Atrial fibrillation (AF) poses significant thromboembolism and bleeding risks, especially in older adults. Warfarin continues to be a primary treatment option, and maintaining the Time in Therapeutic Range (TTR) is critical for ensuring its effectiveness. However, suboptimal TTR is associated with increased risks of stroke, bleeding, and mortality. Despite its importance, there is limited data on warfarin management in Ethiopian older adults with AF. Therefore, this study aimed to determine the TTR, bleeding events, and their determinants, in older patients with AF in Ethiopia receiving warfarin therapy.

In this study, older patients with AF who were treated with warfarin and had follow-up visits between May 2021 and May 2024, and met the inclusion criteria, were included. Patients were categorized based on TTR into two groups: poor anticoagulation (TTR < 65%) and good anticoagulation quality (TTR ≥ 65%). Bivariate and Multivariate Logistic regression was performed to predict determinants of a TTR < 65% and bleeding events. Odds ratios with 95% confidence intervals (CIs) were calculated, and statistical significance was set at P < 0.05.

In this study, 384 patients with AF were included. Of this 53.4% were female. Of these 71% of patients had a TTR below 65%, 29% achieved ≥65%, with a median TTR of 45%. Bleeding events were reported by 13.5% of patients. Poor TTR was significantly associated with age (AOR = 1.199, 95% CI: 1.109-1.297), chronic kidney disease (AOR = 27.809, 95% CI: 7.57-101.76), and infrequent INR monitoring at 31-90-day intervals (AOR = 0.15, 95% CI: 0.004-0.051). Regarding determinants of bleeding events, Patients with diabetes mellitus had a 2.6-fold higher bleeding risk (AOR = 2.585, 95% CI: 1.069-6.250), and a CHA2DS2-VASc score ≥3 significantly increased bleeding risk compared to scores ≤2 (AOR = 7.562, 95% CI: 2.770-20.640).

This study highlights suboptimal warfarin therapy among older Ethiopian patients with AF. Poor anticoagulation was associated with advanced age, chronic kidney disease, and infrequent INR monitoring, while diabetes mellitus and high CHA₂DS₂-VASc scores increased bleeding risks. Close monitoring and frequent INR checks are essential to improving outcomes.

Direct oral anticoagulants (DOACs) are commonly co-prescribed with amiodarone/diltiazem/verapamil, but whether there is a drug interaction between these drugs is unclear.

The purpose of this study was to investigate the risk of clinical outcomes associated with concomitant use of DOACs and amiodarone/diltiazem/verapamil.

We identified DOAC users in the Clinical Practice Research Datalink Aurum from January 1, 2011, to December 31, 2019. We used a cohort design to estimate hazard ratios for ischemic stroke, myocardial infarction, venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, other bleeding, cardiovascular mortality, and all-cause mortality, comparing DOACs + amiodarone/diltiazem/verapamil users and DOACs + beta-blocker users. A case-crossover design comparing odds of exposure to different drug initiation patterns for all outcomes in hazard window vs referent window within an individual also was conducted.

Of 397,459 DOAC users, we included 9075 co-prescribed amiodarone, 9612 co-prescribed diltiazem, and 2907 co-prescribed verapamil. There was no difference in risk of any outcomes between DOACs + amiodarone/diltiazem/verapamil users vs DOACs + beta-blocker users in the cohort design. However, in the case-crossover design, we observed an odds ratio (OR) of 2.09 (99% confidence interval [CI] 1.37-3.18) for all-cause mortality associated with initiation of a DOAC while taking amiodarone, which was greater than that observed for DOAC monotherapy (OR 1.30; 99% CI 1.25-1.35). Similar findings were observed for cardiovascular mortality and all-cause mortality respectively with diltiazem.

Our study showed no evidence of higher bleeding or cardiovascular risk associated with co-prescribed DOACs and amiodarone, diltiazem, or verapamil. Elevated risks of cardiovascular and all-cause mortality were only observed during DOAC initiation when diltiazem/amiodarone were being taken.

Atrial fibrillation (AF) is an increasingly recognized comorbidity in patients with cancer. Indeed, cancer patients have a significantly higher incidence of AF than that observed in the general population. A reciprocal relationship between these two diseases has been observed, as much as some assume AF to be a marker for occult cancer screening, especially in older adults. The pathophysiological mechanisms are many and varied, including the underlying pro-inflammatory state, specific treatments (chemo- and radiotherapy), and surgery. The therapeutic management of patients with cancer and AF involves the same rhythm and frequency control strategies as the general population; however, the numerous interactions with chemotherapeutics, which lead to a significant increase in side effects, as well as the extreme fragility of the patient, should be considered. Anticoagulant therapy is also a complex challenge to address, as bleeding and stroke risk scores have not been fully assessed in this subpopulation. Furthermore, in large studies establishing the efficacy of direct oral anticoagulants (DOACs), cancer patients have been underrepresented. In this review, we elaborate on the mechanisms linking AF to cancer patients with a particular focus on the therapeutic challenges in this population.

