COVID-19 (SARS-CoV-2) and the Heart - An Ominous Association.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cardiovascular manifestations of COVID-19 are diverse and complex and include acute coronary syndrome, myocarditis masquerading as ST-segment elevation myocardial infarction, pericarditis and pericardial effusion. We present 2 cases of COVID-19 infection with myocardial involvement with distinct mechanistic pathways and outcomes. Important decision strategies such as the timing of cardiac catheterization (when indicated) and requirement of early hemodynamic support in critically ill patients are discussed.

Case 1

A 48-year-old man with history of obesity, prediabetes, and obstructive sleep apnea dependent on continuous positive airway pressure developed progressive chest pain while playing video games at home. A week before, he experienced a viral prodrome – fever, chills, myalgias, diarrhea, non-productive cough, and mild shortness of breath. He sought care at an urgent care facility, where he received treatment with ibuprofen and oral steroid taper, which improved his symptoms. The patient recalled having contact with another person with similar symptoms. Upon onset of chest pain, he presented to an outside hospital, where workup showed elevated troponin-I, prompting transfer to our facility. At admission, his vital signs were normal, and a physical examination was unremarkable except for jugular venous distention. A 12‑lead electrocardiogram revealed sinus rhythm with occasional premature ventricular contractions and inferoposterior infarct (age undetermined) without ST-segment elevation (Fig. 1 ). His chest X-ray was unremarkable. His initial troponin-I level was 116 ng/mL (peak at 196 ng/mL, reference range (RR): <0.045 ng/mL). Dual antiplatelet therapy (325 mg aspirin and 600 mg clopidogrel loading dose) and therapeutic intravenous unfractionated heparin were initiated. Other laboratory data showed an elevated white blood cell count (WBC, 23.4 k/μL; RR 4–11 k/μL), platelet count (476 k/μL; RR 150–400 k/μL), erythrocyte sedimentation rate (ESR, 29 mm/h; RR: 0–15 mm/h), high-sensitivity C-reactive protein (hsCRP, 8.58 mg/L; RR <0.5 mg/dL), ferritin (559 ng/mL; RR 11–307 ng/mL), and D-dimer (0.73 μg/mL; RR <0.68 μg/mL) levels. A nasopharyngeal swab was positive for COVID-19 real-time reverse transcriptase–polymerase chain reaction (rRT-PCR) assay. The patient was treated initially with guideline-directed medical therapy (GDMT) pending COVID-19 test results. On day 4, coronary angiography showed mild diffuse atherosclerotic coronary artery disease in all major epicardial vessels and Thrombolysis in Myocardial Infarction-2 flow in the right coronary artery without focal stenosis or filling defects (Fig. 2, panels A–C). Left ventricular end-diastolic pressure was 45 mmHg. Transthoracic echocardiography showed left ventricular systolic dysfunction (ejection fraction [EF] = 45%) and mild hypokinesis of the inferior and inferolateral walls. Aggressive intravenous diuresis and GDMT for coronary artery disease and congestive heart failure were initiated, and after optimization of medical therapy, he was discharged on day 7 with a close outpatient follow-up.

Fig. 1

12‑Lead electrocardiogram (ECG), case 1.

Fig. 2

(Panels A, B, and C): Coronary angiography. CIRC = Circumflex, LAD = Left anterior descending, LMCA = Left main coronary artery, RCA = Right coronary artery, RPDA = Right posterior descending, RPLB = Right posterolateral branch.

Case 2

A 34-year-old woman with no known medical history presented to the emergency room with chest heaviness, generalized weakness, subjective fevers/chills and body aches for 3 days. Vital signs disclosed temperature 37.2 °C, heart rate 141 bpm, respiratory rate 24/min, blood pressure 111/67 mmHg, and oxygen saturation 100% on ambient air. A 12‑lead electrocardiogram showed sinus tachycardia with low-amplitude QRS in the precordial and limb leads, and poor R-wave progression in the anterior leads (Fig. 3 ). Initial troponin-I was elevated at 0.55 ng/mL. Chest radiography revealed a normal cardiac silhouette and no evidence of pulmonary infiltrate or pleural effusions. A nasopharyngeal swab was positive for COVID-19 rRT-PCR assay. A point-of-care echocardiogram showed severe left ventricular systolic dysfunction (EF = 25%), a large pericardial effusion with signs of pericardial tamponade (Fig. 4 ). Successful pericardiocentesis was performed via subxiphoid approach with drainage of 300 mL of serous pericardial fluid, and the drain was left in place. Post-pericardiocentesis, the patient's hemodynamic status did not improve, and she developed cardiogenic shock refractory to escalating doses of inotropic/vasopressors (dobutamine, norepinephrine). Mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was initiated the same day. Laboratory data showed normal inflammatory markers (hsCRP, ESR, WBC), normal renal and liver function studies, elevated lactate (4.8 mmol/L), N-Terminal pro–B-type natriuretic peptide of 3917 pg/mL (RR: <125 pg/mL) and troponin-I peak of 2.7 ng/mL. Pericardial fluid analysis yielded monocyte predominance suggestive of viral etiology; however, the PCR of the pericardial fluid was negative for COVID-19, and the cytology was negative for malignancy. The patient was started on high-dose intravenous methylprednisone for 3 days. Over the next 48 to 72 h, the patient's hemodynamic status improved; the VA-ECMO was decannulated, and the pericardial drain was removed after 3 days. Her lactate levels normalized, and there was no evidence of end-organ damage. Echocardiograms showed recovered left ventricular systolic function, trace pericardial effusion, and no valvular abnormalities. She was transitioned to oral prednisone taper and colchicine and discharged after 9 days.

