Structural abnormalities of great arterial walls in congenital heart disease: light and electron microscopic analyses.

BACKGROUND: Great arteries in congenital heart disease (CHD) may dilate, become aneurysmal, or rupture. Little is known about medial abnormalities in these arterial walls. Accordingly, we studied 18 types of CHD in patients from neonates to older adults. METHODS AND RESULTS: Intraoperative biopsies from ascending aorta, paracoarctation aorta, truncus arteriosus, and pulmonary trunk in 86 patients were supplemented by 16 necropsy specimens. The 102 patients were 3 weeks to 81 years old (average, 32+/-6 years). Biopsies were examined by light (LM) and electron (EM) microscopy; necropsy specimens by LM. Positive aortic controls were from 15 Marfan patients. Negative aortic controls were from 11 coronary artery disease patients and 1 transplant donor. Nine biopsies from acquired trileaflet aortic stenosis were compared with biopsies from bicuspid aortic stenosis. Negative pulmonary trunk controls were from 7 coronary artery disease patients. A grading system consisted of negative controls and grades 1, 2, and 3 (positive controls) based on LM and EM examination of medial constituents. CONCLUSIONS: Medial abnormalities in ascending aorta, paracoarctation aorta, truncus arteriosus, and pulmonary trunk were prevalent in patients with a variety of forms of CHD encompassing a wide age range. Aortic abnormalities may predispose to dilatation, aneurysm, and rupture. Pulmonary trunk abnormalities may predispose to dilatation and aneurysm; hypertensive aneurysms may rupture. Pivotal questions are whether these abnormalities are inherent or acquired, whether CHD plays a causal or facilitating role, and whether genetic determinants are operative.

Cardiac rhythm and conduction in Duchenne's muscular dystrophy: a prospective study of 20 patients.

This study was designed to determine the types and prevalence of rhythm and conduction disturbances in Duchenne's muscular dystrophy, and examine the results in light of known morphologic abnormalities of the myocardium and the small coronary arteries, and in the context of left ventricular function, regional wall motion, mitral valve prolapse and left atrial size. The observed disorders of impulse and conduction extended from the sinus node to the His-Purkinje system. Rhythm disturbances included persistent and labile sinus tachycardia (gradual or abrupt), sinus arrhythmia, sinus pauses, atrial ectopic beats, atrial ectopic rhythm, junctional rhythm, atrial flutter and ventricular premature beats (uniform, multiform, bigeminal and repetitive). Disorders of conduction included abnormal intraatrial or interatrial conduction, Mobitz type I block, nonconducted atrial premature beats, short PR interval, right ventricular conduction delay and rightward axis compatible with left posterior fascicular block. The role of dystrophic involvement of specialized conduction tissues and of the small vessel coronary arteriopathy remains speculative, but mitral valve prolapse, left atrial size and left ventricular size, function and regional wall motion played no discernible part in the genesis of the rhythm and conduction disturbances. Except for end-stage atrial flutter, these disturbances were not clinically deleterious.

The physiologic mechanisms of cardiac and vascular physical signs.

Examination of the heart and circulation includes five items: 1) the patient's physical appearance, 2) the arterial pulse, 3) the jugular venous pulse and peripheral veins, 4) the movements of the heart--observation, palpation and percussion of the precordium, and 5) auscultation. This report deals with specific examples that relate cardiac and vascular physical signs to their mechanisms, focusing on each of the five sources. It draws liberally on early accounts, emphasizing that modern investigative techniques often serve chiefly to verify hypotheses posed in the past.

Facioscapulohumeral muscular dystrophy: evidence for selective, genetic electrophysiologic cardiac involvement.

