Impact of frailty in hospitalized patients undergoing catheter ablation for atrial fibrillation.

BACKGROUND: Catheter Ablation (CA) is an effective treatment for atrial fibrillation (AF). However, frail elderly patients have been understudied due to their exclusion from landmark trials. OBJECTIVES: Our study aims to evaluate outcomes in this population. METHODS: The national readmission database (2016-2020) was queried, and frailty categories were defined based on hospital risk frailty scores ≦5 as low while >5 as intermediate/high frailty (IHF). We used multivariate regression and propensity-matched analysis to compare outcomes in patients undergoing CA for atrial fibrillation based on frailty index. RESULTS: Among 55 936 CAs for AF, 33,248 patients had low frailty, while 22 688 had intermediate/high frailty (IHF). After propensity matching (N 12 448), IHF patients were found to have higher adverse events, including mortality (3% vs. 0.3%, p < .001), stroke (1.9% vs. 0.2%, p < .001), acute heart failure (53.8% vs. 42.2%, p < .001), AKI (42.5% vs. 6.8%, p < .001), pericardial complications (2.8 vs. 1.6%, p < .001), respiratory complications (27.8 vs. 7.2%, p < .001), major adverse cardiovascular events (21.2 vs. 9.4%, p < .001) and net adverse events (76.7 vs. 55%, p < .001). IHF patients had higher readmissions at 30 (15.5 vs. 12.6%, p < .001), 90 (31.9 vs. 25.1%, p < .001), and 180-day (41 vs. 34.7%, p < .001) intervals. A higher median length of stay (LOS) (7 vs. 3 days, p < .001) and cost ($44 287 vs. $27 517, p < .001) at index admission and subsequent readmissions were also observed (p < .001). CONCLUSION: Intermediate/high frailty patients undergoing catheter ablation had worse clinical outcomes, higher healthcare burden, and readmission rates. LOS has decreased in both groups from 2016 to 2020; however, total cost has increased.

Dual vs Single Cardioversion of Atrial Fibrillation in Patients With Obesity: A Randomized Clinical Trial.

Importance: Atrial fibrillation and obesity are common, and both are increasing in prevalence. Obesity is associated with failure of cardioversion of atrial fibrillation using a standard single set of defibrillator pads, even at high output. Objective: To compare the efficacy and safety of dual direct-current cardioversion (DCCV) using 2 sets of pads, with each pair simultaneously delivering 200 J, with traditional single 200-J DCCV using 1 set of pads in patients with obesity and atrial fibrillation. Design, Setting, and Participants: This was a prospective, investigator-initiated, patient-blinded, randomized clinical trial spanning 3 years from August 2020 to 2023. As a multicenter trial, the setting included 3 sites in Louisiana. Eligibility criteria included body mass index (BMI) of 35 or higher (calculated as weight in kilograms divided by height in meters squared), age 18 years or older, and planned nonemergent electrical cardioversion for atrial fibrillation. Patients who met inclusion criteria were randomized 1:1. Exclusions occurred due to spontaneous cardioversion, instability, thrombus, or BMI below threshold. Interventions: Dual DCCV vs single DCCV. Main Outcomes and Measures: Return to sinus rhythm, regardless of duration, immediately after the first cardioversion attempt of atrial fibrillation, adverse cardiovascular events, and chest discomfort after the procedure. Results: Of 2079 sequential patients undergoing cardioversion, 276 met inclusion criteria and were approached for participation. Of these, 210 participants were randomized 1:1. After exclusions, 200 patients (median [IQR] age, 67.6 [60.1-72.4] years; 127 male [63.5%]) completed the study. The mean (SD) BMI was 41.2 (6.5). Cardioversion was successful more often with dual DCCV compared with single DCCV (97 of 99 patients [98%] vs 87 of 101 patients [86%]; P = .002). Dual cardioversion predicted success (odds ratio, 6.7; 95% CI, 3.3-13.6; P = .01). Patients in the single cardioversion cohort whose first attempt failed underwent dual cardioversion with all subsequent attempts (up to 3 total), all of which were successful: 12 of 14 after second cardioversion and 2 of 14 after third cardioversion. There was no difference in the rating of postprocedure chest discomfort (median in both groups = 0 of 10; P = .40). There were no cardiovascular complications. Conclusions and Relevance: In patients with obesity (BMI ≥35) undergoing electrical cardioversion for atrial fibrillation, dual DCCV results in greater cardioversion success compared with single DCCV, without any increase in complications or patient discomfort. Trial Registration: ClinicalTrials.gov Identifier: NCT04539158.

Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation.

Hydropersulfide and hydropolysulfide metabolites are increasingly important reactive sulfur species (RSS) regulating numerous cellular redox dependent functions. Intracellular production of these species is known to occur through RSS interactions or through translational mechanisms involving cysteinyl t-RNA synthetases. However, regulation of these species under cell stress conditions, such as hypoxia, that are known to modulate RSS remain poorly understood. Here we define an important mechanism of increased persulfide and polysulfide production involving cystathionine gamma lyase (CSE) phosphorylation at serine 346 and threonine 355 in a substrate specific manner, under acute hypoxic conditions. Hypoxic phosphorylation of CSE occurs in an AMP kinase dependent manner increasing enzyme activity involving unique inter- and intramolecular interactions within the tetramer. Importantly, both cellular hypoxia and tissue ischemia result in AMP Kinase dependent CSE phosphorylation that regulates blood flow in ischemic tissues. Our findings reveal hypoxia molecular signaling pathways regulating CSE dependent persulfide and polysulfide production impacting tissue and cellular response to stress.

Syncope and Cardiac Arrhythmias Caused by a Paratracheal Mass.

Background: Syncope is a common complaint in clinical practice. The etiologies and mechanisms can be multiple and complex. Syncope caused by a mediastinal mass compressing the vagus nerve is rare. Case Report: We report the case of a patient who presented to the emergency department experiencing recurrent syncope. Imaging revealed a large, calcified mass in the right paratracheal region. After intracranial lesions, cardiac arrhythmias, and orthostatic hypotension were excluded, we suspected that the syncope was related to vagus nerve compression. The patient underwent surgical resection of a mediastinal mass and had complete resolution of syncopal episodes after surgery. Conclusion: This case outcome suggests that recurrent syncope could be the first symptom of an intrathoracic mass.

COVID-19 Vaccination and Cardiac Arrhythmias: A Review.

PURPOSE OF REVIEW: In this review, we aim to delve into the existing literature, seeking to uncover the mechanisms, investigate the electrocardiographic changes, and examine the treatment methods of various cardiac arrhythmias that occur after administration of the COVID-19 vaccine. RECENT FINDINGS: A global survey has exposed an incidence of arrhythmia in 18.27% of hospitalized COVID-19 patients. Furthermore, any type of COVID-19 vaccine - be it mRNA, adenovirus vector, whole inactivated, or protein subunit - appears to instigate cardiac arrhythmias. Among the cardiac adverse events reported post-COVID-19 vaccination, myocarditis emerges as the most common and is thought to be a potential cause of bradyarrhythmia. When a patient post-COVID-19 vaccination presents a suspicion of cardiac involvement, clinicians should perform a comprehensive history and physical examination, measure electrolyte levels, conduct ECG, and carry out necessary imaging studies. In our extensive literature search, we uncovered various potential mechanisms that might lead to cardiac conduction abnormalities and autonomic dysfunction in patients who have received the COVID-19 vaccine. These mechanisms encompass direct viral invasion through molecular mimicry/spike (S) protein production, an escalated inflammatory response, hypoxia, myocardial cell death, and the eventual scar/fibrosis. They correspond to a range of conditions including atrial tachyarrhythmias, bradyarrhythmia, ventricular arrhythmias, sudden cardiac death, and the frequently occurring myocarditis. For treating these COVID-19 vaccination-induced arrhythmias, we should incorporate general treatment strategies, similar to those applied to arrhythmias from other causes.

Wide Complex Tachycardia in a Right-Sided Heart: Diagnostic and Therapeutic Challenges.

