Association between sick sinus syndrome and atrial fibrillation: A systematic review and meta-analysis.

AIMS: Sick sinus syndrome (SSS) and atrial fibrillation (AF) frequently coexist and show a bidirectional relationship. This systematic review and meta-analysis aimed to decipher the precise relationship between SSS and AF, further exploring and comparing different therapy strategies on the occurrence or progression of AF in patients with SSS. METHODS AND RESULTS: A systematic literature search was conducted until November 2022. A total of 35 articles with 37,550 patients were included. Patients with SSS were associated with new-onset AF compared to those without SSS. Catheter ablation was associated with a lower risk of AF recurrence, AF progression, all-cause mortality, stroke and hospitalization of heart failure compared to pacemaker therapy. Regarding the different pacing strategies for SSS, VVI/VVIR has higher risk of new-onset AF than DDD/DDDR. No significant difference was found between AAI/AAIR and DDD/DDDR, as well as between DDD/DDDR and minimal ventricular pacing (MVP) for AF recurrence. AAI/AAIR was associated with higher risk of all-cause mortality when compared to DDD/DDDR, but lower risk of cardiac death when compared to DDD/DDDR. Right atrial septum pacing was associated with a similar risk of new-onset AF or AF recurrence compared to right atrial appendage pacing. CONCLUSION: SSS is associated with a higher risk of AF. For patients with both SSS and AF, catheter ablation should be considered. This meta-analysis re-emphasizes that high percentage of ventricular pacing should be avoided in patients with SSS in order to decrease AF burden and mortality.

CHARGE-AF: A Useful Score For Atrial Fibrillation Prediction?

Atrial fibrillation (AF) is the commonest arrhythmia in clinical practice and is associated with increased morbidity and mortality. Various predictive scores for new-onset AF have been proposed, but so far, none have been widely used in clinical practice. CHARGE-AF score was developed from a pooled diverse population from three large cohorts (Atherosclerosis Risk in Communities study, Cardiovascular Health Study and Framingham Heart Study). A simple 5-year predictive model includes the variables of age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes mellitus, history of myocardial infarction and heart failure. Recent studies report that the CHARGE-AF score has good discrimination for incident AF and seems to be a promising prediction model for this arrhythmia. New screening tools (smartphone apps, smartwatches) are rapidly developing for AF detection. Therefore, the wide application of the CHARGE-AF score in clinical practice and the upcoming usage of mobile health technologies and smartwatches may result in better AF prediction and adequate stroke prevention, especially in high-risk patients.

Association between sodium-glucose cotransporter-2 inhibitors and incident atrial fibrillation/atrial flutter in heart failure patients with reduced ejection fraction: a meta-analysis of randomized controlled trials.

Atrial fibrillation (AF) and atrial flutter (AFL) are associated with adverse outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We investigated the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the incidence of AF and/or AFL in HFrEF patients. PubMed and ClinicalTrials.gov were systematically searched until March 2022 for randomized controlled trials (RCTs) that enrolled patients with HFrEF. A total of six RCTs with 9467 patients were included (N = 4731 in the SGLT2i arms; N = 4736 in the placebo arms). Compared to placebo, SGLT2i treatment was associated with a significant reduction in the risk of AF [relative risk (RR) 0.62, 95% confidence interval CI 0.44-0.86; P = 0.005] and AF/AFL (RR 0.64, 95% CI 0.47-0.87; P = 0.004). Subgroup analysis showed that empagliflozin use resulted in a significant reduction in the risk of AF (RR 0.55, 95% CI 0.34-0.89; P = 0.01) and AF/AFL (RR 0.50, 95% CI 0.32-0.77; P = 0.002). By contrast, dapagliflozin use was not associated with a significant reduction in the risk of AF (RR 0.69, 95% CI 0.43-1.11; P = 0.12) or AF/AFL (RR 0.82, 95% CI 0.53-1.27; P = 0.38). Additionally, a "shorter" duration (< 1.5 years) of treatment with SGLT2i remained associated with a reduction in the risk of AF (< 1.5 years; RR 0.58, 95% CI 0.36-0.91; P = 0.02) and AF/AFL (< 1.5 years; RR 0.52, 95% CI 0.34-0.80; P = 0.003). In conclusion, SGLT2i therapy was associated with a significant reduction in the risk of AF and AF/AFL in patients with HFrEF. These results reinforce the value of using SGLT2i in this setting.

Circulating Vitamin D Concentrations and Risk of Atrial Fibrillation: A Mendelian Randomization Study Using Non-deficient Range Summary Statistics.

