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Table of Contents
Year : 2021  |  Volume : 10  |  Issue : 2  |  Page : 59-61

Does myocardial injury rapidly progress in marfan syndrome following COVID-19?

1 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
2 Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran; Cardiovascular Research Center, Kerman University of Medical Sciences, Kerman, Iran

Date of Submission04-Mar-2021
Date of Acceptance27-Apr-2021
Date of Web Publication29-Jul-2021

Correspondence Address:
Dr. Marzieh Mirtajaddini
Cardiovascular Research Center, Kerman University of Medical Sciences, Kerman
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/rcm.rcm_10_21

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Marfan syndrome is a connective tissue disorder which involves various systems such as the cardiovascular system. One of the cardiovascular manifestations of Marfan syndrome is ventricular dysfunction. In this report, a case of Marfan syndrome was presented who suffered from acute heart failure due to Coronavirus disease 2019 (COVID-19). We discussed about several reasons of heart failure in this case and we suggested that COVID-19 related cardiovascular complications may be more prevalent in Marfan syndrome.

Keywords: Angiotensin-converting enzyme-2, Coronavirus disease 2019, heart failure, Marfan syndrome, myocarditis

How to cite this article:
Khajali Z, Naderi N, Mirtajaddini M, Rezaeian N. Does myocardial injury rapidly progress in marfan syndrome following COVID-19?. Res Cardiovasc Med 2021;10:59-61

How to cite this URL:
Khajali Z, Naderi N, Mirtajaddini M, Rezaeian N. Does myocardial injury rapidly progress in marfan syndrome following COVID-19?. Res Cardiovasc Med [serial online] 2021 [cited 2021 Dec 4];10:59-61. Available from: https://www.rcvmonline.com/text.asp?2021/10/2/59/322579

  Introduction Top

Marfan syndrome is a pleiotropic and autosomal dominant connective tissue disorder which is caused by mutations of gene encoding fibrillin-1. Fibrillin-1 generates glycoprotein components of elastic fibers in the extracellular matrix.[1],[2] The syndrome involves various systems such as skeletal, ocular, and cardiovascular.[3] Marfan patients may have mild-to-severe cardiovascular involvements which influence on their morbidity and mortality.[2],[4] The cardiovascular manifestations of Marfan syndrome are diverse and include mitral valve prolapse and regurgitation, ventricular dysfunction, aortic aneurysm, and dissection. In Marfan syndrome, ventricular dysfunction has several causes including volume overload due to mitral and aortic valves regurgitation, pressure overload because of aortic stiffness, and direct injury of the myocardium.[5],[6],[7]

Coronavirus disease 2019 (COVID-19) is a new infectious disease induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).[8] SARS-CoV-2 mostly involves the respiratory system; although other organs such as the cardiovascular system can also be injured.[9] Myocarditis and ventricular dysfunction due to COVID-19 are reported in several reports and studies.[10],[11],[12]

In this report, we are going to present a young man with Marfan syndrome who was infected with COVID-19 and the cardiac injury rapidly progresses despite the improvement of COVID-19 and standard heart failure therapies.

  Case Report Top

A 19-year-old man, a known case of Marfan syndrome, was admitted with fever and dyspnea in one of the COVID-19 dedicated centers at the beginning days of pandemic. He had a history of the spine and atrial septal defect closure surgeries during childhood. He did not use any medication and his last serial echocardiography, 6 months before his current admission was within normal limits.

On arrival, he had a systemic O2 saturation of 70%, a temperature of 38.5°C, and a heart rate of 110 beats/min. The laboratory tests demonstrated lymphopenia (1000/UL), high hs-CRP level, normal D-dimer, and high cardiac troponin I (CTnI) level (three times more than normal). His real-time polymerase chain reaction (RT-PCR) test for SARS-Cov-2 was positive.

Transthoracic echocardiogram showed normal left ventricle (LV) size with ejection fraction (EF) of about 40% and without regional wall motion abnormality, normal LV diastolic function, normal right ventricle (RV) size and function, no significant valvular disorder, and normal pulmonary arterial pressure (PAP). The first chest computed tomography (CT) scan demonstrated areas of ground-glass appearance in both lungs and the second chest CT, 10 days after the initial scan, showed lobar pneumonia.

According to his discharge note, he had been treated with lopinavir/ritonavir, oseltamivir, ribavirin, hydroxychloroquine, and meropenem for 10 days and discharged with a relatively good clinical condition. Five days later, he had developed progressive dyspnea and was admitted again. In the new admission, he had an O2 saturation of 83% and a temperature of 37.8°C. Laboratory tests showed leukocytosis, lymphopenia, and high CTnI level (four times more than normal). Echocardiography demonstrated mild LV enlargement and LVEF of 30%. The patient was treated as a decompensated heart failure and received a Bi-PAP therapy due to hypoxemia refractory to the nasal O2 therapy. He was discharged after 2 weeks with the following medications: furosemide, spironolactone, metoprolol succinate, and valsartan and Bi-PAP for the sleep times.

