Real-world data of radiofrequency catheter ablation in paroxysmal atrial fibrillation: Short- and long-term clinical outcomes from the prospective multicenter REAL-AF Registry.

BACKGROUND: The safety and long-term efficacy of radiofrequency (RF) catheter ablation (CA) of paroxysmal atrial fibrillation (PAF) has been well established. Contemporary techniques to optimize ablation delivery, reduce fluoroscopy use, and improve clinical outcomes have been developed. OBJECTIVE: The purpose of this study was to assess the contemporary real-world practice approach and short and long-term outcomes of RF CA for PAF through a prospective multicenter registry. METHODS: Using the REAL-AF (Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation; ClincalTrials.gov Identifier: NCT04088071) Registry, patients undergoing RF CA to treat PAF across 42 high-volume institutions and 79 experienced operators were evaluated. The procedures were performed using zero or reduced fluoroscopy, contact force sensing catheters, wide area circumferential ablation, and ablation index as a guide with a target of 380-420 for posterior and 500-550 for anterior lesions. The primary efficacy outcome was freedom from all-atrial arrhythmia recurrence at 12 months. RESULTS: A total of 2470 patients undergoing CA from January 2018 to December 2022 were included. Mean age was 65.2 ±11.14 years, and 44% were female. Most procedures were performed without fluoroscopy (71.5%), with average procedural and total RF times of 95.4 ± 41.7 minutes and 22.1±11.8 minutes, respectively. At 1-year follow-up, freedom from all-atrial arrhythmias was 81.6% with 89.7% of these patients off antiarrhythmic drugs. No significant difference was identified comparing pulmonary vein isolation vs pulmonary vein isolation plus ablation approaches. The complication rate was 1.9%. CONCLUSION: Refinement of RF CA to treat PAF using contemporary tools, standardized protocols, and electrophysiology laboratory workflows resulted in excellent short- and long-term clinical outcomes.

A prospective multi-site registry of real-world experience of catheter ablation for treatment of symptomatic paroxysmal and persistent atrial fibrillation (Real-AF): design and objectives.

PURPOSE: Catheter ablation has become a mainstay therapy for atrial fibrillation (AF) with rapid innovation over the past decade. Variability in ablation techniques may impact efficiency, safety, and efficacy; and the ideal strategy is unknown. Real-world evidence assessing the impact of procedural variations across multiple operators may provide insight into these questions. The Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal (PAF) and Persistent (PsAF) Atrial Fibrillation registry (Real-AF) is a multicenter prospective registry that will enroll patients at high volume centers, including academic institutions and private practices, with operators performing ablations primarily with low fluoroscopy when possible. The study will also evaluate the contribution of advent in technologies and workflows to real-world clinical outcomes. METHODS: Patients presenting at participating centers are screened for enrollment. Data are collected at the time of procedure, 10-12 weeks, and 12 months post procedure and include patient and detailed procedural characteristics, with short and long-term outcomes. Arrhythmia recurrences are monitored through standard of care practice which includes continuous rhythm monitoring at 6 and 12 months, event monitors as needed for routine care or symptoms suggestive of recurrence, EKG performed at every visit, and interrogation of implanted device or ILR when applicable. RESULTS: Enrollment began in January 2018 with a single site. Additional sites began enrollment in October 2019. Through May 2021, 1,243 patients underwent 1,269 procedures at 13 institutions. Our goal is to enroll 4000 patients. DISCUSSION: Real-AF's multiple data sources and detailed procedural information, emphasis on high volume operators, inclusion of low fluoroscopy operators, and use of rigorous standardized follow-up methodology allow systematic documentation of clinical outcomes associated with changes in ablation workflow and technologies over time. Timely data sharing may enable real-time quality improvements in patient care and delivery. Trial registration Clinicaltrials.gov: NCT04088071 (registration date: September 12, 2019).

The combination of coronary sinus ostial atresia/abnormalities and a small persistent left superior vena cava-Opportunity for left ventricular lead implantation and unrecognized source of thromboembolic stroke.

