Catheter ablation versus medical therapy in atrial fibrillation: an umbrella review of meta-analyses of randomized clinical trials.

This umbrella review synthesizes data from 17 meta-analyses investigating the comparative outcomes of catheter ablation (CA) and medical treatment (MT) for atrial fibrillation (AF). Outcomes assessed were mortality, risk of hospitalization, AF recurrence, cardiovascular events, pulmonary vein stenosis, major bleeding, and changes in left ventricular ejection fraction (LVEF) and MLHFQ score. The findings indicate that CA significantly reduces overall mortality and cardiovascular hospitalization with high strength of evidence. The risk of AF recurrence was notably lower with CA, with moderate strength of evidence. Two associations reported an increased risk of pulmonary vein stenosis and major bleeding with CA, supported by high strength of evidence. Improved LVEF and a positive change in MLHFQ were also associated with CA. Among patients with AF and heart failure, CA appears superior to MT for reducing mortality, improving LVEF, and reducing cardiovascular rehospitalizations. In nonspecific populations, CA reduced mortality and improved LVEF but had higher complication rates. Our findings suggest that CA might offer significant benefits in managing AF, particularly in patients with heart failure. However, the risk of complications, including pulmonary vein stenosis and major bleeding, is notable. Further research in understudied populations may help refine these conclusions.

Role of dofetilide in patients with ventricular arrhythmias.

BACKGROUND OR PURPOSE: To assess effectiveness of dofetilide in reducing the burden of ventricular arrhythmias (VAs). BACKGROUND: Prior small sample studies show that dofetilide has benefit in reducing VA. However, large sample investigations with long-term follow-up are lacking. METHODS: Two hundred seventeen consecutive patients admitted between January 2015 and December 2021 for dofetilide initiation for control of VA were assessed. Dofetilide was successfully started in 176 patients (81%) and had to be discontinued in the remaining 41 patients (19%). Dofetilide was initiated for control of ventricular tachycardia (VT) in 136 patients (77%), whereas 40 (23%) patients were initiated on dofetilide for reducing the burden of premature ventricular complexes (PVCs). RESULTS: The mean follow-up was 24 ± 7 months. In total, among the 136 VT patients, 33 (24%) died, 11 (8%) received a left ventricular assist device (LVAD), and 3 (2%) received a heart transplant during follow-up. Dofetilide was discontinued in 117 (86%) patients due to lack of sustained effectiveness during follow-up. Dofetilide use was associated with similar odds of the composite outcome of all-cause mortality/LVAD/heart transplant (OR: 0.97, 0.55-4.23) in patients with ischemic cardiomyopathy (ICM) compared to those with non-ischemic cardiomyopathy (NICM). Dofetilide did not reduce PVC burden during follow-up in the 40 patients with PVCs (mean baseline PVC burden: 15%, at 1-year follow-up: 14%). CONCLUSIONS: Dofetilide use was less effective in reducing VA burden in our cohort of patients. Randomized controlled studies are needed to confirm our findings.

Catheter ablation using pulmonary vein isolation with versus without left atrial posterior wall isolation for persistent atrial fibrillation: an updated systematic review and meta-analysis.

BACKGROUND: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation of atrial fibrillation (AF); however, the results are suboptimal for persistent AF. The left atrial posterior wall (LAPW) is thought to be a major additional area in initiation and perpetuation of persistent AF. Therefore, adjunctive ablation of the posterior wall may reduce AF recurrence in patients with persistent AF. OBJECTIVE: The objective of this study was to compare outcomes of catheter ablation in patients with persistent AF using PVI alone versus a combination of PVI and LAPW isolation. METHODS: Literature search was conducted in PubMed, PubMed Central, Scopus, and Embase since inception to February 2023. Screening of studies was done via Covidence software. Risk of bias assessment was done using appropriate tools. Data extraction and a narrative synthesis were carried out accordingly. RESULTS: Ten studies were included, of which five were randomized controlled trials. PVI with LAPW ablation group had significantly lower recurrence of overall atrial tachyarrhythmia (OR 0.47, CI 0.32-0.70) and AF (OR 0.39, CI 0.23-0.69). In sensitivity analysis, freedom from atrial arrhythmias was noted to be significantly higher in the PVI with LAPW ablation group (OR 2.22, CI 1.36-3.64). However, there was no significant difference in occurrence of atrial flutter (OR 1.36, CI 0.86-2.14) or with periprocedural adverse events (OR 1.10, CI 0.60-1.99). CONCLUSION: LAPW ablation, in addition to PVI, significantly improves the rates of arrhythmia freedom and reduces the recurrence of overall atrial tachyarrhythmia. There was no significant difference in atrial flutter or periprocedural adverse events.

