Impact of the COVID-19 Pandemic on Medical Grand Rounds Attendance: Comparison of In-Person and Remote Conferences.

BACKGROUND: Many academic medical centers transitioned from in-person to remote conferences due to the COVID-19 pandemic, but the impact on faculty attendance is unknown. OBJECTIVE: This study aims to evaluate changes in attendance at medical grand rounds (MGR) following the transition from an in-person to remote format and as a function of the COVID-19 census at Vanderbilt Medical Center. METHODS: We obtained the faculty attendee characteristics from Department of Medicine records. Attendance was recorded using a SMS text message-based system. The daily COVID-19 census was recorded independently by hospital administration. The main attendance metric was the proportion of eligible faculty that attended each MGR. Comparisons were made for the entire cohort and for individual faculty. RESULTS: The observation period was from March 2019 to June 2021 and included 101 MGR conferences with more than 600 eligible faculty. Overall attendance was unchanged during the in-person and remote formats (12,536/25,808, 48.6% vs 16,727/32,680, 51.2%; P=.44) and did not change significantly during a surge in the COVID-19 census. Individual faculty members attendance rates varied widely. Absolute differences between formats were less than -20% or greater than 20% for one-third (160/476, 33.6%) of faculty. Pulmonary or critical care faculty attendance increased during the remote format compared to in person (1450/2616, 55.4% vs 1004/2045, 49.1%; P<.001). A cloud-based digital archive of MGR lectures was accessed by <1% of faculty per conference. CONCLUSIONS: Overall faculty attendance at MGR did not change following the transition to a remote format, regardless of the COVID-19 census, but individual attendance habits fluctuated in a bidirectional manner. Incentivizing the use of a digital archive may represent an opportunity to increase faculty consumption of MGR.

Myeloid Cell Derived IL1ß Contributes to Pulmonary Hypertension in HFpEF.

BACKGROUND: Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are poorly understood. We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF. METHODS: Eight-week-old male and female C57BL/6J mice received either Nγ-nitro-L-arginine methyl ester and high-fat diet or control water and diet for 2, 5, and 12 weeks. The db/db mice were studied as a second model of HFpEF. Early pathways regulating PH were identified by bulk and single-cell RNA sequencing. Findings were confirmed by immunostain in lungs of mice or lung slides from clinically performed autopsies of patients with PH-HFpEF. ELISA was used to verify IL-1ß (interleukin-1 beta) in mouse lung, mouse plasma, and also human plasma from patients with PH-HFpEF obtained at the time of right heart catheterization. Clodronate liposomes and an anti-IL-1ß antibody were utilized to deplete macrophages and IL-1ß, respectively, to assess their impact on pulmonary vascular remodeling in HFpEF in mouse models. RESULTS: Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice developed PH, small vessel muscularization, and right heart dysfunction. Inflammation-related gene ontologies were overrepresented in bulk RNA sequencing analysis of whole lungs, with an increase in CD68+ cells in both murine and human PH-HFpEF lungs. Cytokine profiling showed an increase in IL-1ß in mouse and human plasma. Finally, clodronate liposome treatment in mice prevented PH in Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice, and IL-1ß depletion also attenuated PH in Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice. CONCLUSIONS: We report a novel model for the study of PH and right heart remodeling in HFpEF, and we identify myeloid cell-derived IL-1ß as an important contributor to PH in HFpEF.

Myeloid Cell Derived IL1ß Contributes to Pulmonary Vascular Remodeling in Heart Failure with Preserved Ejection Fraction.

