Gami, Apoor S.

Introduction: Cardiac veins serve as substrate for arrhythmogenesis, and are especially involved as foci in atrial fibrillation. Understanding cardiac vein anatomy along with myocardial extension into these structures can improve electrophysiological mapping and electrical isolation of arrhythmogenic substrate. Accurately defining cardiac vein anatomy is critical in improving success of ablation therapy for atrial fibrillation. Methods: We performed measurements on 620 formalin-fixed autopsy hearts explanted from October 1998 to July 2003. The integrity of the thoracic veins and their cardiac connections were examined and systematic measurements of the superior and inferior vena cavae, azygous vein, vein of Marshall, coronary sinus, and pulmonary veins were performed and data were analyzed using univariate statistics. Results: We found that muscular extensions into the pulmonary veins were visible in 99% of the examined hearts, and were circumferential around the vein ostia (99.6%). Muscle extension into the SVC was found in 78% of examined hearts. These extensions were largely circumferential around the ostium (39%), but were also found to be asymmetric in a majority of hearts. Asymmetry was found in hearts with longer muscle extensions; no symmetry was observed in extensions greater than 0.8cm. Muscle extensions into the IVC were not seen. Occasionally, macroscopic muscle extensions into the azygous vein were visible (6%). The vein of Marshall was found to be patent to probing in the majority of hearts examined (72%) and was almost always overlying the lateral left atrial endocardial ridge. Conclusions: Our data suggest that all pulmonary veins need to be electrically isolated during atrial fibrillation ablation because of the almost universal presence of myocardial tissue extending into the veins. Mapping of the SVC should be done circumferentially and if potentials are noted isolation should also be performed. The IVC did not have muscle extensions and is unlikely to be a site of arrhythmogenesis. The azygous vein occasionally had muscle extensions and thus requires mapping and possible isolation. The vein of Marshall can be a substrate for arrhythmogenesis and is accessible for ablation by targeting the lateral left atrial endocardial ridge.

Background: Endothelial dysfunction assessed by flow mediated dilation (FMD) of the brachial artery has been identified as an independent predictor of cardiovascular events. However, whether weight gain impairs endothelial function is unknown. Methods: A randomized blinded controlled-trial to assess the effects of weight gain on endothelial function. After a weight maintenance period supervised by an experience dietitian, volunteers were randomized to gain weight (4 kg) or maintain weight. We recruited lean (BMI 18.5–24.9 kg/m 2 ) healthy volunteers (no diseases, medications and non-smokers) from the community. Using ultrasound, endothelial function was measured by FMD and non-flow mediated dilation (NFMD) of the brachial artery in the early morning (6:30 a.m.). Endothelial function was measured at baseline, after fat gain at 8 weeks and after weight loss at 16 weeks for fat-gainers and at baseline and follow-up (8 weeks) for weight maintainers. Body composition techniques to measure body fat %, such as dual x-ray absorptiometry and abdominal CT scans were performed. Results: We recruited 35 fat-gainers and 8 weight maintainers. Mean age was 29 ± 6 years and 18 (42 %) were women. There were no differences in age, anthropometric and body composition measurements, blood pressure, heart rate or apnea hypopnea index at baseline between both groups. After an average gain of 4 kg, the fat-gainer group significantly increased their total, visceral and subcutaneous fat. Brachial artery FMD and NFMD remained unchanged in weight maintainers. However, it decreaed in fat-gainers (FMD=9.1 ± 3 vs. 7.6 ± 3.2, p=0.003 and NFMD=12.0 ± 4.9 vs. 10.1 ± 6.0, p=0.01), but recovered to baseline after subjects shed the gained weight (basleline vs. recovery: FMD=9.1 ± 3 vs. 9.0 ± 3, p=NS and NFMD =12.0 ± 4.9 vs.12.6 ± 5.0, p=NS). Visceral fat gain, but not subcutaneous fat gain was significantly correlated with the decrease in brachial artery FMD (rho =−0.42, p=0.004 and rho =−0.22, p=0.15, respectively). Conclusions: In lean healthy young subjects, modest weight gain results in impaired endothelial function, even in the absence of changes in blood pressure. Endothelial funcion recovers after weight loss. Viscerar rather than subcutaneous fat predicts endothelial dysfunction.

