William N. O'Connor

Mechanism of acute myocardial infarction in patients with prior coronary artery bypass grafting and therapeutic implications

Although acute myocardial infarction (AMI) is usually due to thrombotic occlusion when involving a native coronary artery, the mechanism responsible for AMI in patients with previous coronary artery bypass grafting (CABG) is not well understood. Since knowledge of pathophysiology of AMI may alter subsequent management, angiograms obtained between 1 hour and 7 days of AMI (median 1 day) were reviewed in 50 patients greater than 1 year after CABG. The culprit vessel was identified by the presence of residual stenosis and/or thrombus in the vessel supplying the infarct zone or by reviewing previous angiograms. The infarct vessel was identified as a vein graft in 38 (76%) patients, the native vessel in 8 patients (16%) and could not be accurately determined in 4 patients (8%). Among the 38 vein grafts suspected as the infarct vessel, unequivocal angiographic evidence of residual thrombus (filling defect/persistent staining) was present in 31 (82%) and was greater than 2 cm in length in 15 patients. Successful reperfusion occurred in only 2 of 8 (25%) grafts after intravenous thrombolytic therapy. Intragraft thrombolysis with or without additional angioplasty was successful at restoring flow in 8 of 10 (80%) grafts. Data indicate that in patients who have undergone previous CABG, AMI is usually caused by thrombotic occlusion of a saphenous vein graft and that conventional intravenous thrombolytic therapy may be inadequate to restore flow. The large mass of thrombus and absent flow in the graft may require subselective drug infusion, a higher thrombolytic dose or a mechanical means of recanalization.

Ventriculocoronary connections in hypoplastic left hearts: an autopsy microscopic study.

Serial microscopic sections of the left ventricular myocardium were examined in 12 autopsy specimens of hypoplastic left heart syndrome. Multiple ventriculocoronary arterial connections, thickwalled coronary arteries, prominent endocardial fibroelastosis, myofiber disarray and focal calcification/ scarring of the myocardium were noted in the cases with patent left ventricular inflow and obstructed outflow. The persistent embryonic microvascular pattern noted in these cases may be related to intrauterine outflow obstruction and could limit surgical attempts to produce a functional left ventricle in infants with hypoplastic left heart syndrome.

Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: A Ras/MAPK pathway syndrome

Cardiovascular abnormalities are important features of Costello syndrome and other Ras/MAPK pathway syndromes (“RASopathies”). We conducted clinical, pathological and molecular analyses of 146 patients with an HRAS mutation including 61 enrolled in an ongoing longitudinal study and 85 from the literature. In our study, the most common (84%) HRAS mutation was p.G12S. A congenital heart defect (CHD) was present in 27 of 61 patients (44%), usually non‐progressive valvar pulmonary stenosis. Hypertrophic cardiomyopathy (HCM), typically subaortic septal hypertrophy, was noted in 37 (61%), and 5 also had a CHD (14% of those with HCM). HCM was chronic or progressive in 14 (37%), stabilized in 10 (27%), and resolved in 5 (15%) patients with HCM; follow‐up data was not available in 8 (22%). Atrial tachycardia occurred in 29 (48%). Valvar pulmonary stenosis rarely progressed and atrial septal defect was uncommon. Among those with HCM, the likelihood of progressing or remaining stable was similar (37%, 41% respectively). The observation of myocardial fiber disarray in 7 of 10 (70%) genotyped specimens with Costello syndrome is consistent with sarcomeric dysfunction. Multifocal atrial tachycardia may be distinctive for Costello syndrome. Potentially serious atrial tachycardia may present in the fetus, and may continue or worsen in about one‐fourth of those with arrhythmia, but is generally self‐limited in the remaining three‐fourths of patients. Physicians should be aware of the potential for rapid development of severe HCM in infants with Costello syndrome, and the need for cardiovascular surveillance into adulthood as the natural history continues to be delineated.

Pulmonary atresia with intact ventricular septum and ventriculocoronary communications: surgical significance.

The first stage of a repair of pulmonary atresia with intact ventricular septum (type I) was attempted in a 2-day-old infant. At surgery, decompression of the hypertensive small right ventricle was followed by a sudden loss of myocardial contractility and death. Postmortem examination revealed a fistula with a large orifice in the right ventricular infundibulum that communicated directly with the left main coronary artery. Severe hypertensive changes indicative of abnormally high perfusion pressure were noted in the distal left coronary artery branches. The clinical course suggests that the effect of relieving right ventricular outflow obstruction was a reduction of left main coronary artery blood flow, resulting in fatal intraoperative myocardial ischemia. This unusual case draws attention to the anomalous ventriculocoronary communications often present in pulmonary atresia and their potential for limiting a successful surgical repair.

A combination Verhoeff's elastic and Masson's trichrome stain for routine histology.

A method for the combined staining of elastic, muscle and connective tissue for routine use in histopathology is described. The elastica, stained black by Verhoeffs technique, is contrasted with the muscle and connective tissue stained red and green or blue respectively by a modification of Massons trichrome. Cell nuclei stain blue-black with Weigerts iron hematoxylin. The procedure takes approximately two hours and is most suitable for the study of vascular pathology in surgical and autopsy sections.