Background: Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are not well understood. We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH in HFpEF, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF. Methods: Eight week old male and female C57/BL6J mice were given either L-NAME and high fat diet (HFD) or control water/diet for 2,5, and 12 weeks. Bulk RNA sequencing and single cell RNA sequencing was performed to identify early and cell-specific pathways that might regulate pulmonary vascular remodeling in PH-HFpEF. Finally, clodronate liposome and IL1ß antibody treatments were utilized to deplete macrophages or IL1ß, respectively, to assess their impact on pulmonary vascular remodeling in HFpEF. Results: Mice given L-NAME/HFD developed PH, small vessel muscularization, and right heart dysfunction after 2 weeks of treatment. Inflammation-related gene ontologies were over-represented in bulk RNA sequencing analysis of whole lungs, with an increase in CD68+ cells in both murine and human PH-HFpEF lungs. Cytokine profiling of mouse lung and plasma showed an increase in IL1ß, which was confirmed in plasma from patients with HFpEF. Single cell sequencing of mouse lungs also showed an increase in M1-like, pro-inflammatory populations of Ccr2+ monocytes and macrophages, and transcript expression of IL1ß was primarily restricted to myeloid-type cells. Finally, clodronate liposome treatment prevented the development of PH in L-NAME/HFD treated mice, and IL1ß antibody treatment also attenuated PH in L-NAME/HFD treated mice. Conclusions: Our study demonstrated that a well-accepted model of HFpEF recapitulates features of pulmonary vascular remodeling commonly seen in patients with HFpEF, and we identified myeloid cell derived IL1ß as an important contributor to PH in HFpEF.

Measurement of pulmonary transit time and estimation of pulmonary blood volume after exercise using contrast echocardiography.

BACKGROUND: Pulmonary transit time (PTT) and pulmonary blood volume (PBV) derived from non-invasive imaging correlate with pulmonary artery wedge pressure. The response of PBV to exercise may be useful in the evaluation of cardiopulmonary disease but whether PBV can be obtained reliably following exercise is unknown. We therefore aimed to assess the technical feasibility of measuring PTT and PBV after exercise using contrast echocardiography. METHODS: In healthy volunteers, PTT was calculated from time-intensity curves generated as contrast traversed the cardiac chambers before and immediately after participants performed sub-maximal exercise on the Standard Bruce Protocol. From the product of PTT and heart rate (HR) during contrast passage through the pulmonary circulation, PBV relative to systemic stroke volume (rPBV) was calculated. RESULTS: The cohort consisted of 14 individuals (age: 46 ± 8 years; 2 female) without cardiopulmonary disease. Exercise time was 8 ¾ ± 1 ¾ minutes and participants reached 85 ± 9% of age-predicted maximal HR, which corresponded to a near-doubling of resting HR at the time of post-exercise contrast injection. Data sufficient to derive PTT and rPBV were obtained for all participants. With exercise, the change in PBV from baseline ranged from 56 to 138% of systemic stroke volume, consistent with rPBV and absolute PBV values obtained in prior studies. CONCLUSIONS: Acquisition of PTT and rPBV using contrast echocardiography after exercise is achievable and the results are physiologically plausible. As the next step towards clinical implementation, validation of this technique against hemodynamic exercise studies appears reasonable.

Biomarker-specific differences between transpulmonary and peripheral arterial-venous blood sampling in patients with pulmonary hypertension.

Purpose: Transpulmonary biomarkers may provide insight into pulmonary hypertension (PH) pathophysiology, but require cardiac catheterization. We investigated whether the peripheral arterial-venous ratio (PR) could substitute for the transpulmonary ratio (TPR).Materials and methods: Blood from the pulmonary artery (PA), pulmonary arterial wedge (PAW), peripheral venous, and peripheral arterial positions was analysed for ET-1, NT-pro-BNP and cAMP levels in subjects with no PH (n = 18) and PH due to left heart disease (PH-LHD), which included combined pre- and post-capillary PH (Cpc-PH; n = 7) and isolated post-capillary PH (Ipc-PH; n = 9). Bland-Altman comparisons were made between peripheral venous and PA samples and between peripheral arterial and PAW samples. TPR was defined as [PAW]/[PA].Results: For ET-1, Bland-Altman analysis indicated negative bias (-24%) in peripheral arterial compared to PAW concentration and positive bias (23%) in peripheral venous compared to PA concentration. There was <10% absolute bias for NT-pro-BNP and cAMP. For ET-1, there was no difference in PR between Cpc-PH and Ipc-PH (0.87 ± 0.4 vs. 0.94 ± 0.6, p = 0.8), whereas there was a difference in TPR (2.2 ± 1.1 vs. 1.1 ± 0.2, p < 0.05).Conclusions: In PH-LHD, peripheral samples may be inadequate surrogates for transpulmonary samples, particularly when measuring mediators with prominent pulmonary secretion or clearance, such as ET-1.

Individual periodic limb movements with arousal are temporally associated with nonsustained ventricular tachycardia: a case-crossover analysis.

