Vitamin D, vitamin D supplementation and atrial fibrillation risk in the general population: updated systematic review and meta-analysis of prospective studies.

Background: Since the association of vitamin D with atrial fibrillation (AF) risk is still unclear, we conducted this updated meta-analysis of prospective studies to identify the relationship between vitamin D or vitamin D supplementation and AF in the general population. Methods: We conducted a comprehensive search of multiple databases up to May 2023 for studies reporting vitamin D and AF. The hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled by a random-effects model. Results: A total of seven studies were included in this meta-analysis. Vitamin D deficiency (<20 ng/ml) was associated with increased AF incidence (HR: 1.12, 95% CI: 1.005-1.25). The HR was not significant with vitamin D insufficiency (20-30 ng/ml; HR: 1.09, 95% CI: 0.98-1.21). Each 10 ng/ml increase in serum vitamin D was associated with a significantly decreased AF incidence (HR: 0.95, 95% CI: 0.93-0.97). Two studies reported the effect of vitamin D supplements on AF incidence but reached inconsistent results. Conclusions: Vitamin D deficiency or insufficiency was associated with an increased risk of AF in the general population. The role of vitamin D supplementation in AF prevention needs further investigation.

Non-vitamin K antagonist oral anticoagulants versus vitamin K antagonists in atrial fibrillation patients with previous stroke or intracranial hemorrhage: A systematic review and meta-analysis of observational studies.

Several observational studies have compared the effectiveness and safety outcomes between nonvitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with a history of either stroke/transient ischemic attack (TIA) or intracranial hemorrhage. Therefore, our current meta-analysis aimed to address this issue. The Cochrane Library, PubMed, and Embase databases were systematically searched until December 2020 for all relevant observational studies. We applied a random-effects model to pool adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for this meta-analysis. A total of 10 studies were included. Among patients with a history of stroke/TIA, the use of NOACs versus VKAs was associated with decreased risks of stroke (HR, 0.82, 95% CI 0.69-0.97), systemic embolism (HR, 0.73, 95% CI 0.61-0.87), all-cause death (HR, 0.87, 95% CI 0.81-0.94), major bleeding (HR, 0.77, 95% CI 0.64-0.92) and intracranial hemorrhage (HR, 0.54, 95% CI 0.38-0.77). Among patients with a history of intracranial hemorrhage, the use of NOACs versus VKAs was associated with reduced risks of stroke (HR, 0.81, 95% CI 0.68-0.95), all-cause death (HR, 0.68, 95% CI 0.49-0.94), and intracranial hemorrhage (HR, 0.66, 95% CI 0.51-0.84). Compared with VKAs, the use of NOACs exhibited superior efficacy and safety outcomes in AF patients with previous stroke/TIA, and the use of NOACs was associated with reduced risks of stroke, all-cause death, and intracranial hemorrhage in patients with a history of intracranial hemorrhage.

Effects of Intrinsic and Extrinsic Cardiac Nerves on Atrial Arrhythmia in Experimental Pulmonary Artery Hypertension.

Atrial arrhythmia, which includes atrial fibrillation (AF) and atrial flutter (AFL), is common in patients with pulmonary arterial hypertension (PAH), who often have increased sympathetic nerve activity. Here, we tested the hypothesis that autonomic nerves play important roles in vulnerability to AF/AFL in PAH. The atrial effective refractory period and AF/AFL inducibility at baseline and after anterior right ganglionated plexi ablation were determined during left stellate ganglion stimulation or left renal sympathetic nerve stimulation in beagle dogs with or without PAH. Then, sympathetic nerve, ß-adrenergic receptor densities and connexin 43 expression in atrial tissues were assessed. The sum of the window of vulnerability to AF/AFL was increased in the right atrium compared with the left atrium at baseline in the PAH dogs but not in the controls. The atrial effective refractory period dispersion was increased in the control dogs, but not in the PAH dogs, during left stellate ganglion stimulation. The voltage thresholds for inducing AF/AFL during anterior right ganglionated plexi stimulation were lower in the PAH dogs than in the controls. The AF/AFL inducibility was suppressed after ablation of the anterior right ganglionated plexi in the PAH dogs. The PAH dogs had higher sympathetic nerve and ß1-adrenergic receptor densities, increased levels of nonphosphorylated connexin 43, and heterogeneous connexin 43 expression in the right atrium when compared with the control dogs. The anterior right ganglionated plexi play important roles in the induction of AF/AFL. AF/AFL induction was associated with right atrium substrate remodeling in dogs with PAH.

[Beneficial effects of renal denervation on pulmonary vascular remodeling in experimental pulmonary artery hypertension].

OBJECTIVE: To explore the effects of renal sympathetic denervation (RSD) on pulmonary vascular remodeling in a model of pulmonary arterial hypertension (PAH). METHODS: According to the random number table, 24 beagles were randomized into control, PAH and PAH+RSD groups (n=8 each). The levels of neurohormone, echocardiogram and dynamics parameters were measured. Then 0.1 ml/kg dimethylformamide (control group) or 2 mg/kg dehydromonocrotaline (PAH and PAH+RSD groups) were injected. The PAH+RSD group underwent RSD after injection. At week 8 post-injection, the neurohormone levels, echocardiogram, dynamics parameters and pulmonary tissue morphology were observed. RESULTS: The values of right ventricular systolic pressure (RVSP) and pulmonary arterial systolic pressure (PASP) in PAH and PAH+RSD groups were both significantly higher than those in control group ((42.8±8.7), (30.8±6.8) vs (23.2±5.7) mmHg (1 mmHg=0.133 kPa) and (45.1±11.2), (32.6±7.9) vs (24.7±7.1) mmHg). Meanwhile, the values of RVSP and PASP in PAH group were higher than those in PAH+RSD group (all P<0.01). The levels of serum angiotensin II (Ang II) and endothelin-1 significantly increased after 8 weeks in PAH dogs ((228±41) vs (113±34) pg/ml and (135±15) vs (77±7) pg/ml, all P<0.01). And Ang II and endothelin-1 were higher in lung tissues of PAH group ((65±10) and (96±10) pg/ml) than in those of control group ((38±7) and (54±6) pg/ml) and PAH+RSD group ((46±8) and (67±9) pg/ml) (all P<0.01). Pulmonary tissues had marked collagen hyperplasia and lamellar corpuscles of type 2 alveolar cells were damaged more severely in PAH dogs than in PAH+RSD dogs. CONCLUSIONS: RSD suppresses pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental PAH. And the effect of RSD on PAH may contribute to decreased neurohormone levels.

