scholarly journals Neural Mechanisms and Therapeutic Opportunities for Atrial Fibrillation

2021 ◽  
pp. 43-47
Author(s):  
Takashi Kusayama ◽  
Juyi Wan ◽  
Yuan Yuan ◽  
Peng-Sheng Chen
Keyword(s):  
Atrial Fibrillation ◽  
Sympathetic Innervation ◽  
Stellate Ganglion ◽  
Neural Mechanisms ◽  
Cardiac Sympathetic Innervation ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Recent Developments ◽  
Parasympathetic Neurons ◽  
Potential Benefits

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of all-cause mortality and complications. The autonomic nervous system (ANS) plays a central role in AF, with the heart regulated by both extrinsic and intrinsic properties. In the extrinsic ANS, the sympathetic fibers are derived from the major paravertebral ganglia, especially the stellate ganglion (SG), which is a source of cardiac sympathetic innervation since it connects with multiple intrathoracic nerves and structures. The major intrinsic ANS is a network of axons and ganglionated plexi that contains a variety of sympathetic and parasympathetic neurons, which communicate with the extrinsic ANS. Simultaneous sympathovagal activation contributes to the development of AF because it increases calcium entry and shortens the atrial action potential duration. In animal and human studies, neuromodulation methods such as electrical stimulation and renal denervation have indicated potential benefits in controlling AF in patients as they cause SG remodeling and reduce sympathetic outflow. This review focuses on the neural mechanisms relevant to AF and the recent developments of neuromodulation methods for AF control.

Impact of Baseline Neutrophil-to-Lymphocyte Ratio on Long-Term Prognosis in Patients With Atrial Fibrillation

Angiology ◽  
2021 ◽  
pp. 000331972110004
Author(s):  
Shuang Wu ◽  
Yan-min Yang ◽  
Jun Zhu ◽  
Jia-meng Ren ◽  
Juan Wang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Continuous Variable ◽  
Cox Proportional Hazards ◽  
Neutrophil To Lymphocyte Ratio ◽  
Long Term Outcomes ◽  
Lymphocyte Ratio ◽  
Net Reclassification Improvement ◽  
Increased Risk ◽  
All Cause Mortality

We performed a retrospective analysis involving 1269 patients with atrial fibrillation (AF) to evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) on long-term outcomes. The primary outcomes were all-cause mortality and combined end point events (CEEs). Cox proportional hazards regression analysis and net reclassification improvement (NRI) analysis were performed. During a median follow-up of 3.32 years, 285 deaths and 376 CEEs occurred. With the elevation of the NLR, the incidence of all-cause mortality (2.77, 4.14, 6.12, and 12.18/100 person-years) and CEEs (4.19, 7.40, 8.03, and 15.22/100 person-years) significantly increased. Multivariate Cox analysis indicated that the highest NLR quartile was independently associated with the incidence of all-cause mortality (hazard ratio [HR] = 1.77, 95% CI: 1.19-2.65) and CEEs (HR = 1.66, 95% CI: 1.18-2.33). When the NLR was analyzed as a continuous variable, a 1-unit increment in log NLR was related to 134% increased risk of all-cause mortality and 119% increased risk of CEEs. Net reclassification improvement analysis revealed that NLR significantly improved risk stratification for all-cause death and CEEs by 15.0% and 9.6%, respectively. Neutrophil-to-lymphocyte ratio could be an independent predictor of long-term outcomes in patients with AF.

Are Prolonged Ventricular Pauses in Atrial Fibrillation a Marker of Poor Prognosis?

