Acute takeoffs of the coronary arteries along the aortic wall and congenital coronary ostial valve-like ridges: association with sudden death.

Congenital coronary artery anomalies have been associated with sudden death. Twenty-two patients who were victims of sudden death (mean age 46) and who had no significant anatomic cause of death were examined at autopsy and compared with 19 patients who died of known causes (control group). The hearts of these 41 patients were examined for abnormalities of acute angle takeoff of the coronary artery and presence of ostial valve-like ridges. Of the 22 patients who died suddenly, 13 (59%) had acute angle takeoff of the coronary artery and 9 (41%) had ostial valve-like ridges. Of the 19 control subjects, 4 (21%) had acute angle takeoff and only 2 (11%) had an ostial valve-like ridge. The difference was statistically significant (p = 0.015 and 0.031, respectively). It is suggested that aortic root dilation may compress coronary arteries with acute angle takeoff and that ostial valve-like ridges may act as occlusion valves. Thus, either may cause acute obstruction of the proximal coronary artery and lead to sudden death. A very lethal combination for sudden death would be the presence of severe coronary artery disease, an acute angle takeoff and an ostial valve-like ridge.

Atherosclerotic aneurysm of the left main coronary artery.

A large calcified atherosclerotic aneurysm of the left main coronary artery was successfully treated by aortocoronary saphenous vein bypass grafting. This is the second such reported case. The implications of this clinical entity are discussed.

Prevalent myocarditis at necropsy in the acquired immunodeficiency syndrome.

The prevalence of myocarditis was retrospectively evaluated in 71 consecutive necropsy patients who died from acquired immunodeficiency syndrome (AIDS) between 1982 and 1986. Myocarditis was found in 37 cases (52%). Biventricular dilation at necropsy was present in seven cases (10%) and was accompanied by myocarditis in each case; fatal congestive heart failure occurred in four of these seven cases. Although viral, protozoan, bacterial, fungal and mycobacterial opportunistic pathogens were present in myocardial sections of 7 of 37 myocarditis cases, the etiology of myocarditis in the majority of these patients with AIDS remained idiopathic. Thus, myocarditis is a frequent finding at necropsy in patients with AIDS and may contribute to the development of biventricular dilation.

Spontaneous coronary artery dissection and eosinophilic inflammation: a cause and effect relationship?

Spontaneous coronary artery dissection is described in eight patients 26 to 47 years of age. Six died suddenly, and two died after the onset of chest pain. All had normal heart weights and all had dissection of left anterior descending coronary artery, which occurred mainly in the outer one third of the media. The adventitial of the dissected artery contained inflammatory infiltrates which were predominantly eosinophilic granulocytes. Forty-six cases previously published in 32 reports are reviewed. It is suggested that adventitial eosinophilic infiltrate may be responsible for spontaneous coronary artery dissection.

Nontraumatic death in joggers. A series of 30 patients at autopsy.

Since few autopsy data are available on the cause of death in joggers, 30 joggers who underwent autopsy were studied. All were males 18 to 57 years of age (mean 36 years). Information on jogging habits was available in 18 patients who ran 7 to 105 miles per week (mean 33) for one to 28 years (mean 20). Three of the 30 patients were "marathon runners." In 12 patients, the only available information was that they had been jogging for at least six months, but information regarding the distance run was not available. Sixteen patients (53 percent) had clinical histories of systemic hypertension, hypercholesterolemia and/or family histories of coronary heart disease; eight patients had a previous history of coronary heart disease; two had transient ischemic attacks. Nineteen patients died suddenly while jogging; six died suddenly after jogging; three noted chest pains soon after jogging; two were found dead in bed. The heart weights were increased in 16 (53 percent). Twenty-two patients (73 percent) had severe coronary artery atherosclerosis, six of whom had coronary artery thrombi; acute and/or healed myocardial infarction was present in 14 (47 percent). One patient had a floppy mitral valve. In seven patients, no cause of death could be established; three of these had cardia hypertrophy and six had myocytolysis. Myocytolysis was also noted in 11 patients with severe coronary atherosclerosis. Severe coronary artery atherosclerosis was the major finding (73 percent) in the 30 joggers in this series.

