Background: We noticed cardiac complications both in vaccinated as well as post SARS-CoV2 recovering patients weeks after recovery. We started analyzing if this is a new normal and if there is a paradigm shift in how this pandemic is behaving, with new variants/mutations evolving. We present few cases to reflect current scenario in second wave of pandemic in patients admitted to coronary care unit of King George Hospital, Visakhapatnam.
Method and Results: Patients with recent COVID-19 infection (either home-isolated or hospitalized and discharged upon recovery) and readmitted couple of weeks later to our coronary care unit of King George hospital during May to July 2021 have been included for study. They are all rapid antigen test/RT-PCR confirmed in previous admission and negative in this admission. If not confirmed previously, we confirmed with antibody testing in unvaccinated cases. One uninfected case with recent second dose of COVID vaccine was also included. All of them were tested for complete blood picture (CBP), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Ferritin, D- dimer, creatinine, electrolytes, troponin-T, ECG, chest x-ray, HRCT chest and 2D-Echo. Coronary angiogram (CAG) and other relevant investigations were done as needed. Total 12 cases were studied. Of them 10 were hospitalized (moderate infection), 1 was home isolated (mild infection) and 1 had second dose of COVID vaccine (uninfected). All of them were discharged two or more weeks back. 7 cases had acute myocardial infarction (MI), 1 had cardiogenic shock with heart failure, 2 had myocarditis/pericarditis, 1 had incessant wide QRS tachycardia/ Atrio-ventricular re-entry tachycardia (AVRT) with intermittent pre-excitation, 7 had resting sinus tachycardia and 1 patient developed ventricular septal rupture post-MI. Out of 7 MI cases, 1 had mild COVID infection, 5 had moderate COVID infection and 1 was uninfected (recent COVID vaccination and stent thrombosis). While 3 of those MI cases had spontaneous recanalization of coronary vessels, other 3 were stented in view of pre-existing atheromatous lesions. Septal repair is planned for 1 patient after CAG. Case 1: 19-year-old obese male was admitted with chest pain of 12-hour duration with radiation to neck and left arm. He had no breathlessness or palpitations. He had dry cough, myalgia and fever for 2-days. He had mild COVID infection 3-weeks back (home isolated). He wasn’t on anticoagulants and no history of drug abuse or COVID vaccination. His father died of coronary artery disease (CAD) at 40-years age. Physical examination showed rash over limbs, cervical lymphadenopathy and oral mucositis. Systemic examination was normal. His BP 100/60mm Hg and heart rate 140/min. ECG was suggestive of antero-lateral wall ST-elevation Myocardial Infarction (STEMI) with sinus tachycardia.