Spontaneous Coronary Arterial Dissection and Isolated Eosinophilic Coronary Arteritis: Sudden Cardiac Death in a Patient With a Limited Variant of Churg-Strauss Syndrome

Isolated eosinophilic coronary arteritis expressed as a limited variant of the Churg-Strauss syndrome (allergic granulomatosis and angiitis) is a rare condition. Equally as rare is the entity of isolated spontaneous coronary arterial dissection associated with eosinophilic arteritis. A 57-year-old woman with a history of asthma and recurrent hypersensitivity (anaphylactoid) reactions to various exogenous allergens was found dead in her home; no premonitory complaints had been noted during the preceding days. Autopsy revealed focal occlusion of the left anterior descending and first diagonal coronary arteries by discrete dissecting hematomas of the media as the cause of sudden and unexpected death. Histologically, the affected arterial wall showed eosinophilic inflammation characteristic of this limited expression of the Churg-Strauss syndrome. To our knowledge, sudden cardiac death caused by arterial dissection in isolated eosinophilic coronary arteritis has not previously been reported.

Inflammation, neovascularization and intra-plaque hemorrhage are associated with increased reparative collagen content: Implication for plaque progression in diabetic atherosclerosis

Sustained inflammation may stimulate a reparative process increasing early reparative type III collagen synthesis, promoting atherosclerotic plaque progression. We evaluated inflammation, neovascularization, intra-plaque hemorrhage (IPH), and collagen deposition in human aortic atherosclerotic plaques from patients with and without diabetes mellitus (DM). Plaques were procured at autopsy from lower thoracic and abdominal aorta from DM (n = 20) and non-DM (n = 22) patients. Inflammation and neovascularization were quantified by double-label immunochemistry and the IPH grade was scored using H&E-stained sections. Type I and type III collagens were quantified using Picro-Sirius red stain with polarization microscopy and computerized planimetry. In non-DM plaques, 27%, 40%, and 33% had mild, moderate and severe inflammation in the fibrous cap and shoulder compared with 2%, 30% and 68% in DM plaques (p < 0.001). The geometric mean neovessel count was increased in DM versus non-DM plaques (140 [95% CI: 119—165] versus 59 [95% CI: 51—70]; p < 0.001). The IPH grade was increased in DM verses non-DM plaques (0.82 ± 0.11 versus 0.29 ± 0.11; p < 0.001) (percentage grade). The density of type III was increased in DM plaques (0.16 ± 0.01 versus 0.06 ± 0.01; p < 0.001) with a non-significant reduction in type I density in DM when compared with non-DM (0.28 ± 0.03 versus 0.33 ± 0.03; p = 0.303) (content per mm2). The increase in type III collagen content correlated with total neovessel content (r = 0.58; p < 0.001) in DM plaques. In conclusion, our study suggests that enhanced type III collagen deposition was associated with inflammation, neovascularization and IPH, and may be a contributing factor in DM plaque progression.

Fatal neonatal nemaline myopathy with multiple congenital anomalies

The clinical course and autopsy findings in a patient with fatal neonatal nemaline myopathy are described. A hypotonic infant required mechanical ventilatory support immediately following delivery and developed progressive congestive heart failure. He had mild facial dysmorphism, a high-arched palate, clinodactyly, short first metacarpals, abnormal dermatoglyphics, simian creases, and bilateral talipes varus. Light and electron microscopic study of a muscle biopsy was diagnostic of nemaline myopathy. Autopsy revealed a papillary muscle anomaly, myocardial scarring, and hepatic fibrosis. The severe clinical impairment in this infant and the unusual associated anomalies are compared with other examples of nemaline myopathy. Nemaline myopathy is a cause of respiratory insufficiency in the neonatal period.

Endomyocardial ultrastructural findings in preeclampsia

Ultrastructural findings in endomyocardial biopsy specimens obtained during cardiac catheterization in a patient with severe preeclampsia are described. Intramyocardial vessels revealed prominent swelling of the endothelial cell cytoplasm. In addition, cardiac myocyte mitochondria showed swelling and clearing within the matrix. Endomyocardial ultrastructural injury occurs in severe preeclampsia.

Ventriculocoronary connections in hypoplastic right heart syndrome: Autopsy serial section study of six cases

Myocardial sinusoids communicating with the coronary systems occur in pulmonary atresia with intact ventricular septum. To test the hypothesis that the extent of ventriculocoronary connections correlates with the degree of right ventricular outflow obstruction as evidenced by clinical, angiographic and gross anatomic findings, a serial section study of six human autopsy hearts representing a spectrum of hypoplastic right heart was undertaken. Slides were evaluated for the presence and extent of ventriculocoronary connections, associated developmental abnormalities and secondary changes in the ventricular walls. Whereas extensive blind-ended deep sinusoids were a feature of all five cases with unrelieved obstruction, ventriculocoronary connections were identified in three. Changes that suggested ongoing remodeling provide new evidence for the postnatal temporal evolution of these anomalous communications. The regional distribution of myofiber disarray in hypoplastic right heart supports the concept that vascularization parallels myocardial organization in the developing human heart.