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Congestive heart failure due to coronary artery disease without myocardial infarction: Clinicopathologic description of an unusual cardiomyopathy
Congestive Heart Failure Due To Coronary Artery Disease Without Myocardial Infarction: Clinicopathologic Description of an Unusual Cardiomyopathy JAMES B. ATKINSON, MD, PHD, FACC, AND RENU V1RMANI, MD, FACC Cardiomyopathies (CMs) can be classified as idiopathic dilated, hypertrophic, restrictive/obliterative, and so-called "ischemic cardiomyopathy." We have observed a subgroup of patients with congestive heart failure, dilated hearts, and severe coronary artery disease in the absence of myocardial infarction and therefore not fulfilling the criteria for ischemic CM. To better elucidate this group, which we called "coronary" CM, 54 consecutive neeropsy patients who had congestive heart failure were retrospectively studied. Nineteen patients had idiopathic dilated CM, 26 had ischemic CM, and nine had coronary CM. The mean age of the patients with coronary CM and ischemic CM was significandy greater than that of the patients with idiopathic dilated CM (62 ± 10 and 64 ± 10 years versus 47 ± 19 years, respectively). The duration of congestive heart failure was longest in the coronary CM group (4.1 ± 3.4 years); half of these patients died suddenly or from arrhythmias. Hearts from patients with coronary eM had marked biventricular dilatation and severe coronary artery disease (meannumber of coronary arteries with more than 75% narrowing, 2.2). No acute or healed infarcts were grossly visible, but interstitial and focal perivascular fibrosis were present in the myocardium of all coronary CM hearts. Although coronary CM may comprise a subset of 50-called "ischemic cardiomyopathy," these cases may also represent idiopathic dilated CM with coincidental coronary artery disease. HUM PATHOL 20:1155-1162. Cl 1989 by W.B.Saunders Company. Cardiomyopathies (CMs) are diseases that affect the myocardium and are not the result of valvular, congenital, hypertensive, or pericardial diseases. They are classified as dilated (congestive) CM, h ypertrophic CM, and restrictive/obliterative CM.l While "cardiomyopathy" implies myocardial disease of unknown cause," myocardial disease secondary to ischemia is considered by some to be CM resulting from coronary artery disease ("ischemic cardiomyop-
athy").' Cardiomyopathy from coronary artery disease is clinically different from idiopathic dilated CM.3-10 The patient with ischemic CM usually has angina that disappears as failure becomes more severe, a history of prior infarction, and myocardial fibrosis (discreet or diffuse) due to coronary artery disease in the ab-
From the Department of Pathology, Vanderbilt University, Nashville, TN; and the Department of Cardiovascular Pathology, The Armed Forces Institute of Pathology, Washington, DC. Accepted for publication May 16, 1989. Key words: cardiomyopathy, ischemic cardiomyopathy, coronary artery disease. Addresscorrespondenceand reprint requests toJames B. Atkinson, MD, PhD, Department of Pathology, Vanderbilt University, Nashville. TN 37232.
sence of ventricular aneurysm.5 .10.l1 Ross and Roberts -'' described a series of patients with congestive heart failure who had severe coronary artery disease but no clinical or morphologic evidence of myocardial infarction. We have also noted a subgroup of patients who had congestive heart failure with clinical and morphologic features different from ischemic and idiopathic dilated CM. To further elucidate this distinct subgroup, which we called "coronary" CM, we retrospectively reviewed a cohort of necropsy patients with long-standing congestive heart failure who fulfilled the criteria of CM . The patients were classified into idiopathic dilated CM, so-called ischemic CM, and the coronary CM groups.
METHODS Clinical and necropsy records of 54 patients (45 men and nine women) who had clinically documented congestive heart failure for at least 6 months with no evidence of intrinsic valvular, congenital, or pericardial disease were retrospectively studied. These cases were obtained by reviewing consecutive autopsy records from 1983 to 1987 from the Vanderbilt University and Nashville Veterans Administration Medical Centers (Nashville, TN). The following features were recorded : age, sex, cardiovascular risk factors, history of drug or ethanol abuse or previous viral illness, duration of heart failure, radiographic and electrocardiographic (ECG) findings, and cause of death. At autopsy, the hearts were weighed, the coronary arteries were injected with barium-gelatin pigment, and the hearts were fixed overnight in 10% buffered formalin (but not perfusion-fixed). The following morphologic features were reviewed by both authors and recorded : presence or absence of healed and/or acute myocardial infarction, wall thickness (measured at the tip of the posteromedial papillary muscle on the mid posterior wall) of the left and right ventricles, extent of chamber d ilatation (graded on a scale from I + to 4 + , with I + representing "normal" chamber size and 4 + representing severe dilatation), microscopic pattern and location of fibrosis (interstitial versus focal, and grossly visible subendocardial versus transmural scars), and extent of coronary artery narrowing by atherosclerosis in the four major epicardial coronary arteries (left main, anterior descending, left circumflex, and right) after serial sectioning at 2-mm intervals. Tabulation of light microscopic findings was made without knowledge of the diagnosis. Data are expressed as mean ± standard deviation and statistical analyses were by Student'S t test or X2 test. Idiopathic dilated CM was defined by the following criteria: clinically documented heart failure for at least 6 months, increased heart weight (more than 350 g in women and more than 400 g in men), dilatation of all four cardiac
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chambers (ventricles usually more than atria), absence of acute or healed myocardial infarction, anatomically normal cardiac valves (or valves having only minimal, focal scars), all major epicardial coronary arteries narrowed less than 75% in cross-sectional area by atherosclerosis, and no associated systemic or other known cardiovascular conditions. 13 For ischemic CM, patients had clinically documented congestive heart failure for at least 6 months, healed left ventricular myocardial infarction (subendocardial or transmural) in the absence of ventricular aneurysm, no evidence of acute infarction at autopsy, cardiomegaly with dilatation of all four chambers (ventricles usually more than atria), one or more major epicardial coronary arteries narrowed more than 75% in cross-sectional area by atherosclerotic plaque, and normal cardiac valves. Lesions were designated transmural when they involved more than half of the thickness of the myocardium, and subendocardial when involving less than half of the inner portion of the myocardial wall. Only those lesions that had at least one dimension 3 cm or greater were considered to be related to coronary artery disease.!" Patients who defied classification into either group had clinically documented heart failure for at least 6 months, cardiomegaly with four-chamber dilatation, absence of acute or grossly visible healed myocardial infarction, normal cardiac valves, and one or more coronary arteries narrowed more than 75% in cross-sectional area by atherosclerotic plaque. Patients with a documented history of hypertension were excluded from the coronary CM group.