Percutaneous transluminal coronary angioplasty guidewire-induced coronary artery dissection without balloon inflation.

A case of arterial dissection of the right coronary artery secondary to angioplasty guidewire manipulation is presented. No balloon inflation was performed. The histologic appearance of the involved arterial segment was similar to that found in the left anterior descending coronary artery, which had undergone successful balloon dilatation. Both arteries demonstrated medial disruption and fibrointimal proliferation. The pathologic features of angioplasty-induced vascular injury may occur with or without balloon inflation.

Association of eosinophils with cardiac rupture.

Cardiac rupture occurs in 10 per cent of patients who die with acute myocardial infarction, but the pathogenesis remains unclear. Twenty randomly selected patients with cardiac rupture were reviewed retrospectively at autopsy, and the findings were compared with those of 20 age- and sex-matched control subjects who had died of acute transmural myocardial infarction without rupture. The times from the onset of chest pain to death were similar in the two groups (5.7 +/- 5.8 days for patients with rupture versus 4.2 +/- 4.9 days for control subjects), and there were no differences in the incidences of systemic hypertension, diabetes mellitus, hypercholesterolemia, history of myocardial infarction, or angina pectoris. The severity of coronary atherosclerosis was different in the two groups, with 55 per cent of the patients with cardiac rupture having single-vessel disease and 70 per cent of the patients without cardiac rupture having disease in three vessels. Additionally, the incidence of thrombosis was greater in patients with cardiac rupture than in those without. The inflammatory cell response in each patient was quantitated microscopically (number and type of leukocytes) in ten high-power fields. The inflammatory response was greater in patients with cardiac rupture. The number of eosinophils in the inflammatory response was significantly (P less than 0.01) greater in hearts associated with cardiac rupture (29.5 +/- 4 per cent) than in control hearts (11.7 +/- 3.1 per cent). It is postulated that eosinophils rich in arylsulfatase B, peroxidase, glucuronidase, beta-glycerophosphatase, major basic protein, and eosinophilic cationic protein may further weaken the necrotic myocardium and, in part, determine whether acute myocardial infarction will eventually result in cardiac rupture.

Acquired coronary arterial aneurysms: an autopsy study of 52 patients.

In the past decade most studies of coronary arterial aneurysms have been clinical; few have focused on morphology and etiopathogenesis. The subjects of the present autopsy study were 52 patients, 5 months to 80 years of age, with coronary arterial aneurysms. Patients were divided into two groups: 38 with atherosclerotic coronary aneurysms and 14 with aneurysms secondary to inflammation. Of the 38 patients with atherosclerotic aneurysms, 20 (53 per cent) had histories of ischemic heart disease; the aneurysms were in the right coronary artery in 18 (47 per cent), the left coronary artery in 13 (35 per cent), and in the right and left coronary arteries in seven (18 per cent). Of the four major coronary arteries, the average number of severely narrowed arteries (reduction of more than 75 per cent) in cross-sectional luminal area) was 1.8/patient; aortic aneurysms were present in eight of these patients (24 per cent). Of the 14 patients with coronary aneurysms secondary to inflammation, four had histories of ischemic heart disease; 10 had histories of an influenza-like syndrome. Isolated left coronary arterial aneurysms were seen in six of these patients (43 per cent), while eight (51 per cent) had multiple right and left coronary arterial aneurysms. The average number of severely narrowed coronary arteries in this group was 1.5/patient, and only one patient had an aortic aneurysm. Therefore, patients with atherosclerotic aneurysms are more often symptomatic; they have increased heart weights and equal numbers of coronary arterial aneurysms in the right and left vessels, and the majority (89 per cent) have single aneurysms with thrombi in the lumen. Patients with coronary arterial aneurysms secondary to inflammation are younger; the majority of these patients have a prodromal influenza-like syndrome, a low incidence of ischemic heart disease, and multiple coronary arterial aneurysms.

Cardiac fungal infections: review of autopsy findings in 60 patients.