Dextroposition is a rare cardiac malformation defined as heart shift to right of midline. ECG findings vary with degree of displacement within the chest cavity. We report the second known case of dextroposition with accessory pathway (posteroseptal in our patient), presenting as pre-excited atrial tachycardia. Abnormal anatomy complicates pathway localization/ablation. (Level of Difficulty: Intermediate.).

Safety of catheter ablation for atrial fibrillation in patients with cancer: a nationwide cohort study.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in patients with cancer, especially breast, gastrointestinal, respiratory, urinary tract, and hematological malignancies. Catheter ablation (CA) is a well-established, safe treatment option in healthy patients; however, literature regarding safety of CA for AF in patients with cancer is limited and confined to single centers. OBJECTIVE: We aimed to assess the outcomes and peri-procedural safety of CA for AF in patients with certain types of cancer. METHODS: The NIS database was queried between 2016 and 2019 to identify primary hospitalizations with AF and CA. Hospitalizations with secondary diagnosis of atrial flutter and other arrhythmias were excluded. Propensity score matching was used to balance the covariates between cancer and non-cancer groups. Logistic regression was used to analyze the association. RESULTS: During this period, 47,765 CA procedures were identified, out of which 750 (1.6%) hospitalizations had a diagnosis of cancer. After propensity matching, hospitalizations with cancer diagnosis had higher in-hospital mortality (OR 3.0, 95% CI 1.5-6.2, p = 0.001), lower home discharge rates (OR 0.7, 95% CI 0.6-0.9, p < 0.001) as well as other complications such as major bleeding (OR 1.8, 95% CI 1.3-2.7, p = 0.001) and pulmonary embolism (OR 6.1, 95% CI 2.1-17.8, p < 0.001) but not associated with any major cardiac complications (OR 1.2, 95% CI 0.7-1.8, p = 0.53). CONCLUSION: Patients with cancer who underwent CA for AF had significantly higher odds of in-hospital mortality, major bleeding, and pulmonary embolism. Further larger prospective observational studies are needed to validate these findings.

Effect of sacubitril-valsartan on the incidence of atrial fibrillation: A meta-analysis.

INTRODUCTION: Sacubitril/valsartan reduces all-cause mortality in heart failure (HF) patients compared to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). ACEIs/ARBs have been shown to decrease the incidence of atrial fibrillation (AF). We hypothesized sacubitril-valsartan decreases the incidence of AF compared to ACEis/ARBs. METHODS: Clinicaltrials.gov was searched for trials by terms sacubitril/valsartan, entresto, sacubitril, valsartan. Randomized controlled human trials of sacubitril/valsartan reporting AF were included. Data were extracted independently by two reviewers. Data was pooled using a random effect model. Publication bias was evaluated by funnel plots. RESULTS: A total of 11 trials including 11,458 patients on sacubitril/valsartan and 10,128 patients on ACEI/ARBs were identified. A total of 284 AF events were reported in the sacubitril/valsartan group compared to 256 AF events in ACEIs/ARBs. Patients on sacubitril/valsartan were as likely as patients on ACEIs/ARBs to develop AF (pooled odds ratio [OR] = 1.091, 95% confidence interval [CI] = 0.917-1.298, p = .324). Six atrial flutter (AFl) events were reported in six trials; 48 out of 9165 patients in the sacubitril/valsartan group developed AFl compared to 46 out of 8759 in ACEi/ARBs group. There was no difference in AFl risk between the two groups (pooled OR = 1.028, 95% CI = 0.681-1.553, p = .894). Finally, sacubitril/valsartan did not reduce the risk of atrial arrhythmias (AF + AFl) compared to ACEi/ARBs (pooled OR = 1.081, 95% CI = 0.922-1.269, p = .337). CONCLUSION: Although sacubitril/valsartan reduces mortality compared to ACEIs/ARBs in HF patients, they do not reduce AF risk compared to these drugs.

COVID-19 bacteremic co-infection is a major risk factor for mortality, ICU admission, and mechanical ventilation.

