Covid-19 pandemic in ACHD patients

Comments on the background :

Europe has been suffering the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since March 2021. As of June, 2020, the coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 infection had affected over 6.5 million people and had caused more than 380 000 casualties worldwide. SARS-CoV-2 is thought to interact with the cardiovascular system on multiple levels, increasing COVID-19-related morbidity and mortality among patients with acquired cardiovascular disease, such as hypertension, coronary artery disease, cerebrovascular disease or diabetes. Moreover, direct cardiac injury and heart failure may be precipitated by the acute illness among patients with pre-existing cardiovascular disease who suffer from COVID-19. However, the risk for poor outcomes in the current pandemic among adult congenital heart disease (ACHD) patients was, until now, unknown. The study published by Schwerzmann et al. aimed to address this issue.

Comments on the methodology :

This was a multicenter, international, prospective cohort study. Twenty-five ACHD centers among nine European countries participated in the study. From March to June 2020, ACHD patients with confirmed or strongly suspected COVID-19 presenting to or contacting the participating centers were included. A complicated course of disease was defined as hospitalization for COVID-19 requiring non-invasive or invasive ventilation and/or inotropic support, extracorporeal membrane oxygenation or death. In those cases, further detailed information on patient characteristics and disease course was obtained from the treating physicians of the corresponding center. The causality between COVID-19 and death was then assessed by means of meticulous chart review of the fatal cases.

Comments on the results:

A total of 105 patients were included (74% with confirmed and 27% with suspected diagnosis). Seventy-three (70%) patients did not require hospitalization. A complicated course of disease was seen in 13 (12%) patients, five of whom (5%) died. The majority (85%) of the patients recovered without any additional health problems.
When comparing patient characteristics stratified according to the course of the disease, patients with a complicated clinical course were significantly older (47 vs. 37 years), had more often a body mass index (BMI) >25kg/m2 (77% vs. 32%) and had more often ≥2comorbidities than those with a mild clinical course (54% vs. 14%). Cardiac defect complexity, gender and main defect-related residual problems were comparable between groups.

Among the deceased patients, SARS-CoV-2 infection (ARDS related to COVID-19) was considered the main cause of death for four out of five patients. Of the 7 patients with cyanotic heart disease or Eisenmenger syndrome, 4 had a complicated course and 2 died. Of the 5 patients with a Fontan palliation, only one had a complicated disease course.

In univariable analysis, age, overweight and having ≥ 2 comorbidities were predictive of a complicated course of disease. For the different heart defects, the highest risk for a complicated course of disease was observed among patients with unrepaired cyanotic heart defects, including those with Eisenmenger syndrome. In multivariable analysis, ≥2comorbidities (odd ratio [95% confidence interval]: 6.7 [1.2 to 35.8], 0.027), BMI ≥ 25 kg/m2(odd ratio [95% confidence interval]: 16.4 [3.2 to 83.4], 0.001) and cyanotic heart disease (including Eisenmenger syndrome) (odd ratio [95% confidence interval]: 60.0 [7.6 to 474.0], >0.001) were independently associated with poor outcome.

Comments on the discussion:

This is the first multicenter, international, prospective cohort study assessing the risk for poor outcomes among ACHD patients in case of COVID-19. As in the general population, age and multiple comorbidities were strongly associated with complicated course of disease. When regarding specific congenital cardiac defects, only patients with unrepaired cyanotic heart disease or severe pulmonary hypertension with Eisenmenger syndrome were seen to be at a very high risk for poor outcomes in case of COVID-19. As discussed in the manuscript, these patients often present chronic hypoxaemia as a result ofthe combination of right-to-left shunt and marked abnormalities in pulmonary tissue and vascularization, which might put them at risk for respiratory decompensation in case of severe COVID-19. Furthermore, the increased prothrombotic risk among patients with cyanotic heart disease may further contribute to their dismal outcomes.

For younger and otherwise healthy ACHD patients with normal weight, the complexity of the underlying cardiac defect (if other than unrepaired cyanotic heart disease, including Eisenmenger syndrome) did not appear to be prognostically relevant in case of COVID-19. With a mean age of 38 years, the ACHD population in the study was comparable in terms of age with previous reports based on national registries. As age has emerged as the most relevant general risk factor for COVID-19-related mortality, this might explain why even patients after Fontan palliation (mostly young adults) were at lower risk for complications as opposed to one might have anticipated intuitively. Furthermore, and in line with previous reports, overweight and obesity seemed to play a predictive role for young patients without comorbidities.

Key messages:

1. One in eight ACHD patients suffered from a complicated COVID-19 course.
2. COVID-19 outcome in ACHD is not related to cardiac complexity.
3. Independent predictors for a complicated disease course in ACHD are:

1. 1. Cyanotic heart disease / Eisenmenger syndrome
   2. Overweight and obesity (BMI ≥ 25 kg/m2)
   3. Comorbidities (two or more)