BACKGROUND: Coronary sinus (CS) ostial atresia/abnormalities prevent access to the CS from the right atrium (RA) for left ventricular (LV) lead implantation. Some patients with CS ostial abnormalities also have a small persistent left superior vena cava (sPLSVC). OBJECTIVE: The purpose of this study was to describe CS ostial abnormalities and sPLSVC as an opportunity for LV lead implantation and unrecognized source of stroke. METHODS: Twenty patients with CS ostial abnormalities and sPLSVC were identified. Clinical information, imaging methods, LV lead implantation techniques, and complications were summarized. RESULTS: Forty percent had at least 1 previously unsuccessful LV lead placement. In 70%, sPLSVC was identified by catheter manipulation and contrast injection in the left brachiocephalic vein, and in 30% by levophase CS venography. In 30%, sPLSVC was associated with drainage from the CS into the left atrium (LA). When associated with CS ostial abnormalities, the sPLSVC diameter averaged 5.6 ± 3 mm. sPLSVC was used for successful LV lead implantation in 90% of cases. In 80%, the LV lead was implanted down sPLSVC, and in 20%, sPLSVC was used to access the CS from the RA. Presumably because of unrecognized drainage from the CS to the LA, 1 patient had a stroke during implantation via sPLSVC. CONCLUSION: When CS ostial abnormalities prevent access to the CS from the RA, sPLSVC can be used to successfully implant LV leads. In some, the CS partially drains into the LA and stroke can occur spontaneously or during lead intervention. It is important to distinguish sPLSVC associated with CS ostial abnormalities from isolated PLSVC.

Intestinal Parasites and Anthelmintic Treatments in a Laboratory Colony of Wild-caught African Pouched Rats (Cricetomys ansorgei).

African giant pouched rats (Cricetomys spp.) are large rodents native to subSaharan Africa. Wild-caught pouched rats identified as Cricetomys ansorgei (n = 49) were imported from Tanzania. A survey of gastrointestinal parasitism by fecal flotation revealed the presence of multiple parasites, including Nippostrongylus spp., Heterakis spp., Trichuris spp., Hymenolepis spp., Raillietina spp., and Eimeria spp. Oral self-administered fenbendazole (150 ppm), topical moxidectin (2 mg/kg), pyrantel pamoate (15 mg/kg), piperazine (100 mg/kg daily), and injectable ivermectin (0.25 mg/kg) were used to determine effective treatment options for the gastrointestinal parasites present in the colony. Pyrantel pamoate in a treat vehicle and piperazine in water bottles were easily administered and significantly reduced the numbers of animals shedding Nippostrongylus spp. and Heterakis spp. during the study. Moxidectin and ivermectin were clinically ineffective at reducing fecal egg shedding. Fenbendazole was most effective at clearing infection with Trichuris spp. Although 10 mg/kg praziquantel was ineffective, a single dose of 30 mg/kg praziquantel significantly reduced the number of African pouched rats that shed cestode embryos. A combination treatment may be necessary to successfully treat all parasites present in any given animal.

Elevated plasma haptoglobin concentrations following parturition are associated with elevated leukocyte responses and decreased subsequent reproductive efficiency in multiparous Holstein dairy cows.

