Clinical Outcomes of Early Rhythm or Rate Control for New Onset Atrial Fibrillation Following Transcatheter Aortic Valve Replacement.

BACKGROUND: New onset atrial fibrillation (NOAF) is a common occurrence after transcatheter aortic valve replacement (TAVR) and portends a poorer prognosis. The optimal strategy for managing NOAF in this population is uncertain. METHODS: This retrospective cohort study utilized deidentified patient data from the TriNetX Research Network. Patients with TAVR and NOAF were stratified into a rhythm control cohort if they were treated with antiarrhythmics, received AF ablation, or underwent cardioversion within 1 year of AF diagnosis. A rate control cohort was similarly defined by the absence of rhythm control strategies and treatment with a beta blocker, calcium channel blocker, or digoxin. After 1:1 propensity score matching, the Kaplan-Meier survival analysis and Cox proportional hazard ratios (HRs) were used to compare outcomes at 7 years of follow-up. RESULTS: We identified 569 patients in each cohort following propensity matching. At 7 years, the primary composite outcome of all-cause death, myocardial infarction, cerebrovascular accident, and heart failure hospitalization was not significantly different between the rhythm and rate control cohorts (HR 0.99, 95% CI 0.83-1.18). The individual components of the primary outcome in addition to all-cause hospitalization were also similar between the groups. CONCLUSIONS: Similar outcomes were seen among patients receiving an early rhythm or rate control strategy to manage NOAF after TAVR. The attenuated benefits of an early rhythm control strategy observed in this setting may be due to the overall high burden of comorbidities and advanced age of these patients.

Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.

INTRODUCTION: The cardiac conduction system (CCS) is crucial for maintaining adequate cardiac frequency at rest and modulation during exercise. Furthermore, the atrioventricular node and His-Purkinje system are essential for maintaining atrioventricular and interventricular synchrony and consequently maintaining an adequate cardiac output. AREAS COVERED: In this review article, we examine the anatomy, physiology, and pathophysiology of the CCS. We then discuss in detail the most common genetic mutations and the molecular mechanisms of cardiac conduction disease (CCD) and provide our perspectives on future research and therapeutic opportunities in this field. EXPERT OPINION: Significant advancement has been made in understanding the molecular mechanisms of CCD, including the recognition of the heterogeneous signaling at the subcellular levels of sinoatrial node, the involvement of inflammatory and autoimmune mechanisms, and the potential impact of epigenetic regulations on CCD. However, the current treatment of CCD manifested as bradycardia still relies primarily on cardiovascular implantable electronic devices (CIEDs). On the other hand, an If specific inhibitor was developed to treat inappropriate sinus tachycardia and sinus tachycardia in heart failure patients with reduced ejection fraction. More work is needed to translate current knowledge into pharmacologic or genetic interventions for the management of CCDs.

Acute Myocardial Infarction in Pregnancy.

Pregnancy-associated myocardial infarction is an overall uncommon event, but can be associated with significant maternal and fetal morbidity and mortality. In contrast to myocardial infarction in the general nonpregnant population, the mechanism of pregnancy-associated myocardial infarction is most commonly due to nonatherosclerotic mechanisms such as coronary dissection, vasospasm, or thromboembolism. The diagnosis of pregnancy-associated myocardial infarction can be challenging, requiring a high index of suspicion for prompt recognition and management. Furthermore, the management of pregnancy-associated myocardial infarction can be complex due to maternal and fetal considerations and may vary based on the specific underlying mechanism of the myocardial infarction. This review aims to review the recent literature on pregnancy-associated myocardial infarction and summarize the epidemiology, mechanisms, diagnosis, and treatment strategies for this uncommon entity.

Medical Management of Coronary Artery Disease in Patients with Chronic Kidney Disease.

Chronic kidney disease patients are at increased risk of cardiovascular disease, which is the leading cause of mortality among this population. In addition, chronic kidney disease is a major risk factor for the development of coronary artery disease and is widely regarded as a coronary artery disease risk equivalent. Medical therapy is the cornerstone of coronary artery disease management in the general population. However, there are few trials to guide medical therapy of coronary artery disease in chronic kidney disease, with most data extrapolated from clinical trials of mainly non-chronic kidney disease patients, which were not adequately powered to evaluate this subgroup. There is some evidence to suggest that the efficacy of certain therapies such as aspirin and statins is attenuated with declining estimated glomerular filtration rate, with questionable benefit among end-stage renal disease (ESRD) patients. Furthermore, chronic kidney disease and ESRD patients are at higher risk of potential side effects with therapy, which may limit their use. In this review, we summarize the available evidence supporting the safety and efficacy of medical therapy of coronary artery disease in chronic kidney disease and ESRD patients. We also discuss the data on new emerging therapies, including PCSK9i, SGLT2i, GLP1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists, which show promise at reducing risk of cardiovascular events in the chronic kidney disease population and may offer additional treatment options. Overall, dedicated studies directly evaluating chronic kidney disease patients, particularly those with advanced chronic kidney disease and ESRD, are greatly needed to establish the optimal medical therapy for coronary artery disease and improve outcomes in this vulnerable population.

