Dataset Information

Endovascular baroreflex amplification and the effect on sympathetic nerve activity in patients with resistant hypertension: A proof-of-principle study

ABSTRACT:

Background

First in human studies suggest that endovascular baroreflex amplification (EVBA) lowers blood pressure (BP). To explore potential mechanisms for BP reduction, this study examines the effects of EVBA on muscle sympathetic nerve activity (MSNA) and baroreceptor sensitivity (BRS).

Methods

In a single-center sub-study of the CALM-DIEM study (Controlling And Lowering blood pressure with the MobiusHD—Defining Efficacy Markers), 14 patients with resistant hypertension were treated with EVBA. Microneurography and non-invasive continuous BP measurements were performed at baseline and three months after MobiusHD implantation. The primary outcome was change in MSNA. Secondary outcomes were change in baroreflex sensitivity (BRS), cardiovascular responses to a sympathetic stimulus, BP, heart rate (HR) and heart rate variability (HRV).

Results

The primary endpoint was obtained in 10 of 14 patients enrolled in the sub-study. MSNA burst frequency and burst incidence decreased in 6 of 10 patients: mean change -4.1 bursts/min (95% confidence interval -12.2 to 4.0) and -3.8 bursts/100 heartbeats (-15.2 to 7.7). MSNA spike frequency and spike count decreased in 8 of 10 patients: mean change -2.8 spikes/sec (-7.3 to 1.8) and -3.0 spikes/heartbeat (-6.1 to 0.1). Change in MSNA and BP were not correlated. Office BP decreased by -14/-6 mmHg (-27 to -2/-15 to 3). We observed a trend towards decreased HR (-5 bpm, -10 to 1) and increased total power HRV (623 msec2, 78 to 1168). In contrast, BRS and cardiovascular responses remained unchanged after EVBA.

Conclusions

In this proof-of-principle study, EVBA did not significantly decrease MSNA in patients with resistant hypertension. EVBA did not impair baroreflex function.

Trial registration

Clinical trial registration at NCT02827032.

SUBMITTER: van Kleef M

PROVIDER: S-EPMC8594823 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:What is the central question of this study? Our goal was to understand the autonomic responses to eating in patients with congenital afferent baroreflex failure, by documenting changes in blood pressure and heart rate with chewing, swallowing and stomach distension. What is the main finding and its importance? Patients born with lesions in the afferent baroreceptor pathways have an exaggerated pressor response to food intake. This appears to be a sympathetically mediated response, triggered by chewing, that occurs independently of swallowing or distension of the stomach. The chewing-induced pressor response may be useful as a counter-manoeuvre to prevent orthostatic hypotension in these patients. Familial dysautonomia (FD) is a rare genetic disease with extremely labile blood pressure resulting from baroreflex deafferentation. Patients have marked surges in sympathetic activity, frequently surrounding meals. We conducted an observational study to document the autonomic responses to eating in patients with FD and to determine whether sympathetic activation was caused by chewing, swallowing or stomach distension. Blood pressure and R-R intervals were measured continuously while chewing gum (n = 15), eating (n = 20) and distending the stomach by percutaneous endoscopic gastrostomy tube feeding (n = 9). Responses were compared with those of normal control subjects (n = 10) and of patients with efferent autonomic failure (n = 10) who have chronically impaired sympathetic outflow. In patients with FD, eating was associated with a marked but transient pressor response (P < 0.0001) and additional signs of sympathetic activation, including tachycardia, diaphoresis and flushing of the skin. Chewing gum evoked a similar increase in blood pressure that was higher in patients with FD than in control subjects (P = 0.0001), but was absent in patients with autonomic failure. In patients with FD, distending the stomach by percutaneous endoscopic gastrostomy tube feeding failed to elicit a pressor response. The results provide indirect evidence that chewing triggers sympathetic activation. The increase in blood pressure is exaggerated in patients with FD as a result of blunted afferent baroreceptor signalling. The chewing pressor response may be useful as a counter-manoeuvre to raise blood pressure and prevent symptomatic orthostatic hypotension in patients with FD.