Cardiology ◽  
2021 ◽  
Author(s):  
Dorte Marie Stavnem ◽  
Rakin Hadad ◽  
Bjørn Strøier Larsen ◽  
Olav Wendelboe Nielsen ◽  
Mark Aplin Frederiksen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Poor Prognosis ◽  
Pacemaker Implantation ◽  
Real Life ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Long Term Prognosis ◽  
Rate Limiting

Background: In patients with atrial fibrillation (AF), the long-term prognosis of long electrocardiographic pauses in the ventricular action is not well-studied. Methods: Consecutive Holter recordings in patients with AF (n=200) between 2009-2011 were evaluated, focusing on pauses of at least 2.5 s. Outcomes of interest were all-cause mortality and pacemaker implantation. Results: Forty-three patients (21.5%) had pauses with a mean of 3.2 s and SD of 0.9 s. After a median follow-up of 99 months (ranging 89-111), 47% (20/43) of the patients with, and 45% (70/157) without pauses were deceased. Pauses of ≥ 2.5 s did not constitute a risk of increased mortality: HR = 0.75; (95% CI: 0.34 - 1.66); p = 0.48. Neither did pauses of ≥ 3.0 s: HR = 0.43; (95% CI: 0.06 - 3.20); p = 0.41. Sixteen percent of patients with pauses underwent pacemaker implantation during follow-up. Only pauses in patients referred to Holter due to syncope and/or dizzy spells were associated with an increased risk of pacemaker treatment: HR = 4.7 (95% CI: 1.4-15.9), p = 0.014, adjusted for age, sex and rate-limiting medication. Conclusion: In patients with AF, prolonged electrocardiographic pauses of ≥ 2.5 s or ≥ 3.0 s are not a marker for increased mortality in this real-life clinical study.

scholarly journals Acute cardiovascular events and all-cause mortality in patients with hyperthyroidism: a population-based cohort study

2017 ◽  
Vol 176 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Olaf M Dekkers ◽  
Erzsébet Horváth-Puhó ◽  
Suzanne C Cannegieter ◽  
Jan P Vandenbroucke ◽  
Henrik Toft Sørensen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cohort Study ◽  
Ischemic Stroke ◽  
Cardiovascular Events ◽  
Population Based ◽  
Arterial Embolism ◽  
Registration System ◽  
Increased Risk ◽  
All Cause Mortality

Objective Several studies have shown an increased risk for cardiovascular disease (CVD) in hyperthyroidism, but most studies have been too small to address the effect of hyperthyroidism on individual cardiovascular endpoints. Our main aim was to assess the association among hyperthyroidism, acute cardiovascular events and mortality. Design It is a nationwide population-based cohort study. Data were obtained from the Danish Civil Registration System and the Danish National Patient Registry, which covers all Danish hospitals. We compared the rate of all-cause mortality as well as venous thromboembolism (VTE), acute myocardial infarction (AMI), ischemic and non-ischemic stroke, arterial embolism, atrial fibrillation (AF) and percutaneous coronary intervention (PCI) in the two cohorts. Hazard ratios (HR) with 95% confidence intervals (95% CI) were estimated. Results The study included 85 856 hyperthyroid patients and 847 057 matched population-based controls. Mean follow-up time was 9.2 years. The HR for mortality was highest in the first 3 months after diagnosis of hyperthyroidism: 4.62, 95% CI: 4.40–4.85, and remained elevated during long-term follow-up (>3 years) (HR: 1.35, 95% CI: 1.33–1.37). The risk for all examined cardiovascular events was increased, with the highest risk in the first 3 months after hyperthyroidism diagnosis. The 3-month post-diagnosis risk was highest for atrial fibrillation (HR: 7.32, 95% CI: 6.58–8.14) and arterial embolism (HR: 6.08, 95% CI: 4.30–8.61), but the risks of VTE, AMI, ischemic and non-ischemic stroke and PCI were increased also 2- to 3-fold. Conclusions We found an increased risk for all-cause mortality and acute cardiovascular events in patients with hyperthyroidism.

