Long-term effects of device-guided slow breathing in stable heart failure patients with reduced ejection fraction.

BACKGROUND: Slow breathing (SLOWB) alleviates symptoms of chronic heart failure (HF) but its long-term effects are unknown. We examined the acute and long-term impact of device-guided breathing on hemodynamics and prognostic parameters in HF patients with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Twenty-one patients with HFrEF (23.9 ± 5.8%, SD ± mean) on optimal medical therapy underwent blood pressure (BP), heart rate (HR), HR variability, 6-min walk test (6MWT), cardiopulmonary exercise testing (CPET), and echocardiography measurements before and 3 months after SLOWB home training (30 min daily). After 3 months, all patients were assigned to continue SLOWB (Group 1) or no-SLOWB (Group 2). All tests were repeated after 6 months. Acute SLOWB (18 ± 5 vs 8 ± 2 breaths/min, P < 0.001) had no influence on BP and HR but improved saturation (97 ± 2 vs 98 ± 2%, P = 0.01). Long-term SLOWB reduced office systolic BP (P < 0.001) but not central or ambulatory systolic BP. SLOWB reduced SDNN/RMSSD ratio (P < 0.05) after 3 months. One-way repeated measures of ANOVA revealed a significant increase in 6MWT and peak RER (respiratory exchange ratio) from baseline to 6-month follow-up in group 1 (P < 0.05) but not group 2 (P = 0.85 for 6MWT, P = 0.69 for RER). No significant changes in echocardiography were noted at follow-up. No HF worsening, rehospitalisation or death occurred in group 1 out to 6-month follow-up. Two hospitalizations for HF decompensation and two deaths ensued in group 2 between 3- and 6-month follow-up. CONCLUSIONS: SLOWB training improves cardiorespiratory capacity and appears to slow the progression of HFrEF. Further long-term outcome studies are required to confirm the benefits of paced breathing in HFrEF.

Recent advances in the pathophysiology of arterial hypertension: potential implications for clinical practice.

Hypertension remains a major and growing public health problem associated with the greatest global rate of cardiovascular morbidity and mortality. Although numerous factors contribute to poor control of blood pressure (BP) and to pseudoresistance (eg, unawareness, lifestyle habits, nonadherence to medication, insufficient treatment, drug­induced hypertension, undiagnosed secondary causes), true resistant hypertension (RH) is reported in 10.1% of patients treated for elevated BP. While the mechanisms underlying RH remain complex and not entirely understood, sympathetic activation involved in the pathophysiology of hypertension, disease progression, and adverse complications is further augmented in patients with drug­resistant hypertension. The well­established contribution of neurogenic component of hypertension has led to the introduction of new alternative therapies aimed specifically at modulating central and neural reflexes mechanisms involved in BP control. Although clinical benefits of lowering BP with renal denervation, baroreflex activation therapy, carotid body denervation, central arteriovenous anastomosis, and deep brain stimulation have advanced our knowledge on uncontrolled hypertension, the variable BP response has prompted extensive ongoing research to define predictors of treatment effectiveness and further investigation of pathophysiology of RH. Very recently, research on the role of vasopressinergic neurons, masked tachycardia, and impaired brain neural activity has provided novel insights into hypertension. This review briefly summarizes the role of the centrally mediated sympathetic nervous system in hypertension, the therapeutic strategies that distinctively target impaired neural reflex mechanisms, and potential implications for future clinical research and therapies.

Reverse cardiac remodeling after renal denervation: Atrial electrophysiologic and structural changes associated with blood pressure lowering.

BACKGROUND: Hypertension is the most common modifiable risk factor associated with atrial fibrillation. OBJECTIVE: The purpose of this study was to determine the effects of blood pressure (BP) lowering after renal denervation on atrial electrophysiologic and structural remodeling in humans. METHODS: Fourteen patients (mean age 64 ± 9 years, duration of hypertension 16 ± 11 years, on 5 ± 2 antihypertensive medications) with treatment-resistant hypertension underwent baseline 24-hour ambulatory BP monitoring, echocardiography, cardiac magnetic resonance imaging, and electrophysiologic study. Electrophysiologic study included measurements of P-wave duration, effective refractory periods, and conduction times. Electroanatomic mapping of the right atrium was completed using CARTO3 to determine local and regional conduction velocity and tissue voltage. Bilateral renal denervation was performed, and all measurements repeated after 6 months. RESULTS: After renal denervation, mean 24-hour BP reduced from 152/84 mm Hg to 141/80 mm Hg at 6-month follow-up (P < .01). Global conduction velocity increased significantly (0.98 ± 0.13 m/s to 1.2 ± 0.16 m/s at 6 months, P < .01), conduction time shortened (32 ± 5 ms to 27 ± 6 ms, P < .01), and complex fractionated activity was reduced (37% ± 14% to 19% ± 12%, P = .02). Changes in conduction velocity correlated positively with changes in 24-hour mean systolic BP (R(2) = 0.55, P = .01). There was a significant reduction in left ventricular mass (139 ± 37 g to 120 ± 29 g, P < .01) and diffuse ventricular fibrosis (T1 partition coefficient 0.39 ± 0.07 to 0.31 ± 0.09, P = .01) on cardiac magnetic resonance imaging. CONCLUSION: BP reduction after renal denervation is associated with improvements in regional and global atrial conduction and reductions in ventricular mass and fibrosis. Whether changes in electrical and structural remodeling are solely due to BP lowering or are due in part to intrinsic effects of renal denervation remains to be determined.

Effects of acute and long-term slow breathing exercise on muscle sympathetic nerve activity in untreated male patients with hypertension.

OBJECTIVE: Acute slow breathing (SLOWB) affects sympathetic cardiovascular regulation, but its long-term effects are unknown. Using device-guided breathing we explored short-term and long-term SLOWB effects on blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) in essential hypertension. METHODS: We measured BP, HR and MSNA in 10 hypertensive individuals at rest, during laboratory stressors, before and after acute SLOWB, and 8 weeks after SLOWB exercise. Twelve matched hypertensive controls underwent a similar protocol excluding SLOWB intervention. Office and 24-h BP were obtained at baseline and at follow-up. RESULTS: Acute SLOWB had no influence on BP, HR, but decreased MSNA (P < 0.01). BP, HR, MSNA responses to handgrip were comparable before and after acute SLOWB. Acute SLOWB tended to reduce SBP (P = 0.09), HR (P = 0.08), but not MSNA (P = 0.20) responses to mental stress. Long-term SLOWB decreased office SBP (P < 0.001), DBP (P < 0.01), HR (P = 0.004), but not 24-h BP. Resting MSNA was unchanged after long-term SLOWB (P = 0.68). Long-term SLOWB did not influence BP, HR or MSNA responses to handgrip and cold pressor, but reduced SBP (P = 0.03), HR (P = 0.03) responses to mental stress without MSNA changes. In controls BP, HR, MSNA responses to laboratory stressors remained unchanged at baseline and at follow-up. CONCLUSION: In essential hypertension, MSNA is reduced during acute SLOWB, but remains unaltered following long-term SLOWB. Long-term SLOWB reduces office, but not ambulatory BP and HR. SLOWB attenuates cardiovascular response to mental stress, but not physical stressors. These findings may be indicative of beneficial SLOWB effects on stress reduction in essential hypertension.