The objectives were to describe the relationship between the intensity of the acute phase response and the metabolic status and leukocyte responses of early postpartum, multiparous cows and determine if subsequent reproductive performance was impaired in cows with a greater acute phase response. Peripheral blood was collected from 240 Holstein cows, 2-8 days in milk and 2nd-8th parity from 8 dairies in Western TX and Eastern NM across 5 days (n=6 cows/dairy/day). Plasma concentrations of haptoglobin were measured and cows were classified as Low (1st quartile), Moderate (2nd and 3rd quartiles), or High (4th quartile) responders. Metabolic measurements included: plasma glucose, urea nitrogen, non-esterified fatty acids and ß-hydroxybutyrate concentrations. Leukocyte response measurements included: total leukocyte counts and differentials, neutrophil surface expression of L-selectin, neutrophil oxidative burst capacity when co-cultured with an environmental Escherichia coli, as well as the secretion of tumor necrosis factor-α and interferon-γ when diluted whole blood were co-cultured with lipopolysaccharide and phytohemagglutinin-P, respectively. All data are reported as Low, Moderate, and High haptoglobin responders. Plasma haptoglobin concentrations ranged from below the limit of detection to 8.4 µg/mL, 8.5 to 458 µg/mL, and 459 to 1757 µg/mL. The High cows had more severe neutropenia (3.45, 3.31, and 2.23 ± 0.31 × 10(6)cells/mL; P=0.013) Additionally, the innate leukocyte responses of the High cows were stimulated as evident by increased secretion of tumor necrosis factor-α (568, 565, and 730 ± 73.4 pg/mL; P=0.003), surface expression of L-selectin on neutrophils (70.8, 71.9, and 119.8 ± 7.9 geometric mean fluorescence intensity; P=0.001), and greater neutrophil oxidative burst capacity (37.9, 40.4, and 47.9 ± 0.31 geometric mean fluorescence intensity; P=0.002). In contrast, the secretion of the T-lymphocyte derived cytokine, interferon-γ, was suppressed in both the Moderate and High cows when compared with Low cows (718, 408, and 322 ± 92.2 pg/mL; P=0.01). Haptoglobin class had an overall effect on days to conception (P=0.039). The number of days in milk for 75% of the cows in each haptoglobin class to conceive increased from 123 d in the Low group, 139 d in the Moderate group, and 183 d in the High group. These data indicate that a stronger acute phase response during the early postpartum period that is characterized by an activated innate immune system and a suppressed mitogen-induced interferon-γ secretion resulted in impaired reproductive efficiency, and this response was consistent across the large commercial dairy herds sampled.

Prevalence and determinants of electrocardiographic abnormalities in African Americans with type 2 diabetes.

BACKGROUND: Electrocardiographic (ECG) abnormalities are independently associated with poor outcomes in the general population. Their prevalence and determinants were assessed in the understudied African American population with type 2 diabetes. METHODS: Standard 12-lead ECGs were digitally recorded in 635 unrelated African American-Diabetes Heart Study (AA-DHS) participants, automatically processed at a central lab, read, and coded using standard Minnesota ECG Classification. Age- and sex-specific prevalence rates of ECG abnormalities were calculated and logistic regression models were fitted to examine cross-sectional associations between participant characteristics and ECG abnormalities. RESULTS: Participants were 56% women with a mean age of 56 years; 60% had at least one minor or major ECG abnormality [23% ⩾ 1 major (or major plus minor), and 37% ⩾ 1 minor (with no major)]. Men had a higher prevalence of ⩾ 1 minor or major ECG abnormality (66.1% men vs. 55.6% women, p=0.0089). In univariate analysis, age, past history of cardiovascular disease, diabetes duration, systolic blood pressure, sex and statin use were associated with the presence of any (major or minor) ECG abnormalities. In a multivariate model including variables, female sex (OR [95% CI] 0.79 [0.67, 0.93]), statin use (0.79 [0.67, 0.93]) and diabetes duration (1.03 [1.0, 1.05]) remained statistically significant. CONCLUSIONS: Nearly three out of five African Americans with diabetes had at least one ECG abnormality. Female sex and statin use were significantly associated with lower odds of any ECG abnormality and diabetes duration was significantly associated with higher odds of any ECG abnormality in the multivariable model.

DNA methylation in an enhancer region of the FADS cluster is associated with FADS activity in human liver.

Levels of omega-6 (n-6) and omega-3 (n-3), long chain polyunsaturated fatty acids (LcPUFAs) such as arachidonic acid (AA; 20:4, n-6), eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3) impact a wide range of biological activities, including immune signaling, inflammation, and brain development and function. Two desaturase steps (Δ6, encoded by FADS2 and Δ5, encoded by FADS1) are rate limiting in the conversion of dietary essential 18 carbon PUFAs (18C-PUFAs) such as LA (18:2, n-6) to AA and α-linolenic acid (ALA, 18:3, n-3) to EPA and DHA. GWAS and candidate gene studies have consistently identified genetic variants within FADS1 and FADS2 as determinants of desaturase efficiencies and levels of LcPUFAs in circulating, cellular and breast milk lipids. Importantly, these same variants are documented determinants of important cardiovascular disease risk factors (total, LDL, and HDL cholesterol, triglycerides, CRP and proinflammatory eicosanoids). FADS1 and FADS2 lie head-to-head (5' to 5') in a cluster configuration on chromosome 11 (11q12.2). There is considerable linkage disequilibrium (LD) in this region, where multiple SNPs display association with LcPUFA levels. For instance, rs174537, located ∼ 15 kb downstream of FADS1, is associated with both FADS1 desaturase activity and with circulating AA levels (p-value for AA levels = 5.95 × 10(-46)) in humans. To determine if DNA methylation variation impacts FADS activities, we performed genome-wide allele-specific methylation (ASM) with rs174537 in 144 human liver samples. This approach identified highly significant ASM with CpG sites between FADS1 and FADS2 in a putative enhancer signature region, leading to the hypothesis that the phenotypic associations of rs174537 are likely due to methylation differences. In support of this hypothesis, methylation levels of the most significant probe were strongly associated with FADS1 and, to a lesser degree, FADS2 activities.

