• Congenital Heart Disease COVID-19 Mortality Lines Up With General Population, But Worse Physiological Stage at Higher Risk

    COVID-19 mortality in patients with congenital heart disease (CHD) appears to be in line with the general population, despite concerns that these patients could have been at higher risk, according to a new international retrospective cohort study.

    Still, CHD patients who could potentially be most vulnerable to severe infection were identified as those with worse physiological stage, such as cyanosis and pulmonary hypertension. Susceptibility was not found to be related to the complexity of the underlying anatomic defect, however.

    These were the findings from a study of 1,044 infected patients across 58 adult CHD centers, published online Monday that will appear in the April 6 issue of the Journal of the American College of Cardiology.

    Early data on the novel coronavirus suggests that heart disease is a risk factor for mortality, although there has been uncertainty over which specific cardiovascular conditions are linked.

    CHD has a population of more than 1.5 million in the U.S. alone and has significant associated morbidity risk. In the absence of data, consensus recommendations for COVID-19 and CHD have been based on “sensible suppositions regarding at-risk subtypes,” the researchers noted, including a proposed risk stratification for COVID-19 complications and recommendations based on anatomic or physiological stage.

    The goal of the current study, led by Craig S. Broberg, MD, MCR, from the Knight Cardiovascular Institute at Oregon Health and Science University, was to more accurately inform risk stratification for CHD patients and provide guidance.

    The researchers included adults aged 18 or older (mean age 35.1±13 years; range 18 to 86 years; 51% women) with CHD and COVID-19. Of these, 907 patients (87%) had their COVID-19 infection confirmed by positive polymerase chain reaction (PCR) or antibody test, while the remainder (137 patients) had clinically suspected COVID-19. They were recruited in CHD centers across the U.S., Europe, Israel and other regions.

    Those with patent foramen ovale, mitral valve prolapse, hypertrophic cardiomyopathy, ventricular noncompaction, congenital arrhythmia, or those who had undergone heart transplantation, were excluded. However, those with single ventricle and/or Fontan physiology (118 patients, 11%), cyanosis (87 patients, 8%), and pulmonary hypertension (73 patients, 7%) were included.

    Previous atrial arrhythmia occurred in 259 patients (25.9%), and previous ventricular arrhythmia in 103 patients (9.7%), while 132 (12.6%) had been implanted with pacemakers or defibrillators, 161 (15.4%) had hypertension, 88 (8.4%) had known genetic syndromes, 65 (6.2%) diabetes, and 19 (1.8%) had cirrhosis. Additionally, 23 women were pregnant at time of infection. 

    Overall, there were 24 COVID-19-related deaths (2.3%) in the cohort. Their mean age was 40.8 ± 17.6 years (range 18 to 85 years) and all of the deaths occurred in hospitalized subjects.

    The researchers noted that COVID-19 mortality is generally “commensurate” with the general population.

    “This finding was important for both patients and providers worldwide who are now facing high numbers of cases throughout the population,” they said.

    Nevertheless, the researchers did find risk factors for CHD patients, with worse physiological stage associated with mortality (p = 0.001), “whereas anatomic complexity or defect group were not.”

    Risk factors in the CHD cohort included:

    • male sex (83%; p = 0.001)
    • previous atrial arrhythmia (46%; p = 0.019)
    • diabetes (29.2%; p = <0.001)
    • previous heart failure admission (42%; p = 0.001)
    • cyanosis (42%; p = <0.001)
    • lower resting oxygen saturation (92% ± 5 vs. 96% ± 4 in survivors; p = 0.001)
    • pulmonary hypertension (29%; p = 0.001)
    • increased subpulmonic ventricular systolic pressure as estimated by the most recent echocardiogram (mean of 54 mmHg ± 30 in those who died vs. 39 mmHg  ± 22 in survivors; p = 0.006)
    • estimated glomerular filtration rate (eGFR) <60 ml/min/m2 before infection (17% dead patients vs. 3.7% survivors; p = 0.001)
    • higher body mass index, with a mean weight of 91 kg in the group who died, versus 77.5 kg in those surviving (p = 0.016).

    Factors not associated with death included systemic ventricular systolic function (either by reported ejection fraction or semi-quantitative designation), Fontan palliation, systemic hypertension – at least moderate valve dysfunction – smoking and/or vaping history, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers before infection, previous arrhythmias, presence of a pacemaker and/or defibrillator, race/ethnicity and troponin elevation.

    Age was also not significantly associated with death despite a higher proportion of deaths in older groups.

    “Our findings were harmonious with general population studies that showed risks associated with age, male sex, diabetes, and renal insufficiency,” the researchers said. “Systematic efforts are needed to target preventive measures at patients with CHD who are at greatest risk of mortality and severe morbidity due to COVID-19.”

    Early vaccination?

    In an accompanying editorial, Elisa A. Bradley, MD, and Omer Cavus, MD, from the Department of Internal Medicine / Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center and The Dorothy M. Davis Heart and Lung Research Institute, said the sizeable retrospective study is “timely” given that practitioners have been relying thus far on small studies.

    They added that the findings could help decision-making over vaccine prioritization when it comes to adult CHD (ACHD) patients.

    “As a community of ACHD practitioners, the ‘can has been kicked’ to us, to help determine exactly which patients might be at risk for severe COVID-19,” they said.

    “Although the investigators did not set out to determine which patients with ACHD might benefit from early vaccination, this is one of the foremost questions in our minds as we aim to protect high-risk groups in an ethically responsible and data driven way.”


    Broberg CS, Kovacs AH, Sadeghi S, et al. COVID-19 in Adults With Congenital Heart Disease. J Am Coll Cardiol 2021;77:1644-55.

    Bradley EA, Cavus O. ACHD-Specific Risk Factors for Severe COVID-19. J Am Coll Cardiol 2021;77:1656-9.

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