STUDY OBJECTIVES: Both periodic limb movements during sleep (PLMS) and arousals are associated with sympathetic nervous system activation and may be arrhythmogenic. We hypothesize a temporal relationship exists between individual PLMS, particularly with arousal, and nonsustained ventricular tachycardia (NSVT) events. METHODS: A bidirectional time-stratified case-crossover design was used to assess temporal associations between PLMS and NSVT during sleep in 49 Osteoporotic Fractures in Men Sleep Study participants with NSVT in a community-based cohort (n = 2,911). Sleep time was divided into approximate 30-min segments. For each NSVT (n = 141), we selected a preceding 30-s hazard period and three randomly chosen 30-s control periods from sleep within the same segment and evaluated for PLMS, respiratory events, minimum saturation, and arousals. Odds ratios and 95% confidence intervals-OR (95% CI)-were determined by conditional logistic regression; covariates included EEG arousals, minimum saturation, and respiratory events in the same hazard/control period. RESULTS: Participants with NSVT were 79.5 ± 6.2 years with a PLMS index of 32.1 (IQR: 10.1, 61.4) and apnea-hypopnea index of 17.1 (IQR: 9.4, 26.1). PLMS without arousal were not significantly associated with NSVT (OR = 0.80, 95% CI: 0.41-1.59). PLMS with arousal were associated with NSVT in unadjusted analyses (OR = 2.50, 95% CI: 1.11-5.65) and after adjustment (OR = 2.31, 95% CI: 1.02-5.25). Arousals associated with PLMS were associated with NSVT in unadjusted (OR = 2.84, 95% CI: 1.23-6.56) and adjusted analyses (OR = 2.61, 95% CI: 1.13-6.05). CONCLUSIONS: PLMS with (but not without) arousals are temporally associated with a greater than twofold higher odds of subsequent NSVT episodes. PLMS-related arousals may be physiologically important ventricular arrhythmia triggers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00070681.

Copy-and-Paste in Medical Student Notes: Extent, Temporal Trends, and Relationship to Scholastic Performance.

BACKGROUND: Medical students may observe and subsequently perpetuate redundancy in clinical documentation, but the degree of redundancy in student notes and whether there is an association with scholastic performance are unknown. OBJECTIVES: This study sought to quantify redundancy, defined generally as the proportion of similar text between two strings, in medical student notes and evaluate the relationship between note redundancy and objective indicators of student performance. METHODS: Notes generated by medical students rotating through their medicine clerkship during a single academic year at our institution were analyzed. A student-patient interaction (SPI) was defined as a history and physical and at least two contiguous progress notes authored by the same student during a single patient's hospitalization. For some students, SPI pairs were available from early and late in the clerkship. Redundancy between analogous sections of consecutive notes was calculated on a 0 to 100% scale and was derived from edit distance, the number of changes needed to transform one text string into another. Indicators of student performance included United States Medical Licensing Exam (USMLE) scores. RESULTS: Ninety-four single SPIs and 58 SPI pairs were analyzed. Redundancy in the assessment/plan section was high (40%) and increased within individual SPIs (to 60%; p < 0.001) and between SPI pairs over the course of the clerkship (by 30-40%; p < 0.001). Students in the lowest tertile of USMLE step II clinical knowledge scores had higher redundancy in the assessment/plan section than their classmates (67 ± 24% vs. 38 ± 22%; p = 0.002). CONCLUSION: During the medicine clerkship, the assessment/plan section of medical student notes became more redundant over a patient's hospital course and as students gained clinical experience. These trends may be indicative of deficiencies in clinical knowledge or reasoning, as evidenced by performance on some standardized evaluations.

Potential impact of cardiology phone-consultation for patients risk-stratified by the HEART pathway.

