Dennis D. Reichenbach

Characterization of the early lesion of 'degenerative' valvular aortic stenosis. Histological and immunohistochemical studies.

BackgroundNonrheumatic stenosis of trileaflet aortic valves, often termed senile or calcific valvular aortic stenosis, is considered a “degenerative” process, but little is known about the cellular or molecular factors that mediate its development. Methods and ResultsTo characterize the developing aortic valvular lesion, we performed histological and immunohisto-chemical studies on Formalin-fixed and methanol-Carnoys-fixed parafflin-embedded aortic valve leaflets or on frozen sections obtained at autopsy from 27 adults (age, 46 to 82 years) with normal leaflets (n=6), mild macroscopic leaflet thickening (n= 15), or clinical aortic stenosis (n=6). Focal areas of thickening (“early lesions”) were characterized by (1) subendothelial thickening on the aortic side of the leaflet, between the basement membrane (PAS-positive) and elastic lamina (Verhoeff–van Gieson), (2) the presence of large amounts of intracellular and extracellular neutral lipids (oil red O) and fine, stippled mineralization (von Kossa), and (3) disruption of the basement membrane overlying the lesion. Regions of the fibrosa adjacent to these lesions were characterized by thickening and by protein, lipid, and calcium accumulation. Control valves showed none of these abnormalities. Immunohistochemical studies were performed using monoclonal antibodies directed against macrophages (anti-CD68 or HAM-56), and contractile proteins of smooth muscle cells or myofibroblasts (anti-α-actin and HHF-35) or rabbit polyclonal antiserum against T lymphocytes (anti-CD3). In normal valves, scattered macrophages were present in the fibrosa and ventricularis, and occasional muscle actin-positive cells were detected in the proximal portion of the ventricularis near the leaflet base, but no T lymphocytes were found. In contrast, early lesions were characterized by the presence of an inflammatory infiltrate composed of non-foam cell and foam cell macrophages, occasional T cells, and rare α-actin-positive cells. In stenotic aortic valves, a similar but more advanced lesion was seen. ConclusionsThe early lesion of “degenerative” aortic stenosis is an active inflammatory process with some similarities (lipid deposition, macrophage and T-cell infiltration, and basement membrane disruption) and some dissimilarities (presence of prominent mineralization and small numbers of smooth muscle cells) to atherosclerosis.

Catecholamines and cardiomyopathy: The pathogenesis and potential importance of myofibrillar degeneration

Abstract Myofibrillar degeneration is a common form of cardiac injury observed frequently in human beings at autopsy and is produced readily in experimental animals. Administration of exogenous catecholamines such as norepinephrine or isoproterenol has been frequently used as an experimental means of inducing cardiac injury. The potential role of catecholamines in the pathogenesis of this cardiomyopathy becomes more significant with the demonstration that local can induce a similar cardiac lesion. Early, the injured myocardial cells show clumping and disorganization of the cardiac myofibrils. Later, degenerative changes in cell cytoplasm and mineralization of mitochondria are manifest. Such injured cells may either die and be removed by phagocytosis or may be repaired by synthesis of new myofibrils. In the later stages stromal condensation and fibrosis may become evident. This lesion in its acute form in humans and when sufficiently extensive can contribute to or cause death. Since repcated episodes potentially may produce myocadial fibrosis, this lesion is worthy of more serious consideration in the evaluation of human heart disease manifest by impaired cardiac function and interstitial fibrosis.

Pathology of the heart in sudden cardiac death

Clinical and pathologic changes in 87 patients who could not be resuscitated from an episode of sudden cardiovascular collapse are described and compared with observations from patients in the same community who were successfully resuscitated from ventricular fibrillation. Findings in patients who died suddenly generally did not differ when the patients were groups by electrocardiographic rhythm on arrival of the mobile coronary aid unit. The pathologic changes of acute thrombosis and recent myocardial infarction did not occur with sufficient frequency in the entire group to be considered causally related to the sudden collapse, occurring in 10 and 5 percent of cases, respectively. Although most patients had evidence of obstructive coronary disease and old myocardial infarction, 8 percent had no significant vascular disease, acute thrombosis, myocarditis or valve disease that might be implicated as a factor in sudden death. There was no relation between age and severity of obstructive coronary disease or frequency of old myocardial infarction in patients who died suddenly. Complete atherosclerotic occlusion in one or more coronary vessels occurred in 51 of 87 (59 percent) and old myocardial infarction in 48 of 87 (55 percent). Although the mean age of this autopsy population was similar to that of all patients in the community who have had ventricular fibrillation on arrival of the aid unit, the nonsurvivors had a greater incidence of myocardial infarction and symptomatic heart disease (73 of 87) than did survivors. Comparison of this autopsy group with persons from the community who were resuscitated from ventricular fibrillation and subsequently had coronary angiograms indicates that the severity of coronary stenosis does not distinguish between survivors and nonsurvivors of an episode of ventricular fibrillation and suggests that other factors influence the outcome of an episode of ventricular fibrillation.

The Wolff-Parkinson-White syndrome: problems in evaluation and surgical therapy.

Two patients with WPW syndrome underwent surgery to ablate accessory conduction pathways. Endocardial and epicardial mapping in both patients had indicated an area of early right ventricular depolarization. Surgical transection of the areas of early depolarization failed in both cases to normalize the electrocardiogram. In the first patient, additional resection in the area of the A-V node failed to produce heart block and the ECG remained abnormal. However, the paroxysmal tachycardia ceased, and she has remained asymptomatic and active 12 months after surgery. In the second patient, as the A-V node was about to be sectioned, pressure and procaine near the A-V node caused the ECG to normalize transiently and after resection permanently. Microscopic study of this tissue showed “P cells.” Postoperatively the patient demonstrated normal A-V nodal function. He was discharged with a normal ECG but expired soon after discharge. Postmortem examination of the heart demonstrated the A-V node and bundle of His plus the location of the resection adjacent to the bundle of His. These two cases illustrate disparities between electrophysiologic mapping and actual site of the accessory conduction pathway. In one of the cases an accessory bundle was demonstrated histologically.