BACKGROUND: Recent single-center reports have suggested that community-acquired bacteremic co-infection in the context of Coronavirus disease 2019 (COVID-19) may be an important driver of mortality; however, these reports have not been validated with a multicenter, demographically diverse, cohort study with data spanning the pandemic. METHODS: In this multicenter, retrospective cohort study, inpatient encounters were assessed for COVID-19 with community-acquired bacteremic co-infection using 48-h post-admission blood cultures and grouped by: (1) confirmed co-infection [recovery of bacterial pathogen], (2) suspected co-infection [negative culture with ≥ 2 antimicrobials administered], and (3) no evidence of co-infection [no culture]. The primary outcomes were in-hospital mortality, ICU admission, and mechanical ventilation. COVID-19 bacterial co-infection risk factors and impact on primary outcomes were determined using multivariate logistic regressions and expressed as adjusted odds ratios with 95% confidence intervals (Cohort, OR 95% CI, Wald test p value). RESULTS: The studied cohorts included 13,781 COVID-19 inpatient encounters from 2020 to 2022 in the University of Alabama at Birmingham (UAB, n = 4075) and Ochsner Louisiana State University Health-Shreveport (OLHS, n = 9706) cohorts with confirmed (2.5%), suspected (46%), or no community-acquired bacterial co-infection (51.5%) and a comparison cohort consisting of 99,170 inpatient encounters from 2010 to 2019 (UAB pre-COVID-19 pandemic cohort). Significantly increased likelihood of COVID-19 bacterial co-infection was observed in patients with elevated ≥ 15 neutrophil-to-lymphocyte ratio (UAB: 1.95 [1.21-3.07]; OLHS: 3.65 [2.66-5.05], p < 0.001 for both) within 48-h of hospital admission. Bacterial co-infection was found to confer the greatest increased risk for in-hospital mortality (UAB: 3.07 [2.42-5.46]; OLHS: 4.05 [2.29-6.97], p < 0.001 for both), ICU admission (UAB: 4.47 [2.87-7.09], OLHS: 2.65 [2.00-3.48], p < 0.001 for both), and mechanical ventilation (UAB: 3.84 [2.21-6.12]; OLHS: 2.75 [1.87-3.92], p < 0.001 for both) across both cohorts, as compared to other risk factors for severe disease. Observed mortality in COVID-19 bacterial co-infection (24%) dramatically exceeds the mortality rate associated with community-acquired bacteremia in pre-COVID-19 pandemic inpatients (5.9%) and was consistent across alpha, delta, and omicron SARS-CoV-2 variants. CONCLUSIONS: Elevated neutrophil-to-lymphocyte ratio is a prognostic indicator of COVID-19 bacterial co-infection within 48-h of admission. Community-acquired bacterial co-infection, as defined by blood culture-positive results, confers greater increased risk of in-hospital mortality, ICU admission, and mechanical ventilation than previously described risk factors (advanced age, select comorbidities, male sex) for COVID-19 mortality, and is independent of SARS-CoV-2 variant.

Sulfide regulation of cardiovascular function in health and disease.

Hydrogen sulfide (H2S) has emerged as a gaseous signalling molecule with crucial implications for cardiovascular health. H2S is involved in many biological functions, including interactions with nitric oxide, activation of molecular signalling cascades, post-translational modifications and redox regulation. Various preclinical and clinical studies have shown that H2S and its synthesizing enzymes - cystathionine γ-lyase, cystathionine ß-synthase and 3-mercaptosulfotransferase - can protect against cardiovascular pathologies, including arrhythmias, atherosclerosis, heart failure, myocardial infarction and ischaemia-reperfusion injury. The bioavailability of H2S and its metabolites, such as hydropersulfides and polysulfides, is substantially reduced in cardiovascular disease and has been associated with single-nucleotide polymorphisms in H2S synthesis enzymes. In this Review, we highlight the role of H2S, its synthesizing enzymes and metabolites, their roles in the cardiovascular system, and their involvement in cardiovascular disease and associated pathologies. We also discuss the latest clinical findings from the field and outline areas for future study.