Long-term clinical outcomes after major bleeding in patients with atrial fibrillation: the Fushimi AF registry

2020 ◽  
Author(s):  
Hisashi Ogawa ◽  
Yoshimori An ◽  
Kenjiro Ishigami ◽  
Syuhei Ikeda ◽  
Kosuke Doi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Clinical Outcomes ◽  
Major Bleeding ◽  
Bleeding Event ◽  
Community Based ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Aims Oral anticoagulants reduce the risk of ischaemic stroke but may increase the risk of major bleeding in atrial fibrillation (AF) patients. Little is known about the clinical outcomes of patients after a major bleeding event. This study assessed the outcomes of AF patients after major bleeding. Methods and results The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Analyses were performed on 4304 AF patients registered by 81 institutions participating in the Fushimi AF Registry. We investigated the demographics and outcomes of AF patients who experienced major bleeding during follow-up period. During the median follow-up of 1307 days, major bleeding occurred in 297 patients (6.9%). Patients with major bleeding were older than those without (75.6 vs. 73.4 years; P < 0.01). They were more likely to have pre-existing heart failure (33.7% vs. 26.7%; P < 0.01), history of major bleeding (7.7% vs. 4.0%; P < 0.01), and higher mean HAS-BLED score (2.05 vs.1.73; P < 0.01). On landmark analysis, ischaemic stroke or systemic embolism occurred in 17 patients (3.6/100 person-years) after major bleeding and 227 patients (1.7/100 person-years) without major bleeding, with an adjusted hazard ratio (HR) of 1.93 [95% confidence interval (CI), 1.06–3.23; P = 0.03]. All-cause mortality occurred in 97 patients with major bleeding (20.0/100 person-years) and 709 (5.1/100 person-years) patients without major bleeding [HR 2.73 (95% CI, 2.16–3.41; P < 0.01)]. Conclusion In this community-based cohort, major bleeding is associated with increased risk of subsequent all-cause mortality and thromboembolism in the long-term amongst AF patients. Trial registration https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834. (last accessed 22 October 2020)

P4792Dabigatran versus vitamin K antagonists in patients with atrial fibrillation and valvular heart disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J E Strange ◽  
C Sindet-Pedersen ◽  
L Staerk ◽  
E L Grove ◽  
T A Gerds ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Disease ◽  
Vitamin K ◽  
Valvular Heart Disease ◽  
Cox Regression ◽  
Absolute Risk ◽  
Risk Difference ◽  
Increased Risk ◽  
Significant Difference ◽  
All Cause Mortality

Abstract Background Atrial fibrillation (AF) and valvular heart disease (VHD) are both associated with an increased risk of stroke. Outside post-hoc analyses of randomized controlled trials, knowledge on the effectiveness and safety of dabigatran in patients with AF and VHD is scarce. Objectives To compare the risk of all-cause mortality, stroke, and bleeding in patients with AF and VHD treated with dabigatran or a vitamin K antagonist (VKA). Methods All Danish residents are provided a unique personal identification number enabling cross-linking of data from Danish nationwide registries. We identified all patients with AF and VHD initiating treatment with dabigatran or VKA between the 22nd of August 2011 and the 31st of December 2014. We defined VHD as aortic stenosis/regurgitation, mitral regurgitation, bioprosthetic heart valves, mitral-, and aortic valve repair. Outcomes were all-cause mortality, stroke, and bleeding. 2-year standardized absolute risks were calculated from cause-specific Cox regression models with death as competing risk. Results In total, 599 (27.3%) and 1,596 (72.7%) patients initiated treatment with dabigatran and VKA. The 2-year standardized absolute risk of all-cause mortality (95% CI) for VKA was 27.6% (25.1% to 30.1%) and 25.4% (21.8% to 29.0%) for dabigatran with a corresponding absolute risk difference of −2.2% (−6.3% to 1.9%) (Figure 1). The 2-year standardized absolute risk of stroke for VKA was 3.4% (2.3% to 4.5%) and 3.9% (2.2% to 5.5%) for dabigatran with a corresponding absolute risk difference of 0.5% (−1.6% to 2.5%). Lastly, the 2-year standardized absolute risk of bleeding for VKA was 8.2% (6.6% to 9.7%) and 7.6% (5.1% to 10.1%) for dabigatran with a corresponding absolute risk difference of −0.5% (−3.4% to 2.4%). Figure 1 Conclusions In this nationwide cohort study, we found no significant difference in the risk of all-cause mortality, stroke, or bleeding in patients with AF and VHD when comparing VKA to dabigatran.

