Congenitally bicuspid aortic valve causing severe,pure aortic regurgitation without superimposed infective endocarditis: Analysis of 13 patients requiring aortic valve replacement

Although stenosis and infective endocarditis are commonly appreciated complications of the congenitally bicuspid aortic valve, pure severe aortic regurgitation complicating this congenital malformation, unassociated with either stenosis or infection, is not well recognized. Among 189 patients who had aortic valve replacement at the National Heart, Lung, and Blood institute because of isolated pure aortic regurgitation, the congenitally bicuspid aortic valve, never the site of infective endocarditis, was responsible for the aortic regurgitation in 13 (7 percent). This report describes certain clinical and morphologic findings in 13 men, aged 26 to 65 years (mean 43), who required aortic valve replacement because of severe aortic regurgitation secondary to a noninfected, nonstenotic congenitally bicuspid aortic valve. Although not generally recognized, the noninfected congenitally bicuspid aortic valve is an important cause of pure aortic regurgitation severe enough to warrant aortic valve replacement.     

Amounts of coronary arterial narrowing by atherosclerotic plaques in clinically isolated,chronic, pure aortic regurgitation: Analysis of 37 necropsy patients older than 30 years

The degree of cross-sectional area (XSA) narrowing by atherosclerotic plaque in each of the 4 major epicardial coronary arteries (right, left main, left anterior descending and left circumflex) was determined at necropsy in 37 patients (30 men and 7 women) aged 34 to 77 years (mean 54) with severe, isolated, chronic, pure aortic regurgitation (AR). In 7 patients (19%), ≥ 1 major coronary artery was narrowed 76 to 100% in XSA at some point. Of the 148 major coronary arteries examined in the 37 patients, 12 arteries (8% ) were narrowed at some point 76 to 100% in XSA. Each of the 148 major coronary arteries were divided into 5-mm-long segments (average 53 per patient) and a histologic section from each segment was examined. Of the 1,977 segments, 1,087 were narrowed 0 to 25%, 669 (34%) 26 to 50%, 170 (9%) 51 to 75%, 48 (2%) 76 to 95% and 3 (0.001%) 96 to 100%. The average amount of XSA narrowing by atherosclerotic plaque per segment was about 28%. Of the 37 patients, 9 had had angina pectoris, 2 of whom had significant (> 75% XSA reduction) coronary narrowing; 2 other patients had had acute myocardial infarction clinically, 1 of whom had significant coronary narrowing at necropsy. Thus, in general, the amount of coronary narrowing in our 37 adults with severe, pure, isolated, chronic AR was relatively mild.     

Cardiac amyloidosis causing cardiac dysfunction: Analysis of 54 necropsy patients

Clinical and morphologic findings are described in 54 necropsy patients (32 men [59%]) aged 21 to 97 years (mean 64) with cardiac amyloid deposits extensive enough to cause fatal cardiac dysfunction. Chronic congestive heart failure (CHF) was present in 46 (85%). The duration of CHF, known in 39 patients, ranged from 1 to 108 months (mean 18) and lasted ≤ 12 months in 25 patients (64%). All 8 patients without CHF died suddenly and unexpectedly. Systemic arterial pressures were recorded in the last 3 months of life in 43 patients: the peak indirect systolic pressure was ≤ 130 mm Hg and the diastolic pressure < 90 mm Hg in all. Electrocardiograms, recorded in the last 6 months of life in 40 patients, were abnormal in each: low voltage in 35 (63%); “myocardial infarction pattern” in 33 (83%); abnormal QRS axis in 29 (73%); arrhythmias in 29 (73% ); first, second, or third degree heart block in 28 (45%); and complete bundle branch block in 7 (18%). In 30 patients, the QRS amplitude in all 12 leads was measured: in the 15 men it ranged from 60 to 197 mm (mean 99) (10 mm = 1 mV) and in the 15 women from 58 to 199 mm (mean 109). Diagnosis of amyloidosis was established by biopsy of noncardiac organs or tissues during life in only 18 (33%) patients. During life the condition simulated hypertrophic cardiomyopathy in 5 patients, constrictive pericardial disease in 3, and coronary heart disease (because of angina pectoris) in 4.At necropsy, the hearts ranged in weight from 300 to 900 g (mean 554), and all but 1 had a “rubbery,” noncompliant consistency. In addition to their presence in myocardial interstitium (53 patients) and in intramural coronary arteries (54 patients), amyloid deposits were present grossly in mural endocardium in all 54 patients and in valvular endocardium in 46 (85% ). The cardiac ventricles were not dilated in 43 patients (80%), but both atria were dilated in all 54 patients. Intracardiac thrombi were present in 14 patients (26% ). Cardiac amyloidosis must be considered in any elderly patient with chronic CHF unassociated with chest pain when blood pressure is normal and the electrocardiogram discloses low voltage and a pattern of “healed myocardial infarction.”     

