Sudden cardiac death in a case of Crohn's disease with COVID-19: A case report

Neeraj Kumar, Subhajit Ghosh, Abhyuday Kumar, Sanjeev Kumar, Prem Kumar

Departments of 1Trauma & Emergency, 2Anaesthesiology, 3CTVS, and 4Radiology, All India Institute of Medical Sciences, Patna, India

ABSTRACT

KEYWORDS: COVID-19; Sudden cardiac death; Chron’s disease

1. Introduction

Inflammatory bowel diseases (IBD) like Crohn’s disease (CD)and ulcerative colitis (UC) are chronic inflammatory diseases of the intestines that may present with many venous vascular comorbidities such as deep venous thrombosis or portal vein thrombosis. These chronic systemic inflammations may lead to endothelial dysfunction and platelet aggregation and serve as a precursor to the development of atherosclerosis and coronary artery disease (CAD)[1]. As per the literature, SARS-CoV-2 can lead to unfavorable outcomes in elderly patients with comorbidities, for example, cardiovascular dysfunction[2]. Sudden cardiac death (SCD) has emerged as one of the most challenging concerns amid the COVID-19 pandemic[3].Although the direct causal association between SCD and COVID-19 remains unproven, but some published data may suggest a plausible association.

2. Case report

Departmental Ethics Committee, All India Institute of Medical Sciences Patna, Bihar, India, approved the reporting of this case, and the informed consent was obtained from the patient’s relatives.

A 75-year COVID-19 patient was admitted to our intensive care unit because of the shortness of breath for the last 2 days. He was a known case of Crohn’s disease and hypothyroidism and was on tablet mesalamine 1 g and tablet levothyroxine 25 μg daily. He had stable vitals and maintained saturation on the non-rebreathing mask with a reservoir bag. As per our institutional COVID-19 management protocol, remdesivir, antibiotics, steroids, low molecular weight heparin, tablet zinc, tablet vitamin C, and other supportive treatment were started. Because of increased inflammatory markers, itolizumab was given to the patient on the 2nd day. Artery blood gas was within acceptable limits with a PaO2/FiO2ratio of 121. The normal arterial blood gases were PH of 7.36, PaO2of 78 mmHg, PaCO2of 33 mmHg, HCO3of 21 mmol/L. The chest X-Ray finding was typically suggestive of COVID-19 with patchy areas of ground-glass opacity in the middle and lower zones in the right and middle zone in the left,with normal costophrenic angle (Figure 1). On the 3rd day, oxygen requirement was further increased, and oxygen saturation dropped below 90% with a respiratory rate of 38-40 rates per minute. He was put on a high-flow nasal oxygenation machine with a FiO2of 0.8 and with a flow rate of 5 L/ min. On the 4th day, the patient’s condition was improved, and oxygen saturation was maintained between 95%-97% on transnasal high flow oxygen therapy with FiO2of 0.6 and at a flow rate of 5 L/min. Routine investigations on days three and four were almost normal except for the inflammatory markers which were raised (Table 1). A day-by-day clinical progression is shown in Table 2.

Figure 1. The chest X-ray (AP-view) of a 75-year-old man with COVID-19.White arrows show extensive opacities in bilateral lungs.

Table 1. Day wise laboratory and inflammatory markers values.

Table 2. Clinical course of the patient during ICU stay.

On the 5th day, the patient complained of sudden chest pain with respiratory distress. A 12-lead electrocardiograph was taken which showed no significant ST-segment change, and trop T was negative. 2-D bedside echocardiography did not show any evidence of pulmonary embolism with normal chamber size and normal left ventricular ejection fraction. But the patient immediately went into bradycardia and followed by asystole. Cardiopulmonary resuscitation was initiated promptly per Advanced Cardiac Life Support protocol; all reversible causes, including tension pneumothorax, cardiac tamponade, and electrolyte/metabolic disturbances were ruled out. However, the patient was not revived and was declared dead.