(Image-1) 2D-Echo showed hypokinesia of anterior, anterolateral and inferolateral regions of left ventricle (LV). He had good right ventricle (RV) function and mild LV systolic dysfunction with ejection fraction (EF) 42%. There were multiple LV clots and singe RV clot. Although within window period, he wasn’t thrombolysed in view of multiple clots. Investigations: Troponin-T 1 (<0.01ng/dl), C-reactive protein (CRP) 148 mg/L(<5mg/L), D- dimer 620ng/ml(<220), lactate dehydrogenase (LDH) 418U/L(126-220U/L), erythrocyte sedimentation rate (ESR) 92 mm/hour(<12mm 1st hour), Ferritin 530ng/mL(<150ng/mL), Procalcitonin 0.4ng/L(<0.5ng/L), Hemoglobin 8.9g/dl(13.5-18g/dL), Vitamin-B12 126pg/ml (211- 911), Homocysteine 9.34 mmol/L(5.46 – 16.20). ANA profile, Protein-C and protein-S levels were normal. Thyroid stimulating hormone (TSH) 2.2mIU/L(0.5-5mIU/L), creatinine 0.9mg/dl(<1.2mg/dl), total count (TC) 10800 cells/cu.mm (4000-11000), Lymphopenia (0.6 x 109/L). He didn’t have diabetes or dyslipidemia. HRCT chest and chest x-ray were normal. COVID IgM Antibody positive, SARS-CoV2 RT-PCR and Rapid Antigen Test negative. He was diagnosed to have SARS-CoV2 associated multi-system inflammatory syndrome in children (MIS-C). He was treated with low-molecular weight heparin (LMWH), dexamethasone, rivaroxaban, clopidogrel, atorvastatin, metoprolol and antibiotics. Coronary angiogram (CAG) showed normal left-main coronary artery (LMCA) and right coronary artery (RCA), distal cut off of left anterior descending artery (LAD) and major obtuse marginal of left circumflex artery (LCX) with thrombus. No coronary aneurysms were seen. Review 2D-Echo at discharge showed dissolution of most of the clots. He was discharged after 10-days on rivaroxaban, clopidogrel, atorvastatin, metoprolol and hematinics. Follow-up 2D-echo after a month showed mild mitral regurgitation (MR) but no clots or coronary dilatations. Case 2: 54-year-old male was admitted with sudden onset chest pain radiating to left shoulder and breathlessness since 2hours, New York Heart Association (NYHA) class-IV. He had other symptoms like palpitations, giddiness, fever and cough. He had moderate COVID-19 infection 4- weeks back (hospitalized) and discharged on recovery 2weeks back. He is a diabetic. He wasn’t on anticoagulants and wasn’t COVID vaccinated. His BP 80/60mmHg, heart rate 120/min, Spo2 78%. Systemic examination was suggestive of cardiogenic shock and pulmonary edema. ECG was suggestive of acute infero-posterior wall STEMI. (Image-2) Investigations: Troponin-T 1.2(<0.01ng/dl), CRP 160mg/L(<5mg/L), D-dimer 4200 ng/ml(<500ng/ml), ESR 42 mm/hour(<12mm 1st hour), Ferritin 865ng/mL(<150ng/mL), Creatinine 0.6mg/dl(<1.2mg/dl), TC 10,600 cells/cu.mm(4000-11000), RBS 426mg/dl, TSH 2mIU/L(0.5-5mIU/L). SARS-CoV2 RT-PCR negative, Rapid antigen test negative and SARS-CoV2 IgM antibodies positive. Chest X-ray showed pulmonary edema and HRCT chest-CORADS-4. Non-invasive ventilation (NIV), vasopressor support and thrombolysis with Tenecteplase was given. He was treated with LMWH, aspirin, clopidogrel, atorvastatin, piperacillin-tazobactam, insulin, nor-adrenalin, dopamine and dexamethasone. 