Recently, prognosis and survival of cancer patients has improved due to progression and refinement of cancer therapies; however, cardiovascular sequelae in this population augmented and now represent the second cause of death in oncological patients. Initially, the main issue was represented by heart failure and coronary artery disease, but a growing body of evidence has now shed light on the increased arrhythmic risk of this population, atrial fibrillation being the most frequently encountered. Awareness of arrhythmic complications of cancer and its treatments may help oncologists and cardiologists to develop targeted approaches for the management of arrhythmias in this population. In this review, we provide an updated overview of the mechanisms triggering cardiac arrhythmias in cancer patients, their prevalence and management.

Acute atrial fibrillation is defined as atrial fibrillation detected in the setting of acute care or acute illness; atrial fibrillation may be detected or managed for the first time during acute hospitalization for another condition. Atrial fibrillation after cardiothoracic surgery is a distinct type of acute atrial fibrillation. Acute atrial fibrillation is associated with high risk of long-term atrial fibrillation recurrence, warranting clinical attention during acute hospitalization and over long-term follow-up. A framework of substrates and triggers can be useful for evaluating and managing acute atrial fibrillation. Acute management requires a multipronged approach with interdisciplinary care collaboration, tailoring treatments to the patient's underlying substrate and acute condition. Key components of acute management include identification and treatment of triggers, selection and implementation of rate/rhythm control, and management of anticoagulation. Acute rate or rhythm control strategy should be individualized with consideration of the patient's capacity to tolerate rapid rates or atrioventricular dyssynchrony, and the patient's ability to tolerate the risk of the therapeutic strategy. Given the high risks of atrial fibrillation recurrence in patients with acute atrial fibrillation, clinical follow-up and heart rhythm monitoring are warranted. Long-term management is guided by patient substrate, with implications for intensity of heart rhythm monitoring, anticoagulation, and considerations for rhythm management strategies. Overall management of acute atrial fibrillation addresses substrates and triggers. The 3As of acute management are acute triggers, atrial fibrillation rate/rhythm management, and anticoagulation. The 2As and 2Ms of long-term management include monitoring of heart rhythm and modification of lifestyle and risk factors, in addition to considerations for atrial fibrillation rate/rhythm management and anticoagulation. Several gaps in knowledge related to acute atrial fibrillation exist and warrant future research.

Atrial fibrillation (AF) is the most persistent arrhythmia today, with its prevalence increasing exponentially with the rising age of the population. Particularly at elevated heart rates, a functional abnormality known as cardiac alternans can occur prior to the onset of lethal arrhythmias. Cardiac alternans are a beat-to-beat oscillation of electrical activity and the force of cardiac muscle contraction. Extensive evidence has demonstrated that microvolt T-wave alternans can predict ventricular fibrillation vulnerability and the risk of sudden cardiac death. The majority of our knowledge of the mechanisms of alternans stems from studies of ventricular electrophysiology, although recent studies offer promising evidence of the potential of atrial alternans in predicting the risk of AF. Exciting preclinical and clinical studies have demonstrated a link between atrial alternans and the onset of atrial tachyarrhythmias. Here, we provide a comprehensive review of the clinical utility of atrial alternans in identifying the risk and guiding treatment of AF.

To date, the treatment option for tachyarrhythmia is classified into drug therapy, catheter ablation, and implantable device therapy. However, the efficacy of the antiarrhythmic drugs is limited. Although the indication of catheter ablation is expanding, several fatal tachyarrhythmias are still refractory to ablation. Implantable cardioverter-defibrillator increases survival, but it is not a curable treatment. Therefore, a novel therapy for tachyarrhythmias refractory to present treatments is desired. Gene therapy is being developed as a promising candidate for this purpose, and basic research and translational research have been accumulated in recent years.

This paper reviews the current state of gene therapy for arrhythmias, including susceptible arrhythmias, the route of administration to the heart, and the type of vector to use. We also discuss the latest progress in the technology of gene delivery and genome editing.

Gene therapy is one of the most promising technologies for arrhythmia treatment. However, additional technological innovation to achieve safe, localized, homogeneous, and long-lasting gene transfer is required for its clinical application.

Obesity is a chronic disease, which has significant health consequences and is a staggering burden to health care systems. Obesity can have harmful effects on the cardiovascular system, including heart failure, hypertension, coronary heart disease, and atrial fibrillation (AF). One of the possible substrates might be epicardial adipose tissue (EAT), which can be the link between AF and obesity. EAT is a fat deposit located between the myocardium and the visceral pericardium. Numerous studies have demonstrated that EAT plays a pivotal role in this relationship regarding atrial fibrillation.