Experimental drugs for supraventricular tachycardia: an analysis of early phase clinical trials.

INTRODUCTION: Supraventricular tachycardias (SVT) are a diverse group of commonly encountered arrhythmias arising at or above the atrioventricular (AV) node. Conventional anti-arrhythmic medications are restricted by extensive side-effect profiles and limited efficacy. Catheter ablation has emerged as a first-line therapy for many arrhythmias but is not a suitable option for all patients. This has prompted the exploration of novel pharmacological approaches targeting specific molecular mechanisms of SVT. AREAS COVERED: This review article aims to summarize recent advancements in pharmacological therapeutics for SVT and their clinical implications. The understanding of molecular mechanisms underlying these arrhythmias, particularly atrial fibrillation, has opened up new possibilities for targeted interventions. Beyond the manipulation of ion channels and membrane potentials, pharmacotherapy now focuses on upstream targets such as inflammation, oxidative stress, and structural remodeling. This review strives to provide a comprehensive overview of recent advancements in pharmacological therapeutics directed at the management of SVT. We begin by providing a brief summary of the mechanisms and management of commonly encountered SVT before delving into individual agents, which in turn are stratified based on their molecular treatment targets. EXPERT OPINION: The evolving landscape of pharmacologic therapy offers hope for more personalized and tailored interventions in the management of SVT.

Safety and Efficacy of Direct Oral Anticoagulants Versus Warfarin for Atrial Fibrillation in End-Stage Renal Disease on Hemodialysis: A Meta-Analysis of Randomized Control Trials.

End-stage renal disease (ESRD) and atrial fibrillation (AF) are commonly encountered, with ESRD itself serving as a well-established risk factor for AF.1 The 2018 AF guidelines have recommended apixaban across all the spectrums of renal impairment, including patients on hemodialysis (HD), and the 2019 American Heart Association/American College of Cardiology/Heart Rhythm Society updated guidelines have suggested careful consideration of reduced dose of direct oral anticoagulants (DOACs) in patients with ESRD.2,3 The current data on the safety and efficacy of warfarin versus DOACs in patients with AF with ESRD and HD is variable. This study aimed to perform a study-level meta-analysis to evaluate the effectiveness and safety of warfarin and DOACs in patients with AF who require dialysis.

Predictors of pulmonary embolism in hospitalized patients with COVID-19.

BACKGROUND: High venous thromboembolism (VTE) rates have been described in critically ill patients with COVID-19. We hypothesized that specific clinical characteristics may help differentiate hypoxic COVID-19 patients with and without a diagnosed pulmonary embolism (PE). METHODS: We performed a retrospective observational case-control study of 158 consecutive patients hospitalized in one of four Mount Sinai Hospitals with COVID-19 between March 1 and May 8, 2020, who received a Chest CT Pulmonary Angiogram (CTA) to diagnose a PE. We analyzed demographic, clinical, laboratory, radiological, treatment characteristics, and outcomes in COVID-19 patients with and without PE. RESULTS: 92 patients were negative (CTA-), and 66 patients were positive for PE (CTA+). CTA + had a longer time from symptom onset to admission (7 days vs. 4 days, p = 0.05), higher admission biomarkers, notably D-dimer (6.87 vs. 1.59, p < 0.0001), troponin (0.015 vs. 0.01, p = 0.01), and peak D-dimer (9.26 vs. 3.8, p = 0.0008). Predictors of PE included time from symptom onset to admission (OR = 1.11, 95% CI 1.03-1.20, p = 0.008), and PESI score at the time of CTA (OR = 1.02, 95% CI 1.01-1.04, p = 0.008). Predictors of mortality included age (HR 1.13, 95% CI 1.04-1.22, p = 0.006), chronic anticoagulation (13.81, 95% CI 1.24-154, p = 0.03), and admission ferritin (1.001, 95% CI 1-1.001, p = 0.01). CONCLUSIONS: In 158 hospitalized COVID-19 patients with respiratory failure evaluated for suspected PE, 40.8% patients had a positive CTA. We identified clinical predictors of PE and mortality from PE, which may help with early identification and reduction of PE-related mortality in patients with COVID-19.

Genetic and Molecular Mechanisms in Brugada Syndrome.