2D-Echo showed hypokinesia of LV in RCA and LCX territory with moderate LV systolic dysfunction (EF 35%) and grade-III diastolic dysfunction. CAG showed LAD mid cut-off, LCX OM1 proximal 70% stenosis and RCA mid 90% stenosis. He was discharged after 9-days on aspirin, clopidogrel, atorvastatin, oral hypoglycemics and diuretics. Percutaneous transluminal coronary angioplasty (PTCA) was done one month later and culprit vessel (RCA) was stented. PCI for LAD and LCX is planned for a later date. Case 3: 39-year-old male was admitted with chest pain since 2-days. He had fever prior to admission but afebrile later. No breathlessness, syncope or palpitations. He is diabetic on oral hypoglycemics and no previous COVID vaccination. He had moderate SARS-CoV2 infection 3- weeks back (hospitalized) and discharged two weeks back. His ECG showed antero-lateral wall STEMI.(Image-3) His vitals were stable and systemic examination was normal. Investigations: Troponin-T 2(<0.01ng/dl), CRP 203 mg/L(<5mg/L), D-dimer 920ng/ml (<220), Ferritin 890ng/mL(<150ng/mL), LDH 522U/L(126-220U/L), ESR 62 mm/hour(<12mm 1st hour), Hb 11.3g/dl(13.5-18g/dL), Creatinine 0.8(<1.2mg/dl), RBS 253mg/dl. COVID IgM Antibody positive, SARS-CoV2 RT-PCR negative and Rapid Antigen Test negative, TC 10800 cells/cu.mm (4000-11000), Lymphopenia (0.5 x 109/L), (TSH) 3.2mIU/L(0.5-5mIU/L). Chest X-ray and HRCT chest were normal. 2D-Echo showed hypokinesia of anterior and anterolateral walls of LV. Mild MR seen. Good LV systolic function (EF 59%). He wasn’t thrombolysed. He was treated with LMWH, aspirin, clopidogrel, atorvastatin, losartan, metoprolol, dexamethasone, insulin and discharged after a week. CAG 3-weeks later showed normal coronaries with spontaneous recanalization of LAD. Case 4: 76-year-old male was admitted with sudden onset breathlessness (NYHA class III), palpitations and chest discomfort since 6-hours. He had history of CAD, post-PTCA status with drug eluting stent (DES) to LAD and ramus 5-years back. He underwent chemotherapy for Hodgkin’s lymphoma 3-years back and recovered. He took second dose of COVID vaccine 2- weeks ago following which he developed myalgias and fever. He was drug compliant and on anticoagulants. His vitals were BP 120/70mm Hg, pulse rate 86/min, spo2 86%. His general and systemic examination showed raised JVP, basal crepitations of lungs and third heart sound (S3), suggestive of LV failure with pulmonary edema. ECG was suggestive of antero-septal STEMI with sinus tachycardia and new-onset left bundle branch block(LBBB).(Image-4) Investigations: Troponin-T 1ng/dl(<0.01ng/dl), D-Dimer 1230ng/ml(<500ng/ml), ferritin 330ng/ml(<150ng/ml), CRP 25mg/L(<5mg/L), ESR 30mm/hour(<12mm in 1st hour), Hb 13.3(13.5-18g/dL), creatinine 1.1mg/dl(<1.2mg/dl), TC 4900 cells/cu.mm (4000-11000), RBS 65mg/dl, TSH 2.8mIU/L(0.5-5mIU/L). SARS-CoV2 RT-PCR and rapid antigen test negative. HRCT chest-CORADS-4. Chest X-ray showed pulmonary edema. 2D-Echo showed dilated LV. Hypokinesia of anterior, anterolateral, anteroseptal and inferior-septal regions of LV. Moderate LV systolic dysfunction (EF 34%) and grade-I diastolic dysfunction. Mild MR and mild aortic regurgitation (AR). CAG showed LAD proximal 80% eccentric stenosis (proximal to stent- thrombus). LAD stent and Ramus stent were patent. LCX-mild disease and RCA-proximal mild(30%) and mid 80% stenosis. PTCA to LAD with Xience-V drug eluting stent (DES) was done in view of possibility of pre-existing atheromatous lesion apart from thrombus restoring TIMI-3 flow. He was discharged on aspirin, ticagrelor, atorvastatin, telmisartan and diuretics.