Origin of the right coronary artery from the left sinus of Valsalva and its functional consequences: Analysis of 10 necropsy patients

Clinical and necropsy findings are described in 10 patients in whom the right coronary artery arose from the left coronary sinus and then passed to the right atrioventricular (A-V) sulcus by coursing between the aorta and the pulmonary trunk. In 7 of the 10 patients, the coronary anomaly never caused symptoms of cardiac dysfunction. In the other three, all of whom died suddenly, the coronary anomaly was the only significant abnormality found at necropsy: One patient had recurring ventricular tachycardia, one had typical angina pectoris and, in one, sudden death was the initial manifestation of cardiac dysfunction. Review of previous angiographic studies during life of 31 patients reported to have origin of the right coronary artery from the left sinus of Valsalva indicated that 9 had symptoms of cardiac dysfunction in the absence of intraluminal coronary narrowing or associated noncoronary cardiac disease. Thus, origin of the right coronary artery from the left sinus may produce cardiac dysfunction that can be fatal.     

Late (5 to 132 months) clinical and hemodynamic results after either tricuspid valve replacement or anuloplasty for ebstein's anomaly of the tricuspid valve

Late clinical and hemodynamic observations are described in 6 patients who had either tricuspid valve anuloplasty (TVA) (2 patients) or tricuspid valve replacement (TVR) (4 patients) 5 to 132 months earlier for Ebstein's anomaly of the tricuspid valve unassociated with right ventricular outflow obstruction. Of the 6 patients, 4 had improved postoperatively by 1 New York Heart Association functional class and 2 had improved by 2 functional classes. The cardiothoracic ratio decreased 5 to 12 months after either TVR or TVA in all 6 patients (from a mean of 0.72 to 0.62). Repeat cardiac catheterization 5 to 12 months after TVA or TVR disclosed that the right atrial mean pressure had increased from a median of 4.0 to 10.5 mm Hg (p = 0.05); the right ventricular peak systolic pressure had increased from 19.0 to 31.5 mm Hg (p = 0.02); the right ventricular end-diastolic pressure had increased from 5.0 to 9.0 mm Hg (p = 0.05); the systemic arterial peak systolic pressure had increased from 115 to 123 mm Hg (p = 0.03); and the cardiac index had increased (in all 4 patients in whom both pre- and postoperative values were available) from 1.7 to 2.9 liters/min/m² (p = 0.06). Thus, the tricuspid valve operations in our 6 patients with Ebstein's anomaly were associated with a decrease in symptoms of cardiac dysfunction, a decrease in cardiac size, an increase in cardiac index and an increase in right ventricular and right atrial pressures. The elevation of the right atrial pressures postoperatively may have resulted from increased right ventricular filling pressures, persistent tricuspid regurgitation or bioprosthetic stenosis.     