RESULTS Clinical Features
The mean ages of patients with coronary and ischemic CM were greater than those with idiopathic dilated eM (P < .05; Table 1). The duration of congestive heart failure was longest in those with coronary CM (4.1 ± 3.4 years). All patients with coronary CM had a documented history of cardiac arrhythmias, with a higher incidence of atrial fibrillation and ventricular tachycardia (66%) than those with idiopathic dilated CM or ischemic CM (Table 1). The ECG also showed evidence of either conduction defects or ST-T wave changes in two thirds of the coronary CM patients. There were no specific radiographic features that distinguished the three groups, and the majority of patients had radiographic evidence of cardiomegaly (46 of 54,85%). Echocardiography had been performed in only two patients with coronary CM; one patient had global hypokinesia and the other had septal hypokinesia and a poorly contractile left ventricle. Four patients with idiopathic dilated CM had echocardiography, and all showed dilated and poorly functioning ventricles. Six patients with ischemic eM had echocardiograms, showing focal hypokinesis or akinesis.
TABLE 1. Clinical Features of 54 Necropsy Patients With Congestive Heart Failure
No. of patients Male Female Age (yr) (mean ± 50)* Duration of CHF (yr) Arrhythmia (total) Atrial fibrillation Ventricular tachycardia PVC Sinus tachycardia Atrial flutter PAC Other None ECG findings Conduction defect or block ST·T wave changes Axis deviation Myocardial infarction Left ventricular hypertrophy No. of patients receiving medication for heart failure Digoxin Diuretic Antiarrhythmic Total no. of patients Cause of death CHF Sudden death or arrhythmiat Pulmonary embolus
Coronary CM(%)
Ischemic CM (%)
Idiopathic Dilated eM (%)
9 8 1 61.6 ± 9.9 4.1 ± 3.4 9 (100) 3 (33) 3 (33)
26 21 5 63.5 ± 9.5 3.0 ± 3.1 22 (85) 2 (8) 7 (27) 9 (35) 2 (8) 1(4) 3 (12) 4 (15) 4 (15)
19 16 3 47.0 ± 18.9 2.2 ± 2.6 11 (58) 4 (21) 2 (11) 2 (II) 1 (5) 0 0 3 (16) 8 (42)
2 (22)
11(42) II (42) 6 (23) 14 (54) 3 (12)
7 (37) 10 (53) 5 (26) 0 7 (37)
7 (78) 3 (33) 6 (67) 8 (89)
21 (81) 18 (69) 8 (31) 25 (96)
13 (68) 10 (39) 7 (37) 15 (79)
3 (33) 5 (56)
7 (27) 9 (35) 4 (15) 6 (23)
II (58)
0 1 (II)
I (11) 0 2 (22) 0 6 (67) 4 (44) 2 (22)
0
0
Otherj
1 (11)
3 (16) 1(5) 4 (21)
Abbreviations: CHF, congestive heart failure; PAC, premature atrial contraction; PVC, premature ventricular contraction. .05 for coronary CM and ischemic CM versus idiopathic dilated CM. t p < .05 for coronary CM versus ischemic CM and idiopathic dilated CM. :!: Other causes of death include coronary CM-sepsis; ischemic CM-pneumonia (three patients), neoplasm (two patients), and cerebrovascular accident (one patient); idiopathic dilated CM-tamponade after endomyocardial biopsy (one patient), alcoholic hepatitis (one patient), sepsis (one patient) and neoplasm (one patient).
*p <
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Sudden death andlor arrhythmias were the cause of death in five of nine patients in the coronary CM group, whereas death from congestive heart failure was more frequent in the idiopathic dilated CM group (11 of 19, 58%; Table 1). Other causes of death in the coronary CM group included congestive heart failure (three patients) and sepsis (one patient). Patients with ischemic CM had near equal frequencies of sudden death (35%) and death from congestive heart failure (27%). None of the patients with coronary CM had a known history of viral illness prior to onset of symptoms. In contrast, three idiopathic dilated CM patients had a viral illness preceding the onset of congestive heart failure (Table 2). In two ischemic CM patients, a viral illness had occurred after the onset of congestive heart failure. Alcohol use was documented in two coronary CM patients, nine idiopathic dilated CM patients, and 11 ischemic CM patients (P value not significant). Angina pectoris was nearly as frequent in coronary CM patients as in patients with ischemic CM (44% versus 54%).
Morphologic Features Hearts in all three groups of patients were enlarged, with coronary CM patients having the greatest cardiomegaly (P value not significant) (Figs I through 3 and Table 3). Although mild to moderate bilateral chamber dilatation was found in all hearts, severe bilateral dilatation (3 + to 4 +) was most prominent in coronary CM (67%), while dilatation of the left ventricle alone was found more often in ischemic CM (50%). Mural thrombi were present in nearly two thirds of the hearts from patients with ischemic CM and idiopathic dilated CM, but in only three of the nine coronary CM hearts. Two of nine coronary CM hearts had grossly visible endocardial scars (Table 3). Although endocardial fibrosis was observed in 16 of 26 hearts with ischemic CM (Table 3), in only three cases was this fibrosis not related to transmural scar. TABLE 2. Clinical Historyin 54 Necropsy Patients With Congestive Heart Failure
Smoking Diabetes mellitus Hyperlipidemia Hypertension Family history of cardiovascular disease Alcohol use Viral illness Cardiovascular history Angina pectoris Myocardial infarction Average no. of cardiovascular risk factors per patient*
Coronary CM(%)
Ischemic CM (%)
Idiopathic Dilated CM(%)
4 (44) I (11) 0 0
16 (62) II (42) 5 (19) 12 (46)
12 (63) 0 0 0
6 (67) 2 (22) 0
11(42) 9 (35) 2 (8)
9 (47) II (58)
4(44) 0
14 (54) 15 (58)
4 (21) 0
1.8:!; 1.0
1.6:!; 0.9
1.1 :!; 0.9
3 (16)
* Smoking, diabetes mellitus, hyperlipidemia, positive family history.