Left ventricular mass: A comparison of angiocardiographic measurements with autopsy weight☆

Abstract A previously described angiocardiographic method has been used to determine left ventricular mass in 28 patients. Weight of the left ventricle at autopsy has been compared with calculated mass. The method has been shown to be reliable in the absence of marked right ventricular hypertrophy, pericardial effusion, or adhesive pericarditis.

QRS changes, pulmonary edema, and myocardial necrosis associated with subarachnoid hemorrhage

Abstract A 49-year-old Caucasian female without history of cardiovascular diseases presented with a subarachnoid hemorrhage, severe hypertension, and pulmonary edema. Despite QRS changes of extensive myocardial infarction, postmortem examination revealed normal coronary arteries. Microscopic study showed extensive myocardial necrosis unrelated to vascular pattern and similar to that induced by exogenous catecholamines. The ECG changes and pulmonary edema appear to be the result of a neurohumoral myocarditis with left ventricular damage and failure. Implications for heart transplantation are cited.

MYOFIBRILLAR DEGENERATION: A COMMON FORM OF CARDIAC MUSCLE INJURY*

Myocardial lesions that differ from ordinary coagulation necrosis of ischemic infarction have been produced experimentally by several chemical, metabolic. and mechanical One of the striking histological features of these lesions is the segmented or banded appearance of the myocardial cell cytoplasm. Similar changes can be seen in human myocardium at autopsy associated with several clinical conditions. The changes occurring in this lesion do so in a regular and reproducible sequence extending over days to weeks. This indicates that the change is not merely agonal or an artifact. In this communication we shall present the characteristic histological features of cardiac lesions produced experimentally in the dog by electric shock and compare them with those seen in human myocardium after cardiac surgery.

A MYXOMA OF THE PULMONARY VALVE CAUSING SEVERE STENOSIS IN INFANCY.

Abstract A 2-month-old male infant with severe pulmonary stenosis was found to have a myxoma of the pulmonary valve; the diagnosis was suggested by angiocardiography and confirmed by open-heart surgery. Previous reports indicate that myxomas of valvular origin are rare and asymptomatic, relative to mural myxomas.

Morphological Alterations in Vital Organs After Prolonged Cardiac Arrest at Low Body Temperature

Abstract Surface-induced deep hypothermia was carried out in 34 adult mongrel dogs using ether anesthesia, Rheomacrodex, and respiratory alkalosis. Cardiac arrest was instituted for 30, 60, or 90 minutes at a temperature of 18° to 20°C. All animals were resuscitated, rewarmed, and sacrificed up to two and one-half years postoperatively. One other group was only cooled and rewarmed without cardiac arrest. Myocardial sections showed focal areas of cell necrosis with cytoplasmic band formation, and in the later specimens calcification and interstitial fibrosis had developed. These changes were more severe in the animals subjected to cardiac arrest. The alterations in pulmonary tissue consisted only of patchy atelectasis and alveolar hemorrhage in the early specimens. The kidney and spleen were unaltered. Some liver sections showed widening of centrilobular sinusoids and vacuolization of hepatic cells. All the brains examined had slight anoxic changes; however, it was not possible to differentiate normal from hypothermic brains. There was no correlation between morphological changes and duration of total circulatory arrest.

Anatomical Findings in Patients Having Had a Chronically Indwelling Coronary Sinus Defibrillation Lead

The purpose of this report is to review the gross and histological cardiac anatomical findings in patients with chronically indwelling coronary sinus leads at the time of autopsy or cardiac transplantation. Transvenous cardioverter defibrillators offer effective protection against sudden death. The use of a coronary sinus electrode has been shown in some patients to decrease the defibrillation threshold. The anatomical consequences of chronically indwelling coronary sinus cardioversion /defibrillation electrodes in patients having transvenous implantable cardioverter defibrillators is unknown. The hearts of seven patients with chronically indwelling coronary sinus electrodes were evaluated following autopsy (n= 2) or cardiac transplantation (n= 5), The coronary sinus electrode in each case was a 6.5 French silicon lead with a 5‐cm long defibrillation coil (Medtronic CS lead model 6933) that was positioned as distally as possible within the coronary sinus at the time of implantable cardioverter defibrillator surgery. The seven hearts examined were derived from patients whose age ranged between 49 and 69 (mean 56 ± 7 years). Six had coronary artery disease and one had idiopathic dilated cardiomyopathy. The time from implant to death or cardiac transplantation was 8 ± 6 months, range 1–18 months. In all seven patients, there was no evidence of any significant damage from the presence of the coronary sinus lead. The only finding in each case was the scattered presence of a thin white fibrous sheath over the lead that intermittently adhered to the coronary sinus endothelium and, in the two patients transplanted 1–3 months after implantable cardioverter defibrillator insertion, a mild inflammation reaction adjacent to the leads in the coronary sinus endothelium. There was no evidence of coronary sinus occlusion, adjacent coronary artery injury, coronary sinus perforation, coronary sinus burn, or myocardial injury adjacent to the lead. Cause of death was due to end‐stage congestive heart failure and thrombotic stroke, respectively, in the two patients examined at autopsy. Coronary sinus defibrillation leads can be used safely without harmful anatomical effect.