Rationale: Drug-inducing adverse effects may be critical and fatal. There is a reported serious cardiovascular (CV) presentation with sildenafil. Mitral stenosis (MS) is the most common cause of valvular atrial fibrillation (AF) and flutter. Brugada syndrome (BrS) is a genetic disorder with abnormal electrical activity within the heart that carries a higher risk for ventricular fibrillation and sudden death. Hiatal hernia is a herniation of intra-abdominal contents into the thorax. There is a durable relationship between COVID-19 infection and ischemic heart disease. Patient concerns: A 53-year-old, married Egyptian male teacher, mechanically replaced mitral valve (MV) patient was presented to the physician outpatient clinic with intermittent angina within two weeks’ of post-oral sildenafil tablets and COVID-19 pneumonia. Diagnosis: High lateral ischemia and passed sildenafil-inducing inferior infarction with variable atrial fibro-flutter block, alternative right bundle branch block (RBBB) beat with type II BrS in mechanically replaced MV with recent hiatus hernia and COVID pneumonia. Interventions: Cardiothoracic surgery, chest X-ray, electrocardiography, echocardiography, and oxygenation. Outcomes: There is a good outcome despite numerous noteworthy serious risk factors. Lessons: High lateral ischemia, passed inferior myocardial infarction (MI), variable atrial fibro-flutter block, RBBB beat, BrS, hypocalcemia, recent hiatus hernia, and COVID pneumonia in the mechanically replaced MV are a serious constellation of risk factors. Alternative RBBB beat with type II BrS is newly described. BrS may be transient. Hypocalcemia and Wavy triple ECG sign (Yasser’s sign) are confusing issues for ischemic heart disease.