Effect of renal sympathetic denervation on the progression of paroxysmal atrial fibrillation in canines with long-term intermittent atrial pacing.

AIMS: The aim of the present study was to explore the effect of renal sympathetic denervation (RSD) on the progression of paroxysmal atrial fibrillation (AF) in canines with long-term intermittent atrial pacing. METHODS AND RESULTS: Nineteen beagles were randomly divided into sham-operated group (six dogs), control group (six dogs), and RSD group (seven dogs). Sham-operated group were implanted with pacemakers without pacing; control group were implanted with pacemakers with long-term intermittent atrial pacing; and RSD group underwent catheter-based RSD bilaterally and were simultaneously implanted with pacemakers. Atrial pacing was maintained for 8 h a day and a total of 12 weeks in the control group and RSD group. Echocardiography showed that the left atrial structure and function were significantly improved in the RSD group compared with the control group (P < 0.05). Compared with the control group, the RSD group had fewer incidences of AF and a shorter duration of AF (P < 0.05) after long-term intermittent atrial pacing. In addition to increased atrial effective refractory period (AERP) and AF cycle length, AERP dispersion and P-wave duration and dispersion were significantly decreased in the RSD group compared with the control group (P < 0.05). Atrial morphological evaluation suggested that fibrosis and ultrastructural changes induced by long-term intermittent atrial pacing were markedly suppressed in the RSD dogs compared with controls (P < 0.05). Immunohistochemistry results showed that connexin 43 distribution in RSD mid-myocardial was significantly fewer heterogeneous than that in control mid-myocardial (P < 0.05). CONCLUSION: Renal denervation inhibits the progression of paroxysmal AF, which might be related to the suppression of atrial electrophysiology and structural heterogeneity.

Effects of renal sympathetic denervation on the atrial electrophysiology in dogs with pacing-induced heart failure.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are associated with sympathetic activation. Renal sympathetic denervation (RSD) can suppress AF vulnerability. The impact of RSD on atrial electrophysiology in experimental HF is unclear. METHODS: Twenty-two beagles were randomized into control, HF, and HF + RSD groups. Control dogs were implanted cardiac pacemakers without pacing. Dogs in the HF group underwent right ventricular pacing for 3 weeks at 240 beats/min to induce HF. The dogs in the HF + RSD group received RSD and underwent the same HF-inducing procedure. RESULTS: The P-wave dispersion was higher in HF dogs than in the control and HF + RSD dogs (19 ± 3.1 ms vs 13 ± 2.3 ms, 15 ± 2.9 ms, P = 0.04). Conduction time within the interatrium was significantly longer in the HF dogs than that in the control and HF + RSD dogs (39 ± 4 ms vs 31 ± 3 ms, 33 ± 4 ms; P = 0.03). Window of vulnerability (WOV) of AF was widened in the HF dogs than in the HF + RSD dogs (37 ± 5 ms vs 14 ± 3 ms; P < 0.01), while AF could not be induced (WOV = 0) in the control dogs during S1 S2 stimulation. The voltage in the threshold for AF inducibility was lower during ganglionated plexi stimulation in the HF dogs than in the control and HF + RSD dogs (1.8 ± 0.6 V vs 2.5 ± 0.6 V, 2.4 ± 0.4 V; P = 0.04). CONCLUSIONS: RSD could reverse the atrial electrical remodeling and decrease AF inducibility in dogs with pacing-induced HF.

Changes of serum neurohormone after renal sympathetic denervation in dogs with pacing-induced heart failure.

BACKGROUND: Neurohormonal activation is a commonly cited array of phenomena in the body's physiologic response to heart failure (HF). The aim of the present study was to determine the change law of serum neurohormones after renal sympathetic denervation (RSD) in dogs with pacing-induced HF. METHODS: Twenty-eight beagles were randomly divided into control group, RSD group, HF group and HF + RSD group. The control group was implanted pacemakers without pacing; the RSD group underwent renal artery ablation without pacing; the HF group was implanted pacemakers with ventricular pacing at 240 bpm for 3 weeks; and HF + RSD group underwent renal artery ablation and with ventricular pacing at 240 bpm for 3 weeks. Blood samples were taken at baseline, and 3, 6, 9, 12, 15, 18, 21 days in all the dogs for neurohormones measurement. RESULTS: After 3 weeks, the systolic femoral artery pressures in the HF and HF + RSD groups were reduced after pacing 3 weeks. There was an increase significantly in BNP, angiotensin II, aldosterone, endothelin-1 and decrease in renalase after 3 weeks when compared with baseline in HF group. RSD significantly suppressed the changes of plasma neurohormones concentration in experimental HF, but RSD had not obviously impact on the levels of plasma neurohormones during 3 weeks in RSD group. CONCLUSIONS: RSD attenuates the changes of levels of plasma neurohormones in the activated renin-angiotensin-aldosterone system (RAAS) but had not obviously effect in the normal physiology of RAAS.