Objective: Bedside consultation by cardiologists may facilitate safe discharge of selected patients from the emergency department (ED) even when admission is recommended by the History, Electrocardiogram, Age, Risk factors, Troponin (HEART) pathway. If bedside evaluation is unavailable, phone consultation between emergency physicians and cardiologists would be most impactful if the resultant disposition is discordant with the HEART pathway. We therefore evaluate discordance between actual disposition and that suggested by the HEART pathway in patients presenting to the ED with chest pain for whom cardiology consultation occurred exclusively by phone and to assess the impact of phone-consultation on disposition. Methods: We performed a single-center, retrospective study of adults presenting to the ED with chest pain whose emergency physician had a phone consultation with a cardiologist. Actual disposition was abstracted from the medical record. HEART pathway category (low-risk, discharge; high-risk, admit) was derived from ED documentation. For discharged patients, major adverse cardiac events were assessed at 30 days by chart review and phone follow-up. Results: For the 170 patients that had cardiologist phone consultation, discordance between actual disposition and the HEART pathway was 17%. The HEART pathway recommended admission for nearly 80% of discharged patients. Following cardiologist phone-consultation, 10% of high-risk patients were discharged, with the majority having undergone a functional study recommended by the cardiologist. At 30 days, discharged patients had experienced no episodes of major adverse cardiac events or rehospitalization for cardiac reasons. Conclusion: For patients presenting to the ED with chest pain, cardiology phone-consultation has the potential to safely impact disposition, primarily by facilitating functional testing in high-risk individuals.

Signal-averaged P wave area increases during respiratory events in patients with paroxysmal atrial fibrillation and obstructive sleep apnea.

PURPOSE: P wave characteristics change during simulated apneic events in individuals with atrial fibrillation (AF). This study sought to assess whether similar changes occur during nocturnal respiratory events in patients with AF and obstructive sleep apnea (OSA). METHODS: Thirty-five individuals with severe OSA who underwent formal polysomnography and subsequent AF ablation were compared to a matched group without AF. Electrocardiographic segments from each polysomnogram corresponding to the following events were identified: period of wakefulness closest to the initial onset of sleep (baseline-awake), first respiratory event, respiratory event with the lowest nadir oxygen saturation, longest respiratory event, and last respiratory event. Signal-averaged P wave duration and signal-averaged positive P wave area (amplitude*duration for positive P wave amplitudes) were extracted using custom software. P wave characteristics during respiratory events and the baseline-awake condition were compared. RESULTS: Compared to the baseline-awake condition, the signal-averaged positive P wave area was significantly greater during the longest event and the event with the lowest oxygen saturation in those with AF, but not in those without AF. There were no significant differences in signal-averaged P wave duration for any respiratory event compared to the baseline-awake condition, regardless of AF status. CONCLUSION: In patients with paroxysmal AF and obstructive sleep apnea, the signal-averaged positive P wave area is greater during certain respiratory events than during wakefulness. This finding may reflect the acute impact on right atrial volume of increased venous return associated with respiratory events and could be useful to assess AF risk in sleep apnea and to monitor response to treatment.

Pulmonary transit time from contrast echocardiography and cardiac magnetic resonance imaging: Comparison between modalities and the impact of region of interest characteristics.

INTRODUCTION: The degree of correlation of pulmonary transit time (PTT) between contrast echocardiography and cardiac magnetic resonance imaging (MRI) across the spectrum of cardiac disease has not been quantified. In addition, the degree to which PTT estimates are affected by variation in location and size of regions of interest (ROI) is unknown. METHODS: Pulmonary transit time was obtained using an inflection point technique from individuals that underwent contrast echocardiography and cardiac MRI. Right ventricular, left atrial, and left ventricular ROIs were evaluated, and two sizes for each ROI were used. The Spearman correlation coefficient and Bland-Altman analysis were used for comparisons between modalities. Bland-Altman plots were also used to measure the impact of ROI size and location on transit times. RESULTS: Fourteen participants (age: 27-64 years; LV ejection fraction: 30%-60%) underwent both studies a median of 1 week apart. The correlation between modalities was significant for PTT (r = 0.65; P = 0.01) and normalized PTT (r = 0.80; P = 0.001). Cardiac MRI yielded transit times consistently higher than contrast echocardiography (bias ~ 1.4 seconds), but the discordance was not dependent on transit time magnitude. Low bias was observed for comparisons of ROI size and location (<0.5 seconds). CONCLUSIONS: Contrast echocardiography underestimates transit time measurements obtained by cardiac MRI, although the discrepancy was systematic and may have been contributed to by the interval between imaging studies. ROI location and size did not impact transit time values, suggesting that ROIs could be placed without intensive training, a step toward incorporation of real-time PTT measurement into echocardiographic laboratory workflow.