Facioscapulohumeral muscular dystrophy is an autosomal dominant disorder with an incidence of 3 to 10 cases per million. The only type of cardiac involvement ascribed to this neuromuscular disorder is a unique form of heart disease--permanent atrial paralysis. However, reported cases of facioscapulohumeral muscular dystrophy probably represented instead what is now recognized as phenotypically similar Emery-Dreifuss dystrophy. Cardiac involvement, therefore, has not been convincingly reported in facioscapulohumeral muscular dystrophy, but because of the clinical similarity of that disorder to Emery-Dreifuss dystrophy and its genetic variants, a prospective investigation of the electrophysiologic properties of the atria and atrioventricular (AV) node and infranodal conduction was undertaken in 30 rigorously documented cases of facioscapulohumeral muscular dystrophy. All patients had a 12 lead surface electrocardiogram (ECG), 22 had a 24 h ambulatory ECG, 15 patients had two-dimensional echocardiographic/Doppler studies and 10 patients underwent 12 intracardiac electrophysiologic investigations. Left atrial, right atrial or biatrial P wave abnormalities were present in 60% of the surface ECGs. Evidence of abnormal AV node or infranodal conduction was present on intracardiac electrophysiologic study or surface ECG in 27% of patients. Atrial flutter or fibrillation was induced by single atrial extra stimuli in 10 of the 12 intracardiac electrophysiologic studies. Sinus node function was abnormal in three patients. This investigation provides the first secure evidence of cardiac involvement in facioscapulohumeral muscular dystrophy. The involvement is represented by relatively high susceptibility to induced atrial flutter or fibrillation during electrophysiologic study, together with less frequent evidence of abnormal sinus node function and abnormal AV node or infranodal conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac involvement in Friedreich's ataxia: a clinical study of 75 patients.

To establish the prevalence and to characterize the types of cardiac involvement in Friedreich's ataxia, 75 consecutive patients (39 male and 36 female), aged 10 to 66 years (mean 24) were prospectively studied. Electrocardiograms were performed in all patients, vectorcardiograms in 34 and echocardiograms in 58. Electrocardiographic and vectorcardiographic abnormalities occurred in 69 (92%) of the 75 patients. Electrocardiograms revealed ST-T wave abnormalities in 79%, right axis deviation in 40%, short PR interval in 24%, abnormal R wave in lead V1 in 20%, abnormal inferolateral Q waves in 14% and left ventricular hypertrophy (voltage and repolarization criteria) in 16%. Echocardiograms revealed concentric left ventricular hypertrophy in 11%, asymmetric septal hypertrophy in 9% and globally decreased left ventricular function in 7%. Progression from a normal echocardiogram to concentric left ventricular hypertrophy, asymmetric septal hypertrophy or globally decreased left ventricular function was identified in one patient in each category, although the study was not designed for longitudinal follow-up. Two patients died, and necropsy revealed in both a minimally dilated but flabby left ventricle. On the basis of electrocardiographic and vectorcardiographic and echocardiographic data, 95% of patients had one or more disorders. The most common abnormality was segmental myocardial "dystrophy" (electrocardiographic QRS initial force abnormalities), but global left ventricular hypokinesia occurred more often than previously recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional myocardial blood flow and metabolism at rest in mildly symptomatic patients with hypertrophic cardiomyopathy.

