Localized Re-Entry Is a Frequent Mechanism of De Novo Atypical Flutter.

BACKGROUND: Limited data exist about the origins and mechanisms of atypical atrial flutter that occurs in the absence of prior ablation or surgery. OBJECTIVES: The aims of this study were to report a large cohort of patients who presented for catheter ablation of de novo atypical flutters, to identify the most common locations and mechanisms of arrhythmia, and to describe outcomes after ablation. METHODS: Demographic, electrophysiological, and outcome data were collected for patients who underwent ablation of de novo atypical flutter. RESULTS: The mechanisms of 85 atypical flutters were identified in 62 patients and localized to the left atrium (LA) in 58 and right atrium (RA) in 27. In the LA, mechanisms were classified as macro-re-entry in 29 (50%) and localized re-entry in 29 (50%), whereas in the RA, mechanisms were macro-re-entry in 8 (30%) and localized re-entry in 19 (70%) (proportion of localized re-entry in the LA vs. RA, P = 0.08). Nine patients had both localized and macro-re-entrant atypical flutters. In the LA, localized re-entry was commonly found in the anterior LA, followed by the pulmonary veins and septum. In the RA, localized re-entry was found at various sites, including the lateral or posterior RA, septum, and coronary sinus ostium. During 39.4 months (Q1-Q3: 18.2-65.8 months) of follow-up, atrial arrhythmias occurred in 66% of patients after a single ablation and in 50% after >1 ablation. Among patients who underwent repeat ablation, compared with the index arrhythmia, different tachycardia circuits or arrhythmias were documented in 13 of 18 cases (72%). CONCLUSIONS: Atypical atrial flutters in patients without prior surgery or complex ablation are often due to localized re-entry (approximately 50% in the LA and a higher frequency in the RA). Other atrial tachycardias commonly occur during long-term follow-up following ablation, suggesting progressive atrial myopathy in these patients.

Troponin and Other Biomarker Levels and Outcomes Among Patients Hospitalized With COVID-19: Derivation and Validation of the HA2T2 COVID-19 Mortality Risk Score.

Background The independent prognostic value of troponin and other biomarker elevation among patients with coronavirus disease 2019 (COVID-19) are unclear. We sought to characterize biomarker levels in patients hospitalized with COVID-19 and develop and validate a mortality risk score. Methods and Results An observational cohort study of 1053 patients with COVID-19 was conducted. Patients with all of the following biomarkers measured-troponin-I, B-type natriuretic peptide, C-reactive protein, ferritin, and d-dimer (n=446) -were identified. Maximum levels for each biomarker were recorded. The primary end point was 30-day in-hospital mortality. Multivariable logistic regression was used to construct a mortality risk score. Validation of the risk score was performed using an independent patient cohort (n=440). Mean age of patients was 65.0±15.2 years and 65.3% were men. Overall, 444 (99.6%) had elevation of any biomarker. Among tested biomarkers, troponin-I ≥0.34 ng/mL was the only independent predictor of 30-day mortality (adjusted odds ratio, 4.38; P<0.001). Patients with a mortality score using hypoxia on presentation, age, and troponin-I elevation, age (HA2T2) ≥3 had a 30-day mortality of 43.7% while those with a score <3 had mortality of 5.9%. Area under the receiver operating characteristic curve of the HA2T2 score was 0.834 for the derivation cohort and 0.784 for the validation cohort. Conclusions Elevated troponin and other biomarker levels are commonly seen in patients hospitalized with COVID-19. High troponin levels are a potent predictor of 30-day in-hospital mortality. A simple risk score can stratify patients at risk for COVID-19-associated mortality.

Outcomes and mortality associated with atrial arrhythmias among patients hospitalized with COVID-19.

INTRODUCTION: The impact of atrial arrhythmias on coronavirus disease 2019 (COVID-19)-associated outcomes are unclear. We sought to identify prevalence, risk factors and outcomes associated with atrial arrhythmias among patients hospitalized with COVID-19. METHODS: An observational cohort study of 1053 patients with severe acute respiratory syndrome coronavirus 2 infection admitted to a quaternary care hospital and a community hospital was conducted. Data from electrocardiographic and telemetry were collected to identify atrial fibrillation (AF) or atrial flutter/tachycardia (AFL). The association between atrial arrhythmias and 30-day mortality was assessed with multivariable analysis. RESULTS: Mean age of patients was 62 ± 17 years and 62% were men. Atrial arrhythmias were identified in 166 (15.8%) patients, with AF in 154 (14.6%) patients and AFL in 40 (3.8%) patients. Newly detected atrial arrhythmias occurred in 101 (9.6%) patients. Age, male sex, prior AF, renal disease, and hypoxia on presentation were independently associated with AF/AFL occurrence. Compared with patients without AF/AFL, patients with AF/AFL had significantly higher levels of troponin, B-type natriuretic peptide, C-reactive protein, ferritin and d-dimer. Mortality was significantly higher among patients with AF/AFL (39.2%) compared to patients without (13.4%; p < .001). After adjustment for age and co-morbidities, AF/AFL (adjusted odds ratio [OR]: 1.93; p = .007) and newly detected AF/AFL (adjusted OR: 2.87; p < .001) were independently associated with 30-day mortality. CONCLUSION: Atrial arrhythmias are common among patients hospitalized with COVID-19. The presence of AF/AFL tracked with markers of inflammation and cardiac injury. Atrial arrhythmias were independently associated with increased mortality.

Effects of focal impulse and rotor modulation-guided ablation on atrial arrhythmia termination and inducibility: Impact on outcomes after treatment of persistent atrial fibrillation.