Improvement in Sleep-Disordered Breathing Indices Downloaded From a Positive Airway Pressure Machine Following Conversion of Atrial Fibrillation to Sinus Rhythm.

ABSTRACT: Sleep-disordered breathing (SDB) is a contributor to atrial fibrillation (AF) and treatment of obstructive sleep apnea can reduce the recurrence of AF following catheter ablation. However, the effect of AF therapies on measures of SDB severity is less robustly described. We present the case of a middle-aged man with SDB and persistent AF who exhibited improvement in SDB metrics, as characterized by data downloaded from his auto-titrating continuous positive airway pressure (AutoCPAP) machine, very shortly following procedures that restored sinus rhythm. Between procedures, when his rhythm reverted to AF, the downloaded parameters suggested more SDB events. After catheter ablation, the patient maintained sinus rhythm and the improvement in SDB metrics was sustained as well. This case provides support in favor of a bidirectional relationship between SDB and AF and suggests that data available from PAP machines may be useful in serial assessment of SDB status relative to heart rhythm.

The relationship between pulmonary artery wedge pressure and pulmonary blood volume derived from contrast echocardiography: A proof-of-concept study.

BACKGROUND: Pulmonary transit time (PTT) obtained from contrast echocardiography is a marker of global cardiopulmonary function. Pulmonary blood volume (PBV), derived from PTT, may be a noninvasive surrogate for left-sided filling pressures, such as pulmonary artery wedge pressure (PAWP). We sought to assess the relationship between PBV obtained from contrast echocardiography and PAWP. METHODS: Participants were adult survivors of childhood cancer that had contrast echocardiography performed nearly simultaneously with right-heart catheterization. PTT was derived from time-intensity curves of contrast passage through the right ventricle (RV) and left atrium (LA). PBV relative to overall stroke volume (rPBV) was estimated from the product of PTT and heart rate during RV-LA transit. PAWP was obtained during standard right-heart catheterization. The Spearman correlation coefficient was used to assess the relationship between rPBV and PAWP. RESULTS: The study population consisted of 7 individuals who had contrast echocardiography and right-heart catheterization within 3 hours of each other. There was a wide range of right atrial (1-17 mm Hg), mean pulmonary artery (18-42 mm Hg), and PAW pressures (4-26 mm Hg) as well as pulmonary vascular resistance (<1-6 Wood Units). We observed a statistically significant correlation between rPBV and PAWP (r = .85; P = .02). CONCLUSION: Relative PBV derived from contrast echocardiography correlates with PAWP. If validated in larger studies, rPBV could potentially be used as an alternative to invasively determine left-sided filling pressure.

The transpulmonary ratio of endothelin 1 is elevated in patients with preserved left ventricular ejection fraction and combined pre- and post-capillary pulmonary hypertension.

Pulmonary hypertension complicating left heart disease (PH-LHD) is associated with increased morbidity and mortality, especially in patients who develop combined pre- and post-capillary PH (Cpc-PH). Mechanisms underlying PH-LHD are incompletely understood, particularly for individuals with preserved left ventricular ejection fraction (LVEF). We hypothesized that transpulmonary concentrations of biomarkers representing signaling pathways with known effects on the pulmonary circulation could provide insight into the molecular etiology of PH-LHD in patients with preserved LVEF. Blood samples were collected from the pulmonary artery (PA) and wedge positions of outpatients with normal LVEF referred for right heart catheterization. Hemodynamic tracings were reviewed to classify patients as "no PH" (n = 23) or "PH-LHD" (n = 22). A biomarker's transpulmonary ratio (TPR) was calculated as the quotient of wedge and PA concentrations. The TPR of endothelin 1 (ET-1) was elevated in Cpc-PH (n = 10) compared to no PH or isolated post-capillary PH (Ipc-PH, n = 12); cAMP and cGMP TPRs were not different among groups. Higher ET-1 TPR in Cpc-PH was due to increased wedge ET-1 concentration. Pulmonary vascular resistance (PVR) strongly correlated with wedge ET-1 exclusively in Cpc-PH patients. In patients with normal LVEF and Cpc-PH, ET-1 TPR is higher, due to elevated wedge ET-1, compared to those without PH or with Ipc-PH. Strong correlation between PVR and wedge ET-1, observed only in the Cpc-PH group, may suggest increased pulmonary vascular responsiveness to ET-1 in these patients. These findings implicate elevated pulmonary ET-1 as a marker of, and a potential contributor to, development of Cpc-PH in this population.