The various degrees of cross-sectional area luminal narrowing in the coronary arteries are shown in Table 4. The mean number of the four major epicardial coronary arteries narrowed more than 75% was 2.3 ± 0.9 for ischemic CM and 2.2 ± 1.0 for coronary CM. The left anterior descending coronary artery was most often narrowed in coronary CM (nine of nine hearts), followed by the right and left circumflex coronary arteries (five of nine hearts each). In the ischemic CM hearts, the left anterior descending and left circumflex coronary arteries had an equal frequency of severe narrowing (22 of 26 for each), followed by right (19 of 26) and left main coronary arteries (nine of 26). Coronary CM hearts had fewer coronary arteries that were totally occluded compared with ischemic eM (Table 4). Coronary arteries from patients with coronary CM had an approximate equal incidence of significant proximal and distal narrowing, while ischemic CM hearts had critical proximal lesions or severe diffuse disease (data not shown). Idiopathic dilated CM had interstitial fibrosis microscopically in both ventricles. Ischemic CM had subendocardial andlor transmural scarring as well as perivascular fibrosis (Table 3). In contrast, hearts from patients with coronary CM had a pattern of microscopic fibrosis that was interstitial as well as focal, most prominent in the subendocardium of the left ventricle but not comprising a grossly discreet area of healed infarction (ie, not greater than 3 em in greatest dimension) (Fig 1). Only five of 19 idiopathic dilated CM hearts and seven of 26 ischemic CM hearts had a similar combination of interstitial and focal fibrosis in our series. Myofibrillar loss (vacuolization) and hypertrophy of varying degrees were observed in all sections of myocardium in coronary CM and idiopathic dilated CM hearts. DISCUSSION
The diagnosis of idiopathic dilated CM is dependent on the absence of significant coronary artery atherosclerosis, valvular disease, or systemic hypertension. The microscopic picture is one of interstitial, focal, and/or, rarely, transmural fibrosis with myocyte hypertrophy, atrophy, vacuolization, and myofibrillar loSS.I5-22 In cases of long-standing cardiac failure, dense subendocardial fibrosis can be seen which is indistinguishable from ischemic damage. IS Clinically, the left ventricular ejection fraction is reduced (less than 40%), arrhythmias are common, and death is usually due to progressive heart failure, although sudden death or death from pulmonary or systemic emboli may also occur. 20 Patients with ischemic CM have severe coronary artery disease and scarring of the myocardium consistent with a healed transmural or subendocardial infarction. 3-9,11 The diagnosis is usually made in middle-aged or older patients with congestive heart failure and enlarged hearts. Up to 90% of patients with ischemic CM may have exertional angina!" and, although angina may be the principal clinical feature in
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'1GUIIi. Coronary CM. A 62-year-old man with a 5-year history of congestive heart failure and atrial flbrlllat10n died suddenly. (A) The heart was enlarged (850 g). with severe four-chamber dilatation and normal valves. Note the endocardial fibrosis In the left ventricle (arrowheads). LA left atrtum; LV, left ventricle; RA right atrium; rN. right ventricle. The left main (B) and left anterior descending (C) coronary arteries had greater than 75% and approxImately 70% cross-sectional area luminal narrowing by atherosclerosis (arrows ouftlne true lumen), while the left circumflex and right coronary arteries were narrowed up to 50%. (Band C: Movat pentachrome stain. Magnlficat1ons: B. x 7; C, x 11.) There was no eYIdance of ocute or grossly visible healed myocardial Infarction. but the myocardium had Interstltlal fibrosis (0) and focal perivascular subendocardial fibrosis, predominantly In the left ventricle (E) (arrows). (F) An Ischemic area In the subendocardlum consisting of vacuolated myocytes adjacent to an area of fibrosis. (0, E and F: Masson trichrome stain. Magnlflcat1ons: D. x 230; Eo x 91;F, x 230.)
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FIGURE Z. Ischemic CM. A 54-year-old man had an anterior myocardlallnfarctlon at the age of 49 years and subseQuen1ly developed progressive conges11ve heart failure. He died following an episode of ventricular tachycardia and ventricular flbrlilallon. (A) The heart weighed 630 g. with marked lett ventricular dllatatlon and compensatory hypertrophy and healed anterior-septal transmural myocardial Infarctlon (arrowheads) . Note the mar1
some patients, it may diminish with increasing failure. Other patients may not experience angina at all (eg, diabetics).'? A prior history of myocardial infarction mayor may not be known, but the ECG may help establish the etiology of heart failure when evidence of a previous infarction is noted. Otherwise, the ECG shows diffuse myocardial disease (wide QRS complexes . broad-notched P waves, S-T segment, and T wave abnormalities, and evidence of biventricular hypertrophyj.P-'? The left ventricular ejection fraction in patients with ischemic CM is usually less than 40%, similar to idiopathic dilated CM. Survival for ischemic CM parallels idiopathic dilated CM, with death occurring suddenly from fatal arrhythmia or from progressive congestive heart failure. 10 Although a retrospective autopsy study may have inherent bias, we attempted to minimize such bias by
reviewing a consecutive series of patients with chronic congestive heart failure. No single feature was found that could distinguish patients with coronary CM from those with ischemic or idiopathic dilated CM, but a combination of several clinical and morphologic characteristics may help in differentiating coronary CM from other congestive CMs. All nine of our patients with coronary CM had arrhythmias (usually atrial fibrillation or ventricular tachycardia), their duration of congestive heart failure tended to last longer. and they were most likely to die suddenly. Coronary CM patients were older than those with idiopathic dilated CM in our series and similar in age to those with ischemic CM. and they had known coronary risk factors. The hearts from patients with coronary CM were hypertrophied and had bilateral ventricular dilatation. Coronary CM hearts were similar
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FIGURE 3. Idiopathic dilated eM. A 17year-old male developed progressive heart failure over the course of a year. He had multiple pulmonary emboli and died with sepsis. The heart weighed 560 g and had marked four-chamber dilatation. Note the endocardiai fibrosis. representing organized mural thrombus. in left ventricle (arrows). All valves were normal. LA left otrtum; LV, lett ventricle; RA right atrium; IN. right ventricle.
TAiLE 3. Morphologic Fea1ures In Hearts From 54 Necropsy Patients With Congestive Heart Failure
Heart weight (g) Grossly visible healed infarction Chamber dilatation (3+ to 4+) Right atrium Right ventricle Left atrium Left ventricle Bilateral Pattern of fibrosis Focal (replacement) Interstitial Healed Infarction Transmural Subendocardial Mural thrombus Endocardial fibrosis.
Coronary CM(%)
Ischemic CM(%)
Idiopathic Dilated CM(%)
642 ± 95
598 ± 93
616 ± 179
0
26 (100)
0
7 (87) 6 (67) 6 (67) 5 (56) 6 (67)
7 (27) 6 (23) 10 (39) 13 (50) 7 (27)
6 (32) 9 (47) 10 (53) 10 (53) 8 (42)
9 (100) 9 (100)
26 (100) 7 (27)
5 (26) 19 (100)
0 0 3 (33) 2 (22)
18 (59) 12 (46) 16 (62) 16 (62)
0 0 13 (68) 2 (11)
• p < .05 for ischemic CM versus coronary CM and versus idiopathic dilated CM.
to ischemic CM with respect to the presence of coronary artery disease, but grossly visible remote infarcts were not seen. A history of alcohol use was documented in two patients with coronary CM, raising the possibility that they had alcoholic CM. Neither of these two patients were classified clinically as alcohol "abusers," nor did they have any stigmata of chronic alcohol use either clinically (ie, cirrhosis, neuropathy) or at necropsy. However, an accurate history of alcohol use may be difficult to elicit in those who abuse alcohol. Alcoholic eM usually occurs in patients with a history of alcohol use of greater than 10 years 2S and they usually have insignificant atherosclerosis.P" N either of these characteristics was the case in our two patients with coronary CM. The association of coronary artery disease and heart failure both with and without myocardial infarction has been noted previously. Akins et aP~5 reported two patients with severe congestive heart failure who underwent stress thallium-20 1 myocardial imaging which demonstrated clinically silent areas of ischemia, and both improved clinically following coronary artery bypass. Although there were areas iden-
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TABLE 4- Extent of Narrowing In the Four Major Epicardial Coronary Arteries In 54 Necropsy Patients With Congesflve Heart Failure Coronary CM (%) No. of coronary arteries examined Cross-sectional area of luminal narrowing 0---25% 26--50% 51-75% >75% No. of coronary arteries with >75% narrowing per patient I 2 3 4
Mean number of coronary arteries with >75% narrowing Left main Left anterior descending Left circumflex Right No. of coronary arteries with total occlusion Right Left main Anterior descending Left circumflex" Total
36
Ischemic CM (%) 104
Idiopathic Dilated CM(%) 76
7 (19) 6 (17) 6 (17) 17 (47)
17 (16) 13 (13) 9 (9) 65 (63)
2 (22) 4 (44) 2 (22)
1(4) 8 (31) 11 (42) 6 (23)
0 0 0 0
2.2:!: 1.0 0
2.3:!: 0.9 9 (35)
0
9 (100) 5 (56) 5 (56)
22 (85) 22 (85) 19 (73)
2 0
7 I 10 28
I (11)
2
5 9/36 (25)
60 (79) 11 (15) 5 (7) 0
46/104 (44)
* P < .05.