Previous observations and clinical manifestations suggest the presence of ischemia in the disproportionately thickened septum of patients with hypertrophic cardiomyopathy. Metabolic consequences of ischemia can be demonstrated with positron emission tomography. Therefore, 10 patients with hypertrophic cardiomyopathy and an echocardiographic septum to posterior wall thickness ratio of 1.8 +/- 0.4 cm (range 1.3 to 2.5) were studied with the use of nitrogen (N)-13 ammonia, carbon (C)-11 palmitate and fluoro (F)-18 2-deoxyglucose as tracers of myocardial blood flow, fatty acid metabolism and exogenous glucose utilization. The results of positron emission tomography in 9 patients with hypertrophic cardiomyopathy were compared with those in 10 normal volunteers. In the hypertrophic cardiomyopathy group, observed myocardial activity of N-13 ammonia and C-11 palmitate in the septum was similar to that in the lateral wall. Septum to lateral wall tissue activity ratios averaged 1.04 +/- 0.15 for N-13 ammonia and 1.04 +/- 0.18 for C-11 palmitate, and were similar to those in the normal volunteers (0.98 +/- 0.07 and 0.98 +/- 0.03, respectively; p = NS). Myocardial clearance half-time and residual fraction of C-11 palmitate did not differ significantly between the septum and lateral wall. However, F-18 2-deoxyglucose uptake was significantly lower in the septum than in the lateral wall (15,768 +/- 4,314 versus 19,818 +/- 5,234 counts/pixel; p less than 0.003). The mean septum to lateral wall activity ratio of 0.83 +/- 0.21 was less than that observed in normal volunteers (0.92 +/- 0.07; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Eisenmenger syndrome in adults: ventricular septal defect, truncus arteriosus, univentricular heart.

OBJECTIVES: Morbidity and mortality patterns were characterized in adults with the Eisenmenger syndrome when two ventricles with a ventricular septal defect (VSD) joined two great arteries or one great artery, or when one ventricle joined two great arteries. BACKGROUND: Although afterload in these disorders differs, clinical differences have not been defined. METHODS: Seventy-seven patients were studied. Group A comprised 47 patients with VSD, aged 23 to 69 years (mean 39.5+/-10.2), follow-up 5 to 18 years (mean 7.2+/-4.9); group B, 14 patients with truncus arteriosus, aged 27 to 50 years (mean 33.7+/-7.3), follow-up 6 to 18 years (mean 7.7+/-5.1), and group C, 16 patients with univentricular heart, aged 18 to 44 years (mean 30.6+/-8.4), follow-up 5 to 15 years (mean 4.4+/-4.2). Echocardiography established the diagnoses and anatomic and hemodynamic features. Data were compiled on tachyarrhythmias, pregnancy, infective endocarditis, noncardiac surgery and the multisystem disorders of cyanotic adults. RESULTS: Thirty-five percent of the patients died. Sixty-three percent of deaths were sudden, and resulted from intrapulmonary hemorrhage, rupture of either the pulmonary trunk, ascending aorta or a bronchial artery, or vasospastic cerebral infarction, or the cause was unestablished. There were no documented tachyarrhythmic sudden deaths. CONCLUSIONS: Medical management of coexisting cardiac disease, multisystem systemic disorders, noncardiac surgery and pregnancy has reduced morbidity. Increased longevity exposed patients to proximal pulmonary arterial aneurysms, thromboses and calcification; to truncal valve stenosis and regurgitation; to semilunar and atrioventricular valve regurgitation, and to major risks of nontachyarrhythmic sudden death.

Long-term outcome in congenitally corrected transposition of the great arteries: a multi-institutional study.

OBJECTIVES: The purpose of this study was to determine long-term outcome in adults with congenitally corrected transposition of the great arteries (CCTGA), with particular emphasis on systemic ventricular dysfunction and congestive heart failure (CHF). BACKGROUND: Patients with CCTGA have the anatomical right ventricle as their systemic pumping chamber, with ventricular dysfunction and CHF being relatively common in older adults. METHODS: Retrospective analysis of records of 182 patients from 19 institutions were reviewed to determine current status and possible risk factors for systemic ventricular dysfunction and CHF. Factors considered included age, gender, associated cardiac defects, operative history, heart block, arrhythmias and tricuspid (i.e., systemic atrioventricular) regurgitation (TR). RESULTS: Both CHF and systemic ventricular dysfunction were common in groups with or without associated cardiac lesions. By age 45, 67% of patients with associated lesions had CHF, and 25% of patients without associated lesions had this complication. The rates of systemic ventricular dysfunction and CHF were higher with increasing age, the presence of significant associated cardiac lesions, history of arrhythmia, pacemaker implantation, prior surgery of any type, and particularly with tricuspid valvuloplasty or replacement. Aortic regurgitation (a previously unreported problem) was also relatively common in this patient population. CONCLUSIONS: Patients with CCTGA are increasingly subject to CHF with advancing age; this complication is extremely common by the fourth and fifth decades. Tricuspid (systemic atrioventricular) valvular regurgitation is strongly associated with RV (anatomical right ventricle connected to aorta in CCTGA patients; systemic ventricle in CCTGA) dysfunction and CHF; whether it is causative or a secondary complication remains speculative.