Schedule-based metrics for the evaluation of clinic performance and potential recovery of cancelled appointments.

BACKGROUND: Assessment of outpatient clinic performance is important to optimize patient access. Metrics based on schedule data may assist with assessment of operational efficiency and recovering cancelled appointments. OBJECTIVES: To define schedule-based characteristics of clinic operations and to evaluate potential for recovery of cancelled appointments. METHODS: Sixty-seven weekly cardiology clinics from a single provider over 18 months at an academic medical center were analyzed. Parameters included clinic slots eligible to have patients scheduled (available), slots occupied by appointments (scheduled), and slots for which patients attended the associated visit (appeared). Rates of usage (scheduled/available), appearance (appeared/scheduled), and utilization (appeared/available=usage rate*appearance rate) were calculated. Surplus slots were defined as the difference between available slots and slots occupied by patients that appeared. Cancellation lag-time was defined as the interval between a cancellation and the appointment time. If a patient did not notify the clinic regarding a non-appearance, cancellation lag-time was set to zero. To quantify the impact of a change in clinic operations on efficiency, these metrics were used to evaluate a different cardiologist's clinic before and after its physical location moved. RESULTS: For approximately 900 patient visits, usage and appearance rates were∼80%, yielding a utilization rate of ∼2/3. On average, there were nearly 8 surplus slots per clinic. Approximately 30% of cancellation lag-times had positive values and nearly half of positive cancellation lag-times were >3h, indicating potential for recovery of those appointments. The intervention analysis showed that usage rate decreased and surplus slots per clinic increased significantly after a change in clinic location. CONCLUSIONS: Schedule-based analysis provides a framework to assess changes to clinic operations, identify mechanisms underlying inefficiency, and suggest solutions for improving clinic performance (i.e. more schedulers in response to low usage rates). Cancellation lag-time analysis suggests recovering a portion of same-day cancellations is plausible.

Dysfunctional BMPR2 signaling drives an abnormal endothelial requirement for glutamine in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is increasingly recognized as a systemic disease driven by alteration in the normal functioning of multiple metabolic pathways affecting all of the major carbon substrates, including amino acids. We found that human pulmonary hypertension patients (WHO Group I, PAH) exhibit systemic and pulmonary-specific alterations in glutamine metabolism, with the diseased pulmonary vasculature taking up significantly more glutamine than that of controls. Using cell culture models and transgenic mice expressing PAH-causing BMPR2 mutations, we found that the pulmonary endothelium in PAH shunts significantly more glutamine carbon into the tricarboxylic acid (TCA) cycle than wild-type endothelium. Increased glutamine metabolism through the TCA cycle is required by the endothelium in PAH to survive, to sustain normal energetics, and to manifest the hyperproliferative phenotype characteristic of disease. The strict requirement for glutamine is driven by loss of sirtuin-3 (SIRT3) activity through covalent modification by reactive products of lipid peroxidation. Using 2-hydroxybenzylamine, a scavenger of reactive lipid peroxidation products, we were able to preserve SIRT3 function, to normalize glutamine metabolism, and to prevent the development of PAH in BMPR2 mutant mice. In PAH, targeting glutamine metabolism and the mechanisms that underlie glutamine-driven metabolic reprogramming represent a viable novel avenue for the development of potentially disease-modifying therapeutics that could be rapidly translated to human studies.

Relation of Obstructive Sleep Apnea and a Common Variant at Chromosome 4q25 to Atrial Fibrillation.

