14.2 to −1.9 mm Hg) (P=0.012). There were no Moderato device– or CNT-related adverse events. CONCLUSIONS: CNT significantly reduced 24-hour aSBP in patients with hypertension with a clinical indication for a pacemaker. The majority of patients had isolated systolic hypertension, a particularly difficult group of patients to treat.