tified as scars in one of these two patients, the favorable response following coronary revascularization indicated that areas of reversible ischemia contributed significantly to their cardiac failure. Shanes et al 26 described a patient without ECG evidence of infarction who had a congestive cardiomyopathy due to coronary artery disease which was corrected following coronary bypass surgery. Visser et aP7 recently reported that in a small number of patients who had serial angiograms over an interval of up to 10 years, progression of coronary artery narrowing from less than 90% to total occlusion was associated with a decrease in ejection fraction and regional wall motion abnormalities, suggesting that congestive heart failure had progressed in the absence of clinical myocardial infarction. Raftery et al 2B described four patients who had rapidly progressive cardiomyopathy and angiographic and/or necropsy evidence of significant coronary artery disease. While they recognized that it is possible to find coincidental coronary disease in middle-aged patients with congestive heart failure, they favored the possibility that chronic ischemia and fibrosis was the more likely cause of myocardial failure, rather than a selective "idiopathic" process. Our patients are similar to the 18 patients described by Ross and Roberts -s who had congestive heart failure of more than 3 months' duration and
greater than 75% cross-sectional area luminal narrowing of one or more of the major epicardial coronary arteries, but no grossly visible scars or evidence of necrosis. In their series, a mean number of 1.7 of the four major epicardial coronary arteries per patient were narrowed more than 75%, and 42% of the coronary arteries had 76% to 100% narrowing (compared with 44% for our patients). The patients of Ross and Roberts differed from ours, however, in that the majority died from congestive heart failure (67% versus 33% in our series), and mural thrombi were more prevalent (50% versus 33% for our patients). Visible scars were absent (and patients who had "left ventricular or septal replacement fibrosis" were excluded), but these investigators failed to describe the histologic findings in the myocardium. We recognize that, by strict criteria.F? heart failure on the basis of coronary artery disease should not be called "cardiomyopathy," since the etiology is known. We, like others,~-5.9.10 have used the term "ischemic cardiomyopathy" in this study to subgroup patients who have heart failure secondary to severe coronary atherosclerosis and usually (but not always) healed infarctions. to Based on similarities in age, presence of coronary risk factors, and extent of coronary artery disease, coronary CM may represent a subset of "ischemic" CM that is characterized by a longer duration of heart failure, and these patients may have a greater risk for sudden death compared with those with ischemic CM. It is also possible, however, that coronary CM represents idiopathic dilated eM in patients with coronary risk factors who develop coronary artery disease but do not manifest symptoms of ischemia. While we cannot determine whether coronary artery disease and congestive heart failure in these patients was related or simply coincidental, further identification of cases such as these may help elucidate pathogenesis and indicate whether coronary revascularization should be considered a therapeutic modality.
REFERENCES I. Johnson RA, Palacios I: Dilated cardiomyopathies of the heart. N Engl] Med 307:1051-1058,1982 2. GoodwinJF. Oakley CM: The cardiomyopathies. Br Heart J 34:545-552, 1972 3. Burch GE, Giles TO, Cololough HL: Ischemic cardiomyopathy. Am HeartJ 79:291-292, 1970 4. Burch GE, Tsui CY, Harb JM: Ischemic cardiomyopathy. Am HeartJ 83 :340-350.1972 5. Burch GE, Giles TO: Ischemic cardiomyopathy: Diagnostic, pathophysiologic, and therapeutic considerations, in Brest AN (ed): Cardiovascular Clinics, vol 4. Philadelphia, PA, Davis, 1972, pp 204-220 6. Yatteau RF, Peter RN, Behar VS, et al: Ischemic cardiomyopathy: The myopathy of coronary artery disease. Am J Cardiol 34:520-525, 1974 7. Faulkner SL, Stoney WS, Alford WC, et al: Ischemic cardiomyopathy: Medical versus surgical treatment. J Thorac Cardiavase Surg 74:77-82, 1977 8. Dash H ,Johnson RA, Dinsmore RE, et al: Cardiomyopathic syndrome due to coronary artery disease. Br Heart] 39:733-739, 1977 9. Shuster EH, Bulkley BH : Ischemic cardiomyopathy: A clin-
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icopathologic study of fourteen patients. Am Heart ] 100:506-512, 1980 10. Pantely GA, Bristow JD : Ischemic cardiomyopathy. Prog Cardiovasc Dis 27:95-114, 1984 I I. Virmani R, Roberts WC: Quantification of coronary arterial narrowing and ofleft ventricular myocardial scarring in healed myocardial infarction with chronic, eventually fatal , congestive heart failure . Am J Med 68:831-838, 1980 12. Ross EM, Roberts WC: Severe atherosclerotic coronary arterial narrowing and chronic congestive heart failure without myocardial infarction: Analysis of 18 patients studied at necropsy . AmJ Card ioI57:51-56, 1986 13. Isner JM, Virmani R, Itscowitz SB, et al: Left and right ventricular myocardial infarction in idiopathic dilated cardiomyopathy. Am Heart ] 99:235-242, 1980 14. Ridolfi RL, Hutchins GM: The relationship between coronary artery lesions and myocard ial infarcts: Ulceration of atherosclerotic plaques precipitating coronary thrombosis. Am Heart J 93:468-486, 1977 15. Roberts WC, Ferrans Vj: Pathologic anatomy of the cardiomyopathies. HUM PATHOL 6:287-342, 1975 16. Dick MR, Unverferth DV, Baba N: The pattern of myocardial degeneration in nonischemic congestive cardiomyopathy. HUM PATHOL 13:740-744, 1982 17. Schwarz F, Mall G, Zebe H, et al: Quantitative morphologic findings of the myocardium in idiopathic dilated cardiomyopathy. Am] CardioI51:501-506, 1983 18. Davies MJ: The cardiomyopathies: A review of terminology, pathology and pathogenesis. Histopathology 8:363-393, 1984 19. Rose AG, Beck W: Dilated (congestive) card iomyopathy : A syndrome of severe cardiac dysfunction with remarkably few morphological features of myocardial damage. Histopathology 9:367-379 , 1985
20. Roberts WC, Siegel RJ, McManus BM: Idiopathic dilated cardiomyopathy: Analysis of 152 necropsy patients. Am] Cardiol 60:1340-1355,1987 21. Gravan is MB, Ansai AA: Idiopathic cardiomyopathies. A review of pathologic studies and mechanisms of pathogenesis. Arch Pathol Lab Med III :915-929, 1987 22. Edwards WD: Cardiomyopathies. HUM PATHOL 18:625635, 1987 23. Wynne J, Braunwald E: The cardiomyopathies and myocardiudes, in Braunwald W (ed): Heart Disease. A Textbook of Cardiovascular Medicine, ed 2. Philadelphia, PA, Saunders, 1984. pp 1399-1456 24. Vikhert AM, Tsiplenkova VG, Cherpachenko NM: Alcoholic cardiomyopathy and sudden cardiac death. J Am Coil Cardiol 8:3A-I1 A, 1986 25. Akins CWo Pohost GM, Desanctis RW, et al: Selection of angina-free patients with severe left ventricular dysfunction for myocardial revascularizarion. Am J CardioI46:695-699. 1980 26. Shanes JG, Kondos GT, Levitsky S, et al: Coronary artery obstruction : A potentially reversible cause of dilated cardiomyopathy . Am Heart J 110:173-178, 1985 27. Visser RF, van der Werf T, Ascoop CAPL, et al: The influence of anatomic evolution of coronary artery disease on left ventricular contraction: An angiographic follow-up study of 300 nonoperated patients. Am Heart J 112:963-972. 1986 28. Raftery EB, Banks DC, Oram S: Occlusive disease of the coronary arteries presenting as primary congestive cardiornyopa; thy. Lancet 2:1147-1150, 1969 29. World Health Organization/International Society and Federation of Cardiology: Report of the WHOIISFC task force on the definition and classification of cardiomyopathies. Br Heart J 44:672-673, 1980