Background and Aims: Vitamin D deficiency is a common disorder and has been linked with atrial fibrillation (AF) in several observational studies, although the causal relationships remain unclear. We conducted a Mendelian randomization (MR) analysis to determine the causal association between serum 25-hydroxyvitamin D [25(OH)D] concentrations and AF. Methods and Results: The analyses were performed using summary statistics obtained for single-nucleotide polymorphisms (SNPs) identified from large genome-wide association meta-analyses conducted on serum 25(OH)D (N = 79,366) and AF (N = 1,030,836). Six SNPs related to serum 25(OH)D were used as instrumental variables. The association between 25(OH)D and AF was estimated using both the fixed-effect and random-effects inverse variance weighted (IVW) method. The MR analyses found no evidence to support a causal association between circulating 25(OH)D level and risk of AF using random-effects IVW (odds ratio per unit increase in log 25(OH)D = 1.003, 95% CI, 0.841-1.196; P = 0.976) or fixed-effect IVW method (OR = 1.003, 95% CI, 0.876-1.148; P = 0.968). Sensitivity analyses yielded similar results. No heterogeneity and directional pleiotropy were detected. Conclusion: Using summary statistics, this MR study suggests that genetically predicted circulating vitamin D concentrations, especially for a non-deficient range, were not causally associated with AF in the general population. Future studies using non-linear design and focusing on the vitamin D deficiency population are needed to further evaluate the causal effect of vitamin D concentrations on AF.

Does CHA2DS2-VASc score predict mortality in chronic kidney disease?

Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide. Assessment of cardiovascular (CV) and all-cause mortality in CKD patients is of particular importance. CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke, vascular disease, age 65-74 years, and sex) score was originally formulated to predict the annual thromboembolic risk in patients with nonvalvular atrial fibrillation (AF). The calculation of R2CHADS2 and R2CHA2DS2VASc scores awarded an additional 2 points for CrCl < 60 mL/min and GFR < 60 mL/min/1.73 m2. Recent studies have investigated whether CHA2DS2-VASc and R2CHADS ± VASC scores could be used to predict CV or all-cause mortality in patients with CKD. CHA2DS2-VASc score was proven to be a significant predictor of CV and all-cause mortality in CKD patients, and a higher CHA2DS2-VASc score was associated with increased mortality. These findings are quite promising, and they may help physicians to identify high-risk groups in this population.

Should we incorporate obstructive sleep apnea in CHA2DS2-VASc score?

Atrial fibrillation (AF) is considered a significant challenge in cardiovascular medicine related to significant morbidity and mortality. Obstructive sleep apnea (OSA) is associated with stroke and constitutes an important risk factor for AF. However, it is still ambiguous whether OSA is independently related to stroke or systemic embolism in AF patients, and whether or not OSA should be included in CHA2DS2-VASc score. In a recent study, the presence of OSA in patients with AF was associated with higher rates of adverse events, namely stroke and systemic embolism. Patients with OSA have higher CHA2DS2-VASc scores and mean CHA2DS2-VASc scores that increase with OSA severity. The addition of OSA to CHA2DS2-VASc resulted in improved discrimination, but this improvement was modest and clinically non-significant. However, cardiovascular risk factors that accompany OSA and not OSA per se might be responsible for the increased thromboembolic risk in these patients. It is noteworthy that patients with OSA with CHA2DS2-VASc <2 had a higher incidence of stroke compared to those without. Unfortunately, the event rates for stroke in these patients were too low to reach statistically validated conclusions. Therefore, it seems reasonable to suggest that in borderline stroke risk patients (CHA2DS2-VASc <2), the presence of OSA should be taken into account in the treatment decision. More studies are needed to elucidate whether or not OSA should be incorporated in CHA2DS2-VASc score.

Circadian Pattern of Acute Myocardial Infarction and Atrial Fibrillation in a Mediterranean Country: A study in Diabetic Patients.

