The United States is in an acceleration phase of the COVID-19 pandemic. Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2, highlighting urgency around identifying effective therapies. Objective: The purpose of this study was to evaluate the role of hydroxychloroquine therapy alone and in combination with azithromycin in hospitalized patients positive for COVID-19. Design: Multi-center retrospective observational study. Setting: The Henry Ford Health System (HFHS) in Southeast Michigan: large six hospital integrated health system; the largest of hospitals is an 802-bed quaternary academic teaching hospital in urban Detroit, Michigan. Participants: Consecutive patients hospitalized with a COVID-related admission in the health system from March 10, 2020 to May 2, 2020 were included. Only the first admission was included for patients with multiple admissions. All patients evaluated were 18 years of age and older and were treated as inpatients for at least 48 h unless expired within 24 h. Exposure: Receipt of hydroxychloroquine alone, hydroxychloroquine in combination with azithromycin, azithromycin alone, or neither. Main outcome: The primary outcome was in-hospital mortality. Results: Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4-10 days), median age was 64 years (IQR:53-76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3-53). Overall in-hospital mortality was 18.1% (95% CI:16.6%-19.7%); by treatment: hydroxychloroquine + azithromycin, 157/783 (20.1% [95% CI: 17.3%-23.0%]), hydroxychloroquine alone, 162/1202 (13.5% [95% CI: 11.6%-15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%-30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%-31.0%]). Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes. From Cox regression modeling, predictors of mortality were age>65 years (HR:2.6 [95% CI:1.9-3.3]), white race (HR:1.7 [95% CI:1.4-2.1]), CKD (HR:1.7 [95%CI:1.4-2.1]), reduced O2 saturation level on admission (HR:1.5 [95%CI:1.1-2.1]), and ventilator use during admission (HR: 2.2 [95%CI:1.4-3.3]). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine + azithromycin 71% compared to neither treatment (p < 0.001). Conclusions and relevance: In this multi-hospital assessment, when controlling for COVID-19 risk factors, treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality. Prospective trials are needed to examine this impact.

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TMVR with balloon-expandable aortic valves in extreme surgical risk patients with severe MAC is feasible but associated with high 30-day and 1-year mortality. Most patients who survive the 30-day post-procedural period are alive at 1 year and have sustained improvement of symptoms and transcatheter valve performance. The role of TMVR in patients with MAC requires further evaluation in clinical trials.

Background: Transcatheter mitral valve replacement using aortic transcatheter heart valves has recently become an alternative for patients with degenerated mitral bioprostheses, failed surgical repairs with annuloplasty rings or severe mitral annular calcification who are poor surgical candidates. Outcomes of these procedures are collected in the Society of Thoracic Surgeons/American College of Cardiology/Transcatheter Valve Therapy Registry. A comprehensive analysis of mitral valve-in-valve (MViV), mitral valve-in-ring (MViR), and valve-in-mitral annular calcification (ViMAC) outcomes has not been performed. We sought to evaluate short-term outcomes of early experience with MViV, MViR, and ViMAC in the United States. Methods: Retrospective analysis of data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Results: Nine hundred three high-risk patients (median Society of Thoracic Surgeons score 10%) underwent MViV (n=680), MViR (n=123), or ViMAC (n=100) between March 2013 and June 2017 at 172 hospitals. Median age was 75 years, 59.2% female. Technical and procedural success were higher in MViV. Left ventricular outflow tract obstruction occurred more frequently with ViMAC (ViMAC=10%, MViR=4.9%, MViV=0.7%; P <0.001). In-hospital mortality (MViV=6.3%, MViR=9%, ViMAC=18%; P =0.004) and 30-day mortality (MViV=8.1%, MViR=11.5%, ViMAC=21.8%; P =0.003) were higher in ViMAC. At 30-day follow-up, median mean mitral valve gradient was 7 mm Hg, most patients (96.7%) had mitral regurgitation grade ≤1 (+) and were in New York Heart Association class I to II (81.7%). Conclusions: MViV using aortic balloon-expandable transcatheter heart valves is associated with a low complication rate, a 30-day mortality lower than predicted by the Society of Thoracic Surgeons score, and superior short-term outcomes than MViR and ViMAC. At 30 days, patients in all groups experienced improvement of symptoms, and valve performance remained stable. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02245763.

Approximately 9 months of the severe acute respiratory syndrome coronavius-2 (SARS-CoV-2 [COVID-19]) spreading across the globe has led to widespread COVID-19 acute hospitalizations and death. The rapidity and highly communicable nature of the SARS-CoV-2 outbreak has hampered the design and execution of definitive randomized, controlled trials of therapy outside of the clinic or hospital. In the absence of clinical trial results, physicians must use what has been learned about the pathophysiology of SARS-CoV-2 infection in determining early outpatient treatment of the illness with the aim of preventing hospitalization or death. This article outlines key pathophysiological principles that relate to the patient with early infection treated at home. Therapeutic approaches based on these principles include 1) reduction of reinoculation, 2) combination antiviral therapy, 3) immunomodulation, 4) antiplatelet/antithrombotic therapy, and 5) administration of oxygen, monitoring, and telemedicine. Future randomized trials testing the principles and agents discussed will undoubtedly refine and clarify their individual roles; however, we emphasize the immediate need for management guidance in the setting of widespread hospital resource consumption, morbidity, and mortality.