This review will focus on the role of obesity and the occurrence of atrial fibrillation (AF) and examine the connection between these and epicardial adipose tissue (EAT). The first part of this review will explain the pathophysiology of EAT and its association with the occurrence of AF. Secondly, we will review bariatric and metabolic surgery and its effects on EAT and AF.

In this review, the epidemiology, pathophysiology, and treatments methods of AF are explained. Secondly the effects on EAT were elucidated. Due to the complex pathophysiological link between EAT, AF, and obesity, it is still uncertain which treatment strategy is superior.

Hypothermia is an involuntary fall in body temperature, usually below 35°C. Hypothermia is a common condition, especially in frigid zones. However, it should not be forgotten that it can also occur in temperate climates or for iatrogenic reasons. Hypothermia is associated with seriously severe arrhythmias, particularly ventricular fibrillation, and there are many reports of prolonged resuscitation in these patient groups. This case report shows that a standard thermometer, either with Emergency Medical Services or in-hospital, will be incapable of reading the temperature if it is less than 34°C and will falsely read 34°C when in reality it is lower than that; in a clinically relevant scenario, a low-reading thermometer or core body temperature readings, such as rectal or esophageal, should be used.

Cancer and atrial fibrillation (AF) are common co-morbid conditions in older adults. Both cancer and cancer treatment increase the risk of developing new AF which increases morbidity and mortality. Heart rate and rhythm control along with anticoagulation therapy remain the mainstay of treatment of AF in older adults with both cancer and AF. Adjustments to the treatment may be necessary because of drug interactions with concurrent chemotherapy. Cancer and old age increase the risk of both, thromboembolism and bleeding. The risk of these complications is further enhanced by concomitant cancer therapy, frailty, poor nutrition status and, coexisting geriatric syndromes. Therefore, careful attention needs to be given to the risks and benefits of using anticoagulant medications. This review focuses on the management of AF in older patients with cancer, including at the end-of-life care.

Introduction Atrial fibrillation (AF) after coronary artery bypass grafting (CABG) is correlated with poor patient outcomes. The study evaluated the association of patients' clinical and sociodemographic characteristics with the incidence of atrial fibrillation, postoperatively.  Methodology A longitudinal study was performed in the cardiology department of a tertiary care unit, Sindh, Pakistan between October 2019 and November 2020. All patients who underwent CABG surgery irrespective of gender aged 30 to 75 years were included in the study. Patients with a history of atrial fibrillation or severe left ventricular dysfunction were excluded from the study. The incidence of atrial fibrillation was determined by observing an irregular pattern on electrocardiography (ECG) with no definite P-wave and irregular R-R interval. The patients were monitored for seven postoperative days. The final outcome was measured on the seventh postoperative day.  Results A total of 247 patients with a mean age of 63.43 ± 9.72 were enrolled in the study. Out of the 247 patients, 9.7% developed new-onset atrial fibrillation, postoperatively. Age above 65 years was associated with the occurrence of AF but it was not statistically significant (p>0.05). Similarly, patients who developed AF were more likely to have a left ventricle ejection fraction (LVEF) of less than 35% than those without AF (66.67% vs 43.95%; p=0.033).  Conclusion A high rate of AF was observed in the study. Older age and impaired ventricular function were significantly associated with atrial fibrillation. It is recommended that hospitals should devise guidelines and protocols for the prevention and management of atrial fibrillation in patients undergoing cardiothoracic surgeries in order to minimize patient mortality and improve patient outcomes.

Rivaroxaban reduces the risk of thromboembolism in atrial fibrillation (AF) patients, who often also receive antiarrhythmic drugs (AADs) to maintain sinus rhythm. Current guidelines contraindicate concomitant use of rivaroxaban with the popular AAD dronedarone, despite little data demonstrating interactions with AADs. This study investigates the outcomes of concomitant rivaroxaban and AAD drug use in a real-world cohort.

This retrospective study included 1777 non-permanent AF patients taking rivaroxaban for ≥ 1 month between 2011 and 2016 from a multicenter cohort in Taiwan, and compared concomitant AAD use against clinical outcome endpoints for safety, effectiveness, and major adverse cardiac events (MACE). Multivariate Cox proportional hazard analyses were used to evaluate the association between concomitant AAD use and outcomes.