Image 1. Antero-lateral wall ST-elevation Myocardial Infarction
Image 2. Infero-posterior wall ST-elevation Myocardial Infarction
Image 3. Antero-lateral wall ST-elevation Myocardial Infarction
Image 4. Antero-septal ST-elevation Myocardial Infarction and left bundle branch block
Discussion: Pathophysiology of Cardiac Sequalae: SARS-Cov2 Is A Beta-Coronavirus Causing Global Pandemic Of An Unprecedent Nature. It Is A Positive-Sense RNA Virus Made Of Four Structural Proteins (Nucleocapsid, Spike-Glycoprotein, Membrane-Protein, Envelope).(1) Spike-Protein Attaches To Angiotensin-Converting Enzyme-2 Receptor (ACE2) And Enters The Cell Using Transmembrane-Protease-Serine-2 (TMPRSS2). Apart From Lungs, Kidney And Liver, Heart Has High Expression Of ACE2 Receptors.(2) Most Cardiac Sequalae Are Either From Direct Effect Of Viral Myocardial Invasion Or Indirect Effect Of Immune Dysregulation, Dysregulation Of Renin-Angiotensin-Aldosterone Pathways, Plaque Instability, Endothelitis, Hypercoagulable State Of Macro/Microvasculature And Venous-Thromboembolism To Heart. These Subsequently Lead To Inflammation (Myocarditis/Pericarditis), Necrosis (Myocardial Infarction), Arrhythmias And Myocardial Dysfunction (Heart Failure).(3) SARS-Cov2 Associated Multi-System Inflammatory Syndrome In Children (MIS-C)/ Adults (MIS-A): Case Reports Have Been Published Worldwide With Delayed Complications In COVID Patients Weeks After Recovery From Acute Infection, Secondary To Hyperimmune Response. It’s Defined As MIS-C In Patients Aged <21years (Case-1) And MIS-A If Aged >21years (Case-2,3). As Per Centers For Disease Control And Prevention (CDC), USA- These Patients Will Have Fever Lasting >24hours, Raised Inflammatory Markers With Two Or More Organs Involved Requiring Hospitalization. Abnormal Tests Like Elevated C-Reactive Protein (CRP), Ferritin, Erythrocyte Sedimentation Rate (ESR), Interleukin-6 (IL-6), Elevated Fibrinogen, Procalcitonin, D-Dimer, Lactate Dehydrogenase (LDH), Elevated Neutrophils, Reduced Lymphocytes And Low Albumin May Be Detected. They Need To Have Proven SARS-Cov2 Infection (RT-PCR, Serology, Antigen Test Or COVID-19 Exposure) Within 4 Weeks Prior To Onset Of Symptoms.(4) Some MIS-C Cases May Meet Partial Or Full Criteria For Kawasaki Disease.(5) CARDIAC SEQUALAE: Myocardial Infarction (MI) Occurs Secondary To Cardio-Embolic Sequalae Of Endothelitis, Generalized Hypercoagulability State, Increased Susceptibility To Plaque Rupture And Subsequent Thrombosis In Coronaries. Hypertension (HTN), Diabetes (DM), Obesity, Elderly Age And Hypoxia Can Increase The Morbidity Risk. Our Patients Had Acute MI During Recovery Many Days Later, Signifying That Post-COVID Sequelae Are Manifested Beyond The Infectious Period (Cases-1,2,3). We Have Seen These Complications Even In Younger And Mild COVID Patients Who Recovered With Home Isolation (Case-1). Heart Failure (Myocardial Dysfunction) Occurs Secondary To Coronary Artery Disease, Direct Viral Mediated Myocardial Injury Or Abnormal Inflammatory Response.(6) Recovery Depends On Severity Of The Disease As Well As Comorbidities. In Extreme Cases, Patients End Up In Cardiogenic Shock (Case-2).(7) Valvular Regurgitation Can Occur In Dilated Or Ischemic Cardiomyopathies Due To Inadequate Coaptation Of Valves Further Worsening Heart Failure Symptoms.(Case-1,3,4) Venous Thromboembolism From Peripheries To Right Heart Can Lead To Right Ventricular Dysfunction.(7) Some Patients Have Resting Tachycardia Due To Anxiety, Increased Catecholamine Drive, Anemia, Inflammation, Stress, Thyroid Dysfunction Or Subclinical Myocarditis And Some Can Have Autonomic Dysfunction.(8) While Most Cases Go Unnoticed, Some Complain Palpitations. Arrhythmias Occur Due To Hypoxia, Electrolyte Imbalance, Myocardial Injury Or QT-Prolonging Drugs.(9) While Ventricular Tachycardia/Fibrillation Are Most Common Arrhythmias, Cases Of Supraventricular Tachyarrhythmias Like Atrial Tachycardia And Atrial Flutter/Fibrillation Have Been Reported Before.