Women are underrepresented in cardiac resynchronization therapy trials.

INTRODUCTION: Current guidelines for cardiac resynchronization therapy (CRT) device implant are the same across both sexes however women have been traditionally underrepresented in randomized controlled trials (RCTs). We aimed to identify if the number of women included in CRT trials is representative of the real-world burden of heart failure (HF) in women. METHODS: RCTs evaluating the benefit of CRT in HF patients referenced in the 2012 EHRA/HRS expert consensus statement on CRT in HF were included. Studies were evaluated for gender representation, baseline variables, and gender-based analysis of outcomes. RESULTS: A total of 10 CRT trials including 8107 patients were studied. Of the total patient population in these RCTs, only 23% were women. Analysis of outcomes based on sex was reported only in 5 out of 10 trials. Of these five trials reporting sex-based outcomes, multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy (MADIT-CRT) and resynchronization-defibrillation for ambulatory heart failure trial (RAFT) showed a greater benefit in women compared to men. Both MADIT and RAFT trials had a lower ejection fraction (EF) cut-off in the inclusion criteria (EF ≤ 30%) compared to the studies that did not find gender-based differences in the outcome (inclusion criteria: EF ≤ 35% or 40%). Additionally, women had less ischemic cardiomyopathy and more left bundle branch block (LBBB) compared to men in these two trials. CONCLUSION: Women are underrepresented in CRT trials; however, they have been shown to derive a greater benefit from CRT compared to men. Appropriate measures should be taken in future studies to enhance the participation of women in clinical trials for more generalizable evidence.

Methamphetamine causes cardiovascular dysfunction via cystathionine gamma lyase and hydrogen sulfide depletion.

Methamphetamine (METH) is an addictive illicit drug used worldwide that causes significant damage to blood vessels resulting in cardiovascular dysfunction. Recent studies highlight increased prevalence of cardiovascular disease (CVD) and associated complications including hypertension, vasospasm, left ventricular hypertrophy, and coronary artery disease in younger populations due to METH use. Here we report that METH administration in a mouse model of 'binge and crash' decreases cardiovascular function via cystathionine gamma lyase (CSE), hydrogen sulfide (H2S), nitric oxide (NO) (CSE/H2S/NO) dependent pathway. METH significantly reduced H2S and NO bioavailability in plasma and skeletal muscle tissues co-incident with a significant reduction in flow-mediated vasodilation (FMD) and blood flow velocity revealing endothelial dysfunction. METH administration also reduced cardiac ejection fraction (EF) and fractional shortening (FS) associated with increased tissue and perivascular fibrosis. Importantly, METH treatment selectively decreased CSE expression and sulfide bioavailability along with reduced eNOS phosphorylation and NO levels. Exogenous sulfide therapy or endothelial CSE transgenic overexpression corrected cardiovascular and associated pathological responses due to METH implicating a central molecular regulatory pathway for tissue pathology. These findings reveal that therapeutic intervention targeting CSE/H2S bioavailability may be useful in attenuating METH mediated cardiovascular disease.

Sacubitril/valsartan: An antiarrhythmic drug?

INTRODUCTION: Heart failure (HF) is a major cause of morbidity and mortality, with nearly half of all HF-related deaths resulting from sudden cardiac death (SCD), most often from an arrhythmic event. The pathophysiologic changes that occur in response to the hemodynamic stress of HF may lead to increased arrhythmogenesis. Theoretically, medications that block these arrhythmogenic substrates would decrease the risk of SCD. The combined angiotensin receptor and neprilysin inhibitor (ARNi; tradename Entresto) is the newest commercially available medication for the treatment of heart failure. METHODS AND RESULTS: We reviewed and synthesized the available literature regarding sacubitril/valsartan and its effects on cardiac rhythm. ARNi has been shown to decrease cardiovascular mortality and hospitalization in patients with HF with reduced ejection fraction (HFrEF). Emerging evidence suggests that ARNi also may play a role in reducing arrhythmogenesis and thereby SCD. CONCLUSION: This review summarizes the current data regarding this ARNi and its potential antiarrhythmic effects.