Coronavirus Disease 2019 (COVID-19) disease has been associated with different cardiovascular sequelae, which significantly impact the morbidity and mortality of these patients.1 Recent investigations have explored the association between COVID-19 infection and different types of cardiovascular disease, such as myocardial injuries, acute coronary syndromes (ACS), heart failure, arrhythmias and pulmonary embolism.2,3 However, no data have been presented regarding the prevalence and related clinical consequences of congenital atrial septal defects, and specifically patent foramen ovale (PFO).
From a pathophysiological point of view, PFO could be implicated in different aspects of this novel viral infection. As reported by previous epidemiological studies, isolated atrial septal defects (ASDs) represent about 7% of all cardiac anomalies, while PFO represents an endemic variant in the normal population with a prevalence ranging between 25 and 27%.4 As a consequence, many infected patients may have PFO, and in most cases, this congenital disease could have been undiagnosed or not been considered in the patient's management. Furthermore, to date, no evidenced-based recommendations for the management of these individuals have yet been provided.
COVID-induced pulmonary infection, associated with increased pulmonary arterial pressure, coagulation activation and supine or prone position during mechanical ventilation could represent additional risk factors for paradoxical embolism due to increased right atrial pressure. As a matter of a fact, acute cor pulmonale (ACP) and PFO are common in patients under protective ventilation for acute respiratory distress syndrome (ARDS)5; however, their prognostic role has not yet been evaluated in COVID-19 patients admitted to the ICU. Moreover, PFO may be responsible for refractory hypoxemia or paradoxical embolism due to the right-to-left atrial shunt in these individuals. Although PFO has resulted as not impacting the mortality rate in ARDS patients with ACP from any cause,6 these data remain missing in the special subset of COVID-19 patients. Furthermore, prone ventilation, which is widely used to improve hypoxemia in COVID-19 ARDS patients, previous analyses have observed that when PFO is present, pronation could improve or even normalize the atrial shunt present in the supine position.7
It appears clear that there is an urgent need for data and specific recommendations for COVID-19 patients, also considering that many patients with a latent PFO are generally young and healthy before the viral infection.
Some questions arise spontaneously. Should we manage COVID-19 asymptomatic or symptomatic patients with PFO in the same manner? Outpatients and hospitalized? Should these patients benefit from a cardiological follow-up after the resolution of the viral disease to evaluate potential modification on the shunt severity or directly connected an anatomical modification (as left atrial enlargement), which may predispose them to atrial fibrillation?
In the absence of objective data on this subgroup of individuals, those having a concomitant PFO should follow the normal diagnostic path and treatment options. Whether these individuals may have a different clinical course in both the short- and/or long-term periods remains unknown. In this regard, future analyses may be helpful to answer this question.
In the meantime, how should we manage COVID-19 patients with previously known or unknown PFO? previously hospitalized or more severely ill patients with COVID-19 represent a higher-risk cohort. For these individuals, after a minimum of 2 weeks’ rest after symptom resolution and negative nasopharyngeal swab for SARS-CoV-2, a clinical and transthoracic echocardiographic (TTE) evaluation may be useful, followed by a graded resumption of normal physical activity. Further adjunctive testing with transesophageal echocardiography (TEE), brain MRI, transcranial doppler (TCD) or ambulatory rhythm monitoring should be based on the clinical course and initial testing.
Conversely, for asymptomatic patients or those with mild or moderate symptoms, in the absence of cardiological symptoms and no objective evidence of cardiac involvement, after 2 weeks of rest, the resumption for the normal follow-up of PFO would be reasonable. Conversely, for recovered patients with cardiovascular symptoms during the disease, also if not hospitalized, a clinical cardiovascular evaluation in combination with cardiac biomarkers and imaging should be considered always after 2 weeks from symptom resolution.
The suggested approach provided in the current viewpoint is intended to assist clinicians in the management of PFO patients who experience COVID-19 infection, as no other recommendations are available. Considering the relevant clinical uncertainty on this matter, our suggested approach appears to be conservative and subject to change when the prevalence and clinical significance of PFO patents with COVID-19 will be better defined. Considering the prevalence of PFO in the general population, we cannot deny that specific recommendations, based on robust data are needed, to adequately evaluate these patients and avoid further clinical complications due to the cited cardiac congenital disease. In this regard, a registry of patients with PFO experiencing COVID-19 infection would be useful to assess if these patients may have a different clinical course of the disease or experience different long-term sequalae.
Rigatelli G. and Zuin M. equally contributed to the manuscript.
The study received no founding by any third party.
Conflicts of interest
There are no conflicts of interest.
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