Coronary arterial spasm versus esophageal spasm. Response to ergonovine.

In this report we show that coronary arterial and esophageal spasm are sometimes clinically indistinguishable. Pain patterns can be identical, nitroglycerin can bring relief, interval electrocardiograms and exercise electrocardiograms generally disclose no abnormalities, coronary arteriograms may be within normal limits or nearly so, and, importantly, an ergonovine provocative test can provoke esophageal spasm accompanied by pain mistaken for Prinzmetal's angina. Accordingly, chest pain in response to the administration of ergonovine is not evidence of coronary arterial spasm without simultaneous arteriographic proof together with changes in the monitoring electrocardiogram. Conversely, gastroenterologists should not expose patients to the risk of ergonovine without prior assurance that the coronary arterial response is normal. Our observations illustrate these points and identify a patient with symptomatic esophageal spasm previously diagnosed as Prinzmetal's angina.

Development and regression of increased ventricular mass.

This report deals with increased cardiac mass in the light of the following variables: normal ventricular growth (embryo, fetus, neonate and child), the response to work loads (hemodynamic stress) and hypoxia, the cell responses of hyperplasia (increase in cell number), hypertrophy (increase in cell size) and the type of cell (muscle or connective tissue), the age or maturity of the myocardium at the time the hemodynamic or hypoxic stress is imposed, and the biochemistry, ultrastructure and functional morphology (modeling) of the ventricles in response to volume or pressure overload. The desirable physiologic adaptations to work loads are characterized, and the transition from physiologic to pathologic states is examined, comparing and contrasting increased ventricular mass in patients and in trained athletes. Regression of increased ventricular mass is then discussed, first at the cell level (hypertrophy/hyperplasia; muscle cell/connective tissue cell), then at the organ level. The requirements for maintaining or establishing normal ventricular function after removal of overload are reviewed, together with such variables as the type and duration of preoperative hemodynamic stress, the right versus the left ventricle and the relative rates of contractile protein synthesis and degradation.

Upper limb malformations associated with congenital heart disease.

Upper limb malformations occur in patients with congenital heart disease as multifactorial, chromosomal or teratogenic combinations, and can be predictable (nonrandom) or sporadic (random) associations. The cardiac and limb defects represent either essential features of a syndrome or less common or less significant components. A practical classification is proposed based on the frequency and relative consistency of upper limb and cardiac associations. Recognition of upper limb malformations helps to identify accompanying cardiac disease and aids in the choice of diagnostic and therapeutic interventions in determination of prognosis and in genetic counseling. Upper limb malformations are the commonest skeletal abnormalities in patients with congenital heart disease, but it is also important to know with which limb defects concordance is low.

Pathogenesis of the glomerular abnormality in cyanotic congenital heart disease.

We present evidence of 2 distinct glomerular abnormalities in cyanotic congenital heart disease--vascular and nonvascular--each believed to reflect a distinct pathogenesis. Glomeruli from both kidneys were studied with light microscopy in 13 necropsied cyanotic patients and in 8 controls. The vascular study characterized hilar arteriolar dilatation, capillary diameter, glomerular diameter, and capillary engorgement with red blood cells. The nonvascular study characterized juxtaglomerular cellularity, mesangeal cellularity, mesangeal matrix, focal interstitial fibrosis, and megakaryocytic nuclei per cm2 of renal cortex. There was a significant increase in each of the above vascular and nonvascular items of interest relative to controls. Electron microscopy identified whole megakaryocytes with their cytoplasm in glomeruli. The vascular abnormality is believed to result from intraglomerular release of nitric oxide. The nonvascular abnormality is believed to result from platelet-derived growth factor and transforming growth factor-beta.