Relationship between frailty and all-cause mortality in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational research programme AF general long-term registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Proietti ◽  
M Vitolo ◽  
S Harrison ◽  
G.A Dan ◽  
A.P Maggioni ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Frailty Index ◽  
Primary Study ◽  
Funding Source ◽  
Private Company ◽  
Kaplan Meier ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Introduction Frailty is a major health determinant for cardiovascular disease. Thus far, data on frailty in patients with atrial fibrillation (AF) are limited. Aims To evaluate frailty in a large contemporary cohort of European AF patients, the relationship with oral anticoagulant (OAC) prescription and with risk of all-cause death. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. A 38-items frailty index (FI) was derived from baseline characteristics according to the accumulation of deficits model proposed by Rockwood and Mitnitsky. All-cause mortality was the primary study outcome. Results Out of the 11096 AF enrolled patients, data for evaluating frailty were available for 6557 (59.1%) patients who have been included in this analysis (mean [SD] age 68.9 [11.5], 37.7% females). Baseline median [IQR] CHA2DS2-VASc and HAS-BLED were 3 [2–4] and 1 [1–2], respectively. At baseline, median [IQR] FI was 0.16 (0.12–0.23), with 1276 (19.5%) patients considered “not-frail” (FI<0.10), 4033 (61.5%) considered “pre-frail” (FI 0.10–0.25) and 1248 (19.0%) considered “frail” (FI≥0.25). Age, female prevalence, CHA2DS2-VASc and HAS-BLED progressively increased across the FI classes (all p<0.001). Use of OAC progressively increased among FI classes; after adjustments FI was not associated with OAC prescription (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 0.98–1.19 for each 0.10 FI increase). Conversely, FI was directly associated with vitamin K antagonist (VKA) use (OR: 1.26, 95% CI: 1.18–1.34 for each 0.10 FI increase) and inversely associated with non-VKA OACs (NOACs) use (OR: 0.82, 95% CI: 0.77–0.88). FI was significantly correlated with CHA2DS2-VASc (Rho= 0.516, p<0.001). Over a median [IQR] follow-up of 731 [704–749] days, there were 569 (8.7%) all-cause death events. Kaplan-Meier curves [Figure] showed an increasing cumulative risk for all-cause death according to FI categories. A Cox multivariable analysis, adjusted for age, sex, type of AF and use of OAC, found that increasing FI as a continuous variable was associated with an increased risk of all-cause death (hazard ratio [HR]: 1.56, 95% CI: 1.40–1.73 for each 0.10 FI increase). An association with all-cause death risk was found across the FI categories (HR: 1.71, 95% CI: 1.23–2.38 and HR: 2.88, 95% CI: 2.02–4.12, respectively for pre-frail and frail patients compared to non-frail ones). FI was also predictive of all-cause death (c-index: 0.660, 95% CI: 0.637–0.682; p<0.001). Conclusions In a European contemporary cohort of AF patients the burden of frailty is significant, with almost 1 out of 5 patients found to be “frail”. Frailty influenced significantly the choice of OAC therapy and was associated with (and predictive of) all-cause death at follow-up. Kaplan-Meier Curves Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Since the start of EORP programme, several companies have supported it with unrestricted grants.

scholarly journals Focal myocardial infarction induces global remodeling of cardiac sympathetic innervation: neural remodeling in a spatial context