Atrial fibrillation, anticoagulation, fall risk, and outcomes in elderly patients.

Atrial fibrillation (AF) affects 2.5 million patients in the United States. The incidence of this condition increases with age, such that approximately 5% of people > 65 years of age have AF. Because of the lack of organized atrial contraction and thrombus formation in the left atrium, patients with AF are at increased risk of stroke. The estimated risk of stroke among all AF patients is 5% per year. Among patients without mitral stenosis, there is a graded relationship of stroke risk with the number of CHADS2 risk factors. Warfarin is the recommended treatment for embolic stroke prophylaxis in AF in intermediate- to high-risk patients. However, elderly patients who are deemed to be at risk of falls are often not started on warfarin therapy secondary to a perceived higher risk of bleeding complications. These risks have been evaluated, but conclusive data regarding the risk-benefit trade-off are elusive. This review summarizes available data on the use of warfarin in elderly patients with AF, focusing on the risk of bleeding, and will specifically address the utility of falls risk assessment in the decision to initiate warfarin therapy for AF.

A favorable clinical trend is associated with CD8 T-cell immune responses to the human papillomavirus type 16 e6 antigens in women being studied for abnormal pap smear results.

OBJECTIVE: The goal of this study was to examine the role of CD8 T-cell responses to human papillomavirus type 16 (HPV-16) in a favorable clinical trend in women being studied for abnormal Pap smear results. MATERIALS AND METHODS: Human papillomavirus-deoxyribonucleic acid testing and enzyme-linked immunospot assay using the HPV-16 E6 and E7 antigens were performed. The subjects with subsequent normal histologic diagnoses were considered to be "regressors" (n = 28), whereas those with histologic diagnoses of cervical intraepithelial neoplasia 1, 2, or 3 were considered to have short-term persistence of cervical abnormality and were designated to be "persistors" (n = 37). RESULTS: There was a higher percentage of CD8 T-cell responses to the E6 antigen in the regressors (15/28 or 53.6%) when compared with the persistors (10/37 or 27.0%; p = .04), but there was no recorded response difference for the E7 antigen. Results were the same when the analyses for E6 included only subjects who were high-risk HPV-positive (p = .01). CONCLUSIONS: The CD8 T-cell immune responses to the HPV-16 E6 antigens but not to E7 antigens are associated with a favorable clinical trend regardless of HPV types currently detected.

A new generation of antiplatelet agents.

PURPOSE OF REVIEW: Since the development and market entry of clopidogrel, a platelet ADP blocker, physicians have had few new antiplatelet options available to them for the treatment of acute and chronic coronary disease, specifically in the setting of acute coronary syndromes, percutaneous coronary intervention, and chronic stent management. Over the years, limitations of current antiplatelet regimens have emerged, establishing a need for novel antiplatelet drugs. This article discusses potential new targets for platelet inhibition and reviews innovative antiplatelet therapies under investigation. RECENT FINDINGS: There are five main categories of antiplatelet therapies currently undergoing clinical study, consisting of the thienopyridines (P2Y12 receptor antagonists), cyclopentyltriazolopyrimidines (P2Y12 receptor antagonists), anti-von Willebrand factor aptamers, thrombin receptor (protease-activated receptor-1) antagonists, and thromboxane receptor antagonists. Early studies of these agents are discussed. SUMMARY: Each of these new antiplatelet therapies has a unique profile that is aimed at improving clinical response with hopes of incremental efficacy and decreased complications, specifically bleeding.