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.

Stress-induced thrombus: prevalence of thromboembolic events and the role of anticoagulation in Takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TCM), also known as stress-induced cardiomyopathy has a favorable prognosis with expected recovery in weeks. Left ventricular (LV) thrombus is a known complication of TCM, which can lead to embolization and potentially a stroke. The prevalence of LV thrombus and the role of anticoagulation have yet to be fully defined in this condition. METHODS: We performed a search of published literature through PubMed and Scopus, which identified 282 patients with TCM in whom the incidence of LV thrombus and/or thromboembolic event was reported. In order to contrast this to the current anticoagulation strategy of atrial fibrillation, the occurrence of LV thrombus was compared to the adjusted stroke rate using the CHADS2 score. RESULTS: Of the 282 patients identified through a literature search, 26 (9.2%) were noted to have a thromboembolic event in the setting of TCM. The incidence of thromboembolic event ranged from 5.3% to as high as 14.3%. When compared to the CH2sDS2-VASc score, the average incidence of LV thrombus in our study equated to a score between 4 and 5. CONCLUSIONS: While the occurrence of LV thrombus in TCM is variable among studies, the average incidence remains relatively high. Thus, making LV thrombus a significant complication of stress-induced cardiomyopathy. Prophylactic anticoagulation until recovery may have a role in reducing the rate of LV thrombus. Further studies will be needed to determine the rate of embolization and utility of anticoagulation in TCM.

Differential Regulatory Role of Soluble Klothos on Cardiac Fibrogenesis in Hypertension.

BACKGROUND: Soluble Klotho functions as an endocrine factor that plays important roles in a variety of pathophysiological processes. Soluble Klotho contains 130 KDa and 65 KDa isoforms. However, their distinct individual functional heterogeneity remains uncertain. Herein, we investigated the regulatory role of two soluble Klothos on cardiac fibrogenic responses. METHODS AND RESULTS: The effect of soluble Klothos on myofibroblast differentiation, proliferation, and collagen synthesis/degradation were examined in cultured mouse cardiac myofibroblasts. The role of 130 KDa Klotho on fibrosis in hypertensive heart disease were examined in wild type (WT) and Klotho transgenic (Tg/+) mice receiving chronic angiotensin (Ang)II infusion. Our in vitro studies revealed that addition of 130 KDa soluble Klotho isoform increased collagen synthesis in a dose dependent manner. Furthermore, 130 KDa Klotho significantly stimulated myofibroblast differentiation, proliferation, and ERK phosphorylation, which were abolished by fibroblast growth factor (FGF) receptor antagonist (SU5402). In contrast, 65 KDa soluble Klotho treatment significantly suppressed myofibroblast proliferation and collagen synthesis. In vivo study further demonstrated that chronic AngII infusion lead to cardiac fibrosis in both WT and Tg/+ mice. However, cardiac collagen, TGF-ß1, TIMP-2, and α-smooth muscle actin (SMA) levels were markedly upregulated in Tg/+ mice compared to WT cohort. CONCLUSION: Taken together, these findings implicate that 130 KDa soluble Klotho plays a stimulatory role in cardiac myofibroblast growth and activity through FGF pathway, whereas 65 KDa soluble Klotho exerts an anti-fibrotic effect in cardiac myofibroblasts. Thus, two distinct isoforms of soluble Klotho appear to play the counter-regulatory roles in cardiac fibrogenic responses.