Background Acute cardiac and vascular events, including myocardial infarction (MI) exhibit a peak onset between 6 AM and 11 AM. Plasminogen activator inhibitor‐1 (PAI‐1) is a main inhibitor of tissue‐plasminogen activator and a key indicator of prothrombotic state. Elevated levels of PAI‐1 have been linked to increased cardiac and vascular risk. Obstructive sleep apnea (OSA) has also been associated with increased risk of MI. Hypoxemia, as well as OSA, increase PAI‐1. We tested the hypothesis that the early morning after awakening is associated with higher PAI‐1 activity in subjects with acute MI who also have OSA. Methods We studied 56 subjects after acute myocardial infarction (mean age 60±2 years; BMI 28±1 kg/m 2 ). All subjects underwent complete overnight sleep polysomnography within 2 weeks after MI to assess for presence and severity of OSA. PAI‐1 activity was measured in all 56 subjects, first before sleep (at 9 PM), and then immediately after awakening in the morning (at 6 AM). A third measurement of PAI‐1 was obtained in all subjects at 11 AM. Results For the group, PAI‐1 activity almost doubled from 12.5±1.6 U/mL at 9 PM to 22.5±2.5 U/mL after waking at 6 AM and decreased to 14.2±2.4 U/mL by 11 AM (P<0.0001). Fifty seven percent of patients were observed to have OSA, with apnea hypopnea index of >10 events/hour. Sleep apnea did not contribute to further elevation of morning PAI‐1 activity level in acute MI patients (9 PM, 6 AM and 11 AM PAI‐1 activity respectively: no OSA 11.6±2.5 U/mL, 24.1±3.8 U/mL and 15.2±3.5 U/mL; OSA 13.3±2.1 U/mL, 21.1±3.3 U/mL and 13.3±3.3 U/mL; P=0.8 for between group comparison). Conclusions Increased PAI‐1 activity in acute MI patients may be an important mechanism underlying the early morning peak in cardiovascular events. The presence of OSA however does not appear to further accentuate the already elevated PAI‐1 activity in acute MI patients. In patients after acute MI, the diurnal variation in PAI‐1, rather than apnea, may drive the impaired fibrinolysis. Support or Funding Information ‐‐R01 grant HL65176‐‐This study was also supported in part by a gift to the Mayo Foundation by the Philips Respironics Foundation. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Background Excessive daytime sleepiness ( EDS ), a common symptom among patients with sleep‐disordered breathing, is closely associated with the development of cardiovascular diseases, but its long‐term prognostic value is not completely understood. The aim of this study was to investigate whether EDS would be an independent prognostic factor after myocardial infarction. Methods and Results We prospectively recruited 112 post–myocardial infarction patients. The Epworth Sleepiness Scale was completed before polysomnography, and EDS was defined as a score ≥11. After exclusion of 8 patients who accepted treatment with continuous positive airway pressure, 104 patients were followed up for 48 months. The primary composite end point was major adverse cardiac events. Patients with EDS had higher rates of major adverse cardiac events (48.4% versus 27.4%, χ 2 =5.27, P =0.022) and reinfarction (29.0% versus 5.5%, χ 2 =13.51, P =0.0002) compared with those without EDS . In the Cox proportional hazards model, patients with EDS had 2.15 times (95% confidence interval, 1.08–4.18; P =0.030) higher crude risk of major adverse cardiac events, with prognostic significance persisting after adjusting for age, diabetes mellitus, depression, left ventricular ejection fraction, apnea–hypopnea index, and nocturnal nadir oxygen saturation (hazard ratio: 2.13, 95% confidence interval, 1.04–4.26, P =0.039). Furthermore, among participants with moderate to severe sleep‐disordered breathing, the presence of EDS was associated with higher risk of major adverse cardiac events than those without EDS , after adjusting for age and nadir oxygen saturation (hazard ratio: 3.17, 95% confidence interval, 1.22–7.76, P =0.019). Conclusions EDS may be an independent prognostic factor of adverse outcome in post–myocardial infarction patients with moderate to severe sleep‐disordered breathing. Evaluation of EDS may shed new light on risk stratification and identify treatment responders for this patient population.

Background Obstructive sleep apnea ( OSA ) is an important risk factor for the development of cardiovascular diseases including myocardial infarction ( MI ). The aim of this study was to investigate the effects of OSA on prognosis after MI , and to determine which specific measures of OSA severity best predicted outcomes. Methods and Results We performed a prospective study, in which 112 patients without a prior diagnosis of sleep apnea underwent comprehensive polysomnography within a median of 7 days after MI . Patients were followed up at 6‐monthly intervals (±2 weeks) for a total of 48 months. Patients classified with central apnea (n=6) or those using continuous positive airway pressure (n=8) after polysomnography were excluded from analyses. The primary end point was major adverse cardiac events, including death from any cause, recurrent MI , unstable angina, heart failure, stroke, and significant arrhythmic events. Forty of 98 patients (41%) had OSA (apnea‐hypopnea index ≥15 events/h). OSA patients had higher major adverse cardiac event rates when compared to those without OSA (47.5% versus 24.1%; χ 2 =5.41, P =0.020). In a multivariate model that adjusted for clinically relevant variables including age, left ventricular ejection fraction, diabetes mellitus, oxygen desaturation index, and arousal index, significant hypoxemia, as defined by nocturnal nadir oxygen saturation ≤85%, was an independent risk factor for major adverse cardiac events (hazard ratio=6.05, P =0.004) in follow‐up 15 months after baseline. Conclusions Nocturnal hypoxemia in OSA is an important predictor of poor prognosis for patients after MI . These findings suggest that routine use of low‐cost nocturnal oximetry may be an economical and practical approach to stratify risk in post‐ MI patients.