Background and objectives: The circadian pattern seems to play a crucial role in cardiovascular events and arrhythmias. Diabetes mellitus is a complex metabolic disorder associated with autonomic nervous system alterations and increased risk of microvascular and macrovascular disease. We sought to determine whether acute myocardial infarction (AMI) and atrial fibrillation (AF) follow a circadian pattern in diabetic patients in a Mediterranean country. Materials and Methods: This retrospective study included 178 diabetic patients (mean age: 67.7) with AMI or AF who were admitted to the coronary care unit. The circadian pattern of AMI and AF was identified in the 24-h period (divided in 3-h and 1-h intervals). Patients were also divided in 3 groups according to age; 40-65 years, 66-79 years and patients older than 80 years. A chi-square goodness-of-fit test was used for the statistical analysis. Results: AMI seems to occur more often in the midnight hours (21:00-23:59) (p < 0.001). Regarding age distribution, patients between 40 and 65 years were more likely to experience an AMI compared to other age groups (p < 0.001). Autonomic alterations, working habits, and social reasons might contribute to this phenomenon. AF in diabetic patients occurs more frequently at noon (12:00-14:59) (p = 0.019). Conclusions: Diabetic patients with AMI and AF seem to follow a specific circadian pattern in a Mediterranean country, with AMI occurring most often at midnight hours and AF mostly at noon. Autonomic dysfunction, glycemic fluctuations, intense anti-diabetic treatment before lunch, and patterns of insulin secretion and resistance may explain this pattern. More studies are needed to elucidate the circadian pattern of AMI and AF in diabetic patients to contribute to the development of new therapeutic approaches in this setting.

Galectin-3 and risk of atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Galectin-3 is an inflammatory marker that is raised in myocardial fibrosis and inflammation. Recent studies have explored its role in predicting atrial fibrillation (AF) outcomes. The aim of this systematic review and meta-analysis is to examine the association between serum concentration of galectin-3 and AF. METHODS: PubMed, EMBASE, and the Cochrane Database were searched. A total of 280 studies were identified, of which 28 studies involving 10 830 patients were included in our meta-analysis. RESULTS: Galectin-3 is present at higher concentrations in patients with AF than those in sinus rhythm (mean difference [MD] = -0.68 ng/mL, 95% CI: -0.92, -0.44, Z = 5.61, P < .00001). Galectin-3 levels were significantly higher in the persistent AF than in the paroxysmal AF group (MD = -0.94 ng/mL, 95% CI: -1.85, -0.03, Z = 2.04, P = .04). Higher galectin-3 levels were associated with a 45% increase in the odds of developing AF (odds ratio [OR] = 1.45, 95% CI: 1.15, 1.83, Z = 3.11, P = .002) and risk of AF recurrence (hazard ratio [HR] =1.17, 95% CI: 1.06, 1.29, Z = 3.12, P = .002). CONCLUSIONS: Our meta-analysis found that galectin-3 is significantly higher in patients with persistent AF than in those with paroxysmal AF, and can predict both AF development and recurrence after treatment.

Inflammation and atrial fibrillation: A comprehensive review.

Atrial fibrillation (AF) has different underlying substrates. Atrial remodeling involves electrophysiological and structural abnormalities that promote the development and perpetuation of AF. Experimental and clinical data indicate that inflammation is implicated in the pathophysiology of atrial remodeling. The mechanistic links between atrial remodeling and inflammation are complex while diverse underlying diseases and conditions may affect these pathways. Inflammatory markers have also been associated with AF development, recurrence, perpetuation, total AF burden as well as with thromboembolic complications. The development of specific anti-inflammatory interventions in this setting seems to be challenging and complicated. Several agents with pleiotropic properties, including anti-inflammatory, have been tested in experimental and clinical settings with variable results. This updated review provides a concise overview of all available data regarding the role of inflammation in AF including the predictive role of inflammatory markers. Also, current knowledge and future directions on anti-inflammatory strategies are critically discussed.

Inhibition of renin-angiotensin axis reduces the risk of thrombus formation in the left atrial appendage in patients with hypertension complicated by atrial fibrillation.

AIMS: We examined whether the use of a renin-angiotensin-aldosterone system (RAS) inhibitor plays a role in protecting against left atrial appendage thrombus (LAAT) in patients with hypertension complicated by atrial fibrillation (AF). METHODS: Two observational studies were conducted on patients with diagnoses of hypertension and AF, who were categorized into RAS inhibitor user or nonuser groups. Demographic characteristics, clinical characteristics, echocardiographic parameters and hemostatic markers were examined and the occurrence of LAAT during follow-up were recorded. RESULTS: In the first study ( n = 131), LA peak systolic strain and LAA emptying flow velocity (LAA eV) were significantly increased in patients on RAS inhibitors compared with the nonuser group ( p < 0.05). Lower D-dimer and fibrinogen levels were observed in patients on RAS inhibitors ( p < 0.05). In the second study ( n = 99), 25.9% ( n = 11) of patients on RAS inhibitors developed LAAT, compared with 46.7% ( n = 21) in the nonuser group ( p < 0.05). After controlling for risk factors related to LAAT, use of RAS inhibitors remained associated with a significantly lower risk of developing LAAT (HR, 0.406; 95% CI, 0.191-0.862; p = 0.019). CONCLUSIONS: RAS inhibitors use was associated with a significant reduction in the risk of LAAT in patients with hypertension and AF.

