This woman, with a known history of significant coronary artery disease, died suddenly at home. In general, because of the possibility of illegal circumstances, the determination of the cause of death for someone who dies outside of a medical facility would be the responsibility of the Medical Examiner's Office. However, in this case, the history of cardiovascular disease was sufficiently strong to suggest that death was due to natural causes.
Sudden cardiac death (SCD) is virtually always arrhythmic, and is usually caused by a so-called malignant ventricular rhythm such as ventricular fibrillation (VF, often following episodes of ventricular tachycardia or runs of premature supraventricular or ventricular contractions). Asystole also may occur, either as the initial event of cardiac arrest, or following VF. Electromechanical dissociation (EMD) is another pattern, in which a normal or nonfatal electrical pattern is maintained, but there is an uncoupling of electrical activity and muscular contraction. Although this may occur following VF with resuscitation attempts including defibrillation, it can often be seen in the setting of hemopericardium due to ventricular rupture (as a result of myocardial infarction) or aortic rupture (due to aortic dissection). In this case, the patient was initially asystolic, followed by VF shortly thereafter, with unsuccessful resuscitation attempts.
She had a number of risk factors for SCD, all of which are positively and independently associated with this outcome. It is noteworthy that SCD is by far the most common cause of death due to heart disease, and it accounts for 500,000 to one million deaths per year, with the majority occurring outside the hospital. Only a small percentage of individuals experiencing an arrhythmic cardiac arrest will have resuscitation attempted on them, and of those, less than 5-10% are resuscitated successfully to reach a medical facility. Many of the survivors have significant anoxic brain injury that subsequently leads to death or disability. Of the risk factors predisposing to SCD, the following are the most important:
1. left ventricular hypertrophy
2. occlusive coronary artery disease
3. acute coronary artery thrombosis
4. myocardial scarring
5. acute or organizing myocardial infarction
Of these risk factors, this patient had all except #6 and #7: She had significant cardiac hypertrophy with a gross heart weight of 450 g, and a left ventricular wall measuring 1.9 cm in greatest thickness (normal up to 1.5 cm). The estimated cardiac mass for a woman who weighed 63 kg is between 250300 g. The calculation is estimated by taking the weight of the individual in kilograms and multiplying by 0.4%. For males, with somewhat greater lean muscle mass, the multiplier is 0.5%. More precise estimates can be obtained by using the body surface mass-index, but for practical purposes, a 0.4-0.5% multiplier gives a reasonable approximation. The upper limits are equally significant, and are considered pathological, regardless of body size, if more than 350-400 gm in a woman, or more than 400-450 gm in a man. The proviso that the hypertrophy is non-physiologic is also an important consideration. In a well-trained athlete, particularly one performing isometric exercise (e.g. weight lifting), cardiac hypertrophy may ensue; however, it is a physiologic response not associated with myocardial scarring. In general, the difference between pathologic hypertrophy and physiologic hypertrophy is dependent on the presence or absence of fibrosis.
The etiology of this patient's hypertrophy is most likely secondary to longstanding hypertension, although compensatory hypertrophy of the non-infarcted heart may have played a role. Even without the medical history of hypertension, it would be possible to deduce that she was hypertensive based on her kidney pathology. The kidneys were discrepant in size (35 gm and 100 gm), and they had granular cortices. The discordant renal mass was most likely the result of a "Goldblatt kidney" phenomenon. The latter occurs when one kidney is chronically ischemic (usually as a result of renal artery stenosis), and produces excess renin with increases of circulating angiotensin. The angiotensin causes an elevation of the systemic blood pressure that leads to arterionephrosclerosis of the contralateral kidney (e.g. damage and sclerosis of intrarenal arteries and arterioles with secondary localized ischemia and fibrosis of the glomeruli and tubules). The ischemic kidney is "protected" from the effects of hypertension by the renal artery stenosis. Thus, in a classic Goldblatt kidney, the diffusely ischemic kidney is small and generally has a smooth cortex, with the other kidney showing features of a granular cortex consistent with nephrosclerosis. In this case, although one kidney was smaller than the other, even the larger of the two was moderately shrunken (normal kidney weight is approximately 150-200 gm), and both were granular. This suggests that the patient was chronically hypertensive thereby causing nephrosclerosis of both kidneys, and then subsequently she developed renal artery stenosis leading to superimposed ischemia. Thus, she did not have a classic Goldblatt kidney phenomenon, though she did have hypertensive renal disease.
This patient had severe chronic coronary artery disease secondary to atherosclerosis, with predominant involvement of the LAD (e.g. single vessel disease), although her right coronary artery was also affected. The 50-60% narrowing of the RCA is below the critical level of stenosis (defined as greater than 65%), because that level of narrowing at rest will have an associated pressure drop across the stenotic segment. Sub-critical narrowing can certainly be significant during exercise, or if there is an acutely unstable vessel. Furthermore, such sub-critical vessels can progress to critical stenosis over time, or they can be associated with thrombosis.