(10)(11) Our Patient Had Incessant Wide QRS Tachycardia (AVRT With Intermittent Pre-Excitation). While Most Of The Hospitalized COVID Patients Have Myocarditis, It’s Been Reported In Recovering Patients As Well.(12) Majority Of Them Are Asymptomatic While Some Might Complain Of Chest Pain And Palpitations. Some Patients Can Have Borderline Elevation Of Troponin Levels (Biomarker Of Myocardial Injury). This Is Usually Confused With Myocardial Infarction Where There Is Marked Elevation Of Troponins.(13) This Distinction Is Often Needed To Avoid Unnecessary Invasive Procedures As Most Of Them Recover With Medical Management.(14) Cases Of Sudden Death Have Been Reported In Young Athletes With Myocarditis After Returning To Active Sports During Post-COVID Recovery.(15) Hence, Patients Should Be Screened By 2D-Echo Before Returning Back To Active Sports.(16) Stress Cardiomyopathy (Takotsubo Cardiomyopathy) Have Been Reported More Often Than Before As There Is Catecholamine Excess, Anxiety And Stress Related To Covid Infection.(13)(17) Pericarditis Should Be Suspected In A Patient With Chest Pain, ST-Elevation On ECG And Normal Coronaries On Angiogram. Potential Complications Like Cardiac Tamponade Should Also Be Kept In Mind.(18) Cardiac CT Or Cardiac MRI Can Be Used To Detect Pericarditis, Myocarditis And Pulmonary Embolism. SARS-COV2 Post-Vaccination Sequalae: Most Complications Post-Vaccination Are Mild And Majority Recover. Among Them Most Common Are Fever, Myalgia, Arthralgia, Rash, Injection Site Pain And Bruising If On Antiplatelets.(19) There Are Also Few Isolated Cases Of Vaccine Hypersensitivity And Stent Thrombosis (Case-4). Vaccine Induced Thrombocytopenia Have Been Reported In Some.(20) There Are Case Reports Of Myocarditis Post-Vaccination As Well. Although Vaccine Efficacy Is Good, There Are Reports Of People Getting COVID After Vaccination. Majority Of Such Cases Are Mild. However, Death Of Some Healthcare Workers Due To COVID In Recent Past Exposes The Limitations Of Vaccines. These Are Only Isolated Cases And Benefits Of Vaccination Outweigh Risks In Most Cases.(19) Breakthrough Infections Could Be Because Of Inadequate Immune Response, Inappropriate Vaccine Storage Or Break Of Cold Chain And Escape Mechanism Due To Viral Mutations. With Lot Of Subclinical Infections, Unless Suspected One Cannot Detect Cardiac Complications In Majority Of The Population. With Dynamic Nature Of Mutating SARS-Cov2 Virus, Larger Studies For Anticipating Cardiac Complications Are Needed. Future Studies Should Also Reflect And Detect Who Are At Risk For These Complications.
Conclusion: With Changing Dynamics Of The Pandemic, Due Diligence Of Both Treating Doctor And The Patient Is Needed. Early Detection And Management Of Cardiac Issues Can Prevent Undue Complications. MIS-C Cases Might Need More Close Follow Ups For Longer Periods Than Usual As They Are At Risk Of Coronary Dilatations/Aneurysms Late In The Course Especially In Kids Younger Than 8-Years Age. So Also, MIS-A Cases Might End Up Fatal If Not Detected And Managed Early. Too Aggressive Rehabilitation Might Be Detrimental In Post-COVID Recovering Patients As They Are Prone For Postural Orthostatic Tachycardia, Arrythmias, Myocarditis And Myocardial Ischemia Even Weeks After Recovery. Hence, Careful Monitoring And Slow Introduction Of Active Sports After Recovery Based On Clinical Status On An Individual-To-Individual Basis Is Needed. Although, There Are Isolated Cases Of Vaccine Adverse Reactions, Benefits Outweigh Risk In Majority Of People. While Vaccine Efficacy Varies With Changing Strains, Covid Appropriate Behavior Is Of Paramount Importance.
Keywords: COVID-19, SARS-Cov2, Myocarditis, Pericarditis, Arrhythmia, Myocardial Infarction, Vaccine, Heart Failure, Multi-System Inflammatory Syndrome, Coronary Angiogram
Disclaimer: No Conflict Of Interest to the Best of Our Knowledge.
ABCSI21060