Since the beginning of the COVID-19 pandemic, over 200 million cases with over 4 million deaths worldwide have been recorded (1). Cardiovascular disease has emerged as risk factor for increased morbidity and mortality (2–4). Heart failure in particular was shown to be associated with worse outcomes (5). Hypertrophic cardiomyopathy is the most common inherited cardiac disorder and is characterized by cardiac hypertrophy, left ventricular outflow obstruction in the majority of cases, and diastolic dysfunction (6). We were particularly concerned about outcomes of patients with hypertrophic cardiomyopathy (HCM) due to reports of ACE2 gene upregulation in septal myectomy specimens (7) — the ACE2 receptor being the entry point for the SARS-CoV-2 virus. However, the impact of preexisting HCM on the clinical course of COVID-19 is currently unknown. This study aimed to examine the outcomes of COVID-19 in patients with HCM.

To address this question, we performed a retrospective cohort study of consecutive adult patients, age ≥18 years with HCM who underwent testing for COVID-19 PCR or antibodies at NYU Langone Health, a large urban healthcare system in the New York City area with hospitals in Manhattan, Brooklyn, and Nassau County between January 1, 2020 and January 6, 2021. Individuals were included in the study if they had either positive SARS-CoV-2 PCR or antibody testing. The study was approved by the NYU Grossman School of Medicine's Institutional Review Board and informed consent was waived.

Imaging studies were reviewed by one cardiologist (D.M.) to confirm HCM diagnosis by current guidelines (6) and to identify HCM structural characteristics including distribution of left ventricular hypertrophy (LVH), systolic anterior motion (SAM), left ventricular outflow tract (LVOT) obstruction, mid-ventricular obstruction, apical aneurysm, and mitral annular calcification (MAC). Clinical information was recorded, including medical therapy, history of septal myectomy or alcohol septal ablation, comorbid conditions, COVID-19 presenting symptoms, treatment, hospitalizations, and outcomes. Statistical analysis was performed using STATA 16 (StataCorp LLC, College Station, TX) (8). Data were expressed as means and standard deviation (SD) or medians (interquartile range) for continuous variables, and proportions for categorical variables, as appropriate. The unpaired t-test or the Mann Whitney U test were used to compare continuous variables, as appropriate, and the chi-squared or Fisher's exact test for categorical variables. A p < 0.05 was considered significant.

This study is the first to examine the clinical course and outcomes of COVID-19 in patients with HCM, a significant proportion of whom had prior septal myectomy surgery and implantable cardioverter defibrillators. The hospital admission rate was high at 20%.The case fatality rate in this sample was similar to the general population (1). Both individuals who died had multiple co-morbid conditions associated with higher morbidity and mortality [2, 3.] Among hospitalized patients, the distribution of non-obstructive and obstructive HCM patients mirrors the distribution in unselected HCM cohorts (10). There were no significant differences in demographics, HCM characteristics, or COVID-19 risk factors between the hospitalized and not hospitalized group. One reason for this may be that only four patients required an ICU level of care. Moreover, a majority of the non-ICU hospitalized patients were treated with supportive care. It is likely that most were admitted for observation and monitoring of possible COVID-19 related deterioration, given that the presenting COVID-19 related symptom of the vast majority of hospitalized patients was shortness of breath. The overall low numbers of seriously ill HCM patients with COVID-19 in the sample preclude an adequate statistical analysis on risk profiles. Two patients presented with non-fatal pulmonary embolisms, a known complication of COVID-19 (11). Furthermore, even though one patient presented with acute decompensated heart failure, this is not uncommon in the setting of acute illness (12).

Prior reports have noted that there is ACE2 receptor upregulation in HCM tissue specimens (7), and ACE2 is the entry point of SARS-Cov-2. One small study examined cardiac samples from individuals with dilated cardiomyopathy, hypertrophic cardiomyopathy and healthy controls, which also supported upregulation of ACE2 in HCM tissue, but did not observe a difference in ACE2 expression between HCM patients taking ACE inhibitor medicines and those who did not (13). However, the clinical impact of this upregulation in HCM is unclear. Our study is the first to examine the clinical impact of COVID-19 on HCM patients in real world conditions. Our data suggest that HCM may not in itself contribute to worse clinical outcomes from COVID-19, above other established risk factors, such as age and obesity. Further studies in larger cohorts of patients with HCM and COVID-19 are needed.

Limitations of this study include the possibility of selection bias, underreporting and asymptomatic infections leading to a high admission rate. Furthermore, the relatively small sample size may limit the generalization of results. However, our cohort is representative of a diverse population. Last, as patients with HCM were deemed high risk for COVID-19 complications along with other types of cardiovascular disease, this awareness may have led to strict adherence with social distancing recommendations, which may have been the cause of a lower infection rate.

In conclusion, our data suggest that HCM in itself does not carry a higher risk of COVID-19 disease severity and complications. Established risk factors for severe COVID-19, such as age and obesity may be more influential.

The raw data supporting the conclusions of this article will be made available by the authors upon reasonable request.

The studies involving human participants were reviewed and approved by NYU Langone Health Institutional Review Board. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

MA: conceptualization, methodology, formal analysis, investigation, data curation, and writing—original draft. MR: investigation, writing—review, and editing. AS: investigation. MS: writing—review and editing. DM: conceptualization, methodology, data curation, supervision, and writing—original draft. All authors on this manuscript have fulfilled the criteria for authorship as set forth by the ICMJE guidelines.

This study was supported by internal funds from the Leon H. Charney Division of Cardiology, Department of Medicine, NYU Langone Health.

MA reports modest advisory board fees from MyoKardia, Inc. MR reports modest advisory board fees from MyoKardia, Inc. MS reports consulting fees from Celltrion. DM reports consulting fees from Bristol Myers Squibb. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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