Valsalva-derived Measures and Phenylephrine Test in Patients With Heart Failure With Reduced Ejection Fraction Receiving Comprehensive Neurohormonal Blockade Drug Therapy: A 5-year Event-free Survival Analysis.

BACKGROUND: To assess the relationships between Valsalva- and phenylephrine test-derived measures and outcome in patients with heart failure with reduced ejection fraction (HFrEF) receiving comprehensive neurohormonal blockade pharmacotherapy. METHODS AND RESULTS: Data from 56 patients with HFrEF (mean left ventricle ejection fraction of 32 ± 6%) subjected to Valsalva and phenylephrine tests were analyzed retrospectively. Baroreflex-related (Valsalva-ratio and blood pressure-RR interval slope from phase IV) and non-baroreflex-related measures (systolic blood pressure rise in phase IV [ΔSBPPHASE_IV], and pulse amplitude ratio [PAR]) were calculated from Valsalva. Short-term outcomes (HF-related hospitalization, implantable cardioverter-defibrillator shock or all-cause death within 24 months from examination) and long-term outcomes (implantable cardioverter-defibrillator shock or all-cause death within 60 months) were analyzed. The end point occurred in 16 and 18 patients, for the short- and long-term outcomes, respectively. A low ΔSBPPHASE_IV identified patients at risk in the long term, as evidenced by a low vs high ΔSBPPHASE_IV comparison (square-wave response patients assigned to low ΔSBPPHASE_IV group, P = .002), and Cox model (hazard ratio 0.91, 95% confidence interval 0.86-0.96, P < .001), and tended to identify patients at risk in the short term outcome (hazard ratio 0.95, 95% confidence interval 0.91-1.00, P = .055). There was a tendency toward a higher event-free survival in the low PAR group (low vs high PAR; hazard ratio 0.44, 95% CI 0.17-1.18, P = .104). CONCLUSIONS: Non-baroreflex-related measures obtained from Valsalva-namely, ΔSBPPHASE_IV and PAR-might carry prognostic value in patients with HFrEF receiving neurohormonal blockade pharmacotherapy.

Neck Chamber Technique Revisited: Low-Noise Device Delivering Negative and Positive Pressure and Enabling Concomitant Carotid Artery Imaging With Ultrasonography.

Background and Objectives: Recently, novel noiseless device for the assessment of baroreceptor function with the neck suction (NS) has been presented. In this study, we present another in-house approach to the variable-pressure neck chamber method. Our device offers further critical improvements. First, it enables delivery of negative (NS) as well as positive pressure (neck pressurizing, NP) in a noiseless manner. Second, we used small, 3D-printed cups positioned over the carotid sinuses instead of cumbersome neck collar to improve subject comfort and to test feasibility of tracking the pressure-induced changes in carotid artery with ultrasonography. Methods: Five healthy, non-smoking, normal-weight subjects aged 29 ± 3 years (mean ± SD) volunteered for the study. Heart rate (HR, bpm) and mean arterial pressure (MAP, mmHg) responses to short, 7-s long episodes of NS and NP were recorded. Each trial consisted of 12 episodes of variable-pressure: six episodes of NS (suction ranging between -10 and -80 mmHg) and six episodes of NP (pressure ranging between + 10 and + 80 mmHg). Carotid artery sonography was performed during the NS and NP in four subjects, on another occasion. Results: The variable-pressure episodes resulted consistently in the expected pattern of hemodynamic alterations: HR and MAP increases or decreases following the NP and NS, respectively, as evidenced by the coefficient of determination (R2) of ≥0.78 for the carotid-HR response curve (for all five participants) and the carotid-MAP response curve (for four out of five participants; the curve cannot be calculated for one subject). We found a linear, dose-dependent relation between the applied pressure and the systolic-diastolic difference in carotid artery diameter. Conclusion: The novel device enables noiseless stimulation and unloading of the carotid baroreceptors with the negative and positive pressure, respectively, applied on the subject's neck via small, asymmetric and one-side flattened, 3D-printed cups. The unique design of the cups enables concomitant visualizing of the carotid artery during the NS or NP administration, and thereby direct monitoring of the intensity of mechanical stimulus targeting the carotid baroreceptors.