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athy").' Cardiomyopathy from coronary artery disease is clinically different from idiopathic dilated CM.3-10 The patient with ischemic CM usually has angina that disappears as failure becomes more severe, a history of prior infarction, and myocardial fibrosis (discreet or diffuse) due to coronary artery disease in the ab-
From the Department of Pathology, Vanderbilt University, Nashville, TN; and the Department of Cardiovascular Pathology, The Armed Forces Institute of Pathology, Washington, DC. Accepted for publication May 16, 1989. Key words: cardiomyopathy, ischemic cardiomyopathy, coronary artery disease. Addresscorrespondenceand reprint requests toJames B. Atkinson, MD, PhD, Department of Pathology, Vanderbilt University, Nashville. TN 37232.
sence of ventricular aneurysm.5 .10.l1 Ross and Roberts -'' described a series of patients with congestive heart failure who had severe coronary artery disease but no clinical or morphologic evidence of myocardial infarction. We have also noted a subgroup of patients who had congestive heart failure with clinical and morphologic features different from ischemic and idiopathic dilated CM. To further elucidate this distinct subgroup, which we called "coronary" CM, we retrospectively reviewed a cohort of necropsy patients with long-standing congestive heart failure who fulfilled the criteria of CM . The patients were classified into idiopathic dilated CM, so-called ischemic CM, and the coronary CM groups.
METHODS Clinical and necropsy records of 54 patients (45 men and nine women) who had clinically documented congestive heart failure for at least 6 months with no evidence of intrinsic valvular, congenital, or pericardial disease were retrospectively studied. These cases were obtained by reviewing consecutive autopsy records from 1983 to 1987 from the Vanderbilt University and Nashville Veterans Administration Medical Centers (Nashville, TN). The following features were recorded : age, sex, cardiovascular risk factors, history of drug or ethanol abuse or previous viral illness, duration of heart failure, radiographic and electrocardiographic (ECG) findings, and cause of death. At autopsy, the hearts were weighed, the coronary arteries were injected with barium-gelatin pigment, and the hearts were fixed overnight in 10% buffered formalin (but not perfusion-fixed). The following morphologic features were reviewed by both authors and recorded : presence or absence of healed and/or acute myocardial infarction, wall thickness (measured at the tip of the posteromedial papillary muscle on the mid posterior wall) of the left and right ventricles, extent of chamber d ilatation (graded on a scale from I + to 4 + , with I + representing "normal" chamber size and 4 + representing severe dilatation), microscopic pattern and location of fibrosis (interstitial versus focal, and grossly visible subendocardial versus transmural scars), and extent of coronary artery narrowing by atherosclerosis in the four major epicardial coronary arteries (left main, anterior descending, left circumflex, and right) after serial sectioning at 2-mm intervals. Tabulation of light microscopic findings was made without knowledge of the diagnosis. Data are expressed as mean ± standard deviation and statistical analyses were by Student'S t test or X2 test. Idiopathic dilated CM was defined by the following criteria: clinically documented heart failure for at least 6 months, increased heart weight (more than 350 g in women and more than 400 g in men), dilatation of all four cardiac
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chambers (ventricles usually more than atria), absence of acute or healed myocardial infarction, anatomically normal cardiac valves (or valves having only minimal, focal scars), all major epicardial coronary arteries narrowed less than 75% in cross-sectional area by atherosclerosis, and no associated systemic or other known cardiovascular conditions. 13 For ischemic CM, patients had clinically documented congestive heart failure for at least 6 months, healed left ventricular myocardial infarction (subendocardial or transmural) in the absence of ventricular aneurysm, no evidence of acute infarction at autopsy, cardiomegaly with dilatation of all four chambers (ventricles usually more than atria), one or more major epicardial coronary arteries narrowed more than 75% in cross-sectional area by atherosclerotic plaque, and normal cardiac valves. Lesions were designated transmural when they involved more than half of the thickness of the myocardium, and subendocardial when involving less than half of the inner portion of the myocardial wall. Only those lesions that had at least one dimension 3 cm or greater were considered to be related to coronary artery disease.!" Patients who defied classification into either group had clinically documented heart failure for at least 6 months, cardiomegaly with four-chamber dilatation, absence of acute or grossly visible healed myocardial infarction, normal cardiac valves, and one or more coronary arteries narrowed more than 75% in cross-sectional area by atherosclerotic plaque. Patients with a documented history of hypertension were excluded from the coronary CM group.
RESULTS Clinical Features
The mean ages of patients with coronary and ischemic CM were greater than those with idiopathic dilated eM (P < .05; Table 1). The duration of congestive heart failure was longest in those with coronary CM (4.1 ± 3.4 years). All patients with coronary CM had a documented history of cardiac arrhythmias, with a higher incidence of atrial fibrillation and ventricular tachycardia (66%) than those with idiopathic dilated CM or ischemic CM (Table 1). The ECG also showed evidence of either conduction defects or ST-T wave changes in two thirds of the coronary CM patients. There were no specific radiographic features that distinguished the three groups, and the majority of patients had radiographic evidence of cardiomegaly (46 of 54,85%). Echocardiography had been performed in only two patients with coronary CM; one patient had global hypokinesia and the other had septal hypokinesia and a poorly contractile left ventricle. Four patients with idiopathic dilated CM had echocardiography, and all showed dilated and poorly functioning ventricles. Six patients with ischemic eM had echocardiograms, showing focal hypokinesis or akinesis.
