The Cost of Return to Play Protocols in Collegiate Athletes Recovering from Coronavirus Disease 2019.

INTRODUCTION/PURPOSE: SARS-CoV-2 infection (COVID-19) can result in myocarditis. Protocols were developed to allow competitive athletes to safely return to play (RTP) after a COVID-19 infection, but the financial impact of these protocols is unknown. Our objective was to determine the differential cost of post-COVID-19 RTP protocols for competitive collegiate athletes. METHODS: This multicenter retrospective cohort study of clinical evaluation of 295 athletes after COVID-19 infection was performed at four institutions with three RTP protocols. Costs were calculated using adjusted Center for Medicare and Medicaid Services pricing. All athletes underwent electrocardiogram and clinical evaluation. A tiered approach performed cardiac imaging and biomarker analysis for major symptoms. A universal transthoracic echocardiogram (TTE) approach performed TTE and biomarkers for all athletes. A universal exercise stress echocardiogram (ESE) approach performed ESE and biomarkers for all athletes. RESULTS: The cost per athlete was $632.51 ± 651.80 ($44,908 total) in tiered group (n = 71), $1,072.30 ± 517.93 ($87,928 total) in the universal TTE group (n = 82), and $1357.38 ± 757.05 ($192,748 total) in the universal ESE group (n = 142) (P < 0.001). Extrapolated national costs for collegiate athletes would be $39 to 64 million higher for universal imaging approaches versus a tiered approach. Only seven athletes had probable/possible myocarditis with no significant difference between approaches. CONCLUSIONS: Cardiac screening in collegiate athletes after COVID-19 infection resulted in significant cost to the health care system. A tiered-based approach was more economical, and a universal exercise echocardiogram group detected slightly more myocardial abnormalities by cardiac magnetic resonance imaging. The clinical consequences of these approaches are unknown.

Exercise based assessment of cardiac autonomic function in type 1 versus type 2 diabetes mellitus.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that is associated with increased mortality. Exercise-based assessment of autonomic function has identified diminished parasympathetic reactivation after exercise in type 2 DM. It is postulated herein, that this would be more prominent among those with type 1 DM. METHODS: Sixteen subjects with type 1 DM (age 32.9 ± 10.1 years), 18 subjects with type 2 DM (55.4 ± 8.0 years) and 30 controls (44.0 ± 11.6 years) underwent exercise-based assessment of autonomic function. Two 16-min submaximal bicycle tests were performed followed by 45 min of recovery. On the second test, atropine (0.04 mg/kg) was administered near end-exercise so that all of the recovery occurred under parasympathetic blockade. Plasma epinephrine and norepinephrine levels were measured at rest, during exercise, and during recovery. RESULTS: There were no differences in resting or end-exercise heart rates in the three groups. Parasympathetic effect on RR-intervals during recovery (p < 0.03) and heart rate recovery (p = 0.02) were blunted in type 2 DM. Type 1 DM had higher baseline epinephrine and norepinephrine levels (p < 0.03), and exhibited persistent sympathoexcitation during recovery. CONCLUSIONS: Despite a longer duration of DM in the study patients with type 1 versus type 2 DM, diminished parasympathetic reactivation was not noted in type 1 DM. Instead, elevation in resting plasma catecholamines was noted compared to type 2 DM and controls. The variable pathophysiology for exercise-induced autonomic abnormalities in type 1 versus type 2 DM may impact prognosis.

COVID-19 cardiac injury: Implications for long-term surveillance and outcomes in survivors.

Up to 20%-30% of patients hospitalized with coronavirus disease 2019 (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment of COVID-19 may affect the convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk of cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19-associated cardiac injury is needed. The type of testing and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of "post-COVID-19 cardiac syndrome."

Disparities and Temporal Trends in Stroke Care Outcomes in Patients with Atrial Fibrillation: The FLiPER-AF Stroke Study.