Patients were divided into rivaroxaban alone (n = 1205) and with concomitant amiodarone (n = 177), dronedarone (n = 231), or propafenone (n = 164) groups. The proportion of patients using rivaroxaban 10 mg was highest in the concomitant dronedarone group: rivaroxaban alone, 53.6%; with amiodarone, 57.6%; with dronedarone, 77.1%; and with propafenone, 46.3% (p < 0.001). The cumulative incidences of safety (p = 0.892), effectiveness (p = 0.336), and MACE (p = 0.674) were similar between the four groups; however, there were significantly fewer new systemic thromboembolisms in the dronedarone group: rivaroxaban alone, 2.5%; with amiodarone, 0.6%; with dronedarone, 0%; and with propafenone, 1.2% (p = 0.029). The all-cause death rate was also lowest in the dronedarone group: rivaroxaban alone, 9.0%; with amiodarone, 9.6%; with dronedarone, 3.0%; and with propafenone: 6.1% (p = 0.013). After covariate adjustment, there were no differences in the safety, effectiveness, and MACE endpoints between patients receiving or not receiving AADs.

Concomitant use of rivaroxaban with AADs appears to be well tolerated, warranting further investigation into the apparent benefits of a reduced dose of rivaroxaban combined with dronedarone.

Heart rate (HR) is an important factor in atrial fibrillation (AF); however, it remains unclear whether the impact of HR differs between paroxysmal AF and sustained (persistent and permanent) AF.

The association of resting HR during AF with adverse events (composite of all-cause death, hospitalization for heart failure, stroke/systemic embolisms, myocardial infarction, and arrhythmic events) in 1,064 paroxysmal and 1,610 sustained AF patients from the Fushimi AF Registry were investigated. These patients were divided into 4 groups based on their resting HR; ≥110 beats/min (bpm), 80-109 bpm, 60-79 bpm, and <60 bpm. The number of patients in each group was 486, 400, 172, and 22 for paroxysmal AF, and 205, 734, 645, and 71 for sustained AF, respectively. Among patients with sustained AF, a HR ≥110 bpm was associated with a higher incidence of adverse events at 1 year and during the entire follow up (median of 1,833 days) (hazard ratio [95% confidence interval] compared with a HR of 60-79 bpm: 1.90 [1.31-2.72] at 1 year, 1.38 [1.10-1.72] during the entire follow up). Patients with a HR <60 bpm showed higher incidence of adverse events at 1 year; however, the incidence of adverse events did not differ among all HR groups of paroxysmal AF.

Baseline HR was associated with adverse events in sustained AF, but not in paroxysmal AF.

In the last decade, interest in gene therapy as a therapeutic technology has increased, largely driven by an exciting yet modest number of successful applications for monogenic diseases. Setbacks in the use of gene therapy for cardiac disease have motivated efforts to develop vectors with enhanced tropism for the heart and more efficient delivery methods. Although monogenic diseases are the logical target, cardiac arrhythmias represent a group of conditions amenable to gene therapy because of focal targets (biological pacemakers, nodal conduction, or stem cell-related arrhythmias) or bystander effects on cells not directly transduced because of electrical coupling.

This review provides a contemporary narrative of the field of gene therapy for experimental cardiac arrhythmias, including those associated with stem cell transplant. Recent articles published in the English language and available through the PubMed database and other prominent literature are discussed.

The promise of gene therapy has been realized for a handful of monogenic diseases and is actively being pursued for cardiac applications in preclinical models. With improved vectors, it is likely that cardiac disease will also benefit from this technology. Cardiac arrhythmias, whether inherited or acquired, are a group of conditions with a potentially lower threshold for phenotypic correction and as such hold unique potential as targets for cardiac gene therapy.

There has been a proliferation of research on the potential of gene therapy for cardiac arrhythmias. This body of investigation forms a strong basis on which further developments, particularly with viral vectors, are likely to help this technology progress along its translational trajectory.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia and is associated with significant morbidity and mortality. The autonomic nervous system (ANS) plays an important role in the initiation and development of AF, causing alterations in atrial structure and electrophysiological defects. The intrinsic ANS of the heart consists of multiple ganglionated plexi (GP), commonly nestled in epicardial fat pads. These GPs contain both parasympathetic and sympathetic afferent and efferent neuronal circuits that control the electrophysiological properties of the myocardium. Pulmonary vein isolation and other cardiac catheter ablation targets including GP ablation can disrupt the fibers connecting GPs or directly damage the GPs, mediating the benefits of the ablation procedure. Ablation of GPs has been evaluated over the past decade as an adjunctive procedure for the treatment of patients suffering from AF. The success rate of GP ablation is strongly associated with specific ablation sites, surgical techniques, localization techniques, method of access and the incorporation of additional interventions. In this review, we present the current data on the clinical utility of GP ablation and its significance in AF elimination and the restoration of normal sinus rhythm in humans.

