A Randomized Trial of High vs Standard Power Radiofrequency Ablation for Pulmonary Vein Isolation: SHORT-AF.

BACKGROUND: High-power, short duration (HPSD) radiofrequency ablation (RFA) is a commonly used strategy for pulmonary vein isolation (PVI). OBJECTIVES: This study sought to compare HPSD with standard power, standard duration (SPSD) RFA in patients undergoing PVI. METHODS: Patients with paroxysmal or persistent (<1 year) atrial fibrillation (AF) were randomized to HPSD (50 W) or SPSD (25-30 W) RFA to achieve PVI. Outcomes assessed included time to achieve PVI (primary), left atrial dwell time, total procedure time, first-pass isolation, PV reconnection with adenosine, procedure complications including asymptomatic cerebral emboli (ACE), and freedom from atrial arrhythmias. RESULTS: Sixty patients (median age 66 years; 75% male) with paroxysmal (57%) or persistent (43%) AF were randomized to HPSD (n = 29) or SPSD (n = 31). Median time to achieve PVI was shorter with HPSD vs SPSD (87 minutes vs 126 minutes; P = 0.003), as was left atrial dwell time (157 minutes vs 180 minutes; P = 0.04). There were no differences in first-pass isolation (79% vs 76%; P = 0.65) or PV reconnection with adenosine (12% vs 20%; P = 0.26) between groups. At 12 months, recurrent atrial arrhythmias occurred less in the HPSD group compared with the SPSD group (n = 3 of 29 [10%] vs n = 11 of 31 [35%]; HR: 0.26; P = 0.027). There was a trend toward more ACE with HPSD RFA (40% HPSD vs 17% SPSD; P = 0.053). CONCLUSIONS: In patients undergoing AF ablation, HPSD compared with SPSD RFA results in shorter time to achieve PVI, greater freedom from AF at 12 months, and a trend toward increased ACE.

Iatrogenic Atrioventricular Block.

Iatrogenic atrioventricular (AV) block can occur in the context of cardiac surgery, percutaneous transcatheter, or electrophysiologic procedures. In cardiac surgery, patients undergoing aortic and/or mitral valve surgery are at the highest risk for developing perioperative AV block requiring permanent pacemaker implantation. Similarly, patients undergoing transcatheter aortic valve replacement are also at increased risk for developing AV block. Electrophysiologic procedures, including catheter ablation of AV nodal re-entrant tachycardia, septal accessory pathways, para-Hisian atrial tachycardia, or premature ventricular complexes, are also associated with risk of AV conduction system injury. In this article, we summarize the common causes for iatrogenic AV block, predictors for AV block, and general management considerations.

Iatrogenic Atrioventricular Block.

Iatrogenic atrioventricular (AV) block can occur in the context of cardiac surgery, percutaneous transcatheter, or electrophysiologic procedures. In cardiac surgery, patients undergoing aortic and/or mitral valve surgery are at the highest risk for developing perioperative AV block requiring permanent pacemaker implantation. Similarly, patients undergoing transcatheter aortic valve replacement are also at increased risk for developing AV block. Electrophysiologic procedures, including catheter ablation of AV nodal re-entrant tachycardia, septal accessory pathways, para-Hisian atrial tachycardia, or premature ventricular complexes, are also associated with risk of AV conduction system injury. In this article, we summarize the common causes for iatrogenic AV block, predictors for AV block, and general management considerations.

Effect of Continuous Electrocardiogram Monitoring on Detection of Undiagnosed Atrial Fibrillation After Hospitalization for Cardiac Surgery: A Randomized Clinical Trial.