BACKGROUND AND PURPOSE: Atrial Fibrillation (AF) is the most common cardiac cause of ischemic stroke. However, the relation between AF and stroke care outcomes in diverse populations is understudied. We aimed to evaluate sex and race-ethnic disparities associated with AF in hospital stroke outcomes utilizing data from the FLorida PuErto Rico Atrial Fibrillation (FLiPER-AF) Stroke Study. METHODS: The study included 104,308 ischemic stroke cases with available information on AF status enrolled in a state-wide stroke registry from 2010 to 2016. Multivariable logistic regression models were performed to evaluate the association between AF and stroke outcomes and the modification effects on the associations by sex and by race-ethnicity, adjusted for socio-demographic status, vascular risk factors and stroke severity. RESULTS: AF was present in 23% of ischemic stroke cases. AF was associated with worse disability at discharge (OR=1.11, 95% CI, 1.04-1.18), less discharge to home (OR=0.89, 0.85-0.92), and longer length of hospital stay (LOS>6 days, OR=1.53, 1.46-1.60). Interaction analyses showed that the association between AF and less discharge to home was stronger in women than men (p for interaction <0.001), as well as in FL-whites than in FL-blacks, FL-Hispanics or PR-Hispanics (p for interaction=0.002). The association between AF and prolonged LOS was more prominent in PR-Hispanics than in FL-blacks, FL-Hispanics, or FL-whites (p for interaction <0.001). From 2010 to 2016, the effects of AF on hospital length of stay attenuated (p for interaction<0.001). CONCLUSIONS: AF was associated with poor disability at discharge, less discharge to home, and prolonged hospital length of stay for acute stroke care. The effect of AF on length of stay attenuated over time. Sex and race-ethnic disparities were observed in the effect of AF on being less discharge to home and prolonged hospital stay. Further research is needed to identify and modify the biologic and systems of care contributors to these disparities.

Sudden Cardiac Arrest Risk Assessment: Population Science and the Individual Risk Mandate.

Importance: High-resolution stratification of risk of sudden cardiac arrest (SCA) in individual patients is a tool that is necessary for achieving effective and efficient application of data generated by population-based research. This concept is at the core of initiatives for merging cost effectiveness with maximized clinical efficiency and individual patient treatment. Observations: For this review, we analyzed data on sudden cardiac death and SCA available from population studies that included large longitudinal and cross-sectional databases, observational cohort studies, and randomized clinical trials. In the context of population science, we treated clinical trials as small, scientifically rigid population studies that generate outcomes focused on defined segments of the population. Application of probabilistic outcomes from these available sources to individual patients generally and patients at risk for SCA and sudden cardiac death in particular is limited by the diversity of the study population based on inclusion criteria and/or the absence of uniformly large effect sizes. Limited information is available on the requirements for defining small high-risk density subgroups that would lead to identification of individuals at a sufficiently high probability of SCA to have a significant effect on clinical decision making. Conclusions and Relevance: Synthesis of available population and clinical science data demonstrates the limitations for prediction and prevention of SCA and sudden cardiac death and provides justification for a research mandate for improving risk prediction at the level of individual patients. This leads to suggested approaches to new data generation and required research funding to address this large public health burden.

Hospital Admissions for Chest Pain Associated with Cocaine Use in the United States.