2013 ◽  
Vol 305 (7) ◽  
pp. H1031-H1040 ◽  
Author(s):  
Olujimi A. Ajijola ◽  
Daigo Yagishita ◽  
Krishan J. Patel ◽  
Marmar Vaseghi ◽  
Wei Zhou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Sympathetic Innervation ◽  
Stellate Ganglion ◽  
Sympathetic Stimulation ◽  
Global Pattern ◽  
Cardiac Sympathetic Innervation ◽  
Dispersion Of Repolarization ◽  
Border Zones ◽  
The Impact ◽  
Neural Remodeling

Myocardial infarction (MI) induces neural and electrical remodeling at scar border zones. The impact of focal MI on global functional neural remodeling is not well understood. Sympathetic stimulation was performed in swine with anteroapical infarcts (MI; n = 9) and control swine ( n = 9). A 56-electrode sock was placed over both ventricles to record electrograms at baseline and during left, right, and bilateral stellate ganglion stimulation. Activation recovery intervals (ARIs) were measured from electrograms. Global and regional ARI shortening, dispersion of repolarization, and activation propagation were assessed before and during sympathetic stimulation. At baseline, mean ARI was shorter in MI hearts than control hearts (365 ± 8 vs. 436 ± 9 ms, P < 0.0001), dispersion of repolarization was greater in MI versus control hearts (734 ± 123 vs. 362 ± 32 ms2, P = 0.02), and the infarcted region in MI hearts showed longer ARIs than noninfarcted regions (406 ± 14 vs. 365 ± 8 ms, P = 0.027). In control animals, percent ARI shortening was greater on anterior than posterior walls during right stellate ganglion stimulation ( P = 0.0001), whereas left stellate ganglion stimulation showed the reverse ( P = 0.0003). In infarcted animals, this pattern was completely lost. In 50% of the animals studied, sympathetic stimulation, compared with baseline, significantly altered the direction of activation propagation emanating from the intramyocardial scar during pacing. In conclusion, focal distal anterior MI alters regional and global pattern of sympathetic innervation, resulting in shorter ARIs in infarcted hearts, greater repolarization dispersion, and altered activation propagation. These conditions may underlie the mechanisms by which arrhythmias are initiated when sympathetic tone is enhanced.

scholarly journals Exclusive Peripheral Overexpression of 5-HT5A Receptors is Involved in 5‑HT‑Induced Cardiac Sympatho-Inhibition in Type 1 Diabetic Rats

2020 ◽  
Author(s):  
Jose Ángel Garcia-Pedraza ◽  
Oswaldo Hernández-Abreu ◽  
Asunción Morán ◽  
José Carretero ◽  
Mónica García-Domingo ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Sympathetic Innervation ◽  
Stellate Ganglion ◽  
Cardiovascular Complications ◽  
Diabetic Rats ◽  
Cardiac Autonomic Neuropathy ◽  
Sympathetic Outflow ◽  
Cardiac Sympathetic Innervation ◽  
Pithed Rats