Epicardial adipose tissue and atrial fibrillation: pathophysiological mechanisms, clinical implications, and potential therapies.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with increased cardiovascular morbidity and mortality. Epicardial adipose tissue (EAT) serves as a biologically active organ with important endocrine and inflammatory function. Review An accumulating body of evidence suggests that EAT is associated with the initiation, perpetuation, and recurrence of AF, but the precise role of EAT in AF pathogenesis is not completely elucidated. Pathophysiological mechanisms involve adipocyte infiltration, profibrotic and pro-inflammatory paracrine effects, oxidative stress, neural mechanisms, and genetic factors. CONCLUSIONS: Notably, EAT accumulation seems to be associated with stroke and adverse cardiovascular outcomes in AF. Weight loss, specific medications and ablation of ganglionated plexi (GP) seem to be potential therapies in this setting.

Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: A Promising Medication for Chronic Obstructive Pulmonary Disease?

Chronic obstructive pulmonary disease (COPD) is a complex disorder that primarily affects the lungs and is characterized not only by local pulmonary, but also by systemic inflammation which promotes the development of extrapulmonary and cardiovascular co-morbidities. Angiotensin converting enzyme (ACE) inhibitors and ARBs (angiotensin receptor blockers) are widely used drugs in the treatment of cardiovascular diseases, with growing evidence suggesting potential benefits in COPD patients. The purpose of this review is to describe the correlation of renin-angiotensin system (RAS) with COPD pathophysiology and to present the latest data regarding the potential role of RAS blockers in COPD.

Doxycycline attenuates chronic intermittent hypoxia-induced atrial fibrosis in rats.

INTRODUCTION: Atrial structural remodeling in the form of fibrosis contributes to the arrhythmic substrate in atrial fibrillation (AF). The aim of this study was to investigate the effects of doxycycline on chronic intermittent hypoxia (CIH)-induced atrial fibrosis and the pathophysiological mechanisms underlying such changes. METHODS: A total of 30 Sprague Dawley rats were randomized into three groups: control group, CIH group, and CIH with doxycycline treatment (CIH-D) group. CIH lasted 5 hours per day for 4 weeks. CIH-D rats were administrated doxycycline for 4 weeks, while they received CIH. Masson's trichrome staining was used to determine collagen deposit in the atrial myocardium. Protein and mRNA levels of Matrix Metalloproteinase-2 (MMP-2) and -9 (MMP-9), microRNA-21 (miR-21) and its downstream target Sprouty1 (Spry1), and extracellular signal-regulated kinases 1/2 (ERK1/2) were measured using Western blotting or real-time qRT-PCR, respectively. RESULTS: Compared to the control group, the CIH group showed higher interstitial collagen fraction, increased MMP-9, miR-21, and p-ERK1/2 levels, and decreased MMP-2 and Spry1 levels. Doxycycline treatment attenuated CIH-induced atrial fibrosis, reduced MMP-2, MMP-9, miR-21, and p-ERK1/2, and increased Spry1. CONCLUSIONS: CIH treatment induced significant atrial fibrosis in our rat model, which was attenuated by doxycycline. These changes can be explained by alterations in the MMP and miR-21/ERK signaling pathways.

Chronic obstructive pulmonary disease and atrial fibrillation: An unknown relationship.

Chronic obstructive pulmonary disease (COPD) is independently associated with atrial fibrillation (AF). Decreased oxygenation, hypercapnia, pulmonary hypertension, diastolic dysfunction, oxidative stress, inflammation, changes in atrial size by altered respiratory physiology, increased arrhythmogenicity from nonpulmonary vein foci commonly located in the right atrium, and respiratory drugs have been implicated in the pathogenesis of AF in COPD. The understanding of the relationship between COPD and AF is of particular importance, as the presence of the arrhythmia has significant impact on mortality, especially in COPD exacerbations. On the other hand, COPD in AF is associated with AF progression, success of cardioversion, recurrence of AF after catheter ablation, and increased cardiovascular and all-cause mortality. Treatment of the underlying pulmonary disease and correction of hypoxia and acid-base imbalance represents first-line therapy for COPD patients who develop AF. Cardioselective ß-blockers are safe and can be routinely used in COPD. In addition, AF ablation was proved to be efficient and safe, and improves quality of life in these patients. This review presents the association between COPD and AF, describes the pathophysiological mechanisms implicated in AF development in COPD, underlines the prognostic significance of AF in COPD patients and vice versa, and highlights emerging therapeutic approaches in this setting.