New-onset atrial fibrillation (NOAF) remains common arrhythmia in acute myocardial infarction (AMI), and is closely associated with increased subsequent cardiovascular mortality. Our meta-analysis aims to summarize more clinical risk factors for NOAF.Comprehensive systematic search of MEDLINE, EMBASE, and the Cochrane Library were carried out to find relevant studies inception to December 2017. Pooled mean difference (MD) and 95% confidence interval (CI) were calculated to evaluate the value of clinical risk factors in the prediction of NOAF after AMI.Eleven studies containing 9570 patients were included in the meta-analysis. Overall, older age and increased heart rate (HR) levels had a significant positive association with NOAF in patients with AMI. The MD in age between the patients with, and those without NOAF, was 8.22 units (95% confidence interval [CI]: 7.44-9.01), test for overall effect z score = 20.51 (P < .00001, I = 0%). Moreover, the MD in a subgroup analysis for HR levels between the patients with, and those without NOAF was 4.34 units (95% Cl: 2.56-6.11), test for overall effect z score = 4.78 (P < .00001, I = 31%).In patient with AMI, our meta-analysis demonstrated that older age and increased HR levels on admission are related to greater risk of NOAF.

Rate-control medications are considered first-line treatment for patients with atrial fibrillation (AF). However, obstructive lung disease (OLD), a condition prevalent in those with AF, often makes it difficult to use those medications because of the lack of studies on new-onset AF in patients with OLD.

The purpose of this study was to investigate clinical outcomes after administration of each class of rate-control medication in patients with concomitant AF and OLD (AF-OLD).

This study used the entire database provided by the National Health Insurance Service from 2002 to 2015. Risk of all-cause mortality was compared between use of calcium channel blocker (CCB) and use of other drug classes in AF-OLD patients using Cox regression analyses after propensity score matching.

Among the 13,111 patients, the number of AF-OLD patients treated with a CCB, cardioselective β-blocker (BB), nonselective BB, and digoxin was 2482, 2379, 2255, and 5995, respectively. The risk of mortality was lower with use of selective BB (hazard ratio [HR] 0.84; 95% confidence interval [CI] 0.75-0.94; P = .002) and nonselective BB (HR 0.85; 95% CI 0.77-0.95; P = .003) compared to use of CCBs. Digoxin use was related with worse survival, with marginal statistical significance (HR 1.09; 95% CI 1.00-1.18; P = .053).

Among patients with AF-OLD, rate-control treatment using selective and nonselective BB was associated with a significant reduction in mortality compared with CCB use. Further prospective randomized trials are required to confirm these findings.

Association of heart rate (HR) with mortality in patients with acute coronary syndrome (ACS) and aged ≥ 80 years are underrepresented in clinical trials. We therefore aimed to investigate the association of HR in atrial fibrillation (AF) versus sinus rhythm (SR) with all-cause mortality in octogenarian patients with ACS.

A total of 336 patients with ACS patients and aged ≥ 80 years were enrolled into the current study. The end point of interest was death from any cause. Association of HR in AF versus SR with mortality was analyzed by Kaplan-Meier curve following log-rank test and multivariable Cox regression analysis.

In total, 63 (87.5%) of patients with AF were dead and 147 (59.8%) of patients with SR were dead during the follow-up period. The best cut-off was 80 bpm, with a sensitivity of 62% and specificity of 66%. HR ≤ 80 bpm in SR but not in AF was associated with better outcome as compared with HR > 80 bpm (Chi-Square = 26.55, Log rank P < 0.001). In SR subgroup, the hazard ratios of HR ≤ 80 bpm were 0.51(95% CI 0.37-0.70, P < 0.001) adjusted for age, 0.46 (95%CI 0.33-0.63, P < 0.001) adjusted for gender, 0.62 (95%CI 0.42- 0.93, P = 0.020) adjusted for multivariables respectively. In AF subgroup, the hazard ratios of HR ≤ 80 bpm were 0.83(95% CI 0.49-1.38, P = 0.464) adjusted for age, 0.96 (95%CI 0.59-1.58, P = 0.882) adjusted for gender, 0.72(95% CI 0.41-1.26, P = 0.249) adjusted for multivariables respectively.

The current study demonstrates that heart rate is an independent prognostic predictor for all-cause mortality, and HR ≤ 80 bpm is associated with improved outcome in SR but not in AF in octogenarian patients with ACS.