Clinical outcomes of conduction system pacing versus biventricular pacing for cardiac resynchronization therapy: A systematic review and meta-analysis.

INTRODUCTION: Conduction system pacing (CSP) is observed to produce greater improvements in echocardiographic and hemodynamic parameters as compared to conventional biventricular pacing (BiVP). However, whether these surrogate endpoints directly translate to improvements in hard clinical outcomes such as death and heart failure hospitalization (HFH) with CSP remains uncertain as studies reporting these outcomes are scarce. The aim of this meta-analysis was to analyze the existing data to compare the clinical outcomes of CSP versus BiVP. METHODS: A systematic search of the Embase and PubMed database was performed for studies comparing CSP and BiVP for patients indicated to receive a CRT device. The coprimary endpoints were all-cause mortality and HFH. Other secondary outcomes included change in left ventricular ejection fraction (LVEF), change in NYHA class, and increase in NYHA class ≥1. A random-effects model was chosen a priori to analyze the composite effects given the anticipated heterogeneity of included trials. RESULTS: Twenty-one studies (4 randomized and 17 observational) were identified reporting either primary outcome and were included in the meta-analysis. In total 1960 patients were assigned to CSP and 2367 to BiVP. Median follow-up time was 10.1 months (ranging 2-33 months). CSP was associated with a significant reduction in all-cause mortality (odds ratio [OR] 0.68, 95% confidence interval [CI]: 0.56-0.83) and HFH (OR 0.52, 95% CI: 0.44-0.63). Mean improvement in LVEF was also greater with CSP (mean difference 4.26, 95% CI: 3.19-5.33). Reduction in NYHA class was significantly greater with CSP (mean difference -0.36, 95% CI: -0.49 to -0.22) and the number of patients with an increase in NYHA class ≥1 was significantly greater with CSP (OR 2.02, 95% CI: 1.70-2.40). CONCLUSIONS: CSP was associated with a significant reduction in all-cause mortality and HFH when compared to conventional BiVP for CRT. Further large-scale randomized trials are needed to verify these observations.

Innovations in atrial fibrillation ablation.

BACKGROUND: Catheter-based ablation to perform pulmonary vein isolation (PVI) has established itself as a mainstay in the rhythm control strategy of atrial fibrillation. This review article aims to provide an overview of recent advances in atrial fibrillation ablation technology. METHODS: We reviewed the available literature and clinical trials of innovations in atrial fibrillation ablation technologies including ablation catheter designs, alternative energy sources, esophageal protection methods, electroanatomical mapping, and novel ablation targets. RESULTS: Innovative radiofrequency (RF) catheter designs maximize energy delivery while avoiding overheating associated with conventional catheters. Single-shot balloon catheters in the form of cryoballoons, radiofrequency, and laser balloons have proven effective at producing pulmonary vein isolation and improving procedural efficiency and reproducibility. Pulsed field ablation (PFA) is a highly anticipated novel nonthermal energy source under development, which demonstrates selective ablation of the myocardium, producing durable lesions while also minimizing collateral damage. Innovative devices for esophageal protection including esophageal deviation and cooling devices have been developed to reduce esophageal complications. Improved electroanatomical mapping systems are being developed to help identify additional non-pulmonary triggers, which may benefit from ablation, especially with persistent atrial fibrillation. Lastly, the vein of Marshall alcohol ablation has been recently studied as an adjunct therapy for improving outcomes with catheter ablation for persistent atrial fibrillation. CONCLUSIONS: Numerous advances have been made in the field of atrial fibrillation ablation in the past decade. While further long-term data is still needed for these novel technologies, they show potential to improve procedural efficacy and safety.

Sinus node dysfunction: current understanding and future directions.

The sinoatrial node (SAN) is the primary pacemaker of the heart. Normal SAN function is crucial in maintaining proper cardiac rhythm and contraction. Sinus node dysfunction (SND) is due to abnormalities within the SAN, which can affect the heartbeat frequency, regularity, and the propagation of electrical pulses through the cardiac conduction system. As a result, SND often increases the risk of cardiac arrhythmias. SND is most commonly seen as a disease of the elderly given the role of degenerative fibrosis as well as other age-dependent changes in its pathogenesis. Despite the prevalence of SND, current treatment is limited to pacemaker implantation, which is associated with substantial medical costs and complications. Emerging evidence has identified various genetic abnormalities that can cause SND, shedding light on the molecular underpinnings of SND. Identification of these molecular mechanisms and pathways implicated in the pathogenesis of SND is hoped to identify novel therapeutic targets for the development of more effective therapies for this disease. In this review article, we examine the anatomy of the SAN and the pathophysiology and epidemiology of SND. We then discuss in detail the most common genetic mutations correlated with SND and provide our perspectives on future research and therapeutic opportunities in this field.

Recent Developments in the Evaluation and Management of Cardiorenal Syndrome: A Comprehensive Review.