Morphologic features of the normal and abnormal mitral valve

Anatomic and functional features of the normal and abnormal mitral valve are reviewed. Of 1,010 personally studied necropsy patients with severe (functional class III or IV, New York Heart Association) cardiac dysfunction from primary valvular heart disease, 434 (43%) had mitral stenosis (MS) with or without mitral regurgitation (MR): unassociated with aortic valve stenosis or regurgitation or with tricuspid valve stenosis in 189 (44%) patients, and associated with aortic stenosis in 152 (35%), with pure (no element of stenosis) aortic regurgitation in 65 (15%) patients, and with tricuspid valve stenosis with or without aortic valve stenosis in 28 (6%) patients. The origin of MS was rheumatic in all 434 patients. Of the 1,010 necropsy patients, 165 (16%) had pure MR (papillary muscle dysfunction excluded): unassociated with aortic valve stenosis or regurgitation or with tricuspid valve stenosis in 97 (59%) patients, and associated with pure aortic regurgitation in 45 (27%) and with aortic valve stenosis in 23 (14%) patients. When associated with dysfunction of the aortic valve, pure MR was usually rheumatic in origin, but when unassociated with aortic valve dysfunction it was usually nonrheumatic in origin. Review of operatively excised mitral valves in patients with pure MR unassociated with aortic valve dysfunction disclosed mitral valve prolapse (most likely an inherent congenital defect) as the most common cause of MR. Excluding the patients with MR from coronary heart disease (papillary muscle dysfunction), mitral prolapse was the cause of MR in 60 (88%) of the other 68 patients, and a rheumatic origin was responsible in only 3 of the 68 patients, all 68 of whom were greater than 30 years of age. Mitral anular calcification in persons aged greater than 65 years is usually associated with calcific deposits in the aortic valve cusps and in the coronary arteries. Because calcium in each of these 3 sites is common in older individuals residing in the Western World, it is most reasonable to view mitral anular calcification in older individuals as a manifestation of atherosclerosis. Mitral anular calcium appears to be extremely uncommon in persons with total serum cholesterol levels less than 150 mg/dl. Mitral anular calcium may produce mild MR and, if the deposits are heavy enough, MS.     

Sudden death in prinzmetal's angina with coronary spasm documented by angiography: Analysis of three necropsy patients

Clinical and necropsy findings are described in three patients who had angina pectoris at rest, S-T segment elevation on electrocardiography during chest pain, coronary arterial spasm on angiography and sudden death. Although significant “fixed” coronary narrowing (that is, narrowing due to atherosclerotic plaques) was appreciated by angiography in only one of the three patients, necropsy disclosed in all three patients severe fixed coronary narrowings involving particularly the artery in which spasm had been demonstrated during life. Additionally, examination of each 5-mm long segment of the coronary artery that had been spastic during life (two patients) disclosed several focally spastic segments at necropsy, indicating that spasm persisted after death. Although most previously described necropsy patients with Prinzmetal's angina had some fixed coronary narrowing, underlying fixed narrowing may be difficult to identify angiographically as demonstrated by the three patients in this study.     

Quantitative comparison of extent of coronary narrowing and size of healed myocardial infarct in 33 necropsy patients with clinically recognized and in 28 with clinically unrecognized (“silent”) previous acute myocardial infarction

Clinical and necropsy observations are described in 61 patients with a healed transmural myocardial infarction, 33 with and 28 without a clinical history of acute myocardial infarction. There were no significant differences between the 2 groups of patients in mean age, sex, or frequency of angina pectoris, chronic congestive heart failure, systemic hypertension, sudden coronary death, or fatal acute myocardial infarction. Compared with the patients with clinically recognized acute myocardial infarction, the patients with clinically unrecognized (silent) infarction had a significantly (p < 0.05) higher incidence of diabetes mellitus (43 versus 15%), death from noncardiac causes (39 versus 9%), posterior (inferior) wall infarcts (82 versus 55%), and smaller infarcts (mean size 7 versus 17% of left ventricular wall). The patients with and without clinically recognized infarction had similar numbers of the 4 major coronary arteries severely (76 to 100% in cross-sectional area) narrowed (mean 2.8 versus $\text{2.9}\text{4.0}$ per patient), insignificant differences in incidence of severe narrowing of the left main coronary artery (18 versus 29%), similar overall percents of 5 mm segments of the 4 major coronary arteries severely narrowed (43 versus 42%), and similar percents of severely narrowed 5 mm segments of the right (46 versus 55%), left anterior descending (39 versus 33%), and left circumflex (41 versus 41%) coronary arteries.     