Obstructive sleep apnea (OSA) and single nucleotide polymorphisms (SNPs) at the 4q25 locus are associated with increased risk of atrial fibrillation (AF). Whether these associations are independent of traditional risk factors for AF remains unknown. Using billing code queries and manual chart review, we assembled a cohort of adults that underwent overnight polysomnography and at least 1 12-lead electrocardiogram. Case status was defined by electrocardiographic data in support of AF or documentation of AF by a staff cardiologist. Controls were defined by a lack of primary evidence of AF and absence of a diagnosis of AF in the medical record. OSA severity was categorized based on Apnea-Hypopnea Index. Genotyping for a key 4q25 SNP (rs2200733) was performed using the Sequenom platform. Logistic regression was used to test for associations of AF with OSA category and 4q25 SNP genotype while adjusting for age, gender, body mass index, ancestry, hypertension status, and heart failure status. The cohort consisted of 674 subjects (62 ± 13 years; 44% women), including 132 patients with AF. After adjustment for established risk factors, the association between AF and OSA severity was borderline significant (odds ratio 1.2, 95% CI 1.0 to 1.5). The association between AF and 4q25 SNP status remained significant in a fully adjusted model that included OSA severity (odds ratio 1.5, 95% CI 1.3 to 5.7). In conclusion, OSA severity and the chromosome 4q25 SNP genotype were associated with AF status independent of clinical risk factors. Knowledge of AF-related SNPs may enhance AF risk stratification for those undergoing polysomnography.

Documentation of HEART score discordance between emergency physician and cardiologist evaluations of ED patients with chest pain.

INTRODUCTION: A triage cardiology program, in which cardiologists provide consultation to the Emergency Department (ED), may safely reduce admissions. For patients with chest pain, the HEART Pathway may obviate the need for cardiology involvement, unless there is a difference between ED and cardiology assessments. Therefore, in a cohort concurrently evaluated by both specialties, we analyzed discordance between ED and cardiology HEART scores. METHODS: We performed a single-center, cross-sectional, retrospective study of adults presenting to the ED with chest pain who had a documented bedside evaluation by a triage cardiologist. Separate ED and cardiology HEART scores were computed based on documentation by the respective physicians. Discrepancies in HEART score between ED physicians and cardiologists were quantified using Cohen κ coefficient. RESULTS: Thirty-three patients underwent concurrent ED physician and cardiologist evaluation. Twenty-three patients (70%) had discordant HEART scores (κ = 0.13; 95% confidence interval, -0.02 to 0.32). Discrepancies in the description of patients' chest pain were the most common source of discordance and were present in more than 50% of cases. HEART scores calculated by ED physicians tended to overestimate the scores calculated by cardiologists. When categorized into low-risk or high-risk by the HEART Pathway, more than 25% of patients were classified as high risk by the ED physician, but low risk by the cardiologist. CONCLUSION: There is substantial discordance in HEART scores between ED physicians and cardiologists. A triage cardiology system may help refine risk stratification of patients presenting to the ED with chest pain, even when the HEART Pathway tool is used.

Automated detection of atrial fibrillation from the electrocardiogram channel of polysomnograms.

PURPOSE: Accurate identification of atrial fibrillation episodes from polysomnograms is important for research purposes but requires manual review of a large number of long electrocardiographic tracings. As automated assessment of these tracings for atrial fibrillation may improve efficiency, this study aimed to evaluate this approach in polysomnogram-derived electrocardiographic data. METHODS: A previously described algorithm to detect atrial fibrillation from single-lead electrocardiograms was applied to polysomnograms from a large epidemiologic study of obstructive sleep apnea in older men (Osteoporotic Fractures in Men [MrOS] Sleep Study). Atrial fibrillation status during each participant's PSG was determined by independent manual review. Models to predict atrial fibrillation status from a combination of algorithm output and clinical/polysomnographic characteristics were developed, and their accuracy was evaluated using standard statistical techniques. RESULTS: Derivation and validation cohorts each consisted of 1395 individuals; 5 % of each group had atrial fibrillation. Model parameters were optimized for the derivation cohort using the Akaike information criterion. Application to the validation cohort of these optimized models revealed high sensitivity (85-90 %) and specificity (90-95 %) as well as good predictive ability, as assessed by the C statistic (>0.9) and generalized R (2) values (∼0.6). Addition of cardiovascular or polysomnogram data to the models did not improve their performance. CONCLUSIONS: In a research setting, automated detection of atrial fibrillation from polysomnogram-derived electrocardiographic signals appears feasible and agrees well with manual identification. Future studies can evaluate the utility of this technique as applied to clinical polysomnograms and ambulatory electrocardiographic monitoring.