Atrial fibrillation (AF) affects more than three million people per year in the United States and is associated with high morbidity and mortality. Both electrical and structural remodeling contribute to AF, but the molecular pathways underlying AF pathogenesis are not well understood. Recently, a role for Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) in the regulation of persistent "late" Na⁺ current ( I_Na,L) has been identified. Although I_Na,L inhibition is emerging as a potential antiarrhythmic strategy in patients with AF, little is known about the mechanism linking I_Na,L to atrial arrhythmogenesis. A computational approach was used to test the hypothesis that increased CaMKII-activated I_Na,L in atrial myocytes disrupts Ca²⁺ homeostasis, promoting arrhythmogenic afterdepolarizations. Dynamic CaMKII activity and regulation of multiple downstream targets [ I_Na,L, L-type Ca²⁺ current, phospholamban, and the ryanodine receptor sarcoplasmic reticulum Ca²⁺-release channel (RyR2)] were incorporated into an existing well-validated computational model of the human atrial action potential. Model simulations showed that constitutive CaMKII-dependent phosphorylation of Na_v1.5 and the subsequent increase in I_Na,L effectively disrupt intracellular atrial myocyte ion homeostasis and CaMKII signaling. Specifically, increased I_Na,L promotes intracellular Ca²⁺ overload via forward-mode Na⁺/Ca²⁺ exchange activity, which greatly increases RyR2 open probability beyond that observed for CaMKII-dependent phosphorylation of RyR2 alone. Increased I_Na,L promotes atrial myocyte repolarization defects (afterdepolarizations and alternans) in the setting of acute β-adrenergic stimulation. We anticipate that our modeling efforts will help identify new mechanisms for atrial Na_V1.5 regulation with direct relevance for human AF. NEW & NOTEWORTHY Here, we present a novel computational model to study the effects of late Na⁺ current ( I_Na,L) in human atrial myocytes. Simulations predict that I_Na,L promotes intracellular accumulation of Ca²⁺, with subsequent dysregulation of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) signaling and ryanodine receptor 2-mediated Ca²⁺ release. Although I_Na,L plays a small role in regulating atrial myocyte excitability at baseline, CaMKII-dependent enhancement of the current promoted arrhythmogenic dynamics. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/camkii-dependent-regulation-of-atrial-late-sodium-current-and-excitability/ .

We report a case of new-onset atrial fibrillation with rapid ventricular response in a 37-year-old male who presented to the emergency department. This patient was not admitted to the hospital or placed on observation, but rather placed on a cellular outpatient 12-lead telemetry (COTLT) device with emergency response capabilities and discharged home. We define a new modality that allows these patients to be managed via telemedicine and receive care similar to that which would be rendered in a hospital or observation unit.

Atrial fibrillation (AF) is the most prevalent arrhythmia in the world, due both to its tenacious treatment resistance, and to the tremendous number of risk factors that set the stage for the atria to fibrillate. Cardiopulmonary, behavioral, and psychological risk factors generate electrical and structural alterations of the atria that promote reentry and wavebreak. These culminate in fibrillation once atrial ectopic beats set the arrhythmia process in motion. There is growing evidence that chronic stress can physically alter the emotion centers of the limbic system, changing their input to the hypothalamic-limbic-autonomic network that regulates autonomic outflow. This leads to imbalance of the parasympathetic and sympathetic nervous systems, most often in favor of sympathetic overactivation. Autonomic imbalance acts as a driving force behind the atrial ectopy and reentry that promote AF. Careful study of AF pathophysiology can illuminate the means that enable AF to elude both pharmacological control and surgical cure, by revealing ways in which antiarrhythmic drugs and surgical and ablation procedures may paradoxically promote fibrillation. Understanding AF pathophysiology can also help clarify the mechanisms by which emerging modalities aiming to correct autonomic imbalance, such as renal sympathetic denervation, may offer potential to better control this arrhythmia. Finally, growing evidence supports lifestyle modification approaches as adjuncts to improve AF control.

In the United States (U.S.), atrial fibrillation (AF) is the second-most common cardiovascular condition after hypertension, affecting four million Americans each year. Individuals with AF are three times more likely to be hospitalized over the span of a year when compared to medically matched control groups. The considerably large clinical population of individuals with AF mandates that the cost-effectiveness and efficacy of current treatment regimens for AF have egregious implications for health care spending and public health. Unfortunately, catheter ablation for AF treatment has been shown to make only modest gains in quality-adjusted life years, has yet to demonstrate cost-utility advantages over conventional therapies for AF, and has a reported rate of recurrence for AF that is notably high. Thus, there is a major unmet clinical need for a therapeutic option to treat AF that produces more consistent and efficacious results that are cost-effective. Cardiac radiosurgery as a therapy for AF has the potential to be remarkably cost-effective and produce robust patient outcomes. CyberHeart Inc. has developed the world's first-ever cardiac radiosurgery (CRS) system designed to ablate the heart non-invasively. Procedures that ablate the heart utilizing the Cyberheart CRS system are anticipated to allow higher efficacy and more consistent results than current techniques such as catheter ablation. The aim of this study is to present the current healthcare utilization and expenditures in AF treatment, report the cost-effectiveness of catheter ablation for AF, and project the potential cost-effectiveness of cardiac radiosurgery for the treatment of AF.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting 1% to 2% of the general population. It is characterized by rapid and disorganized atrial activation leading to impaired atrial function, which can be diagnosed on an EKG by lack of a P-wave and irregular QRS complexes. AF is associated with increased morbidity and mortality and is a risk factor for embolic stroke and worsening heart failure. Current research on AF support and explore the hypothesis that initiation and maintenance of AF require pathophysiological remodeling of the atria, either specifically as in lone AF or secondary to other heart disease as in heart failure-associated AF. Remodeling in AF can be grouped into three categories that include: (i) electrical remodeling, which includes modulation of L-type Ca(2+) current, various K(+) currents and gap junction function; (ii) structural remodeling, which includes changes in tissues properties, size, and ultrastructure; and (iii) autonomic remodeling, including altered sympathovagal activity and hyperinnervation. Electrical, structural, and autonomic remodeling all contribute to creating an AF-prone substrate which is able to produce AF-associated electrical phenomena including a rapidly firing focus, complex multiple reentrant circuit or rotors. Although various remodeling events occur in AF, current AF therapies focus on ventricular rate and rhythm control strategies using pharmacotherapy and surgical interventions. Recent progress in the field has started to focus on the underlying substrate that drives and maintains AF (termed upstream therapies); however, much work is needed in this area. Here, we review current knowledge of AF mechanisms, therapies, and new areas of investigation.