Sudden coronary death: comparison of patients with to those without coronary thrombus at necropsy

Among 70 victims of sudden coronary death (SCD), certain clinical and morphologic findings in the 13 with a coronary thrombus are compared with the findings in 57 victims without a coronary thrombus. The 13 with a thrombus were younger than those without (mean age 43 vs 51 years, p less than 0.02); had a lower mean percent of cross-sectional area (XSA) narrowing by plaque at the site of maximal coronary stenosis (89% vs 95%, p less than 0.01); and had a higher mean percent of 5-mm segments of the 4 major epicardial coronary arteries minimally narrowed (0 to 25% in XSA) by plaque (27% vs 19%, p less than 0.001). No differences occurred in the 2 groups with regard to sex, previous angina pectoris or clinical acute myocardial infarction, healed myocardial infarction at necropsy, mean heart weight, number of major coronary arteries narrowed 76 to 100% in XSA by atherosclerotic plaque, or the mean percent of 5-mm segments of the 4 major epicardial coronary arteries narrowed 76 to 100% in XSA by atherosclerotic plaque. Thus, coronary thrombi are infrequent in victims of SCD, and when observed, their significance is uncertain because victims of SCD without coronary thrombi have similar amounts of severe coronary narrowing.     

The floating heart or the heart too fat to sink: Analysis of 55 necropsy patients

Certain clinical and morphologic findings are described in 55 patients whose hearts at necropsy contained so much fat that they floated in water. The patients were 47 to 89 years old (mean 67). Symptomatic coronary heart disease was present in 28 (51%) and valvular heart disease (mitral stenosis) in 3 (5%). The heart at necropsy was enlarged (>350 g for women and >400 g for men) in 45 patients (82%). The mean heart weight for the 31 women was 470 g and for the 24 men, 515 g. In addition to the severe increase in fat in the atrioventricular sulci and over both ventricles, the amount of fat in the atrial septum was increased in all patients. In 14 patients (25%), the thickness of the atrial septum cephaled to the fossa ovale was ≥2 cm. Excessive fat in this location is called “lipomatous hypertrophy of the atrial septum.” Of the 16 patients (29%) with fatal acute myocardial infarction, 7 (44%) had rupture of either the left ventricular free wall or ventricular septum. The high frequency of cardiac rupture in these patients supports the contention that rupture during acute myocardial infarction is more common in the fatty than in the non-fatty heart.     

Complications of the intraaortic balloon counterpulsation device: Clinical and morphologic observations in 45 necropsy patients

Of 45 patients who died after insertion of an intraaortic balloon assist device and who were studied at necropsy, 16 (36 percent) were found to have one or more complications (total 20) related to use of the device. The 20 complications consisted of dissection of the aorta or its distal branches, or both (9), arterial perforation (3), arterial thrombi (3), arterial emboli (3), limb ischemia (1) and local wound infection (1). Of the nine cases of arterial dissection, none were diagnosed or suspected before necropsy. Of the entire 20 complications, only 4 (20 percent) were suspected before death. Although the operating team frequently encountered no difficulty at the time of insertion of the device, 12 of the 20 complications were a direct result of insertion of the intraaortic balloon assist device. In two patients in whom insertion of the balloon caused dissection of the aorta, hemodynamic improvement occurred for 2 and 3 days, respectively, even though the “intraaortic” balloon (as well as the catheter) was not located in the true lumen of the aorta. Thus, clinical evaluation of complications related to use of the intraaortic balloon assist device underestimates their frequency. Most complications are consequences of insertion of the device, not consequences of its being in place.     

Status of the major epicardial coronary arteries 80 to 150 days after percutaneous transluminal coronary angioplasty. Analysis of 3 necropsy patients

Certain clinical and necropsy cardiac findings are described in 3 men who had percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending (LAD) coronary artery 80, 90, and 150 days before sudden death. Each patient had a decrease in the mean transstenotic coronary gradient (17, 38, and 43 mm Hg) and an angiographic increase in the LAD luminal diameter (55, 60, and 65%). At necropsy, the LAD coronary artery in the area of the PTCA in each patient was narrowed 76 to 95% in cross-sectional area by atherosclerotic plaques. No cracks in plaques or other lesions which may have resulted from the PTCA procedure were identified histologically in the LAD coronary artery of any patient.     