Abstract Background: In normoglycaemic pithed rats, cardiac sympathetic control is modulated by serotonin (5-hydroxytryptamine; 5‑HT), which inhibits the cardioaccelerator sympathetic outflow via the activation of 5-HT 1B , 5-HT 1D and 5-HT 5A receptors. Notwithstanding, type 1 diabetes impairs the functionality of the cardiac sympathetic innervation and leads to cardiovascular complications including cardiac autonomic neuropathy. On this basis, the present study investigated whether the influence of 5-HT on cardiac noradrenergic neurotransmission is altered in type 1 diabetic rats, by analysing the profile of the 5-HT receptors involved and their peripheral expression. Methods: Type 1 diabetes was induced in male Wistar rats with a single injection of streptozotocin (50 mg/kg, i.p.). Four weeks later, the rats were anaesthetized, pithed and prepared for producing tachycardic responses by either electrical preganglionic stimulation (C 7 ‑T 1 ) of the cardioaccelerator sympathetic outflow or i.v. bolus injections of exogenous noradrenaline. Immunohistochemistry analyses were performed to study the expression of 5‑HT 1B , 5-HT 1D and 5-HT 5A receptors in the stellate (sympathetic) ganglion obtained from normoglycaemic and diabetic rats. Results: The increases in heart rate evoked by both cardiac sympathetic stimulation and exogenous noradrenaline were not modified after saline in diabetic rats. Moreover, i.v. continuous infusions of 5‑HT induced a cardiac sympatho-inhibition that was mimicked by the 5‑HT 1/5A receptor agonist 5‑carboxamidotryptamine, but not by the agonists indorenate (5-HT 1A ), CP 93,129 (5‑HT 1B ), PNU 142633 (5-HT 1D ), or LY344864 (5‑HT 1F ) in the diabetic group. In contrast, the above agonists at 5-HT 1B , 5-HT 1D and 5-HT 1/5A receptors mimicked 5-HT-induced sympatho-inhibition in normoglycaemic rats. In diabetic animals, i.v. administration of SB 699551 (1 mg/kg; 5‑HT 5A receptor antagonist) abolished 5‑CT-induced cardiac sympatho-inhibition. Finally, the immunohistochemistry analysis in the stellate ganglion showed that, as compared to normoglycaemic rats, in diabetic rats (P<0.05): (i) the expression of 5-HT 1B receptors was slightly higher, whereas that of 5-HT 1D receptors was slightly lower; and (ii) there was a clear overexpression of 5-HT 5A receptors. Conclusions: Taken together, these results show the prominent role of the peripheral overexpression of prejunctional 5-HT 5A receptors in the inhibition of the cardiac sympathetic drive in type 1 diabetic rats. These findings may represent a new pharmacological strategy for the treatment of diabetes-related cardiac abnormalities.

scholarly journals Prognostic significance of diabetes mellitus in patients with atrial fibrillation

2021 ◽  
Author(s):  
Andreas S Papazoglou ◽  
Anastasios Kartas ◽  
Athanasios Samaras ◽  
Evangelos Akrivos ◽  
Ioannis Vouloagkas ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Prognostic Significance ◽  
Competing Risk ◽  
Composite Outcome ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Hba1c Levels

Abstract Background: There are limited data on the association of diabetes mellitus (DM) and levels of glycated hemoglobin (HbA1c) with outcomes in patients with atrial fibrillation (AF).Methods: This retrospective cohort study included patients who were recently hospitalized with a primary or secondary diagnosis of AF from December 2015 through June 2018. Kaplan-Meier curves and Cox-regression adjusted hazard ratios (aHR) were calculated for the primary outcome of all-cause mortality and for the secondary outcomes of cardiovascular (CV) mortality and the composite outcome of CV death or hospitalization. Competing-risk regression analyses were performed to calculate the cumulative risk of stroke, major bleeding, AF- or HF-hospitalizations adjusted for the competing risk of all-cause death. Spline curve models were fitted to investigate associations of HbA1c values and mortality among patients with AF and DM.Results: In total 1140 AF patients were included, of whom 373 (32.7%) had DM. During a median follow-up of 2.6 years, 414 (37.3%) patients died. The presence of DM was associated with a higher risk of all-cause mortality (aHR=1.40 95% confidence intervals [CI]: 1.11-1.75), CV mortality (aHR=1.39, 95% CI: 1.07-1.81), sudden cardiac death (aHR=1.73, 95% CI: 1.19-2.52), stroke (aHR=1.87, 95% CI: 1.01-3.45) and the composite outcome of hospitalization or CV death (aHR=1.27, 95% CI: 1.06-1.53). In AF patients with comorbid DM, the spline curves showed a positive linear association between HbA1c levels and outcomes, with values 7.6-8.2% being independent predictors of increased all-cause mortality, and values <6.2% predicting significantly decreased all-cause and CV mortality.Conclusions: The presence of DM on top of AF was associated with substantially increased risk for all-cause or CV mortality, sudden cardiac death and excess morbidity. HbA1c levels lower than 6.2% were independently related to better survival rates suggesting that optimal DM control could be associated with better clinical outcomes in AF patients with DM.

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