Importance: Postoperative atrial fibrillation (POAF) occurring after cardiac surgery is associated with adverse outcomes. Whether POAF persists beyond discharge is not well defined. Objective: To determine whether continuous cardiac rhythm monitoring enhances detection of POAF among cardiac surgical patients during the first 30 days after hospital discharge compared with usual care. Design, Setting, and Participants: This study is an investigator-initiated, open-label, multicenter, randomized clinical trial conducted at 10 Canadian centers. Enrollment spanned from March 2017 to March 2020, with follow-up through September 11, 2020. As a result of the COVID-19 pandemic, enrollment stopped on July 17, 2020, at which point 85% of the proposed sample size was enrolled. Cardiac surgical patients with CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, prior stroke or transient ischemic attack, vascular disease, age 65-74 years, female sex) score greater than or equal to 4 or greater than or equal to 2 with risk factors for POAF, no history of preoperative AF, and POAF lasting less than 24 hours during hospitalization were enrolled. Interventions: The intervention group underwent continuous cardiac rhythm monitoring with wearable, patch-based monitors for 30 days after randomization. Monitoring was not mandated in the usual care group within 30 days after randomization. Main Outcomes and Measures: The primary outcome was cumulative AF and/or atrial flutter lasting 6 minutes or longer detected by continuous cardiac rhythm monitoring or by a 12-lead electrocardiogram within 30 days of randomization. Prespecified secondary outcomes included cumulative AF lasting 6 hours or longer and 24 hours or longer within 30 days of randomization, death, myocardial infarction, ischemic stroke, non-central nervous system thromboembolism, major bleeding, and oral anticoagulation prescription. Results: Of the 336 patients randomized (163 patients in the intervention group and 173 patients in the usual care group; mean [SD] age, 67.4 [8.1] years; 73 women [21.7%]; median [interquartile range] CHA2DS2-VASc score, 4.0 [3.0-4.0] points), 307 (91.4%) completed the trial. In the intent-to-treat analysis, the primary end point occurred in 32 patients (19.6%) in the intervention group vs 3 patients (1.7%) in the usual care group (absolute difference, 17.9%; 95% CI, 11.5%-24.3%; P < .001). AF lasting 6 hours or longer was detected in 14 patients (8.6%) in the intervention group vs 0 patients in the usual care group (absolute difference, 8.6%; 95% CI, 4.3%-12.9%; P < .001). Conclusions and Relevance: In post-cardiac surgical patients at high risk of stroke, no preoperative AF history, and AF lasting less than 24 hours during hospitalization, continuous monitoring revealed a significant increase in the rate of POAF after discharge that would otherwise not be detected by usual care. Studies are needed to examine whether these patients will benefit from oral anticoagulation therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT02793895.

Arrhythmias in Cardiac Amyloidosis: Challenges in Risk Stratification and Treatment.

Cardiac amyloidosis occurs secondarily to the deposition of insoluble protein fibrils in cardiac tissue leading to progressive myocardial dysfunction, clinical heart failure, and arrhythmia. In recent years, increasing awareness and improved screening have resulted in an increased prevalence of cardiac amyloidosis, with contemporary estimates reporting a prevalence of 18-55 cases per 100,000 person-years, accounting for > 13% of heart failure hospitalizations. The arrhythmic manifestations of cardiac amyloidosis can range from conduction-system disease and bradyarrhythmias to atrial fibrillation and sudden cardiac death. Bradyarrhythmias and conduction system disease may occur secondarily to amyloid infiltration, but the timing of pacemaker implantation remains unclear. When available, biventricular pacing should be considered in symptomatic patients, particularly in those expected to receive a high burden of ventricular pacing (> 40%). The management of atrial fibrillation can be challenging, because contemporary agents for rate and rhythm control may be poorly tolerated in patients with cardiac amyloidosis. Patients with cardiac amyloidosis also have a high rate of intracardiac thrombus and should be anticoagulated in the presence of atrial fibrillation (regardless of CHADS2 score). We generally consider transesophageal echocardiography before cardioversion regardless of anticoagulation status or duration of arrhythmia. Ventricular arrhythmias may also occur in patients with cardiac amyloidosis, and decisions surrounding implantable cardioverter-defibrillator implantation should balance the risks of ventricular arrhythmia and sudden cardiac death with the competing risks of worsening heart failure and noncardiac death. In this review, we cover the primary arrhythmic manifestations of cardiac amyloidosis and discuss their management considerations.

Atrial fibrillation detected initially during acute medical illness: A systematic review.