BACKGROUND: The outcomes related to chest pain associated with cocaine use and its burden on the healthcare system are not well studied. METHODS: Data were collected from the Nationwide Inpatient Sample (2001-2012). Subjects were identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Primary outcome was a composite of mortality, myocardial infarction, stroke, and cardiac arrest. RESULTS: We identified 363,143 admissions for cocaine-induced chest pain. Mean age was 44.9 (±21.1) years with male predominance. Left heart catheterizations were performed in 6.7%, whereas the frequency of acute myocardial infarction and percutaneous coronary interventions were 0.69% and 0.22%, respectively. The in-hospital mortality was 0.09%, and the primary outcome occurred in 1.19% of patients. Statistically significant predictors of primary outcome included female sex (odds ratio [OR], 1.16; confidence interval [CI], 1.00-1.35; P = .046), age >50 years (OR, 1.24, CI, 1.07-1.43; P = .004), history of heart failure (OR, 1.63, CI, 1.37-1.93; P <.001), supraventricular tachycardia (OR, 2.94, CI, 1.34-6.42; P = .007), endocarditis (OR, 3.5, CI, 1.50-8.18, P = .004), tobacco use (OR, 1.3, CI, 1.13-1.49; P <.001), dyslipidemia (OR, 1.5, CI, 1.29-1.77; P <.001), coronary artery disease (OR, 2.37, CI, 2.03-2.76; P <.001), and renal failure (OR, 1.27, CI, 1.08-1.50; P = .005). The total annual projected economic burden ranged from $155 to $226 million with a cumulative accruement of more than $2 billion over a decade. CONCLUSION: Hospital admissions due to chest pain and concomitant cocaine use are associated with low rates of adverse outcomes. For the low-risk cohort in whom acute coronary syndrome has been ruled out, hospitalization may not be beneficial and may result in unnecessary cardiac procedures.

Differences Between Access to Follow-Up Care and Inappropriate Shocks Based on Insurance Status of Implantable Cardioverter Defibrillator Recipients.

Differences in implantable cardioverter defibrillator (ICD) utilization based on insurance status have been described, but little is known about postimplant follow-up patterns associated with insurance status and outcomes. We collected demographic, clinical, and device data from 119 consecutive patients presenting with ICD shocks. Insurance status was classified as uninsured/Medicaid (uninsured) or private/Health Maintenance Organization /Medicare (insured). Shock frequencies were analyzed before and after a uniform follow-up pattern was implemented regardless of insurance profile. Uninsured patients were more likely to present with an inappropriate shock (63% vs 40%, p = 0.01), and they were more likely to present with atrial fibrillation (AF) as the shock trigger (37% vs 19%, p = 0.04). Uninsured patients had a longer interval between previous physician contact and index ICD shock (147 ± 167 vs 83 ± 124 days, p = 0.04). Patients were followed for a mean of 521 ± 458 days after being enrolled in a uniform follow-up protocol, and there were no differences in the rate of recurrent shocks based on insurance status. In conclusion, among patients presenting with an ICD shock, underinsured/uninsured patients had significantly longer intervals since previous physician contact and were more likely to present with inappropriate shocks and AF, compared to those with private/Medicare coverage. After the index shock, both groups were followed uniformly, and the differences in rates of inappropriate shocks were mitigated. This observation confirms the importance of regular postimplant follow-up as part of the overall ICD management standard.

Methods of assessment of the post-exercise cardiac autonomic recovery: A methodological review.

The analysis of post-exercise cardiac autonomic recovery is a practical clinical tool for the assessment of cardiovascular health. A reduced heart rate recovery - an indicator of autonomic dysfunction - has been found in a broad range of cardiovascular diseases and has been associated with increased risks of both cardiac and all-cause mortality. For this reason, over the last several years, non-invasive methods for the assessment of cardiac autonomic recovery after exercise - either based on heart rate recovery or heart rate variability indices - have been proposed. However, for the proper implementation of such methods in daily clinical practice, the discussion of their clinical validity, physiologic meaning, mathematical formulation and reproducibility should be better addressed. Therefore, the aim of this methodological review is to present some of the most employed methods of post-exercise cardiac autonomic recovery in the literature and comprehensively discuss their strengths and weaknesses.

Assessment of left and right atrial 3D hemodynamics in patients with atrial fibrillation: a 4D flow MRI study.