Brugada syndrome is a rare hereditary arrhythmia disorder characterized by a distinctive electrocardiogram pattern and an elevated risk of ventricular arrhythmias and sudden cardiac death in young adults. Despite recent advances, it remains a complex condition, encompassing mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The underlying electrophysiological mechanism of Brugada syndrome requires further investigation, with current theories focusing on abnormalities in repolarization, depolarization, and current-load match. The genetic basis of the syndrome is strong, with mutations found in genes encoding subunits of cardiac sodium, potassium, and calcium channels, as well as genes involved in channel trafficking and regulation. While the initial discovery of mutations in the SCN5A gene provided valuable insights, Brugada syndrome is now recognized as a multifactorial disease influenced by several loci and environmental factors, challenging the traditional autosomal dominant inheritance model. This comprehensive review aims to provide a current understanding of Brugada syndrome, focusing on its pathophysiology, genetic mechanisms, and novel models of risk stratification. Advancements in these areas hold the potential to facilitate earlier diagnosis, improve risk assessments, and enable more targeted therapeutic interventions.

Postural Orthostatic Tachycardia Syndrome in COVID-19: A Contemporary Review of Mechanisms, Clinical Course and Management.

The long-term implications of COVID-19 have garnered increasing interest in recent months, with Long-COVID impacting over 65 million individuals worldwide. Postural orthostatic tachycardia syndrome (POTS) has emerged as an important component of the Long-COVID umbrella, estimated to affect between 2 and 14% of survivors. POTS remains very challenging to diagnose and manage - this review aims to provide a brief overview of POTS as a whole and goes on to summarize the available literature pertaining to POTS in the setting of COVID-19. We provide a review of available clinical reports, outline proposed pathophysiological mechanisms and end with a brief note on management considerations.

Kinase Inhibitors and Atrial Fibrillation: Mechanisms of Action and Clinical Implications.

Recent advances have significantly expanded the options of available therapeutics for cancer treatment, including novel targeted cancer therapies. Within this broad category of targeted therapies is the class of kinase inhibitors (KIs), which target kinases that have undergone aberrant activation in cancerous cells. Although KIs have shown a benefit in treating various forms of malignancy, they have also been shown to cause a wide array of cardiovascular toxicities, with cardiac arrhythmias, in particular atrial fibrillation (AF), being 1 of the predominant side effects. The occurrence of AF in patients undergoing cancer treatment can complicate the treatment approach and poses unique clinical challenges. The association of KIs and AF has led to new research aimed at trying to elucidate the underlying mechanisms. Furthermore, there are unique considerations to treating KI-induced AF because of the anticoagulant properties of some KIs as well as drug-drug interactions with KIs and some cardiovascular medications. Here, we review the current literature pertaining to KI-induced AF.

An overview of mineralocorticoid receptor antagonists as a treatment option for patients with heart failure: the current state-of-the-art and future outlook.

INTRODUCTION: Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in patients with heart failure. These benefits of MRAs vary in different heart failure populations based on left ventricular ejection fraction and associated comorbidities. AREAS COVERED: We define the pharmacologic properties of MRAs and the pathophysiological rationale for their utility in heart failure. We outline the current literature on the use of MRAs in different heart failure populations, including reduced and preserved ejection fraction (HFrEF/HFpEF) and acute heart failure decompensation. Finally, we describe the limitations of currently available data and propose future directions of study. EXPERT OPINION: While there is strong evidence supporting the use of MRAs in HFrEF, evidence in patients with HFpEF or acute heart failure is less definitive. Comorbidities such as obesity or atrial fibrillation could be clinical modifiers of the response to MRAs and potentially alter the risk/benefit ratio in these subpopulations. Emerging evidence for new non-steroidal MRAs reveal promising preliminary results that, if confirmed in large randomized clinical trials, could favor a change in clinical practice.

Postural orthostatic tachycardia syndrome: pathophysiology, management, and experimental therapies.

INTRODUCTION: Postural orthostatic tachycardia syndrome (POTS) is an increasingly well-recognized condition encountered in clinical practice. Diagnosis and treatment remain extremely challenging. The limited success of currently available therapies has laid the foundation for a number of experimental therapies. AREAS COVERED: In this review, we will briefly outline the pathophysiology and clinical features of this syndrome, before moving on to its management, with a specific focus on experimental pharmacological therapies. Finally, we briefly discuss POTS related to the SARS CoV-2 (COVID-19) pandemic. EXPERT OPINION: Despite tremendous advances, the diagnosis and management of POTS remains extremely challenging. The multitude of contributory mechanisms, which predominate to varying degrees in different patients further complicates management. Improved characterization of pathophysiological phenotypes is essential to individualize management. Lifestyle measures form the first line of therapy, followed by beta-blockers, ivabradine, fludrocortisone, and midodrine. Supplemental therapies such as iron, vitamin D and α lipoic acid are quite safe and a trial of their use is reasonable. The use of erythropoietin, IVIG, desmopressin, etc., are more specialized and nuanced alternatives. In recent years, interest has grown in the use of cardiac neuromodulation. Though preliminary, some of these therapies are quite promising.