3. Discussion

The mechanism of SCD in COVID-19 can be multifactorial. However,it remains difficult to ascertain the most common mechanism involved due to a lack of data. Both tachyarrhythmia and bradyarrhythmia have been reported in COVID-19. Fatal arrhythmias in COVID-19 may also result from hypoxia, cardiac dysfunction, severe systemic inflammatory state, electrolyte derangements, intravascular volume imbalances,and drug side effects[4]. Guo et al.[5] suggested life-threatening arrhythmias have been variably reported from 10% to 16% of patients hospitalized for severe COVID-19, more commonly in the setting of elevated troponin indicating myocardial injury. Some of the proposed causes of sudden cardiac death in COVID-19 are acute myocarditis(stress-induced cardiomyopathy), acute coronary syndrome, hypoxia,pulmonary thromboembolism, coronary thrombosis, stroke, cardiac tamponade, electrolyte imbalance, underlying channelopathies, and drug-induced arrhythmias. Direct arrhythmogenesis by COVID-19 cytokines has a direct electrophysiological effect on the myocardium,IL-6, tumor necrosis factor-α, and IL-1 can prolong ventricular action potential duration. These cytokines may induce cardiac sympathetic system hyperactivation, which can trigger life-threatening arrhythmic events in patients with long QT[6]. In our case, QT/QTc was 348/452 ms, so the possibility of any QTc prolongation was ruled out. The deep vein thrombosis and pulmonary embolism was also ruled out because of normal echocardiography findings with normal d-dimer and prothrombin time.

Studies have found that IBDs are associated with an increased risk of CAD, cerebrovascular diseases, and peripheral arterial diseases[7]. High levels of circulating cytokines and C-reactive protein are characteristic of IBD, and it is therefore expected to contribute to endothelial dysfunction and atherogenesis. The possible causes of increased cardiovascular events in patients with IBD can be raised inflammatory markers, endothelial dysfunction, hypercoagulability, and release of endotoxins and lipoproteins[7].

The drug mesalazine (5-ASA) is efficacious in active Crohn’s and ulcerative colitis and are generally regarded as a safe and well-tolerated medication[8]. Cardiac hypersensitivity to 5-ASA therapy leading to myocarditis has been reported in some case studies, and the first reported death from myocarditis associated with mesalazine use was in 1990[9]. In documented literature, hypersensitivity appears to be an idiosyncratic reaction rather than dose-dependent due to its occurrence in patients on very low amounts of mesalazine such as 0.5 g a day[10].

In our case, sudden cardiac death was possibly due to cardiovascular complications caused by cytokine storm syndrome (raised inflammatory markers) and idiosyncratic reaction with mesalazine use. Our patient had a high-risk factor for cardiovascular complications due to COVID-19, IBD, and mesalazine. Mesalazine is very safe and efficacious in the management of inflammatory bowel disease but we should be aware of its serious and potentially life-threatening complications that may occur especially if it has to be used in COVID-19 infected patients.

To sum up, immunosuppressants in hospitalized COVID-19 patients should be continued with caution. There should be a baseline electrocardiograph to check QTc interval and look for other risk markers of tachy or bradyarrhythmias. Metabolic parameters including electrolytes, fluid volume, and acidosis should be actively sought and treated at the earliest possible, especially in the ICU. Every patient deserves risk stratification based on his/her clinical background with complete available information.

Conflict of interest statement

圖3無擋板結構，中心區域因氣流進入時無阻擋，而以較大流速直接沖入腔室，從而產生流場擾動，且中心區域孔密度較高，邊緣孔密度小，邊緣流線較稀疏；

The authors report no conflict of interest.

Funding

This study received no extramural founding.

Authors’ contributions

N.K.: Manuscript writing, proofreading, and final drafting; S.G.:Case management; manuscript writing A.K.: Final drafting; S.K.:Proofreading; P.K.: Proofreading.