Obstructive sleep and atrial fibrillation: Pathophysiological mechanisms and therapeutic implications.

Atrial fibrillation (AF) is the commonest arrhythmia in clinical practice and is associated with increased cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA), a common breathing disorder, is an independent risk factor for AF. Several pathophysiological mechanisms, including apnea-induced hypoxia, intrathoracic pressure shifts, sympathovagal imbalance, atrial remodeling, oxidative stress, inflammation and neurohumoral activation have been implicated in the occurrence of AF in OSA patients. In addition, OSA has been shown to reduce success rates of antiarrhythmic drugs, electrical cardioversion and catheter ablation in AF. Effective prevention of obstructive respiratory events by continuous positive airway pressure ventilation (CPAP) reduces sympathovagal activation and recurrence of AF. The present review describes the relationship between OSA and AF, presents the pathophysiological mechanisms implicating OSA in AF occurrence, and provides an update of the potential therapeutic interventions for patients with OSA and AF.

Electrocardiographic abnormalities and cardiac arrhythmias in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is independently associated with an increased burden of cardiovascular disease. Besides coronary artery disease (CAD) and congestive heart failure (CHF), specific electrocardiographic (ECG) abnormalities and cardiac arrhythmias seem to have a significant impact on cardiovascular prognosis of COPD patients. Disturbances of heart rhythm include premature atrial contractions (PACs), premature ventricular contractions (PVCs), atrial fibrillation (AF), atrial flutter (AFL), multifocal atrial tachycardia (MAT), and ventricular tachycardia (VT). Of note, the identification of ECG abnormalities and the evaluation of the arrhythmic risk may have significant implications in the management and outcome of patients with COPD. This article provides a concise overview of the available data regarding ECG abnormalities and arrhythmias in these patients, including an elaborated description of the underlying arrhythmogenic mechanisms. The clinical impact and prognostic significance of ECG abnormalities and arrhythmias in COPD as well as the appropriate antiarrhythmic therapy and interventions in this setting are also discussed.

Electrophysiological and Electroanatomical Mapping of the Right Atrium in Persistent Atrial Fibrillation: Relation to Collagen Turnover.

BACKGROUND: Atrial fibrillation (AF) is associated with abnormal atrial substrate. We investigated whether patients with persistent lone AF and patients with persistent AF and nonischemic dilated cardiomyopathy (NIDCM) exhibit any differences in electrophysiological and electroanatomical properties of right atrium (RA) and collagen turnover. We also investigated the relationship between mean RA bipolar voltage and collagen turnover. METHODS: Ten patients with a history of persistent lone AF and eight patients with a history of persistent AF and NIDCM were studied. Sinus node recovery times (SNRTs) and effective refractory periods (ERPs) at 600 ms, 500 ms, and 400 ms from the high (HLRA) and low (LLRA) lateral RA, proximal coronary sinus (pCS), and right atrial appendage (RAA) were evaluated, and RA electroanatomic mapping was created. Serum N-terminal propeptide of collagen type I (PINP), cross-linked C-terminal telopeptide of collagen type I (CTx), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of matrix metalloproteinases (TIMP-1) were measured as markers of collagen synthesis and degradation. RESULTS: No differences were found in SNRTs, ERPs from the HLRA, LLRA at 600 ms, pCS and RAA, mean RA bipolar voltage, serum PINP, CTx, MMP-1, and TIMP-1 between the two groups. In persistent lone AF, serum levels of TIMP-1 were related with mean HLRA and HPRA bipolar voltage. CONCLUSIONS: Persistent AF patients with or without NIDCM, demonstrate similar changes in electrophysiological and electroanatomical properties of the RA, as well as similar structural changes. Moreover, serum markers of collagen synthesis are correlated with bipolar voltage in specific regions of RA in persistent lone AF.

Obesity and atrial fibrillation: A comprehensive review of the pathophysiological mechanisms and links.

Obesity is a worldwide health problem with epidemic proportions that has been associated with atrial fibrillation (AF). Even though the underlying pathophysiological mechanisms have not been completely elucidated, several experimental and clinical studies implicate obesity in the initiation and perpetuation of AF. Of note, hypertension, diabetes mellitus, metabolic syndrome, coronary artery disease, and obstructive sleep apnea, represent clinical correlates between obesity and AF. In addition, ventricular adaptation, diastolic dysfunction, and epicardial adipose tissue appear to be implicated in atrial electrical and structural remodeling, thereby promoting the arrhythmia in obese subjects. The present article provides a concise overview of the association between obesity and AF, and highlights the underlying pathophysiological mechanisms.