Meta-Analysis Comparing Venoarterial Extracorporeal Membrane Oxygenation With or Without Impella in Patients With Cardiogenic Shock.

Cardiogenic shock is associated with high short-term mortality. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a mechanical circulatory support strategy for patients with refractory cardiogenic shock. A drawback of this hemodynamic support strategy is increased left ventricular (LV) afterload, which is mitigated by concomitant use of Impella (extracorporeal membrane oxygenation with Impella [ECPELLA]). However, data regarding the benefits of this approach are limited. We conducted a systematic search of Medline, EMBASE, and Cochrane databases to identify studies including patients with cardiogenic shock reporting clinical outcomes with Impella plus VA-ECMO compared with VA-ECMO alone. Primary outcome was short-term all-cause mortality (in-hospital or 30-day mortality). Secondary outcomes included major bleeding, hemolysis, continuous renal replacement therapy, weaning from mechanical circulatory support, limb ischemia, and transition to destination therapy with LV assist device (LVAD) or cardiac transplant. Of 2,790 citations, 7 observational studies were included. Of 1,054 patients with cardiogenic shock, 391 were supported with ECPELLA (37%). Compared with patients on only VA-ECMO support, patients with ECPELLA had a lower risk of short-term mortality (risk ratio [RR] 0.89 [0.80 to 0.99], I2 = 0%, p = 0.04) and were significantly more likely to receive a heart transplant/LVAD (RR 2.03 [1.44 to 2.87], I2 = 0%, p <0.01). However, patients with ECPELLA had a higher risk of hemolysis (RR 2.03 [1.60 to 2.57], I2 = 0%, p <0.001), renal failure requiring continuous renal replacement therapy (RR 1.46 [1.23 to 174], I2 = 11%, p <0.0001), and limb ischemia (RR 1.67 [1.15 to 2.43], I2 = 0%, p = 0.01). In conclusion, among patients with cardiogenic shock requiring VA-ECMO support, concurrent LV unloading with Impella had a lower likelihood of short-term mortality and a higher likelihood of progression to durable LVAD or heart transplant. However, patients supported with ECPELLA had higher rates of hemolysis, limb ischemia, and renal failure requiring continuous renal replacement therapy. Future prospective randomized are needed to define the optimal treatment strategy in this high-risk cohort.

One year outcomes of atrial fibrillation ablation: Contemporary analysis of the United States Nationwide Readmission Database.

BACKGROUND: Data on long-term outcomes of catheter ablation (CA) for atrial fibrillation (AF) in outside of clinical trials settings are sparse. OBJECTIVE: We aimed to assess outcomes and readmissions at 1 year following admission for CA for AF. METHODS: Utilizing the Nationwide Readmissions Database (2016-2018), we identified patients with CA among all patients with a primary admission diagnosis of AF, and a control group by propensity score match adjusted for age, sex, comorbidities, CHA2DS2-VASc scores, and the hospital characteristics. The primary outcome was a composite of unplanned heart failure (HF), AF and stroke-related readmissions, and death at 1 year, and secondary outcomes were hospital outcomes and all-cause readmission rates. RESULTS: The study cohort consisted of 29,771 patients undergoing CA and 63,988 controls. Patients undergoing CA were younger with lower CHA2DS2-VASc scores and less comorbidities. Over a follow-up of 170 ±1.1 days, the primary outcome occurred in 5.2% in CA group and 6.0% of controls (hazard ratio [HR] and 95% confidence interval [CI]: 0.86 [0.76-0.94], p = .002). CA affected AF and stroke related readmission, but showed no effect on HF and mortality outcome. Male sex (HR: 0.83 [0.74-0.94], p = .03), younger age (HR: 0.71 [0.61-0.83], p < .001], and lower CHA2DS2-VASc scores (HR: 0.68 [0.55-0.84], p < .001) were associated with lower risk of primary outcome with CA. CONCLUSION: In this study, CA for AF was associated with significantly lower AF and stroke-related admissions, but not to HF or all-cause readmission. Better outcomes were seen among males, younger patients, and in patients with less comorbidities and low CHA2DS2-VASc scores.