An autopsy study of 60 patients with fungal infections of the heart was undertaken. The patients ranged in age from 2 months to 79 years. Fifteen of the patients had undergone cardiac surgery; neoplasms were found in 13, renal failure in eight, bacterial infections in five, liver disease in five, gastrointestinal disorders in five, and immune disease in four; two had been intravenous drug abusers; other miscellaneous disorders were observed in three. The fungal infection was limited to the myocardium in 27 patients and to the endocardium in 17 patients. Myocardium and endocardium were involved in nine patients and pericardium and myocardium in five; two patients had pericarditis alone. The most frequent organism was Candida (62 per cent). Aspergillus (12 per cent) and Phycomycetes (12 per cent) were also found frequently. In 51 patients (85 per cent) other deep organs, usually lung, kidney, brain, or spleen were involved. Cultures for fungus had been positive in 26 patients prior to death, and postmortem cultures were positive in 29 patients. Patients who had undergone cardiac surgery had a higher incidence of endocarditis (93 per cent), with Candida (53 per cent) being the most frequent cause. Patients who had received antineoplastic drugs, antibiotics, or corticosteroids had a higher incidence of myocarditis (79 per cent), again most often due to Candida (60 per cent).

Eosinophilic products lead to myocardial damage.

Eosinophils have been associated with endomyocardial fibrosis. However, their effect on the myocardium and the reactions they elicit have not been emphasized. We describe four patients with extensive myocardial eosinophilic infiltration with and without endomyocardial fibrosis. Patients with a short duration of disease had eosinophilic infiltrates, myocardial eosinophilic abscesses containing granular eosinophilic material, and/or Charcot-Leyden crystals with and without profuse histiocytic and giant cell reaction with granuloma formation. In the early phase, the granular eosinophilic material can be visualized by the Luna stain and/or by electron microscopic examination. In patients with a long duration of symptoms, well-developed granulomas and profuse fibrosis are seen and eosinophilic material may not be visualized. Toxic eosinophil granular protein may be involved in the development of these lesions.

Coronary ostial stenosis in Takayasu's arteritis.

A patient with Takayasu's arteritis with left coronary ostial narrowing is presented. The dramatic clinical and pathologic findings are discussed in detail. Emphasis is placed on making the diagnosis as soon as possible, in order to expedite bypass surgery to prolong life.

Successful correction of a subendocardial hamartoma of the left ventricular free wall and mitral valve papillary muscles.

We describe a case of subendocardial hamartoma of the left ventricular free wall and mitral valve papillary muscles that resulted in a pseudoparachute mitral valve, a decrease in effective left ventricular cavity size, and the hemodynamic picture of a cardiomyopathy.

Morphologic changes in long-term saphenous vein bypass grafts.

A retrospective autopsy study was performed in 56 patients who had undergone saphenous vein bypass graft (SVBG) surgery 12 to 168 months prior to death. Twenty-five grafts had atherosclerosis, 66 grafts had fibrointimal proliferation, and 26 grafts were fibrotic with total occlusion. No significant differences were noted among the three morphologic groups with regard to age of the patient or number of native coronary arteries severely narrowed. Vein grafts with fibrointimal proliferation occurred with greater frequency in patients with systemic hypertension (p less than 0.001), and atherosclerotic grafts were more prevalent in patients with hypercholesterolemia (p less than 0.02). Therefore, the presence of risk factors may determine the type of change that occurs in saphenous vein bypass grafts: systemic hypertension leads to fibrointimal proliferation, whereas hypercholesterolemia leads to atherosclerotic change.

Early and late healing responses of normal canine artery to excimer laser irradiation.