Cardiorenal syndrome (CRS) is an increasingly recognized diagnostic entity associated with high morbidity and mortality among acutely ill heart failure (HF) patients with acute and/ or chronic kidney diseases (CKD). While traditionally viewed as a state of decline in glomerular filtration rate (GFR) due to decreased renal perfusion, mainly due to therapeutic interventions to relieve congestive in HF, recent insights into the underlying pathophysiologic mechanisms of CRS led to a broader definition and further classification of CRS into 5 distinct types. In this comprehensive review, we discuss the classification of CRS, highlighting the underlying common pathogenetic pathways of heart failure and kidney injury, including increased congestion, neurohormonal dysregulation, oxidative stress as well as inflammation, and cytokine storm that are particularly evident in COVID-19 patients with multiorgan failure and also in those with other disorders including sepsis, systemic lupus erythematosus and amyloidosis. In this review we also present the recent advances in the diagnostic strategies of CRS including cardiac and renal biomarkers as well as advanced cardiac and renal imaging techniques that are available to aid in the diagnosis as well as in the prognostication of this disorder. Finally, we discuss the various therapeutic options available to-date, including fluid optimization, hemofiltration, renal replacement therapy as well as the role of SGLT2 inhibitors in light of recent data from RCTs. It is important to note that, CRS population are either excluded or underrepresented, at best, in major RCTs and therefore, therapeutic recommendations are largely extrapolated from HF and CKD clinical trials.

Comparison of cryoballoon and radiofrequency ablation for persistent atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: There is limited data comparing radiofrequency (RF) and cryoballoon (CB) ablation for persistent atrial fibrillation (AF), which tends to have higher recurrence rates following ablation compared to paroxysmal AF. METHODS: A systematic search of the Embase, PubMed, and Cochrane database was performed for studies comparing RF vs CB ablation for persistent AF. An inverse-variance random-effects model was used to calculate the composite effects. RESULTS: One randomized and 9 observational studies were identified, with 1650 patients receiving CB and 1706 patients receiving RF ablation. Mean follow-up time ranged from 12 to 48 months. Freedom from recurrent atrial tachyarrhythmia was similar with the two modalities (HR 0.93, 95% CI 0.80 to 1.08, I2 0%). Total complications were similar in both groups (RR 1.05, 95% CI 0.73 to 1.53, I2 0%) although rates of phrenic nerve palsy (PNP) were greater with CB (RR 4.13, 95% CI 1.49 to 11.46, I2 0%). Shorter procedure times were observed with CB (mean reduction 43.77 min, 95% CI 66.45 to 21.09 min, I2 96%) with no difference in fluoroscopy time (mean difference 0.82 min, 95% CI - 11.92 to 13.55 min, I2 100%). CONCLUSIONS: In persistent AF patients, CB ablation has similar efficacy and overall safety as compared to RF ablation. While CB is associated with significantly shorter procedure times, the improved procedural efficiency with CB is offset by increased rates of PNP and the potential need for touch-up RF ablation.

Innovations in Cardiac Implantable Electronic Devices.

Cardiac implantable electronic devices (CIEDs) are essential for the management of a variety of cardiac conditions, including tachyarrhythmias, bradyarrhythmias, and medically refractory heart failure (HF). Recent advancements in CIED technology have led to innovative solutions that overcome shortcomings associated with traditional devices or address unmet needs. Leadless pacemakers, subcutaneous implantable cardioverter defibrillators (ICDs), and extravascular ICDs eliminate lead-related complications common with conventional pacemakers or ICDs. Conduction system pacing (His bundle pacing and left bundle branch pacing) is a more physiologic method of pacing and avoids the deleterious consequences associated with long-term right ventricular pacing. For HF-related devices, cardiac contractility modulation is an emerging therapy that bridges a gap for many patients ineligible for cardiac resynchronization therapy and has been shown to improve HF symptoms and decrease hospitalizations and mortality in select patients. Implantable pulmonary artery pressure monitors help guide HF management and reduce hospitalizations. Lastly, new phrenic nerve stimulating devices are being utilized to treat central sleep apnea, a common comorbidity associated with HF. While further long-term studies are still underway for many of these new technologies, it is anticipated that these devices will become indispensable therapeutics in the expanding cardiovascular armamentarium.

Genetics of atrial fibrillation.

PURPOSE OF REVIEW: Atrial fibrillation is the most common sustained cardiac arrhythmia. In addition to traditional risk factors, it is increasingly recognized that a genetic component underlies atrial fibrillation development. This review aims to provide an overview of the genetic cause of atrial fibrillation and clinical applications, with a focus on recent developments. RECENT FINDINGS: Genome-wide association studies have now identified around 140 genetic loci associated with atrial fibrillation. Studies into the effects of several loci and their tentative gene targets have identified novel pathways associated with atrial fibrillation development. However, further validations of causality are still needed for many implicated genes. Genetic variants at identified loci also help predict individual atrial fibrillation risk and response to different therapies. SUMMARY: Continued advances in the field of genetics and molecular biology have led to significant insight into the genetic underpinnings of atrial fibrillation. Potential clinical applications of these studies include the identification of new therapeutic targets and development of genetic risk scores to optimize management of this common cardiac arrhythmia.