Fig. 3

ECG, case 2.

Fig. 4

Sonosite point-of-care echocardiogram demonstrating a large anterior pericardial effusion (yellow star) with end-diastolic compression of the right ventricle.

Discussion

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initially identified in Wuhan, China, in December 2019, the disease has spread rapidly worldwide, resulting in an ongoing pandemic and a public health crisis. Cardiovascular manifestations of COVID-19 can be diverse and complex, including myocardial injury, infarction, myocarditis simulating ST-segment elevation myocardial infarction, non-ischemic cardiomyopathy, coronary vasospasm, pericarditis, or stress (takotsubo) cardiomyopathy [1]. Elevated cardiac biomarkers portend an unfavorable prognosis [1]. The initial experience from Wuhan demonstrated that approximately 27.8% (52/187) of patients with COVID-19 exhibited myocardial injury as demonstrated by elevated cardiac troponin-T levels [2]. Myocardial injury was associated with worse outcomes of COVID-19, whereas the prognosis of patients with underlying cardiovascular disease but without myocardial injury was comparatively favorable. Underlying cardiovascular disease and associated risk factors such as hypertension, coronary heart disease, and cardiomyopathy put patients at higher risk of developing myocardial injury during the course of their COVID-19 infection. In another study of 416 hospitalized patients from Wuhan, 82 patients (19.7%) with myocardial injury were compared to 334 patients (80.3%) without myocardial injury [3]. Patients with cardiac injury were noted to develop more complications, including acute respiratory distress syndrome, acute kidney injury, electrolyte disturbances, and coagulation disorders. Furthermore, the inpatient mortality was higher in patients with myocardial injury. The exact mechanism for development of myocardial injury in COVID-19 remains elusive, but some postulated mechanisms may include the following: plaque rupture, cytokine storm, exaggerated hypoxia, systemic inflammatory response, coronary vasospasm, microthrombi or microangiopathy caused by a prothrombotic or coagulopathic state, and direct endothelial or vascular injury. COVID-19 can also affect the myocardium, causing myocarditis, which can induce focal or global myocardial inflammation and, consequently, ventricular dysfunction. Autopsy specimens have suggested infiltration of the myocardium by interstitial mononuclear inflammatory cells [4]. Pericardial involvement has rarely been reported with possible mechanism including pericardial inflammation via direct cytotoxic effects and/or immune-mediated mechanisms [5]. Amid the ongoing COVID-19 pandemic, management of patients with acute coronary syndrome and concomitant COVID-19 has become challenging. Primary percutaneous coronary intervention remains the standard of care for such patients when it can be provided in a timely and safe fashion with appropriate personal protective equipment and in a dedicated cardiac catheterization laboratory. For patients with myopericarditis, mainstay therapies include glucocorticoids, anti-inflammatories (such as colchicine), and GDMT for associated cardiomyopathy.

In summary, we present two patients with COVID-19 infection and myocardial involvement. The first patient had conventional risk factors for coronary artery disease, presented with non-ST-segment myocardial infarction (NSTEMI), and had evidence of non-obstructive coronary atherosclerosis on angiography. Potential mechanisms of myocardial injury in this patient include acute infection triggering an intense myocardial demand with resultant ischemia and ultimately infarction or a cytokine storm caused by the severe inflammatory stress precipitating plaque instability and rupture. The key decision in this case was the timing of coronary angiography, which was performed 4 days after his admission. In patients with NSTEMI without ongoing angina, signs of ischemia or hemodynamically instability and suspected COVID-19, it appears reasonable to first pursue GDMT pending COVID-19 test results, rather than immediate cardiac catheterization, because urgent angiography and possible revascularization are not necessarily the priority. The second patient presented with COVID-19 myopericarditis and hemodynamically significant pericardial effusion requiring pericardial drainage with no consequent improvement in hemodynamics, progressing to cardiogenic shock requiring mechanical circulatory support with VA-ECMO, with eventual full recovery.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

Toby Rogers – Consultant and proctor: Medtronic, Edwards Lifesciences; Advisory board: Medtronic. Equity interest: Transmural Systems.

Ron Waksman – Advisory Board: Amgen, Boston Scientific, Cardioset, Cardiovascular Systems Inc., Medtronic, Philips, Pi-Cardia Ltd.; Consultant: Amgen, Biotronik, Boston Scientific, Cardioset, Cardiovascular Systems Inc., Medtronic, Philips, Pi-Cardia Ltd.; Grant Support: AstraZeneca, Biotronik, Boston Scientific, Chiesi; Speakers Bureau: AstraZeneca, Chiesi; Investor: MedAlliance.

All other authors – None.