Acute in vitro histologic studies have shown that the pulsed xenon chloride excimer laser causes precise microablation without the surrounding thermal tissue injury associated with frequently used continuous-wave lasers such as the argon, carbon dioxide, and neodymium:yttrium aluminum garnet lasers. However, the in vivo healing response of artery wall to excimer laser injury is not known. Accordingly, a xenon chloride excimer laser (308 nm, 40 nsec pulse width, 39 mJ/mm2/pulse) was transmitted via a 600 micron fused silica fiber to create 420 craters of varying depths (30 to 270 micron) in 21 normal canine femoral and carotid arteries. At 2 hours, 2 days, 10 days, and 42 days after excimer laser ablation, the artery segments were perfusion fixed in situ and analyzed by light, scanning, and transmission electron microscopy. At 2 hours, craters were covered by a carpet of platelets and entrapped red blood cells. Fibrin and exposed collagen fibers were seen at the crater base. There was a sharp demarcation of the crater-artery wall interface without lateral laser tissue injury. At 2 days, adherent platelets persisted with thrombus covering the base of the craters. Early healing responses were present, consisting of polymorphonucleated leukocytes and new endothelial cells, which extended over the crater rims. At 10 days, no thrombi were seen, and healing continued with almost complete reendothelialization. Macrophages, fibroblasts, fibrin, and entrapped red blood cells were present below the reendothelialized surface. At 42 days, healing was complete with obliteration of the craters by fibrointimal ingrowth. The surface was completely covered by a smooth monolayer of axially aligned endothelial cells. There were no aneurysms or surface hyperplastic responses. These favorable healing responses in normal canine arteries suggest that pulsed lasers with high tissue absorption coefficients, such as the xenon chloride excimer laser, may be suitable energy sources for clinical laser angioplasty procedures. However, further studies in atherosclerotic animals are required before human clinical responses can be accurately predicted.

Differentiation of vascular prostheses in dogs with serial tests of in vivo platelet reactivity.

Three different vascular prostheses (standard weight knitted Dacron, double velour knitted Dacron, and expanded polytetrafluoroethylene) were implanted in the aortas of dogs, and serial determinations of platelet survival and platelet serotonin were monitored at 12-week intervals for 1 year. Prostheses were then removed and luminal coverage with endothelialized neointima and production of prostacyclin were measured. Changes in platelet survival were correlated with changes in platelet serotonin, and both measurements reflected in vivo platelet reactivity with the vascular prostheses. These changes were unique for each type of prosthesis and were dependent upon physical characteristics and the rate and degree of coverage of the prosthetic surface with endothelialized neointima that produced prostacyclin. Prostheses that reduced platelet survival and platelet serotonin the least as shown by serial evaluation were found at harvest to be the most completely paved with nonthrombogenic neointima. In dogs, these techniques allow differentiation of vascular prostheses and provide a useful animal model for their evaluation.

The antithrombotic nature of vascular prosthetic pseudointima.

Morphologic functional, and biochemical studies were performed on pseudointima obtained from woven Dacron aortic prostheses harvested from eight dogs 2 to 3 years after placement. In vivo platelet reactivity with prostheses was assessed by serial 51Cr-platelet survival measurements which documented that platelet survival returned towards normal but never attained preoperative levels. The extent of luminal coverage of prosthesis with pseudointima of the time of harvest was 60.3% +/- 2.4%. Morphologic techniques, including conventional light microscopy, immunoperoxidase light microscopy for endothelial factor VIII-related antigen, and scanning and transmission electron microscopy, demonstrated that pseudointima was composed of endothelial cells of varying maturity lining mesenchymal tissue. Areas of the prostheses with poorly formed pseudointima containing exposed Dacron fibers were covered with exuberant, platelet-rich thrombi. Ability of pseudointima to produce prostacyclin was assessed by bioassay of platelet antiaggregatory activity and radioimmunoassay of 6 keto PGF1 alpha, a metabolite of prostacyclin. These experiments confirmed that pseudointima produced abundant prostacyclin, although not as much as native aortic tissue. These studies document that vascular prosthetic pseudointima is nonreactive with platelets, presumably because of prostacyclin generation.

Coronary artery dissections.

Isolated spontaneous coronary artery dissections are rare and usually occur in women, the majority of whom are less than 40 years of age. Coronary artery dissection may also be caused by an extension of aortic dissection, especially in Marfan's syndrome. Iatrogenic coronary artery dissections are extremely rare, especially those secondary to coronary catheterization. The consequences of dissection may be fatal; therefore, early recognition and prompt therapy may be lifesaving.