The autopsy revealed obvious disease progression in the RCA (e.g. 90% occlusion), and it showed changes of LAD re-stenosis proximal to the CABG. Re-stenosis is a commonly recognized complication of balloon angioplasty that occurs in up to 40% of patients within 3-4 months following the procedure. The precise explanation of why it occurs preferentially in some patients, while sparing others, is not understood; nor are there predictors of who will re-stenose. The process of re-stenosis is an exuberant proliferation of smooth muscle cells and myxomatous stroma in the intimal layer of the ballooned vessel, leading to a neo-intima that impinges on the lumen. The pathogenesis of this tissue proliferation is complex. It is partially dependent on the injury to endothelial cells following the balloon damage to the vessel wall that generally causes a local compression and dissection of the occluding plaque. The balloon injury leads to an "uncovering" of subendothelial connective tissue with adherence of platelets that release the prostaglandin thromboxane (TXa, a smooth muscle vasoconstricting agent), and platelet-derived growth factor (PDGF, which is a mitogen for smooth muscle cell proliferation), thereby stimulating smooth muscle cell migration into the intima. Additionally, there is release of endothelin-1, a potent vasoconstrictor, and other hormones and cytokines, which can also stimulate smooth muscle and connective tissue proliferation.
In this case, the patient did re-stenose following the balloon angioplasty, and then she underwent an internal mammary artery to LAD graft. The internal mammary artery is a useful arterial graft that is relatively devoid of atherosclerosis, and does not develop atherosclerosis when interposed in the coronary circulation. Its major limitation is that it can only be grafted to the anterior heart surface, because of its location and length; therefore it is primarily used for LAD grafts. At autopsy, the native LAD was severely narrowed proximal to the patent graft, and it showed evidence of restenosis.
Prior to her death, this woman had several other significant conditions that made her susceptible to a sudden fatal arrhythmia. She had evidence of a healed scar in lateral left ventricle, which was at least 3 months old (it takes a minimum of 3 months for scar tissue to mature). In the same geographic area of the ventricle as the scar tissue, she had granulation tissue, which represents a healing response to myocardial necrosis composed of endothelial cell and fibroblastic proliferation. Granulation tissue generally begins to form at 7-10 days after tissue injury, and then it progressively matures for several weeks until immature scar tissue develops. Thus, this region represents a subacute infarction that presumably developed silently (e.g. without clinical signs and symptoms) at least several weeks prior to her death. The temporal changes link this area of necrosis to the organizing right coronary artery thrombus, which was also approximately 1-2 weeks in age. Individuals with myocardial scarring are at risk to develop cardiac arrhythmias; however, those with healing infarction are at markedly higher risk. The myocardial tissue immediately adjacent to a healing infarction has increased irritability as a result of inflammation, interstitial edema, and slight hypoxemia, and is therefore more likely to cause a generalized arrhythmic event.
It is most probable that the sudden arrhythmia that led to this woman's death was a direct result of the acute event that was temporarily related to her cardiac arrest. We are referring to the acute thrombosis of the left circumflex coronary artery. Sudden occlusion of this vessel, together with prior complete occlusion in the right coronary artery, made her ventricle ischemic, and susceptible to generate fatal electrical rhythms. It is noteworthy that she developed an acute thrombosis of her circumflex artery within a few weeks of an RCA thrombus. It is not that rare for patients to develop thrombi in multiple vessels, sometimes concurrently. This suggests an increased tendency for thrombus formation in already diseased atherosclerotic arteries, possibly as the result of enhanced plaque instability and/or systemic or local hormonal factors. In this case, no specific etiology could be determined.
1. Levine GN, Ali MN. The role of percutaneous revascularization in the treatment of ischemic heart disease: insights from published reports and randomized clinical trials. Chest. 1997; 112:805-21.
2. Kawasuji M, Sakakibara N, Takemura H, Tedoriya T, Ushijima T, Watanabe Y. Is internal thoracic artery grafting suitable for a moderately stenotic coronary artery? J Thorac Cardiovasc Surg. 1996; 112:253-9.
3. Jensen J, Eriksson SV, Lindvall B, Lundin P, Sylven C. Women react with more myocardial ischemia and angina pectoris during elective percutaneous transluminal coronary angioplasty. Coron Artery Dis. 2000; 11:527-35.
4. Friesinger GC, Ryan TJ. Coronary heart disease. Stable and unstable syndromes. Cardiol Clin. 1999; 17:93-122.
5. Cishek MB, Gershony G. Roles of percutaneous transluminal coronary angioplasty and bypass graft surgery for the treatment of coronary artery disease. Am Heart J. 1996; 131:1012-7.
6. Tennant M, McGeachie JK. A biological basis for re-stenosis after percutaneous transluminal angioplasty: possible underlying mechanisms. Aust N Z J Surg. 1992; 62:135-4.
7. Weiner DA. Significance of silent myocardial ischemia after coronary artery bypass surgery. Am J Cardiol. 1992; 70:35F-38F.
8. Factor SM, Minase T, Cho S, Fein F, Capasso JM, Sonneblick EH. Coronary microvascular abnormalities in the hypertensive-diabetic rat. A cause of cardiomyopathy? Am J Pathol 1984; 116:9-20.
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