TABLE 1. Clinical Features of 54 Necropsy Patients With Congestive Heart Failure
No. of patients Male Female Age (yr) (mean ± 50)* Duration of CHF (yr) Arrhythmia (total) Atrial fibrillation Ventricular tachycardia PVC Sinus tachycardia Atrial flutter PAC Other None ECG findings Conduction defect or block ST·T wave changes Axis deviation Myocardial infarction Left ventricular hypertrophy No. of patients receiving medication for heart failure Digoxin Diuretic Antiarrhythmic Total no. of patients Cause of death CHF Sudden death or arrhythmiat Pulmonary embolus
Coronary CM(%)
Ischemic CM (%)
Idiopathic Dilated eM (%)
9 8 1 61.6 ± 9.9 4.1 ± 3.4 9 (100) 3 (33) 3 (33)
26 21 5 63.5 ± 9.5 3.0 ± 3.1 22 (85) 2 (8) 7 (27) 9 (35) 2 (8) 1(4) 3 (12) 4 (15) 4 (15)
19 16 3 47.0 ± 18.9 2.2 ± 2.6 11 (58) 4 (21) 2 (11) 2 (II) 1 (5) 0 0 3 (16) 8 (42)
2 (22)
11(42) II (42) 6 (23) 14 (54) 3 (12)
7 (37) 10 (53) 5 (26) 0 7 (37)
7 (78) 3 (33) 6 (67) 8 (89)
21 (81) 18 (69) 8 (31) 25 (96)
13 (68) 10 (39) 7 (37) 15 (79)
3 (33) 5 (56)
7 (27) 9 (35) 4 (15) 6 (23)
II (58)
0 1 (II)
I (11) 0 2 (22) 0 6 (67) 4 (44) 2 (22)
0
0
Otherj
1 (11)
3 (16) 1(5) 4 (21)
Abbreviations: CHF, congestive heart failure; PAC, premature atrial contraction; PVC, premature ventricular contraction. .05 for coronary CM and ischemic CM versus idiopathic dilated CM. t p < .05 for coronary CM versus ischemic CM and idiopathic dilated CM. :!: Other causes of death include coronary CM-sepsis; ischemic CM-pneumonia (three patients), neoplasm (two patients), and cerebrovascular accident (one patient); idiopathic dilated CM-tamponade after endomyocardial biopsy (one patient), alcoholic hepatitis (one patient), sepsis (one patient) and neoplasm (one patient).
*p <
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CORONARY CARDIOMYOPATHY (Atkinson et al)
Sudden death andlor arrhythmias were the cause of death in five of nine patients in the coronary CM group, whereas death from congestive heart failure was more frequent in the idiopathic dilated CM group (11 of 19, 58%; Table 1). Other causes of death in the coronary CM group included congestive heart failure (three patients) and sepsis (one patient). Patients with ischemic CM had near equal frequencies of sudden death (35%) and death from congestive heart failure (27%). None of the patients with coronary CM had a known history of viral illness prior to onset of symptoms. In contrast, three idiopathic dilated CM patients had a viral illness preceding the onset of congestive heart failure (Table 2). In two ischemic CM patients, a viral illness had occurred after the onset of congestive heart failure. Alcohol use was documented in two coronary CM patients, nine idiopathic dilated CM patients, and 11 ischemic CM patients (P value not significant). Angina pectoris was nearly as frequent in coronary CM patients as in patients with ischemic CM (44% versus 54%).
Morphologic Features Hearts in all three groups of patients were enlarged, with coronary CM patients having the greatest cardiomegaly (P value not significant) (Figs I through 3 and Table 3). Although mild to moderate bilateral chamber dilatation was found in all hearts, severe bilateral dilatation (3 + to 4 +) was most prominent in coronary CM (67%), while dilatation of the left ventricle alone was found more often in ischemic CM (50%). Mural thrombi were present in nearly two thirds of the hearts from patients with ischemic CM and idiopathic dilated CM, but in only three of the nine coronary CM hearts. Two of nine coronary CM hearts had grossly visible endocardial scars (Table 3). Although endocardial fibrosis was observed in 16 of 26 hearts with ischemic CM (Table 3), in only three cases was this fibrosis not related to transmural scar. TABLE 2. Clinical Historyin 54 Necropsy Patients With Congestive Heart Failure
Smoking Diabetes mellitus Hyperlipidemia Hypertension Family history of cardiovascular disease Alcohol use Viral illness Cardiovascular history Angina pectoris Myocardial infarction Average no. of cardiovascular risk factors per patient*
Coronary CM(%)
Ischemic CM (%)
Idiopathic Dilated CM(%)
4 (44) I (11) 0 0
16 (62) II (42) 5 (19) 12 (46)
12 (63) 0 0 0
6 (67) 2 (22) 0
11(42) 9 (35) 2 (8)
9 (47) II (58)
4(44) 0
14 (54) 15 (58)
4 (21) 0
1.8:!; 1.0
1.6:!; 0.9
1.1 :!; 0.9
3 (16)
* Smoking, diabetes mellitus, hyperlipidemia, positive family history.