Cardiac infections in the immunocompromised host.

Bacterial infections of the heart in compromised patients are uncommon but may be increasing in relative frequency. They are associated with near-equal frequencies in patients who have pre-existing or simultaneous infections at other sites, patients with neoplasms (usually solid tumors), those who have undergone cardiac surgery, and intravenous drug or ethanol abusers. Staphylococcus aureus is the bacteria most often identified, in contrast to a preponderance of Streptococcus isolated in the pre- and early antibiotic era. Gram-negative bacilli are the causative organisms in a significant number of cases. The endocardium remains the most common site of infection, and left-sided valves are most commonly involved, especially the mitral valve, often in the absence of pre-existing valvular damage. The majority of cases are associated with involvement at other sites, and premortem blood cultures are positive in approximately two thirds of patients who undergo autopsy. Fungal infections involving the heart do not occur as often as bacterial infections. The frequency, however, is increasing. Fungal infections usually occur in patients who have received treatment with antineoplastic agents, antibiotics, or corticosteroids, alone or in combination, or who have had abdominal or cardiac surgery. Candida is the organism found most frequently and usually causes myocarditis or endocarditis, whereas Aspergillus involves the myocardium but may be invasive to the endocardium or pericardium. Other fungi that occasionally infect the heart include Phycomycetes and Cryptococcus. Dissemination is usually present and involves the lungs, kidneys, brain, or gastrointestinal tract. The diagnosis may be difficult prior to death, because blood cultures are positive in only one third of patients who come to autopsy. Precipitin tests and antibody titers for specific organisms may be helpful in providing early diagnosis. Survival rates can be improved by early diagnosis and the institution of aggressive antifungal treatment.

Study design in the evaluation of breast cancer imaging technologies.

RATIONALE AND OBJECTIVES: Bringing a new imaging technology to market is a complex process. Beyond conceptualization and proof of concept, obtaining U.S. Food and Drug Administration (FDA) approval for clinical use depends on the documented experimental establishment of safety and efficacy. In turn, safety and efficacy are evaluated in the context of the intended use of the technology. The purpose of this study was to examine a conceptual framework for technology development and evaluation, focusing on new breast imaging technologies as a highly visible and current case in point. MATERIALS AND METHODS: The FDA views technology development in terms of a preclinical and four clinical phases of assessment. With a concept of research and development as a learning model, this phased-assessment concept of regulatory review against intended use was integrated with a five-level version of a hierarchy-of-efficacy framework for evaluating imaging technologies. Study design and analysis issues are presented in this context, as are approaches to supporting expanded clinical indications and new intended uses after a new technology is marketed. CONCLUSION: Breast imaging technologies may be intended for use as replacements for standard-of-care technologies, as adjuncts, or as complementary technologies. Study designs must be appropriate to establish claims of superiority or equivalence to the standard for the intended use. Screening technologies are ultimately judged on their demonstrated effectiveness in decreasing cause-specific mortality through early detection, but they may be brought to market for other uses on the basis of lesser standards of efficacy (eg, sensitivity, specificity, positive and negative predictive value, and stage of disease detected).

Coronary heart disease in 48 autopsy patients 30 years old and younger.

We studied 48 autopsy patients younger than 30 years who had severe coronary atherosclerosis. Twenty-one patients (44%) died suddenly, 26 (54%) had a history of chest pain, and one had chronic congestive heart failure. Twenty-one patients (44%) had single-vessel disease, 19 (40%) had two-vessel disease, and only nine (16%) had three or four major coronary arteries severely narrowed (greater than 75% cross-sectional area luminal narrowing) by atherosclerotic plaques. Thrombi in coronary arteries were noted in 27 patients (56%) and the left anterior descending coronary artery was the most frequently involved. The severity of coronary atherosclerosis was much less in patients younger than 30 years, and the atherosclerotic plaque consisted largely of foam cells, fibrous tissue, and pultaceous debris, with minimal calcific deposits. Thus, it is this population that is most likely to be susceptible to regression of the atherosclerotic plaque.