Atrial fibrillation (AF) is associated with embolic stroke due to thrombus formation in the left atrium (LA). Based on the relationship of atrial stasis to thromboembolism and the marked disparity in pulmonary versus systemic thromboembolism in AF, we tested the hypothesis that flow velocity distributions in the left (LA) versus right atrium (RA) in patients with would demonstrate increased stasis. Whole heart 4D flow MRI was performed in 62 AF patients (n = 33 in sinus rhythm during imaging, n = 29 with persistent AF) and 8 controls for the assessment of in vivo atrial 3D blood flow. 3D segmentation of the LA and RA geometry and normalized velocity histograms assessed atrial velocity distribution and stasis (% of atrial velocities <0.2 m/s). Atrial hemodynamics were similar for RA and LA and significantly correlated (mean velocity: r = 0.64; stasis: r = 0.55, p < 0.001). RA and LA mean and median velocities were lower in AF patients by 15-33 % and stasis was elevated by 11-19 % compared to controls. There was high inter-individual variability in LA/RA mean velocity ratio (range 0.5-1.8) and LA/RA stasis ratio (range 0.7-1.7). Patients with a history of AF and in sinus rhythm showed most pronounced differences in atrial flow (reduced mean velocities, higher stasis in the LA). While there is no systematic difference in LA versus RA flow velocity profiles, high variability was noted. Further delineation of patient specific factors and/or regional atrial effects on the LA and RA flow velocity profiles, as well as other factors such as differences in procoagulant factors, may explain the more prevalent systemic versus pulmonary thromboembolism in patients with AF.

Disparities in sleep characteristics by race/ethnicity in a population-based sample: Chicago Area Sleep Study.

BACKGROUND: Prior studies report less favorable sleep characteristics among non-Whites as compared with non-Hispanic Whites. However, few population-based studies have used objective measures of sleep duration, especially in more than two racial/ethnic groups. We tested whether objectively estimated sleep duration and self-reported sleep quality varied by race and whether differences were at least partially explained by the variability in clinical, psychological, and behavioral covariates. METHODS: Adults aged 35-64 years who self-identified as White, Black, Asian, or Hispanic were randomly sampled from Chicago, IL, and the surrounding suburbs. Our analytic sample included adults who had an apnea-hypopnea index <15 after one night of screening and who completed seven nights of wrist actigraphy for determination of sleep duration, sleep percentage, minutes of wake after sleep onset, and sleep fragmentation (n = 495). Daytime sleepiness was estimated using the Epworth Sleepiness Scale (ESS), and sleep quality was estimated from the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Following statistical adjustment for age, gender, education, work schedule (ie, day vs. night shift), smoking status, depressive symptoms, body mass index (BMI), hypertension, and diabetes, sleep duration (minutes) was significantly (all p < 0.01) shorter in Black (mean = 399.5), Hispanic (mean = 411.7), and Asian (mean = 409.6) participants than in White participants (mean = 447.4). All remaining sleep characteristics were significantly less favorable among Black participants as compared with White participants. Asian participants also reported significantly more daytime sleepiness than did White participants. CONCLUSIONS: Differences in sleep characteristics by race/ethnicity are apparent in a sample of adults with a low probability of sleep apnea and following adjustment for known confounders.

QT dynamics early after exercise as a predictor of mortality.