To review digoxin use in systolic congestive heart failure, atrial fibrillation, and after myocardial infarction.

A comprehensive PubMed search was performed using the key words "digoxin and congestive heart failure", "digoxin and atrial fibrillation", "digoxin, atrial fibrillation and systolic congestive heart failure", and "digoxin and myocardial infarction". Only articles written in English were included in this study. We retained studies originating from randomized controlled trials, registries and included at least 500 patients. The studies included patients with atrial fibrillation or heart failure or myocardial infarction and had a significant proportion of patients (at least 5%) on digoxin. A table reviewing the different hazard ratios was developed based on the articles selected. Our primary endpoint was the overall mortality in the patients on digoxin vs those without digoxin, among patients with atrial fibrillation and also among patients with atrial fibrillation and systolic heart failure. We reviewed the most recent international guidelines to discuss current recommendations.

A total of 18 studies were found that evaluated digoxin and overall mortality in different clinical settings including systolic congestive heart failure and normal sinus rhythm (n = 5), atrial fibrillation with and without systolic congestive heart failure (n = 9), and myocardial infarction (n = 4). Overall, patients with systolic congestive heart failure with normal sinus rhythm, digoxin appears to have a neutral effect on mortality especially if close digoxin level monitoring is employed. However, most of the observational studies evaluating digoxin use in atrial fibrillation without systolic congestive heart failure showed an increase in overall mortality when taking digoxin. In the studies evaluated in this systematic review, the data among patients with atrial fibrillation and systolic congestive heart failure, as well as post myocardial infarction were more controversial. The extent to which discrepancies among studies are based on statistical methods is currently unclear, as these studies' findings are generated by retrospective analyses that employed different techniques to address confounding.

Based on the potential risks and benefits, as well as the presence of alternative drugs, there is a limited role for digoxin in the management of patients with normal sinus rhythm and congestive heart failure. Based on the retrospective studies reviewed there is a growing volume of data showing increased mortality in those with only atrial fibrillation. The proper role of digoxin is, however, less certain in other subgroups of patients, such as those with both atrial fibrillation and systolic congestive heart failure or after a myocardial infarction. Further studies may provide helpful information for such subgroups of patients.

Higher heart rate predicts higher mortality in chronic heart failure (HF). We studied the prognostic impact of admission heart rate in acute HF and analysed the importance of its change during hospitalization.

Acute HF patients were studied. Endpoint was all-cause death. Patients were followed-up for 12 months from hospital admission. Cox-regression analysis was used to study the association of heart rate (both as a continuous and as a categorical variable) with mortality. Analysis was stratified according to admission rhythm and to systolic dysfunction. Multivariate models were built. Patients surviving hospitalization were additionally cross-classified attending to admission and discharge heart rates – cut-offs: 100 and 80 beats per minute (bpm), respectively.

We analysed 564 patients. Median age was 78 years and median admission heart rate 87 bpm. In a 12-month period 205 patients died, 23 in-hospital. Mortality increased steadily with heart rate decrease. Patients with heart rate ≥ 100 bpm had a multivariate-adjusted HR of 12-month death of 0.57 (95%CI: 0.39-0.81), and the HR was 0.92 (0.85-0.98) per 10 bpm increase in heart rate. Association of heart rate with mortality was stronger in patients in sinus rhythm (SR) and in those with systolic dysfunction. Eighty-seven patients had admission heart rate ≥ 100 and discharge heart rate < 80 bpm. In them, death rate was 14.9%; in the remaining patients it was 37.7%.

Higher admission heart rate predicted survival advantage in acute HF. Patients presenting with tachycardia and discharged with a controlled heart rate had better outcome than those admitted non-tachycardic or discharged with a non-controlled heart rate.