OBJECTIVE:: There is uncertainty about the incidence of and prognosis associated with atrial fibrillation that is documented for the first time in the setting of an acute stressor, such as surgery or medical illness. Our objective was to perform a systematic review of the incidence and long-term recurrence rates for atrial fibrillation occurring transiently with stress in the setting of acute medical illness. DATA SOURCES:: Medline, Embase and Cochrane Central to September 2017. STUDY SELECTION:: We included retrospective and prospective observational studies, and randomised controlled trials. The population of interest included patients hospitalised for medical (i.e. non-surgical) illness who developed newly diagnosed atrial fibrillation. Studies were included if they included data on either the incidence of atrial fibrillation or the rate of atrial fibrillation recurrence in atrial fibrillation occurring transiently with stress patients following hospital discharge. DATA EXTRACTION:: Two reviewers collected data independently and in duplicate. We characterised each study's methodology for ascertainment of prior atrial fibrillation history, atrial fibrillation during hospitalisation and atrial fibrillation recurrence after hospital discharge. DATA SYNTHESIS:: Thirty-six studies reported the incidence of atrial fibrillation. Ten used a prospective design and included a period of continuous electrocardiographic (ECG) monitoring. Atrial fibrillation incidence ranged from 1% to 44%, which was too heterogeneous to justify meta-analysis ( I2=99%). In post-hoc meta-regression models, the use of continuous ECG monitoring explained 13% of the variance in atrial fibrillation incidence, while care in an intensive care unit explained none. Two studies reported the long-term rate of atrial fibrillation recurrence following atrial fibrillation occurring transiently with stress. Neither of these studies used prospective, systematic monitoring. Recurrence rates at 5 years ranged from 42% to 68%. CONCLUSIONS:: The incidence of atrial fibrillation with medical illness may be as high as 44%, with higher estimates in reports using continuous ECG monitoring. Within 5 years following hospital discharge, atrial fibrillation recurrence is documented in approximately half of patients; however, the true rate may be higher. PROTOCOL REGISTRATION: PROSPERO CRD42016043240.

Eosinophilic Myocarditis.

Persistent eosinophilia can cause cardiac tissue damage, typically in the form of eosinophilic myocarditis, whether the underlying cause is reactive, a clonal myeloid disorder, or idiopathic hypereosinophilic syndrome (HES). Eosinophilic myocarditis ranges from mild localized disease to multifocal widespread infiltrates associated with myocardial necrosis, thrombotic complications and endomyocardial fibrosis. Systemic treatment varies widely depending on the underlying cause, so thorough investigation and precise diagnosis are essential. Evaluation includes assessment for reactive causes of eosinophilia (vasculitis such as eosinophilic granulomatosis and polyangiitis or Churg-Strauss, parasitic infection, autoimmune disease, immunoglobulinG4-related disease, medications and other causes), genetic lesions characteristic of clonal myeloid disorders (platelet-derived growth factor receptor-α, platelet-derived growth factor receptor-ß and fibroblast growth factor receptor 1) and flow cytometry and molecular studies for the aberrant T cells characteristic of lymphocyte-variant HES . Patients with reactive eosinophilia require treatment for the underlying cause, such as antiparasitic therapy for helminthic infection or immunosuppression for eosinophilic granulomatosis and polyangiitis or Churg-Strauss. Those with a myeloid clone often benefit from the tyrosine kinase inhibitor imatinib. Steroids are the first-line treatment for idiopathic HES and lymphocyte-variant HES, and hydroxyurea or (pegylated) interferon-α may be used for relapsed or refractory disease. Mepolizumab, an anti-interleukin-5 monoclonal antibody, is an effective steroid-sparing agent in HES but is not widely available for this indication.

Predictors of intraoperative hypotension and bradycardia.

BACKGROUND: Perioperative hypotension and bradycardia in the surgical patient are associated with adverse outcomes, including stroke. We developed and evaluated a new preoperative risk model in predicting intraoperative hypotension or bradycardia in patients undergoing elective noncardiac surgery. METHODS: Prospective data were collected in 193 patients undergoing elective, noncardiac surgery. Intraoperative hypotension was defined as systolic blood pressure <90 mm Hg for >5 minutes or a 35% decrease in the mean arterial blood pressure. Intraoperative bradycardia was defined as a heart rate of <60 beats/min for >5 minutes. A logistic regression model was developed for predicting intraoperative hypotension or bradycardia with bootstrap validation. Model performance was assessed using area under the receiver operating curves and Hosmer-Lemeshow tests. RESULTS: A total of 127 patients developed hypotension or bradycardia. The average age of participants was 67.6 ± 11.3 years, and 59.1% underwent major surgery. A final 5-item score was developed, including preoperative Heart rate (<60 beats/min), preoperative hypotension (<110/60 mm Hg), Elderly age (>65 years), preoperative renin-Angiotensin blockade (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers), Revised cardiac risk index (≥3 points), and Type of surgery (major surgery), entitled the "HEART" score. The HEART score was moderately predictive of intraoperative bradycardia or hypotension (odds ratio, 2.51; 95% confidence interval, 1.79-3.53; C-statistic, 0.75). Maximum points on the HEART score were associated with an increased likelihood ratio for intraoperative bradycardia or hypotension (likelihood ratio, +3.64). CONCLUSIONS: The 5-point HEART score was predictive of intraoperative hypotension or bradycardia. These findings suggest a role for using the HEART score to better risk-stratify patients preoperatively and may help guide decisions on perioperative management of blood pressure and heart rate-lowering medications and anesthetic agents.