About 2 months later, he was admitted again following an episode of abdominal pain and nausea and considering the significant reduction in LV function and progressed heart failure signs and symptoms, referred to our center. In our hospital, he had an O2 saturation of 91% at room air, a blood pressure of 115/70 mmHg, a heart rate of 110 bpm, and a temperature of 37.2°C. A considerable lower extremities edema and ascites were obvious in physical examination. The electrocardiogram showed sinus tachycardia and inverted T-wave in V4-V6. The laboratory tests demonstrated high sensitivity C-reactive protein and B-type natriuretic peptide levels, normal lymphocyte count, normal CTnI, and D-dimer level. Coagulation, kidney, and liver function tests were within normal limits. COVID-19 RT-PCR test was negative for two separate specimens. Transthoracic echocardiogram showed severe LV and RV enlargement, globally hypokinetic LV with a LVEF of about 15%, severely impaired diastolic function, severe RV dysfunction, no significant valvular disorder, and PAP of 40 mmHg. The chest CT demonstrated mild fibrotic changes in both lungs and bilateral pleural effusion. Although performing cardiac magnetic resonance (CMR) was difficult due to the skeletal malformation of the patient, we tried for it and his CMR study demonstrated severely enlarged LV with LVEF of 18%, no evidence of myocardial edema, and a tiny strip of mild myocardial fibrosis [Figure 1]. The clinical and imaging findings were mostly in favor of a dilated cardiomyopathy (DCM).
Figure 1: Late gadolinium enhancement sequences in short axis (a) and two-chamber view (b) show severe dilation of the left ventricle and no significant myocardial fibrosis

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The standard guideline-directed medical therapies were continued for him, the hospital course was uneventful and heart failure signs and symptoms were controlled. In his outpatient follow-up visit, he was symptom-free, had a good clinical condition, and no need for using Bi-PAP anymore.

  Discussion Top

In this report, a case of Marfan syndrome with relatively normal cardiovascular condition that rapidly progressed into an advanced biventricular failure following a COVID-19 infection, was presented.

Ventricular dysfunction can be seen in 7%–68% of patients with Marfan syndrome which is usually considered mild.[13],[14] End-stage heart failure is rare and may have several reasons.[15] The most common cause of heart failure in patients with Marfan syndrome is valvular disorders such as mitral valve regurgitation secondary to mitral valve prolapse (MVP). Other causes of heart failure include pressure overload due to stiff aorta and intrinsic problem in the myocardium.[5],[6],[7],[16] In Marfan syndrome, mutations in encoding fibrillin-1 gene may lead to a reduction in fibrillin matrix strength and elevation of serum level of transforming growth factor-beta (TGF-β).[17] Increase in the TGF-β signaling is associated with the development of MVP, aortic dilation, and myopathy.[18] It has also been shown that in some forms of the hereditary DCM, the upregulation of TGF signaling pathways can lead to interstitial fibrosis.[19] The myocardial involvement and heart failure progression are gradual in Marfan syndrome and usually occur over several years.[20] Rapid progression to a full-blown heart failure following a COVID-19 infection may be suggestive for an acceleration in pathophysiologic mechanisms of myocardial dysfunction by SARS-Cov-2 in this patient. Some pandemic reports demonstrate the development of the Marfan-related complications following COVID-19 infection in patients with near-normal cardiovascular condition despite Marfan syndrome.[10],[21],[22] The activation of angiotensin II receptor type 1 and production of TGF-β have been suggested as pathophysiologic mechanism for aortic aneurysm in patients with Marfan syndrome.[17] It has also been shown that angiotensin-converting enzyme-2 (ACE-2) upregulates in patients with bicuspid aortic valve and dilated aorta.[23]

COVID-19 can injure the myocardium through autoimmune mechanisms and direct viral involvement.[24],[25] SARS-CoV-2 needs to bind ACE-2 to enter host cells. ACE-2 metabolizes angiotensin I to angiotensin-(1–9) and angiotensin II to angiotensin-(1–7). In other words, ACE-2 regulates reninangiotensin system[23] [Figure 2]. Therefore, upregulation of ACE-2, which is required for the entrance of SARS-CoV-2 to host cells, could be considered as an explanation for acceleration in the development of myocardial dysfunction in our Marfan patient.
Figure 2: Reninangiotensin system. Renin converts angiotensinogen to angiotensin I. Angiotensin I is converted to angiotensin II by ACE or to angiotensin-(1–9) by ACE-2. Another role of ACE-2 is conversion of angiotensin II to angiotensin-(1–7). ATR-1 and ATR-2 are receptors of angiotensin II. ACE: angiotensin-converting enzyme, ATR: angiotensin II receptor

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However, although using cardiotoxic antiviral therapies can also be considered as one of the causes of myocardial injury in this patient, further investigation is needed to shed light on our suggestion and show whether the COVID-19 related cardiovascular complications are more prevalent in Marfan syndrome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Ethical clearance

Ethical clearance: This study was approved by the ethical committee of Rajaie Cardiovascular Medical and Research Center.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1], [Figure 2]


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