The various degrees of cross-sectional area luminal narrowing in the coronary arteries are shown in Table 4. The mean number of the four major epicardial coronary arteries narrowed more than 75% was 2.3 ± 0.9 for ischemic CM and 2.2 ± 1.0 for coronary CM. The left anterior descending coronary artery was most often narrowed in coronary CM (nine of nine hearts), followed by the right and left circumflex coronary arteries (five of nine hearts each). In the ischemic CM hearts, the left anterior descending and left circumflex coronary arteries had an equal frequency of severe narrowing (22 of 26 for each), followed by right (19 of 26) and left main coronary arteries (nine of 26). Coronary CM hearts had fewer coronary arteries that were totally occluded compared with ischemic eM (Table 4). Coronary arteries from patients with coronary CM had an approximate equal incidence of significant proximal and distal narrowing, while ischemic CM hearts had critical proximal lesions or severe diffuse disease (data not shown). Idiopathic dilated CM had interstitial fibrosis microscopically in both ventricles. Ischemic CM had subendocardial andlor transmural scarring as well as perivascular fibrosis (Table 3). In contrast, hearts from patients with coronary CM had a pattern of microscopic fibrosis that was interstitial as well as focal, most prominent in the subendocardium of the left ventricle but not comprising a grossly discreet area of healed infarction (ie, not greater than 3 em in greatest dimension) (Fig 1). Only five of 19 idiopathic dilated CM hearts and seven of 26 ischemic CM hearts had a similar combination of interstitial and focal fibrosis in our series. Myofibrillar loss (vacuolization) and hypertrophy of varying degrees were observed in all sections of myocardium in coronary CM and idiopathic dilated CM hearts. DISCUSSION
The diagnosis of idiopathic dilated CM is dependent on the absence of significant coronary artery atherosclerosis, valvular disease, or systemic hypertension. The microscopic picture is one of interstitial, focal, and/or, rarely, transmural fibrosis with myocyte hypertrophy, atrophy, vacuolization, and myofibrillar loSS.I5-22 In cases of long-standing cardiac failure, dense subendocardial fibrosis can be seen which is indistinguishable from ischemic damage. IS Clinically, the left ventricular ejection fraction is reduced (less than 40%), arrhythmias are common, and death is usually due to progressive heart failure, although sudden death or death from pulmonary or systemic emboli may also occur. 20 Patients with ischemic CM have severe coronary artery disease and scarring of the myocardium consistent with a healed transmural or subendocardial infarction. 3-9,11 The diagnosis is usually made in middle-aged or older patients with congestive heart failure and enlarged hearts. Up to 90% of patients with ischemic CM may have exertional angina!" and, although angina may be the principal clinical feature in
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'1GUIIi. Coronary CM. A 62-year-old man with a 5-year history of congestive heart failure and atrial flbrlllat10n died suddenly. (A) The heart was enlarged (850 g). with severe four-chamber dilatation and normal valves. Note the endocardial fibrosis In the left ventricle (arrowheads). LA left atrtum; LV, left ventricle; RA right atrium; rN. right ventricle. The left main (B) and left anterior descending (C) coronary arteries had greater than 75% and approxImately 70% cross-sectional area luminal narrowing by atherosclerosis (arrows ouftlne true lumen), while the left circumflex and right coronary arteries were narrowed up to 50%. (Band C: Movat pentachrome stain. Magnlficat1ons: B. x 7; C, x 11.) There was no eYIdance of ocute or grossly visible healed myocardial Infarction. but the myocardium had Interstltlal fibrosis (0) and focal perivascular subendocardial fibrosis, predominantly In the left ventricle (E) (arrows). (F) An Ischemic area In the subendocardlum consisting of vacuolated myocytes adjacent to an area of fibrosis. (0, E and F: Masson trichrome stain. Magnlflcat1ons: D. x 230; Eo x 91;F, x 230.)
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FIGURE Z. Ischemic CM. A 54-year-old man had an anterior myocardlallnfarctlon at the age of 49 years and subseQuen1ly developed progressive conges11ve heart failure. He died following an episode of ventricular tachycardia and ventricular flbrlilallon. (A) The heart weighed 630 g. with marked lett ventricular dllatatlon and compensatory hypertrophy and healed anterior-septal transmural myocardial Infarctlon (arrowheads) . Note the mar1
some patients, it may diminish with increasing failure. Other patients may not experience angina at all (eg, diabetics).'? A prior history of myocardial infarction mayor may not be known, but the ECG may help establish the etiology of heart failure when evidence of a previous infarction is noted. Otherwise, the ECG shows diffuse myocardial disease (wide QRS complexes . broad-notched P waves, S-T segment, and T wave abnormalities, and evidence of biventricular hypertrophyj.P-'? The left ventricular ejection fraction in patients with ischemic CM is usually less than 40%, similar to idiopathic dilated CM. Survival for ischemic CM parallels idiopathic dilated CM, with death occurring suddenly from fatal arrhythmia or from progressive congestive heart failure. 10 Although a retrospective autopsy study may have inherent bias, we attempted to minimize such bias by
reviewing a consecutive series of patients with chronic congestive heart failure. No single feature was found that could distinguish patients with coronary CM from those with ischemic or idiopathic dilated CM, but a combination of several clinical and morphologic characteristics may help in differentiating coronary CM from other congestive CMs. All nine of our patients with coronary CM had arrhythmias (usually atrial fibrillation or ventricular tachycardia), their duration of congestive heart failure tended to last longer. and they were most likely to die suddenly. Coronary CM patients were older than those with idiopathic dilated CM in our series and similar in age to those with ischemic CM. and they had known coronary risk factors. The hearts from patients with coronary CM were hypertrophied and had bilateral ventricular dilatation. Coronary CM hearts were similar
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HUMAN PATHOLOGY
FIGURE 3. Idiopathic dilated eM. A 17year-old male developed progressive heart failure over the course of a year. He had multiple pulmonary emboli and died with sepsis. The heart weighed 560 g and had marked four-chamber dilatation. Note the endocardiai fibrosis. representing organized mural thrombus. in left ventricle (arrows). All valves were normal. LA left otrtum; LV, lett ventricle; RA right atrium; IN. right ventricle.
TAiLE 3. Morphologic Fea1ures In Hearts From 54 Necropsy Patients With Congestive Heart Failure
Heart weight (g) Grossly visible healed infarction Chamber dilatation (3+ to 4+) Right atrium Right ventricle Left atrium Left ventricle Bilateral Pattern of fibrosis Focal (replacement) Interstitial Healed Infarction Transmural Subendocardial Mural thrombus Endocardial fibrosis.
Coronary CM(%)
Ischemic CM(%)
Idiopathic Dilated CM(%)
642 ± 95
598 ± 93
616 ± 179
0
26 (100)
0
7 (87) 6 (67) 6 (67) 5 (56) 6 (67)
7 (27) 6 (23) 10 (39) 13 (50) 7 (27)
6 (32) 9 (47) 10 (53) 10 (53) 8 (42)
9 (100) 9 (100)
26 (100) 7 (27)
5 (26) 19 (100)
0 0 3 (33) 2 (22)
18 (59) 12 (46) 16 (62) 16 (62)
0 0 13 (68) 2 (11)
• p < .05 for ischemic CM versus coronary CM and versus idiopathic dilated CM.
to ischemic CM with respect to the presence of coronary artery disease, but grossly visible remote infarcts were not seen. A history of alcohol use was documented in two patients with coronary CM, raising the possibility that they had alcoholic CM. Neither of these two patients were classified clinically as alcohol "abusers," nor did they have any stigmata of chronic alcohol use either clinically (ie, cirrhosis, neuropathy) or at necropsy. However, an accurate history of alcohol use may be difficult to elicit in those who abuse alcohol. Alcoholic eM usually occurs in patients with a history of alcohol use of greater than 10 years 2S and they usually have insignificant atherosclerosis.P" N either of these characteristics was the case in our two patients with coronary CM. The association of coronary artery disease and heart failure both with and without myocardial infarction has been noted previously. Akins et aP~5 reported two patients with severe congestive heart failure who underwent stress thallium-20 1 myocardial imaging which demonstrated clinically silent areas of ischemia, and both improved clinically following coronary artery bypass. Although there were areas iden-
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TABLE 4- Extent of Narrowing In the Four Major Epicardial Coronary Arteries In 54 Necropsy Patients With Congesflve Heart Failure Coronary CM (%) No. of coronary arteries examined Cross-sectional area of luminal narrowing 0---25% 26--50% 51-75% >75% No. of coronary arteries with >75% narrowing per patient I 2 3 4
Mean number of coronary arteries with >75% narrowing Left main Left anterior descending Left circumflex Right No. of coronary arteries with total occlusion Right Left main Anterior descending Left circumflex" Total
36
Ischemic CM (%) 104
Idiopathic Dilated CM(%) 76
7 (19) 6 (17) 6 (17) 17 (47)
17 (16) 13 (13) 9 (9) 65 (63)
2 (22) 4 (44) 2 (22)
1(4) 8 (31) 11 (42) 6 (23)
0 0 0 0
2.2:!: 1.0 0
2.3:!: 0.9 9 (35)
0
9 (100) 5 (56) 5 (56)
22 (85) 22 (85) 19 (73)
2 0
7 I 10 28
I (11)
2
5 9/36 (25)
60 (79) 11 (15) 5 (7) 0
46/104 (44)
* P < .05.
