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Most adults with congenital heart disease (CHD) do not face an increased risk of COVID-19 mortality, although certain subgroups remain at high risk, an international study suggests.
“When the COVID pandemic started and the early data was coming out of China and Italy showing that there was a very concerningly high morbidity and mortality for those that had cardiovascular disease, we didn’t know how to interpret that when it came to patients with congenital heart disease,” explained senior author Jamil Aboulhosn, MD, Ahmanson/UCLA Adult Congenital Heart Center, Los Angeles, California, in an interview.
Adults with CHD are typically younger than those with heart disease but have been largely lumped together and considered high risk. An early study from Italy, however, reported a mild clinical course and no deaths among 76 CHD patients, whereas a second study reported 3 deaths (6%) among 53 PCR-positive patients from New York City and suggested worse risk with an underlying genetic condition and advanced physiological stage.
CHD physicians had been sharing their experiences on weekly Zoom meetings since early March 2020 and quickly formed a global registry with the help of the Adult Congenital Heart Association and International Society for Adult Congenital Heart Disease, he noted. It now includes 58 CHD centers from North America, Europe, and the Middle East contributing data on 1044 infected adults. Their mean age was 35 years (range, 18 to 86 years), 51% were women, and 87% had laboratory confirmation of COVID-19.
Fever, dry cough, and malaise were the most common presenting symptoms. Sixty patients had no presenting symptoms but were tested based on a known exposure or an upcoming procedure. In all, 179 patients (17%) were hospitalized and 67 patients (6.4%) required ICU care, 36 of whom were intubated.
As reported in the Journal of the American College of Cardiology, there were 24 adjudicated COVID-19 related deaths, resulting in a case/fatality rate of 2.3% (95% CI, 1.4% – 3.2%), which is “harmonious” with a reported cumulative world fatality rate of 2.2%.
Mortality rates and/or severe course varied by CHD diagnosis and were highest in patients with Eisenmenger physiology (13%), cyanosis (12%), and pulmonary arterial hypertension (10%).
Patients with physiological stage C and D, based on the 2018 American College of Cardiology/American Heart Association Adult CHD guidelines, had a higher risk of death than those with stage A and B disease (3.9% and 7.9% vs 0% and 1.1%). There were no deaths in patients with simple lesions and physiological stage A and/or B disease.
Significant univariate predictors of COVID-19-related death were cyanosis, previous heart failure admission, diabetes, physiological stage C or D, supplemental oxygen use, pulmonary hypertension, male sex, estimated glomerular filtration rate less than 60 ml/min/1.73 m2, body mass index, and age. Variables significantly predicting the secondary outcome of severe COVID-19 were identical.
On binary regression, advanced physiological stage C or D was an independent predictor of death (odds ratio [OR], 6.6; 95% CI, 2.2 – 19.4) but complex anatomy was not (OR, 0.7; 95% CI, 0.3 – 1.9).
“For many forms of congenital heart disease, this is good news,” Aboulhosn said. “What it tells us is that adverse events, whether it be death or severe cases of COVID requiring ICU admission or intubation, are not driven by anatomic complexity of congenital heart disease. So you can have a really complex heart problem and that, in itself, doesn’t actually portend the higher risk.”
This includes, for example, patients with a Fontan single ventricle, “who don’t have a pump to the lungs basically and are so dependent on normal lung mechanics that we thought a respiratory illness like COVID would be deadly for them,” he said.
A European Society of Cardiology position paper last summer highlighted Fontan single ventricle patients as being high risk and consideration of admission, even if they were asymptomatic, observed Aboulhosn, who co-authored the paper with his current co-principal investigators Craig Broberg, MD, and Adrienne Kovacs, PhD, both with Oregon Health & Science University, Portland.
“We didn’t have much data, so we erred on the side of being really conservative and careful,” Aboulhosn said. “So I was somewhat surprised that stable Fontan patients did well.”
Elisa A. Bradley, MD, and Omer Cavus, MD, both with The Ohio State University Wexner Medical Center, Columbus, say in a related editorial that one of the study’s most important findings is that anatomic complexity in and of itself does not portend worse survival. However, “it must be acknowledged that historical advances in care likely affected the current age-based heterogeneity in this group and perhaps confounded this outcome.”
A critical part of the story that unfolded, they suggest, is that advanced physiologic stages had the highest risk of death. Cyanosis, resting hypoxia, atrial arrhythmia, renal dysfunction, and heart failure admissions are routinely assessed in assigning physiologic stage, and “therefore, begin to identify patients with [adult] ACHD who are at elevated risk for severe COVID-19, perhaps strictly due to their underlying CHD (so-called ACHD-specific risk factors). This is increasingly important as vaccination strategies evolve and priorities to protect those at high risk begin to emerge,” the editorialists write.
Aboulhosn said it would be fair to prioritize vaccination in patients with Eisenmenger syndrome, cyanotic heart disease, pulmonary hypertension, congestive heart failure, and arrhythmias, but that the data also highlight the need to address the well-known non–CHD-specific risk factors of diabetes, hypertension, and obesity.
“Those things really drive events and we should do whatever we can to make patients aware they need to modify these risk factors,” he said. “So, diet and exercise are really important in our population, as they are in everybody.”
The team is planning several substudies, including a deeper dive into the effect of race/ethnicity on outcomes, which trended worse among Black and Hispanic patients in the US population; and longer follow-up of the entire cohort. “We don’t want to assume that these short-term results are applicable long-term, so it’s imperative that we try to look at the longer-term implications and the burden of COVID longer-term on this population.”
The study authors and Cavus have disclosed no relevant financial relationships. Br adley is supported by a grant from the National Institutes of Health.
J Am Coll Cardiol. Published online March 28, 2021. Full text, Editorial
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