BACKGROUND: Exercise and QT dynamics during ambulatory monitoring impact mortality in a variety of populations. Heart rate recovery (HRR) after exercise is a known strong predictor of mortality. OBJECTIVE: This study assessed the independent prognostic significance of the QT response to changing heart rate (QT dynamics) during recovery from exercise. METHODS: The cohort included patients referred for treadmill exercise stress testing over a 5-year period. Patients had to have at least 4 electrocardiographic tracings within 5 minutes of peak exercise. One had to be recorded 60 seconds into recovery to calculate the HRR. Linear regression of the QT-RR relation during recovery was used to predict the QT interval at cycle lengths of 500 and 600 ms (QT-500 and QT-600). Only studies with an R(2) > or = 0.9 (72%) were retained. Optimal binary cut points were chosen. All-cause mortality was determined from either the Social Security Death Index or hospital records. RESULTS: A total of 2,994 patients met inclusion criteria; 228 (7.6%) died during an average follow-up of 7.6 +/- 1.9 years. Abnormal QT-500 (>316 ms) was the strongest univariate QT dynamics predictor in a Cox proportional hazards model (hazard ratio = 2.13, P <.001). It remained an independent predictor of mortality after adjustment for age, exercise capacity, medications, single photon emission computed tomography defects, and abnormal (<12 beats/min) HRR (hazard ratio = 1.46, P = .014). CONCLUSION: An abnormal predicted QT interval at 500 ms (120 beats/min) during recovery from exercise independently predicts all-cause mortality. Because QT dynamics in recovery incorporate information on both repolarization and autonomic responsiveness, its role in risk prediction for sudden cardiac death should be further explored.

Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications.

Certain abnormalities of autonomic function in the setting of structural cardiovascular disease have been associated with an adverse prognosis. Various markers of autonomic activity have received increased attention as methods for identifying patients at risk for sudden death. Both the sympathetic and the parasympathetic limbs can be characterized by tonic levels of activity, which are modulated by, and respond reflexively to, physiological changes. Heart rate provides an index of the net effects of autonomic tone on the sinus node, and carries prognostic significance. Heart rate variability, though related to heart rate, assesses modulation of autonomic control of heart rate and carries additional prognostic information, which in some cases is more powerful than heart rate alone. Heart rate recovery after exercise represents the changes in autonomic tone that occur immediately after cessation of exercise. This index has also been shown to have prognostic significance. Autonomic evaluation during exercise and recovery may be important prognostically, because these are high-risk periods for sudden death, and the autonomic changes that occur with exercise could modulate this high risk. These markers provide related, but not redundant information about different aspects of autonomic effects on the sinus node.

Assessment of parasympathetic reactivation after exercise.

The objective of this study was to evaluate whether heart rate variability (HRV) can be used as an index of parasympathetic reactivation after exercise. Heart rate recovery after exercise has recently been shown to have prognostic significance and has been postulated to be related to abnormal recovery of parasympathetic tone. Ten normal subjects [5 men and 5 women; age 33 +/- 5 yr (mean +/- SE)] exercised to their maximum capacity, and 12 subjects (10 men and 2 women; age 61 +/- 10 yr) with coronary artery disease exercised for 16 min on two separate occasions, once in the absence of atropine and once with atropine (0.04 mg/kg) administered during exercise. The root mean square residual (RMS), which measures the deviation of the R-R intervals from a straight line, as well as the standard deviation (SD) and the root mean square successive difference of the R-R intervals (MSSD), were measured on successive 15-, 30-, and 60-s segments of a 5-min ECG obtained immediately after exercise. In recovery, the R-R interval was shorter with atropine (P < 0.0001). Without atropine, HRV, as measured by the MSSD and RMS, increased early in recovery from 4.1 +/- 0.4 and 3.7 +/- 0.4 ms in the first 15 s to 7.2 +/- 1.0 and 7.4 +/- 0.9 ms after 1 min, respectively (P < 0.0001). RMS (range 1.7-2.1 ms) and MSSD were less with atropine (P < 0.0001). RMS remained flat throughout recovery, whereas MSSD showed some decline over time from 3.0 to 2.2 ms (P < 0.002). RMS and MSSD were both directly related (r(2) = 0.47 and 0.56, respectively; P < 0.0001) to parasympathetic effect, defined as the difference in R-R interval without and with atropine. In conclusion, RMS and MSSD are parameters of HRV that can be used in the postexercise recovery period as indexes of parasympathetic reactivation after exercise. These tools may improve our understanding of parasympathetic reactivation after exercise and the prognostic significance of heart rate recovery.