key: cord-0793770-ozzkzsvd authors: Broberg, Craig S.; Kovacs, Adrienne H.; Sadeghi, Soraya; Rosenbaum, Marlon S.; Lewis, Matthew J.; Carazo, Matthew R.; Rodriguez, Fred H.; Halpern, Dan G.; Feinberg, Jodi; Galilea, Francisca Arancibia; Baraona, Fernando; Cedars, Ari M.; Ko, Jong M.; Porayette, Prashob; Maldonado, Jennifer; Sarubbi, Berardo; Fusco, Flavia; Frogoudaki, Alexandra A.; Nir, Amiram; Chaudhry, Anisa; John, Anitha S.; Karbassi, Arsha; Hoskoppal, Arvind K.; Frischhertz, Benjamin P.; Hendrickson, Benjamin; Bouma, Berto J.; Rodriguez-Monserrate, Carla P.; Broda, Christopher R.; Tobler, Daniel; Gregg, David; Martinez-Quintana, Efren; Yeung, Elizabeth; Krieger, Eric V.; Ruperti-Repilado, Francisco J.; Giannakoulas, George; Lui, George K.; Ephrem, Georges; Singh, Harsimran S.; Almeneisi, Hassan MK.; Bartlett, Heather L.; Lindsay, Ian; Grewal, Jasmine; Nicolarsen, Jeremy; Araujo, John J.; Cramer, Jonathan W.; Bouchardy, Judith; Al Najashi, Khalid; Ryan, Kristi; Alshawabkeh, Laith; Andrade, Lauren; Ladouceur, Magalie; Schwerzmann, Markus; Greutmann, Matthias; Meras, Pablo; Ferrero, Paolo; Dehghani, Payam; Tung, Poyee P.; Garcia-Orta, Rocio; Tompkins, Rose O.; Gendi, Salwa M.; Cohen, Scott; Klewer, Scott; Hascoet, Sebastien; Mohammadzadeh, Shabnam; Upadhyay, Shailendra; Fisher, Stacy D.; Cook, Stephen; Cotts, Timothy B.; Aboulhosn, Jamil A. title: COVID-19 in Adults With Congenital Heart Disease date: 2021-04-06 journal: J Am Coll Cardiol DOI: 10.1016/j.jacc.2021.02.023 sha: e40eb4b7c4b8216daec853424e5fcbf041dbf9a9 doc_id: 793770 cord_uid: ozzkzsvd BACKGROUND: Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications. OBJECTIVES: This study sought to define the impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes. METHODS: Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined. RESULTS: From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not. CONCLUSIONS: COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity. E arly data on the coronavirus disease-2019 (COVID-19) pandemic identified heart disease as a risk factor for mortality (1, 2) , but there is also uncertainty about what conditions merit inclusion under this general term (3) . Adults with congenital heart disease (CHD), numbering >1.5 million in the United States (4, 5) , are recognized as a population with significant morbidity (6) and as vulnerable to many types of cardiovascular deterioration and dysfunction. As such, they have largely been considered high risk and often adopt a highly restrictive lifestyle and employment choices accordingly. Early publications in CHD reported different risks (7, 8) but suggested worse risk in higher physiological stages (9) . In the absence of data, consensus recommendations for COVID- 19 and CHD have been made based on sensible suppositions regarding at-risk subtypes, including a proposed risk stratification for COVID-19 complications (10) . Another group outlined the potential viral impact of CHD (11) . Others have based recommendations on anatomic and/or physiological stage (12) . To more accurately inform risk stratification and provide guidance for individual patients with CHD and their providers, we established this large international study. Our overarching objectives were to determine which adults with CHD are most vulnerable to the adverse consequences of COVID-19 and to quantify the magnitude of those consequences. Specifically, we aimed to determine risk factors associated with death (primary outcome) or Statistical significance was defined as p < 0.05. Because of the exploratory nature of this study, no corrections were made for multiple tests. Fever, dry cough, and malaise were the most common presenting symptoms, occurring in approximately one-half of the cohort ( Table 1 ). There were 60 (6%) patients who had no presenting symptoms but were tested based upon a known incidental exposure or need for clearance before a procedure. Of the total Chest pain 130 (12) Diarrhea 108 (10) Congestion 107 (10) Productive cough 65 (6) None* 60 (6) Loss of taste 66 (6) Abdominal pain, nausea, vomiting 57 (5) Chills 39 (4) Other/miscellaneous 48 (5) Values are n (%). *Asymptomatic subjects tested before an elective procedure or in response to a suspected exposure to the novel coronavirus. Table 3 . Previous heart failure admission, cyanosis, diabetes, and physiological stage were all strongly predictive. Death and severe cases were distributed across the age spectrum (Figure 3 ), although as a percentage were proportionately greater in older age decades. Anatomic complexity was not associated with death, Total Table 2 . subjects with CHD who received care in New York City, there were 3 (6%) deaths (8) . Those at highest risk of death or severe infections were adults with advanced physiological stages (C and D) (9) . The present study, which was approximately 20-fold higher than these previous publications, showed a case/fatality ratio similar to that of the general population (19) . Concern for myocardial damage from these and other viruses is inherently justifiable. Historical data from previous viral epidemics confirmed adverse pulmonary and cardiovascular effects in the patient population with CHD (20) (21) (22) . Cardiac injury from these challenges might have resulted from an overwhelming immune inflammatory cytokine response, direct viral invasion of cardiomyocytes, or poor myocardial oxygenation from severe hypoxia due to lung injury (23) . These mechanisms might have plausibly complicated patients with CHD who were already prone to myocardial dysfunction, limited myocardial oxygenation, or pulmonary vascular disease. Yet. it could also be postulated that pre-conditioning in CHD paradoxically protects the myocardium to such stresses, and thus lessens the overall impact on the myocardium (12) . We found little risk from systolic dysfunction or valve dysfunction, although our assessments of these were subjective and not uniformly assessed among centers. However, we did find significant risk in those with previous heart failure admission, which was consistent with other reports of CHD and PAH (24, 25) . Our data confirmed that cyanosis and PAH, especially when combined (Eisenmenger syndrome), portends a high rate of adverse events. This was not surprising because of the reduced functional capacity, multiorgan consequences of chronic cyanosis and the limited reserve of these patients (26) (27) (28) (29) . Increased risk from COVID-19 in PAH was documented (30) . It was less clear whether cyanosis or PAH conveyed the most vulnerability; our limited experience suggested that cyanosis might be the stronger risk factor. We found that 6% of patients with CHD required ICU admission, a lower rate than that observed in non-CHD hospitalized patients (31) . 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