Case 1 -

Sudden Cardiac Death Due to Non-Atherosclerotic Coronary Artery Lesions Michael Graham Chief Medical Examiner St. Louis, MO

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Clinical History The decedent is a 23-year-old Caucasian woman who had no known serious disease. She did have a history of chronic fatigue but had no significant limitation of activities. An examination by her internist 1 week prior to death yielded no findings of apparent diagnostic significance. Laboratory studies at that time demonstrated no anemia. Her sed rate was 35. She was "not feeling well" on the day prior to her death but did attend a picnic and participate in activities. On the day of her death she experienced "stomach pain" and nausea. Maalox did not offer relief from the discomfort. She was talking with a relative and suddenly collapsed. Resuscitative efforts were unsuccessful. A postmortem examination was performed. The autopsy demonstrated her to be a normally developed, nourished and hydrated woman who was 67 inches long and weighed 130 pounds. Her heart weighed 290 grams. There was gray-white relatively diffuse thickening of the intima of the proximal few centimeters of the ascending aorta. A single coronary ostium was present. The coronary ostium arose normally in proximity to the left sinus of Valsalva. The left main, left anterior descending and circumflex arteries arose in the usual fashion from this ostium. Branches of the left coronary artery supplied blood to the posterior aspect of the heart. The left main artery had a gray-white thickened wall in association with adventitial fibrosis. There was fibrointimal proliferation of the left main artery resulting in greater than 95% narrowing of the lumen. No right coronary ostium was identified. The right coronary artery was not identified. There was mottling of the posterior left ventricular myocardium. The heart was otherwise unremarkable. The remainder of the autopsy revealed no additional lesions of significance. No ethanol or drugs were detected during routine toxicologic screening of blood, urine and vitreous fluid. H&E and Movat stained microscopic sections of the ascending aorta, coronary ostium/initial coronary artery segment and left coronary artery are available for your review. Case 1 - Figure 1 Case 1 - Figure 2 Case 1 - Figure 3 Case 1 - Figure 4 Case 1 - Figure 5 Case 1 - Figure 6 Case 1 - Figure 7 Death Investigation Determinations Cause of death—disease or injury initiating sequence of events culminating in death Immediate Underlying Mechanism of death—pathophysiologic derangement through which the cause of death exerts its lethality Manner of death—death certification term describing conditions under which death occurs Natural Non-natural Accident Homicide Suicide Undetermined (unclassified) Components History Circumstances of death Stress Physical Emotional Past medical history Decedent Family Examination Scene Body Ancillary Studies Toxicology and/or Other Laboratory Studies Electrocardiogram Decedent Antemortem Agonal Family Radiographic Correlations Morphology / Function "A" cause / "The" cause Sudden Cardiac Death Definition—Death occurring within 1 hour of the apparent onset of symptoms/signs Incidence 1-20 years of age 1-9/100,000 M:F::2:1 35-74 years of age 191/100,000 (M) 57/100,000 (F) (50% due to ASHD) Cause Congenital / Acquired Localized to heart Isolated anomaly / Associated cardiac anomalies / Associated Extra-cardiac anomalies Associated with systemic disorder Site of lesion Vasculature Myocardium Valve / Endocardium Conduction system Mechanism Most common--Dysrhythmia (93%) Type V-tach / V-fib (80%) Asystole (15%) PEA (3%) Pathogenesis Automaticity Re-entry Triggered event Cause Most common--Ischemia Acute Old (fibrosis) Activity at onset Regular daily routine (49%) Sleep (23%) Exercise (23%) Emotional stress (6%) Coronary Artery Anomalies--General Variables Ostium Number Location Size Initial segment Angle Intramural component Epicardial and Myocardial segments Tunnel Size Structure Dysplasia Connection Fistula Classification and Incidence Normal / Abnormal Classification Morphology (presence) Physiology Exertion / stress Rest Significance Function Prognosis Incidence Depends on definition and population (referral bias) Angiography—1-6% Autopsy (0.3%) Hospital Medical examiner Pediatric (0.6%) Cardiac surgery Cause of death General population (<40 y/o)—0.6% Exercise (8-66 y/o)—11% Competitive athlete (average age, 17 yrs)—14-23% Joggers/marathon runners (30-46 y/o)—1.6% Coronary Artery Anomalies—Specific Ostium / initial segment anomalies Ectopic origin Arising from wrong Sinus of Valsalva Left coronary artery arising from right sinus Right coronary artery arising from left sinus Left circumflex artery arising from right sinus (or RCA) Coronary artery arising from posterior aortic sinus High take-off Ostial ridge / fold Coronary artery arising from pulmonary artery Left coronary artery—most common Ischemia in distribution of left coronary artery "Steal" phenomenon Right coronary artery—less common Number Single ostium Course of Epicardial Coronary Artery Intramyocardial left anterior descending coronary artery (supra-arterial myocardial bridge; tunnel coronary artery) Common finding Autopsy—30% (15-85%) Angiography—1% (0.5-2.5%) Rarely significant Morphologic features in significant cases Long, deep segment Peri-arterial myocardial sheath, disarray, fibrosis Attenuated potential collateral blood flow Antemortem morphological and hemodynamic alterations phasic systolic vessel compression persistent diastolic lumen diameter reduction increased blood flow velocities retrograde systolic flow reduced coronary flow reserve Associated factors Left ventricular hypertrophy Exertion Size, structure and connections Hypoplasia/aplasia Fibromuscular dysplasia AV node artery Fistula Mechanisms of ischemia Fixed obstruction Ostial stenosis Ostial plication / fold / shelf Episodic obstruction Acute angulation Exertion-related Intramural left anterior descending coronary artery Steal Persistent Episodic Acquired Non-Arteriosclerotic Coronary Artery Lesions Arteritis Primary Takayasu arteritis Coronary artery involvement in 15-25% of cases Most common site of involvement is at/near ostium as a direct extension of aortic disease Giant cell arteritis Polyarteritis group Classic polyarteritis nodosa Churg-Strauss syndrome Kawasaki disease Hypersensitivity angiitis Wegener's granulomatosis Thromboangiitis obliteratins (exceedingly rare) Secondary Non-infective Connective tissue disorders Others (numerous) Infective Sequelae Dissection Primary Strong propensity for LAD involvement 80% occur in women 1/3 associated with pregnancy Embolus Atherosclerosis Thrombus Vegetation Tumor Air Substance abuse Spasm Trauma Metabolic and coagulation disorders Iatrogenic Other Idiopathic arterial calcification of infancy References Cohle SD, Graham MA and Pounder DJ, “Nonatherosclerotic Sudden Coronary Death”. 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