Coronary artery disease in the hurler syndrome: Qualitative and quantitative analysis of the extent of coronary narrowing at necropsy in six children

The amount of cross-sectional area luminal narrowing in each 5 mm segment of each of the four major epicardial coronary arteries (right, left main, left anterior descending and left circumflex) is described at necropsy in six children (aged 3 to 16 years) with the Hurler syndrome. In five patients at least one of the four major coronary arteries was narrowed 76 to 100 percent, and in four of these five patients all four major arteries were narrowed to this extent. Of the 24 major coronary arteries in the six patients, 17 (71 percent) were narrowed 76 to 100 percent at some point. A total of 182 segments were examined from the 24 major coronary arteries, and the extent of narrowing was as follows: 96 to 100 percent, 14 (8 percent); 76 to 95 percent, 61 (34 percent); 51 to 75 percent, 59 (32 percent); 26 to 50 percent, 39 (21 percent) and 0 to 25 percent, 9 (5 percent). By applying a score of 1 to 4 to each 5 mm segment according to its category of narrowing (1 = 0 to 25 percent; 2 = 26 to 50 percent; 3 = 51 to 75 percent and 4 = 76 to 100 percent), the 182 segments had a total score of 570 and a mean score of 3.2, indicating that each segment was narrowed an average of about 67 percent in cross-sectional area. Thus, narrowing of the major epicardial coronary arteries at necropsy is usually diffuse and severe in the Hurler syndrome, which is the cause of the most severe coronary narrowing in childhood.     

Amount of narrowing by atherosclerotic plaque in 44 nonbypassed and 52 bypassed major epicardial coronary arteries in 32 necropsy patients who died within 1 month of aortocoronary bypass grafting

In 32 necropsy patients who died within 30 days of an aortocoronary bypass operation performed for relief of angina pectoris, the lumens in 42 (95 percent) of 44 nonbypassed and in 52 (100 percent) or 52 bypassed arteries were narrowed 76 to 100 percent in cross-sectional area by atherosclerotic plaque. Of 616 five mm segments of the 44 nonbypassed arteries examined histologically, 292 (47 percent) were narrowed 76 to 100 percent in cross-sectional area by atherosclerotic plaque; of 728 segments examined in the 52 bypassed arteries, 375 (52 percent) were similarly narrowed. Thirty-two (73 percent) of the 44 nonbypassed coronary arteries (in 23 patients) had been judged to be narrowed 50 percent or less in diameter on preoperative coronary angiography, but at necropsy 31 (97 percent) of these arteries were narrowed 76 to 100 percent in cross-sectional area and the other artery was narrowed 51 to 75 percent. Thus, significant amounts of atherosclerotic plaque tend to be present at necropsy in all three major coronary systems of patients with angina pectoris who die early after an aortocoronary bypass operation.     

Frequency and extent of calcific deposits in purely regurgitant mitral valves: Analysis of 108 operatively excised valves

Operatively excised purely regurgitant mitral valves in 108 patients aged 21 to 73 years (mean 55) (63% men) undergoing isolated mitral valve replacement were examined for calcific deposits. Of the 108 patients, 19 (18%) had leaflet or chordal calcific deposits or both, but in each the deposits were small and did not appear to alter mitral function. Of the 19 patients with mitral calcium, 6 had had active infective endocarditis and the calcium likely represented healed vegetations; In 6 other patients, the leaflet calcium had extended from the mitral anulus in the setting of mitral valve prolapse. The average total serum cholesterol levels were higher in the patients with compared with those without mitral calcium. Thus, calcium deposits are relatively infrequent in adults with clinically isolated pure mitral regurgitation, and when they occur, the deposits are small and in themselves do not appear to contribute to mitral dysfunction.     

Relation of level of total serum cholesterol to amount of calcific deposits in operatively excised stenotic mitral valves: Analysis of 155 cases

This report analyzes 155 patients with rheumatic mitral stenosis in whom the Operatively excised mitral valve was x-rayed to determine the presence of and extent of calcific deposits and the preoperative level of total serum cholesterol (TC). The amount of mitral calcium was graded 0 to 4+ and the average TC for each of the 5 groups was: 0 deposits—21 patients (14%) (TC = 188 mg/dl); 1+—50 patients (32%) (TC = 196 mg/dl);2+—22 patients (14%) (TC = 198 mg/dl);3+—37 patients (24%) (TC = 205 mg/dl), and 4+—25 patients (16% ) (TC = 184 mg/dl). These average values of TC and the mean ages of the patients in each of the 5 groups of mitral calcium were not significantly different.     