INTRODUCTION: The role of focal impulse and rotor modulation (FIRM)-guided ablation for the treatment of atrial fibrillation (AF) remains unclear. Previous studies on the FIRM-guided ablation outcomes have been limited by a focus on AF termination as an endpoint and by patient population heterogeneity. We sought to determine differences in rates of AF termination, inducibility, and recurrence in patients with persistent AF undergoing first-time ablation with a FIRM-guided approach compared with patients undergoing conventional ablation. METHODS AND RESULTS: Eight-five consecutive patients (38 FIRM, 47 conventional) with persistent AF undergoing first-time ablation were retrospectively analyzed. There were no significant differences in the rates of AF termination in the FIRM group compared to the conventional group (26% vs 15%; P = .15). Rates of inducible AF after ablation were 37% in the FIRM group and 30% in the conventional group (P = .32). Over a median follow-up of 2.4 years, the rates of freedom from AF were similar between the FIRM and conventional groups (1-year freedom from AF 65% vs 50%, respectively; P = .18). Procedural termination of AF with either FIRM ablation or conventional ablation was not associated with any significant reduction in AF recurrence. CONCLUSION: A FIRM-guided approach was not associated with a significant difference in freedom from AF when compared to conventional ablation. Termination of AF with ablation was not associated with increased freedom from AF. While AF termination using substrate-based ablation may have mechanistic implications for understanding AF rotor physiology, its impact on clinical outcomes remains unclear.

Long-term Management of the Arterial Switch Patient.

PURPOSE OF REVIEW: This review paper describes the management of patients with dextro-transposition of the great arteries (D-TGA) with a focus on the complications seen and the appropriate care required to identify and prevent adverse events. RECENT FINDINGS: D-TGA is a form of cyanotic congenital heart disease (CHD) representing ~ 3% of all CHD and almost 20% of all cyanotic CHD. Since the late 1980s, standard of care is to repair these patients with an arterial switch operation (ASO) as opposed to a Mustard/Senning operation. The long-term survival and complication rates are superior in the ASO. Long-term follow-up is recommended for all D-TGA patients and includes management with adult congenital heart disease specialists and the use of echocardiography and advanced imaging with CT or MRI. The most common complications seen are pulmonary stenosis, coronary artery stenosis, and neo-aortic regurgitation. Careful evaluation of new symptoms or declining function is essential in preventing and treating these long-term sequelae.

Sorafenib tosylate as a radiosensitizer in malignant astrocytoma.

Progress in research on the molecular aspects of glioblastoma has yet to provide a medical therapy that significantly improves prognosis. Glioblastoma invariably progress through current treatment regimens with radiotherapy as a key component. Activation of several signaling pathways is thought to be associated with this resistance to radiotherapy. Ras activity is exceptionally high in glioblastoma and may regulate sensitivity to radiotherapy. Raf-1, a downstream effector of Ras, demonstrates a high amount of activity in glioblastoma. Therefore, Raf-1 inhibition should be considered as a mechanism to increase the effectiveness of radiotherapy in treatment regimen. In vitro analysis was performed with a novel Raf-1 kinase inhibitor (BAY 54-9085) in culture with the glioblastoma cell line U1242. The cell line was treated in serum-containing media and analyzed for the effect of the BAY 54-9085 alone and BAY 54-9085 combined with radiation on cell death. BAY 54-9085 displayed a cytocidal effect on glioblastoma cells following a 3 day incubation with the drug in serum-containing media. A dose of 2.5 µM displayed moderate cell death which significantly increased with a dose of 5.0 µM. In addition, glioblastoma cells treated with both the BAY 54-9085 and gamma radiation displayed a significant increase in cell death (85.5%) as compared to either BAY 54-9085 (73.1%) or radiation (34.4%) alone. Radiation therapy is a key component of treatment for glioblastoma. A novel Raf-1 inhibitor displayed in vitro evidence of synergistically increasing cell death of glioblastoma cells in combination with radiation.

Increased sweetened beverage intake is associated with reduced milk and calcium intake in 3- to 7-year-old children at multi-item laboratory lunches.

Dietary survey data show that intake of sugar-sweetened beverages is negatively associated with intake of milk, but these findings have yet to be confirmed by laboratory feeding studies. The objectives of the present study were to analyze children's intake across two laboratory-based ad libitum lunches to (a) investigate the relationships between intake of sweetened beverages, milk, and calcium, and (b) explore relationships between beverage consumption and child age and weight status. Data were extracted from a cohort of 126 3- to 7-year-old twins from diverse ethnic backgrounds who participated in a cross-sectional study (conducted from November 1999 to September 2002) designed to determine the genetic and environmental contributions to eating and body weight. At two visits, children ate ad libitum from lunches that offered a variety of sugar-sweetened and calcium-rich beverages. Total beverage and nutrient intakes were computed from the test meals. Weight, height, and waist circumference were assessed on the final visit. Regression analyses tested the associations among intake of sweetened beverages, calcium, and milk (primary aim), and whether these variables were associated with child age and weight status (secondary aim). Sweetened beverage intake was negatively correlated with both milk (P<0.01) and calcium (P<0.01) intakes, and these relationships remained after controlling for age, sex, and ethnicity (P<0.01). Child age was negatively associated with milk intake (r=-0.22, P<0.01) but positively associated with intake of sweetened beverages (r=0.27, P<0.01). Results support the notion that sugar-sweetened beverages displace milk in a single meal, and this phenomenon may vary with child age. Due to the cross-sectional nature of this study, future investigations are needed to determine the long-term implications of this consumption pattern. The possibility that limiting sweetened beverages may help optimize dietary calcium during childhood is a topic that merits further research.