Resveratrol is a bioactive polyphenol, found in grapes, red wine, and peanuts, and has recently garnered much media and scientific attention for its diverse beneficial health effects as a nutritional supplement or nutraceutical. Of particular interest are the well-documented cardioprotective effects of resveratrol that are mediated by diverse mechanisms, including its antioxidant and vascular effects. However, it is now becoming clear that resveratrol may also exhibit direct effects on cardiac function and rhythm through modulation of signaling pathways that regulate cardiac remodeling and ion channel activity that controls cardiac excitability. Resveratrol may therefore possess antiarrhythmic properties that contribute to the cardiovascular benefits of resveratrol. Atrial fibrillation (AF) is the most common cardiac arrhythmia, although current therapies are suboptimal. Our laboratory has been studying resveratrol's effects on cardiac ion channels and remodeling pathways, and we initiated a drug development program aimed at generating novel resveratrol derivatives with improved efficacy against AF when compared to currently available therapeutics. This review therefore focuses on the effects of resveratrol and new derivatives on a variety of cardiac ion channels and molecular pathways that contribute to the development and maintenance of atrial fibrillation.

Atrial fibrillation (AF) is a factor in the development of thrombi that can lead to ischemic strokes. Anticoagulants are crucial in preventing strokes among patients with AF but are associated with bleeding risks. Recent studies have shown that despite anticoagulants' efficacy in stroke prevention, many patients with AF receive subtherapeutic levels of anticoagulation because of concerns about bleeding. Of particular interest is to quantify the perceived relative importance of treatment-related benefits and risks and how these perceptions vary between patients and physicians in different countries.

Patients' and physicians' preferences were elicited using a discrete-choice experiment. We evaluated disagreements in preferences for the benefits and risks of anticoagulants.

A total of 186 patients with AF and 107 physicians in the United States completed the survey. In Japan, 152 patients and 164 physicians completed the same survey. Japanese patients were relatively less averse than US patients to bleeding risks. Physicians in both countries did not distinguish between nondisabling and disabling strokes. US patients were less tolerant than physicians of nonmajor clinically relevant bleeding risk when this risk was a consequence of preventing nondisabling strokes. Japanese patients were generally more tolerant than physicians of bleeding risks when the risks were consequences of preventing both nondisabling and disabling strokes.

Overall, preferences for anticoagulant benefits and risks were not statistically different between patients and physicians in the United States, nor were there differences in preferences for different stroke risks between physicians in the United States and Japan; however, preferences were different between patients and physicians in Japan.

This study sought to investigate the relationship between resting ventricular rate and mortality in patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction (LVEF) who were in sinus rhythm (SR) or atrial fibrillation (AF).

Slower heart rates are associated with better survival in patients with CHF in SR, but it is not clear whether this is true for those in AF.

We assessed 2,039 outpatients with CHF and LVEF ≤50% undergoing baseline assessment, of whom 24% (n = 488) were in AF; and 841 outpatients reassessed after attempted treatment optimization at 1 year, of whom 22% (n = 184) were in AF. Cox proportional hazards models were used to assess the relationships between heart rate and survival in patients with CHF and AF or sinus rhythm. We analyzed heart rate and rhythm data recorded at the baseline review and after 1-year follow-up. Proportional hazards assumptions were checked by Schoenfeld and Martingale residuals.

The median survival for those in AF was 6.1 years (interquartile range [IQR]: 5.3 to 6.9 years) and 7.3 years (IQR: 6.5 to 8.1 years) for those in SR. In univariable analysis, patients with AF had a worse survival (hazard ratio [HR]: 1.26, 95% confidence interval [CI]: 1.08 to 1.47; p = 0.003) but after covariate adjustment, survival rates were similar. After adjusting Cox regression models, there was no association between heart rate (per 10 beats/min increments) and survival in patients with AF before (HR: 0.94, 95% CI: 0.88 to 1.00, p = 0.07) or after (HR: 1.00, 95% CI: 0.99 to 1.00, p = 0.84) therapy optimization. For patients in SR, higher heart rates were associated with worse survival, both before (HR: 1.10, 95% CI: 1.05 to 1.15, p <0.0001) and after (HR: 1.13, 95% CI: 1.03 to 1.24, p = 0.008) therapy optimization.

In patients with CHF and a reduced LVEF, slower resting ventricular rate is associated with better survival for patients in SR but not for those with AF.

Atrial fibrillation is the most common arrhythmia affecting patients today. Disease prevalence is increasing at an alarming rate worldwide, and is associated with often catastrophic and costly consequences, including heart failure, syncope, dementia, and stroke. Therapies including anticoagulants, anti-arrhythmic medications, devices, and non-pharmacologic procedures in the last 30 years have improved patients' functionality with the disease. Nonetheless, it remains imperative that further research into AF epidemiology, genetics, detection, and treatments continues to push forward rapidly as the worldwide population ages dramatically over the next 20 years.