Author + information
- John D. Bisognano, MD, PhD⁎ (, )
- Christopher L. Kaufman, PhD,
- David S. Bach, MD,
- Eric G. Lovett, PhD,
- Peter de Leeuw, MD,
- DEBuT-HT and Rheos Feasibility Trial Investigators
- ↵⁎Department of Internal Medicine, Cardiology Division, University of Rochester Medical Center, 601 Elmwood Avenue, Box 679-7, Rochester, New York 14642-8679
To the Editor:
Hypertension (HTN) is associated with adverse prognosis, accompanied by changes in left ventricular (LV) size, structure, and function (1,2). Echocardiographic LV measures, including left ventricular mass index (LVMI), are correlated with outcome among patients with systemic HTN (3). Despite known adverse effects of HTN (4) and several drugs for its treatment, many patients have persistent HTN despite aggressive medical therapy.
The Rheos system uses baroreflex activation therapy (BAT) to chronically activate the baroreflex at the carotid sinus with electrical impulses from a pulse generator. Preliminary results showed that BAT significantly reduced blood pressure in patients with drug-resistant HTN (5). This investigation aimed to assess the impact of BAT on echocardiographic measures of cardiac structure and function in patients with drug-resistant HTN.
As a substudy of the proof-of-principle DEBuT-HT (Device Based Therapy in Hypertension Extension Trial; NCT00710294) and U.S. feasibility trials (NCT01077180 and NCT00710190), this investigation involved acquiring serial echocardiograms on 34 patients at 8 different centers, of whom 21 patients had complete paired data after 1 year of BAT. Inclusion criteria included drug-resistant HTN with systolic blood pressure (SBP) ≥160 mm Hg and stable medication of ≥3 anti-HTN drugs including a diuretic at maximally tolerated dose. Ethics committees and/or institutional review boards reviewed and approved the study protocol. All participants provided written informed consent.
Office heart rate (HR) and BP were obtained using automated electronic BP measurement devices (BPM-200, BpTRU Medical Devices, Coquitlam, British Columbia, Canada; or Omron 907XL, Omron Healthcare, Kyoto, Japan) using standard methods.
Patients were implanted with the Rheos system (CVRx Inc., Minneapolis, Minnesota), consisting of a pulse generator and leads tunneled subcutaneously to attach to each carotid sinus. Therapy was activated approximately 1 month after device implantation. Stimulation parameters were gradually adjusted over time such that optimal therapy was delivered by 4 months after device implantation.
Transthoracic echocardiographic and Doppler imaging were performed by trained sonographers before Rheos implant and 3 and 12 months after active BAT. Left ventricular measurements were made from 2-dimensional images using standard techniques (6). Images were analyzed with commercially available software (ProSolv version 3.0.48, Prosolv Cardiovascular Solutions, Indianapolis, Indiana) by a single investigator blinded to treatment status, study visit time point, and clinical data.
Comparisons before and after intervention were made with paired t tests with the exception of 3 variables that were found to have non-normal distributions. The Wilcoxon signed-rank nonparametric test was used to test for significant change over time in those variables found to have non-normal distributions. Statistical analyses were performed with SAS (version 9.1.3, SAS Institute Inc., Cary, North Carolina). Data are presented as means ± SE for variables in which parametric testing was performed and as median and quartiles for variables in which nonparametric testing was performed.
The study included 34 patients (19 men, 15 women; age 52.5 ± 1.8 years). Follow-up echocardiographic data after 12 months of BAT was available for 21 patients. No significant differences in response to BAT for variables characterizing cardiac structure and function or hemodynamic response (SBP, diastolic BP, and HR) were observed between those with versus without 12-month follow-up data at the 3-month time point. At the time of enrollment, patients averaged 5.3 ± 0.3 anti-HTN medications (range 3 to 10).
Systolic and diastolic BP, HR, and rate pressure product were significantly reduced following 3 and 12 months of BAT (Table 1). One year of BAT reduced left atrial (LA) dimension, LV wall thicknesses, LV mass, and LV stroke work (p < 0.001). Significant reduction in mitral A-wave velocity, LA dimension, and LVMI suggested reduced LV diastolic filling pressures with BAT. Abnormal LVMI was present at pre-implant in 17 of 21 patients with data at 1 year. Eight of those 17 patients (47%) had LVMI in the reference range after 12 months. No signs of deteriorating LV systolic function were present (i.e., no reduced LV ejection fraction, no increased LV end-diastolic diameter).
Our findings indicated that BAT improved LA and LV structure and function in patients with drug-resistant HTN against a background of aggressive medical therapy. Previous trials of antihypertensive medications have found LVMI reductions of 2% to 14% with monotherapy (4,7,8). Baroreflex activation therapy reduced LVMI by approximately 18%, with baseline LVMI being greater than that in many previous studies. This large reduction in LVMI achieved by BAT was incremental to benefits conferred by antihypertensive medications (including 91% of patients using angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers).
This study had limitations, including lack of control group, potential placebo effect, and medication adjustment per physician discretion (medication actually decreased at 12 months [data not shown], suggesting that remodeling was not explained by intensified medication).
In summary, significant improvements were observed in LA and LV structure and function after chronic BAT in patients with resistant HTN. Cardioprotective effects of BAT on BP and LV structure and function are being further evaluated in ongoing randomized clinical trials.
Please note: This study was funded by CVRx Inc., Minneapolis, Minnesota. Drs. Bisognano, Bach, and de Leeuw have received modest research grant support from CVRx and have previously or are currently serving as consultants/advisors for CVRx. Drs. Kaufman and Lovett are employees of CVRx.
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