Pacemaker-Mediated Programmable Hypertension Control Therapy

Abstract

Background: Many patients requiring a pacemaker have persistent hypertension with systolic blood pressures above recommended levels. We evaluated a pacemaker-based Programmable Hypertension Control (PHC) therapy that uses a sequence of variably timed shorter and longer atrioventricular intervals.

Methods and results: Patients indicated for dual-chamber pacing with office systolic blood pressure (oSBP) >150 mm Hg despite stable medical therapy were implanted with a Moderato™ pulse generator that delivers PHC therapy. Patients were followed for 1 month (Run-In period) with conventional pacing; those with persistent oSBP >140 mm Hg were included in the study and had PHC therapy activated. The co-primary efficacy end points were changes in 24-hour ambulatory systolic blood pressure and oSBP between baseline and 3 months. Safety was assessed by tracking adverse events. Thirty-five patients met the initial inclusion criteria and underwent Moderato implantation. At 1 month, oSBP was <140 mm Hg in 7 patients who were excluded. PHC was activated in the remaining 27 patients with baseline office blood pressure 166±11/80±10 mm Hg despite an average of 3.2 antihypertensive medications. During the Run-In period, oSBP and 24-hour ambulatory systolic blood pressure decreased by 8±13 and 5±12 mm Hg (P<0.002), respectively. Compared with pre-PHC activation measurements, oSBP decreased by another 16±15 mm Hg and 24-hour ambulatory systolic blood pressure decreased by an additional 10±13 mm Hg (both P<0.01) at 3 months. No device-related serious adverse effects were noted.

Conclusions: In pacemaker patients with persistent hypertension despite medical therapy, oSBP and 24-hour ambulatory systolic blood pressure are decreased by PHC therapy. Initial indications are that this therapy is a safe and promising therapy for such patients.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02282033.

Keywords: AV Delay; Hypertension; Isolated Systolic Hypertension; Pacing.

Figure 1

CONSORT flow chart showing number of patients coursing through the various stages of the protocol. CONSORT indicates Consolidated Standards of Reporting Trials; HTN, hypertension; IPG, implantable pulse generator; PHC, programmable hypertension control; SBP, systolic blood pressure.

Figure 2

A, Beat‐by‐beat measurements of systolic blood pressure (by Finapres device) in response to a change of pacing from normal AV delay to pacing with an AV delay of 40 ms (green arrow). Note initial large drop and subsequent exponential rise of pressure to a new steady level only ≈5 mm Hg less than the original baseline. When normal AV delay pacing is resumed (red arrow), there is an initial overshoot of pressure followed by a more rapid return to baseline. B, When a repeating sequence of 10 short AV paced beats (at 40 ms) and 2 beats with longer AV delays (140 ms) is initiated (green arrow), there are no significant transients in blood pressure changes, even when constant, long AV delay pacing is resumed (red arrow). This repeating sequence, which is PHC pacing therapy, prevents sympathetic activation despite reduction of systolic blood pressure. AV indicates atrioventricular; PHC, programmable hypertension control.

Figure 3

A, Example of a histogram of systolic blood pressure distribution obtained from 24‐h ambulatory blood pressure monitoring before and +3 months after activation of programmable hypertension control (PHC) therapy. B, Mean±95% confidence intervals of 24‐hour ambulatory systolic pressures at baseline, immediately after activation, and +3 months of PHC therapy from the 27 patients included in the Hypertension Therapy phase of the study. C, Sixteen of the patients were enrolled after a protocol modification that allowed additional measurements of 24‐hour ambulatory blood pressures (shown in blue). These measurements showed a 5.3±11.7 mm Hg (P=0.09) reduction in SBP from baseline to 2 weeks (−0.5 months) during the Run‐In phase. Results from the first 11 patients in whom measurements were made at baseline, just after and at +3 months (shown in red), show similar results at common time points. SBP indicates systolic blood pressure.

Figure 4

A, Office systolic blood pressure (SBP) measurements (means±95% confidence intervals) from the 27 patients included in the hypertension study. B, Changes in office SBP (means±95% confidence intervals) compared with preactivation, for all available time points following activation of programmable hypertension control (PHC) therapy. Numbers below or above error bars denote numbers of patients available for SBP measurement at the respective time point (all patients who reached the specific time point were included).

Figure 5

Changes in 24‐h ambulatory systolic blood pressure (24hASBP) and office systolic blood pressure (oSBP) from baseline (A and C) and from pre‐PHC activation (B and D). Numbers quantify number of patients whose SBP decreased (in green) and those whose SBP did not decrease (in red). PHC indicates programmable hypertension control.