tified as scars in one of these two patients, the favorable response following coronary revascularization indicated that areas of reversible ischemia contributed significantly to their cardiac failure. Shanes et al 26 described a patient without ECG evidence of infarction who had a congestive cardiomyopathy due to coronary artery disease which was corrected following coronary bypass surgery. Visser et aP7 recently reported that in a small number of patients who had serial angiograms over an interval of up to 10 years, progression of coronary artery narrowing from less than 90% to total occlusion was associated with a decrease in ejection fraction and regional wall motion abnormalities, suggesting that congestive heart failure had progressed in the absence of clinical myocardial infarction. Raftery et al 2B described four patients who had rapidly progressive cardiomyopathy and angiographic and/or necropsy evidence of significant coronary artery disease. While they recognized that it is possible to find coincidental coronary disease in middle-aged patients with congestive heart failure, they favored the possibility that chronic ischemia and fibrosis was the more likely cause of myocardial failure, rather than a selective "idiopathic" process. Our patients are similar to the 18 patients described by Ross and Roberts -s who had congestive heart failure of more than 3 months' duration and
greater than 75% cross-sectional area luminal narrowing of one or more of the major epicardial coronary arteries, but no grossly visible scars or evidence of necrosis. In their series, a mean number of 1.7 of the four major epicardial coronary arteries per patient were narrowed more than 75%, and 42% of the coronary arteries had 76% to 100% narrowing (compared with 44% for our patients). The patients of Ross and Roberts differed from ours, however, in that the majority died from congestive heart failure (67% versus 33% in our series), and mural thrombi were more prevalent (50% versus 33% for our patients). Visible scars were absent (and patients who had "left ventricular or septal replacement fibrosis" were excluded), but these investigators failed to describe the histologic findings in the myocardium. We recognize that, by strict criteria.F? heart failure on the basis of coronary artery disease should not be called "cardiomyopathy," since the etiology is known. We, like others,~-5.9.10 have used the term "ischemic cardiomyopathy" in this study to subgroup patients who have heart failure secondary to severe coronary atherosclerosis and usually (but not always) healed infarctions. to Based on similarities in age, presence of coronary risk factors, and extent of coronary artery disease, coronary CM may represent a subset of "ischemic" CM that is characterized by a longer duration of heart failure, and these patients may have a greater risk for sudden death compared with those with ischemic CM. It is also possible, however, that coronary CM represents idiopathic dilated eM in patients with coronary risk factors who develop coronary artery disease but do not manifest symptoms of ischemia. While we cannot determine whether coronary artery disease and congestive heart failure in these patients was related or simply coincidental, further identification of cases such as these may help elucidate pathogenesis and indicate whether coronary revascularization should be considered a therapeutic modality.
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icopathologic study of fourteen patients. Am Heart ] 100:506-512, 1980 10. Pantely GA, Bristow JD : Ischemic cardiomyopathy. Prog Cardiovasc Dis 27:95-114, 1984 I I. Virmani R, Roberts WC: Quantification of coronary arterial narrowing and ofleft ventricular myocardial scarring in healed myocardial infarction with chronic, eventually fatal , congestive heart failure . Am J Med 68:831-838, 1980 12. Ross EM, Roberts WC: Severe atherosclerotic coronary arterial narrowing and chronic congestive heart failure without myocardial infarction: Analysis of 18 patients studied at necropsy . AmJ Card ioI57:51-56, 1986 13. Isner JM, Virmani R, Itscowitz SB, et al: Left and right ventricular myocardial infarction in idiopathic dilated cardiomyopathy. Am Heart ] 99:235-242, 1980 14. Ridolfi RL, Hutchins GM: The relationship between coronary artery lesions and myocard ial infarcts: Ulceration of atherosclerotic plaques precipitating coronary thrombosis. Am Heart J 93:468-486, 1977 15. Roberts WC, Ferrans Vj: Pathologic anatomy of the cardiomyopathies. HUM PATHOL 6:287-342, 1975 16. Dick MR, Unverferth DV, Baba N: The pattern of myocardial degeneration in nonischemic congestive cardiomyopathy. HUM PATHOL 13:740-744, 1982 17. Schwarz F, Mall G, Zebe H, et al: Quantitative morphologic findings of the myocardium in idiopathic dilated cardiomyopathy. Am] CardioI51:501-506, 1983 18. Davies MJ: The cardiomyopathies: A review of terminology, pathology and pathogenesis. Histopathology 8:363-393, 1984 19. Rose AG, Beck W: Dilated (congestive) card iomyopathy : A syndrome of severe cardiac dysfunction with remarkably few morphological features of myocardial damage. Histopathology 9:367-379 , 1985
20. Roberts WC, Siegel RJ, McManus BM: Idiopathic dilated cardiomyopathy: Analysis of 152 necropsy patients. Am] Cardiol 60:1340-1355,1987 21. Gravan is MB, Ansai AA: Idiopathic cardiomyopathies. A review of pathologic studies and mechanisms of pathogenesis. Arch Pathol Lab Med III :915-929, 1987 22. Edwards WD: Cardiomyopathies. HUM PATHOL 18:625635, 1987 23. Wynne J, Braunwald E: The cardiomyopathies and myocardiudes, in Braunwald W (ed): Heart Disease. A Textbook of Cardiovascular Medicine, ed 2. Philadelphia, PA, Saunders, 1984. pp 1399-1456 24. Vikhert AM, Tsiplenkova VG, Cherpachenko NM: Alcoholic cardiomyopathy and sudden cardiac death. J Am Coil Cardiol 8:3A-I1 A, 1986 25. Akins CWo Pohost GM, Desanctis RW, et al: Selection of angina-free patients with severe left ventricular dysfunction for myocardial revascularizarion. Am J CardioI46:695-699. 1980 26. Shanes JG, Kondos GT, Levitsky S, et al: Coronary artery obstruction : A potentially reversible cause of dilated cardiomyopathy . Am Heart J 110:173-178, 1985 27. Visser RF, van der Werf T, Ascoop CAPL, et al: The influence of anatomic evolution of coronary artery disease on left ventricular contraction: An angiographic follow-up study of 300 nonoperated patients. Am Heart J 112:963-972. 1986 28. Raftery EB, Banks DC, Oram S: Occlusive disease of the coronary arteries presenting as primary congestive cardiornyopa; thy. Lancet 2:1147-1150, 1969 29. World Health Organization/International Society and Federation of Cardiology: Report of the WHOIISFC task force on the definition and classification of cardiomyopathies. Br Heart J 44:672-673, 1980
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