A novel evidence-based predictor tool for hospitalization and length of stay: insights from COVID-19 patients in New York city.

Predictive models for key outcomes of coronavirus disease 2019 (COVID-19) can optimize resource utilization and patient outcome. We aimed to design and internally validate a web-based calculator predictive of hospitalization and length of stay (LOS) in a large cohort of COVID-19-positive patients presenting to the Emergency Department (ED) in a New York City health system. The study cohort consisted of consecutive adult (> 18 years) patients presenting to the ED of Mount Sinai Health System hospitals between March 2020 and April 2020, diagnosed with COVID-19. Logistic regression was utilized to construct predictive models for hospitalization and prolonged (> 3 days) LOS. Discrimination was evaluated using area under the receiver operating curve (AUC). Internal validation with bootstrapping was performed, and a web-based calculator was implemented. From 5859 patients, 65% were hospitalized. Independent predictors of hospitalization and extended LOS included older age, chronic kidney disease, elevated maximum temperature, and low minimum oxygen saturation (p < 0.001). Additional predictors of hospitalization included male sex, chronic obstructive pulmonary disease, hypertension, and diabetes. AUCs of 0.881 and 0.770 were achieved for hospitalization and LOS, respectively. Elevated levels of CRP, creatinine, and ferritin were key determinants of hospitalization and LOS (p < 0.05). A calculator was made available under the following URL: https://covid19-outcome-prediction.shinyapps.io/COVID19_Hospitalization_Calculator/ . This study yielded internally validated models that predict hospitalization risk in COVID-19-positive patients, which can be used to optimize resource allocation. Predictors of hospitalization and extended LOS included older age, CKD, fever, oxygen desaturation, elevated C-reactive protein, creatinine, and ferritin.

Readmission in Patients With ST-Elevation Myocardial Infarction in 4 Age Groups (<45, >45 to <60, 60 to <75, and >75).

The incidence of ST-elevation myocardial infarction (STEMI) among younger adults is increasing due to an increased prevalence of cardiometabolic risk factors. Readmissions after STEMI in young patients could lead to substantial health care costs and a significant burden on health care resources. Although STEMI readmissions are well studied in elderly patients, limited data are available regarding readmissions after STEMI in young patients and the etiologies remain poorly understood. Because younger patients with STEMI have different sociodemographic profiles th;an older patients with STEMI, one would postulate that the risk factors for readmissions in young patients would differ from that reported in the older patients with STEMI. We performed a contemporary nationwide study using the 2016 and 2017 Nationwide Readmissions Database to identify patterns of readmissions after STEMI in the young adult population. Our analysis of the Nationwide Readmissions Database revealed a total of 243,747 hospitalizations for STEMI between 2016 and 2017. Readmission rates demonstrated a steady increase from discharge, increasing to 7.8% at 30 days and 10.3% at 60 days before relatively plateauing at 12.1% at 90 days. Cardiovascular etiologies were the most common cause of readmission (53.6%). After multivariable analysis, development of cardiogenic shock (adjusted odds ratio 1.48, 95% confidence interval 1.11 to 1.97; p = 0.008) and acute renal failure (adjusted odds ratio 1.46, 95% confidence interval 1.14 to 1.87; p = 0.003) during the index admission were associated with significantly higher rates of readmission. In conclusion, close monitoring in young patients who presented with STEMI and concomitant with cardiogenic shock or acute renal failure, and possibly, aggressive therapy during index admission may be needed. However, this population may be heterogeneous and further research is needed.

Evolving concept of dyssynchrony and its utility.

The role of electromechanical dyssynchrony in heart failure gained prominence in literature with the results of trials of cardiac resynchronization therapy (CRT). CRT has shown to significantly decrease heart failure hospitalization and mortality in heart failure patients with dyssynchrony. Current guidelines recommend the use of electrical dyssynchrony based on a QRS > 150 ms and a left bundle branch block pattern on surface electrocardiogram to identify dyssynchrony in patients who will benefit from CRT implantation. However, predicting response to CRT remains a challenge with nearly one-third of patients gaining no benefit from the device. Multiple echocardiographic measures of mechanical dyssynchrony have been studied over the past two decade. However, trials where mechanical dyssynchrony used as an additional or lone criteria for CRT failed to show any benefit in the response to CRT. This shows that a deeper understanding of cardiac mechanics should be applied in the assessment of dyssynchrony. This review discusses the evolving role of imaging techniques in assessing cardiac dyssynchrony and their application in patients considered for device therapy.