Estradiol attenuates high glucose-induced endothelial nitrotyrosine: role for neuronal nitric oxide synthase.

Hyperglycemia in diabetes causes increased oxidative stress in the vascular endothelium with generation of free radicals such as superoxide. Peroxynitrite, a highly reactive species generated from superoxide and nitric oxide (NO), induces proinflammatory tyrosine nitration of intracellular proteins under such conditions. The female sex hormone estrogen appears to exert protective effects on the nondiabetic endothelium. However, several studies show reduced vascular protection in women with diabetes, suggesting alterations in estrogen signaling under high glucose. In this study, we examined the endothelial effects of estrogen under increasing glucose levels, focusing on nitrotyrosine and peroxynitrite. Human umbilical vein endothelial cells were incubated with normal (5.5 mM) or high (15.5 or 30.5 mM) glucose before addition of estradiol (E2, 1 or 10 nM). Selective NO synthase (NOS) inhibitors were used to determine the role of specific NOS isoforms. Addition of E2 significantly reduced high glucose-induced increase in peroxynitrite and consequently, nitrotyrosine. The superoxide levels were unchanged, suggesting effects on NO generation. Inhibition of neuronal NOS (nNOS) reduced high glucose-induced nitrotyrosine, demonstrating a critical role for this enzyme. E2 increased nNOS activity under normal glucose while decreasing it under high glucose as determined by its phosphorylation status. These data show that nNOS contributes to endothelial peroxynitrite and subsequent nitrotyrosine generation under high glucose, which can be attenuated by E2 through nNOS inhibition. The altered regulation of nNOS by E2 under high glucose is a potential therapeutic target in women with diabetes.

Role of neuronal nitric-oxide synthase in estrogen-induced relaxation in rat resistance arteries.

Estrogen has antihypertensive and vasorelaxing properties, partly via activation of endothelial nitric-oxide synthase (eNOS). Recently, neuronal nitric-oxide synthase (nNOS) has been detected in vascular cells, although the significance of this is unclear. Estrogen was found to stimulate nNOS in certain cultured cells. We hypothesized that estrogen regulates vascular tone partly via endothelium-derived nNOS. Human umbilical vein endothelial cells were used to test whether acute (5 min) stimulation with 17ß-estradiol (E2) at 1 or 10 nM affected nNOS activity. Small mesenteric arteries from Sprague-Dawley rats were examined for relaxation to E2 (0.001-10 µM) in the absence or presence of selective nNOS inhibitor [N-propyl-L-arginine (L-NPA); 2 µM] or pan-NOS inhibitor [Nω-nitro-L-arginine methyl ester (L-NAME); 100 µM] using a wire myograph. Immunostaining was used to visualize nNOS in rat mesenteric artery cross-sections. Western blotting measured total and phospho-nNOS in endothelial cell lysates and thoracic aorta homogenates. E2 rapidly increased (p < 0.001) activating phosphorylation of nNOS and nitric oxide (NO) production (as measured by 4-amino-5-methylamino-2,7-difluorofluorescein fluorescence) in endothelial cells. Likewise, E2 caused dose-dependent relaxation of arteries from female rats, which was blunted by both l-NPA and l-NAME (p < 0.001). In contrast, E2 response was modest in male animals and unaffected by NOS inhibition. It is noteworthy that there was a greater baseline presence of phospho-nNOS in male relative to female aortas. Although eNOS is believed to be the main source of NO in the vascular endothelium, we confirmed nNOS expression in endothelial cells. Endothelial nNOS mediated E2 relaxation in isolated arteries from female animals. Altogether, these data suggest vascular nNOS as a novel mechanism in E2 signaling.