Sudden death while running in conditioned runners aged 40 years or over

Clinical and necropsy observations are described in five white male runners aged 40 to 53 years (average 46 years) who ran 22 to 176 km/week (mean 53 km) for 1 to 10 years (mean 5). None had clinical evidence of cardiac disease before they became habitual runners, and all died while running. At necropsy all had severe atherosclerotic luminal narrowing of their major epicardial coronary arteries. Of the five runners, at least four had hypercholesterolemia, two had systemic hypertension, one had angina pectoris and none had clinical evidence of an acute myocardial infarct. The single symptomatic runner also had an abnormal resting electrocardiogram and a positive exercise stress test. The electrocardiogram (four patients) and exercise stress tests (three patients) in the other four runners were normal. At autopsy, all five men had greater than 75 percent narrowing of cross-sectional area by atherosclerotic plaques of the right, left anterior descending and left circumflex coronary arteries. In three men the entire lengths of these three coronary arteries and also the left main coronary artery were examined histologically (total 5 mm segments = 153); 73 (48 percent) of the segments were narrowed greater than 75 percent in cross-sectional area by atherosclerotic plaques and 32 (21 percent) were narrowed by 51 to 75 percent. Four of the five runners had healed (clinically silent) myocardial infarcts. Thus, coronary heart disease appears to be the major killer of conditioned runners aged 40 years and over who die while running.     

True left ventricular aneurysm and healed myocardial infarction: Clinical and necropsy observations including quantification of degrees of coronary arterial narrowing

Clinical and necropsy observations are described in 28 patients (24 men) aged 31 to 85 years (mean 62) with healed myocardial infarction and a true left ventricular aneurysm. In contrast to findings in other subsets of necropsy patients with fatal coronary heart disease, chronic congestive heart failure was frequent (22 patients); angina pectoris was infrequent (4 patients) and, when present, never severe; recurrence of acute myocardial infarction (2 patients), sudden death (2 patients) and clinically evident systemic emboli (1 patient) were infrequent; survival for more than 5 years after healing of the acute infarction was infrequent (in 3 of 21 patients with clinically diagnosed acute myocardial infarcts); and survival for longer than 1 year after aneurysmectomy was lacking (0 of 7 patients). Additionally, 23 of the 28 patients had a large heart (greater than 400 g [mean 523], 26 had dilated nonaneurysmal portions of the left ventricle, and all but 1 had a large (greater than 30 percent of the left ventricular wall) myocardial infarct. In 25 of the 28 patients, two or more of the four major epicardial coronary arteries were greater than 75 percent narrowed in cross-sectional area by atherosclerotic plaques. In 992 segments (each 5 mm long) of a major coronary artery examined in 22 patients (45 segments/patient), narrowing was greater than 75 percent in 323 segments (33 percent) and ranged from 51 to 75 percent in 419 (42 percent), from 26 to 50 percent in 210 (21 percent) and from 0 to 25 percent in 40 (4 percent). Thus, the scarred, hypertrophied and aneurysmally dilated left ventricle infrequently produces chest pain or fatal arrhythmia despite diffuse, severe coronary narrowing.     

Congenital hypoplasia of portions of both right and left ventricular myocardial walls: Clinical and necropsy observations in two patients with parchment heart syndrome

Clinical and morphologic findings are described in two patients with congenital hypoplasia of portions of both right and left ventricular free walls in the absence of associated coronary or valvular heart disease. One, a 61 year old man who had never had clinical evidence of cardiac dysfunction, died suddenly and unexpectedly. The second, a 55 year old woman, died of progressive, eventually intractable congestive heart failure of 29 months' duration. Although at least 22 necropsy patients have previously been reported to have “parchment-like” thinning of portions of the right ventricular free wall, only one patient has previously been described with such thinning of portions of both right and left ventricular free walls. The spectrum of right or right and left ventricular wall congenital hypoplasia is a broad one, with nearly half of described patients dying of congestive heart failure in the 1st year of life and the other half reaching adulthood with or without manifestations of cardiac dysfunction.