Characterization of Myocardial Injury in Patients With COVID-19.

BACKGROUND: Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data. OBJECTIVES: This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19. METHODS: We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization. RESULTS: A total of 305 patients were included. Mean age was 63 years and 205 patients (67.2%) were male. Overall, myocardial injury was observed in 190 patients (62.3%). Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions. Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities. Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities. CONCLUSIONS: Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present.

Infective Endocarditis of a Left Ventricular Myxoma in a Heroin User.

Infected cardiac myxomas are rare and can have disastrous sequelae; urgent surgical resection is typically indicated. We report the case of a 43-year-old user of intravenous heroin who presented with weakness and dyspnea. He was diagnosed with infective endocarditis of a myxoma attached to the left ventricular lateral wall. The patient underwent successful surgical resection of the myxoma and then completed 4 weeks of antibiotic therapy. In addition to discussing this patient's case, we briefly review the relevant medical literature, in which we found only 4 previous reports of left ventricular myxoma associated with infective endocarditis.

Feasibility of subcutaneous implantable cardioverter-defibrillator implantation with opioid sparing truncal plane blocks and deep sedation.

INTRODUCTION: The subcutaneous implantable cardioverter-defibrillator (S-ICD) is most commonly implanted under general anesthesia (GA), due to the intraoperative discomfort associated with tunneling and dissection. Postoperative pain can be substantial and is often managed with opioids. There is a growing interest in transitioning away from the routine use of GA during S-ICD implantation, while also controlling perioperative discomfort without the use of narcotics. As such, we assessed the feasibility of a multimodal analgesia regimen that included regional anesthesia techniques in patients undergoing S-ICD implantation. METHODS AND RESULTS: Twenty patients received truncal plane block (TBL) immediately before S-ICD implantation. The first 10 patients were implanted under general anesthesia (GA + TBL), and the next 10 patients were implanted under deep sedation (DS + TBL). Additionally, the DS + TBL patients were also prescribed a structured regimen of nonopioid analgesics in the perioperative period. Opioid consumption was calculated as milligram morphine equivalents (MME). In-hospital opioid consumption was significantly lower in the patients implanted with DS + TBL (MME = 0) as compared with patients receiving GA + TBL (MME = 60; P = 0.004). CONCLUSIONS: Subcutaneous ICD implantation with anesthesia-delivered DS and a multimodal anesthetic regimen that includes TBL is feasible and associated with significantly less perioperative opioid consumption.

Stem cell delivery in tissue-specific hydrogel enabled meniscal repair in an orthotopic rat model.

Interest in non-invasive injectable therapies has rapidly risen due to their excellent safety profile and ease of use in clinical settings. Injectable hydrogels can be derived from the extracellular matrix (ECM) of specific tissues to provide a biomimetic environment for cell delivery and enable seamless regeneration of tissue defects. We investigated the in situ delivery of human mesenchymal stem cells (hMSCs) in decellularized meniscus ECM hydrogel to a meniscal defect in a nude rat model. First, decellularized meniscus ECM hydrogel retained tissue-specific proteoglycans and collagens, and significantly upregulated expression of fibrochondrogenic markers by hMSCs versus collagen hydrogel alone in vitro. The meniscus ECM hydrogel in turn supported delivery of hMSCs for integrative repair of a full-thickness defect model in meniscal explants after in vitro culture and in vivo subcutaneous implantation. When applied to an orthotopic model of meniscal injury in nude rat, hMSCs in meniscus ECM hydrogel were retained out to eight weeks post-injection, contributing to tissue regeneration and protection from joint space narrowing, pathologic mineralization, and osteoarthritis development, as evidenced by macroscopic and microscopic image analysis. Based on these findings, we propose the use of tissue-specific meniscus ECM-derived hydrogel for the delivery of therapeutic hMSCs to treat meniscal injury.

Endothelial cells enhance the migration of bovine meniscus cells.

OBJECTIVE: To study the interactions between vascular endothelial cells and meniscal fibrochondrocytes from the inner avascular and outer vascular regions of the meniscus and to identify angiogenic factors that enhance cell migration and integrative repair. METHODS: Bovine meniscal fibrochondrocytes (bMFCs) from the inner and outer regions of meniscus were cultured for 7 days with or without human umbilical vein endothelial cells (HUVECs) in a micropatterned 3-dimensional hydrogel system for assessment of cell migration. Angiogenic factors secreted by HUVECs were probed for their role in paracrine mechanisms governing bMFC migration and applied to a full-thickness defect model of meniscal repair in explants from the inner and outer meniscal regions over 4 weeks. RESULTS: Endothelial cells enhanced the migration of inner and outer bMFCs in the micropatterned system via endothelin 1 (ET-1) signaling. Supplementation with ET-1 significantly enhanced the integration strength of full-thickness defects in the inner and outer explants, as well as cell migration at the macroscale level, as compared to controls without ET-1 treatment. CONCLUSION: This study is the first to show that bMFCs from both the avascular and vascular regions of the meniscus respond to the presence of endothelial cells with increased migration. Paracrine signaling by endothelial cells regulates the bMFCs differentially by region, but we identified ET-1 as an angiogenic factor that stimulates the migration of inner and outer cells at the microscale level and the integrative repair of inner and outer explants at the macroscale level. These findings reveal the regional interactions between the vasculature and MFCs, and suggest ET-1 as a potential new treatment for avascular meniscus injuries in order to prevent the development of osteoarthritis.

Electrical stimulation enhances cell migration and integrative repair in the meniscus.

Electrical signals have been applied towards the repair of articular tissues in the laboratory and clinical settings for over seventy years. We focus on healing of the meniscus, a tissue essential to knee function with limited innate repair potential, which has been largely unexplored in the context of electrical stimulation. Here we demonstrate for the first time that electrical stimulation enhances meniscus cell migration and integrative tissue repair. We optimize pulsatile direct current electrical stimulation parameters on cells at the micro-scale, and apply these to healing of full-thickness defects in explants at the macro-scale. We report increased expression of the adenosine A2b receptor in meniscus cells after stimulation at the micro- and macro-scale, and propose a role for A2bR in meniscus electrotransduction. Taken together, these findings advance our understanding of the effects of electrical signals and their mechanisms of action, and contribute to developing electrotherapeutic strategies for meniscus repair.