Reassessment of echocardiographic criteria for diagnosis of mitral valve prolapse.

Commonly used echocardiographic criteria for mitral valve prolapse (MVP) include a sizable proportion of persons whose hearts are normal. Nevertheless, the echocardiogram is generally used as an independent standard for the diagnosis of MVP despite lack of consensus on the criteria to be used and the probability of interobserver variability. Conversely, there is a relatively uniform consensus that classic auscultatory signs establish the diagnosis of MVP beyond reasonable doubt. Accordingly, in 148 patients referred for evaluation of known or suspected MVP, the echocardiographic patterns that coincide with diagnostic auscultatory signs were studied prospectively to compare those patterns with criteria commonly used for the echocardiographic diagnosis of MVP and to determine interobserver variability in echocardiographic interpretation. Eighty patients (54%) had a classic mid- to late systolic click or an apical late systolic murmur, or both. Eleven patients (7%) had the apical holosystolic murmur of mitral regurgitation with no discernible clinical or echocardiographic cause other than the consideration of MVP. Doppler echocardiography was performed in 80 of the 148 patients. The degree of superior systolic bowing of each mitral leaflet and the location of leaflet coaptation relative to the presumed plane of the mitral anulus were graded on apical 4-chamber and parasternal long-axis views. The only patterns absolutely specific for auscultatory MVP were: severe bowing of the anterior or posterior leaflet; coaptation of leaflets on the left atrial side of the anular plane; moderate to severe Doppler mitral regurgitation accompanied by any degree of leaflet bowing; and mild Doppler mitral regurgitation accompanied by moderate bowing of a leaflet.(ABSTRACT TRUNCATED AT 250 WORDS)

New guidelines for the clinical diagnosis of mitral valve prolapse.

Because the term mitral valve prolapse has pathologic connotations, considerable effort has been expended to establish acceptable diagnostic standards, but without general agreement. This report combines information from the history, physical examination, electrocardiogram, chest x-ray and 2-dimensional echocardiogram in an effort to avoid the artifice of using the 2-dimensional echocardiogram as a categoric reference standard and to establish new clinical guidelines that distinguish pathologic mitral valve prolapse--a primary connective tissue abnormality of leaflets, chordae tendineae and anulus--from normal superior systolic displacement of mitral leaflets. The objective is to avoid implications of heart disease in healthy young persons within the gaussian distribution of normal. To this end, and with the Jones criteria as a model, major and minor criteria are proposed for the clinical diagnosis of mitral valve prolapse as a pathologic entity.

Ventricular inversion without transposition of the great arteries. A rarity found in association with atresia of the left-sided (tricuspid) atrioventricular valve.

Clinical and morphologic features are described in a 13 week old male infant with ventricular inversion without associated transposition of the great arteries but with concomitant atresia of the left-sided (tricuspid) atrioventricular valve. Isolated ventricular inversion without situs inversus or visceral heterotaxy has previously been reported in English in only three patients, none with tricuspid atresia.

Cardiac involvement in myotonic muscular dystrophy (Steinert's disease): a prospective study of 25 patients.

The presence, degree and frequency of disorders of cardiac conduction and rhythm and of regional or global myocardial dystrophy or myotonia have not previously been studied prospectively and systematically in the same population of patients with myotonic dystrophy. Accordingly, 25 adults with classic Steinert's disease underwent electrocardiography, 24-hour ambulatory electrocardiography, vectorcardiography, chest x-rays, echocardiography, electrophysiologic studies, and technetium-99m angiography. Clinically important cardiac manifestations of myotonic dystrophy reside in specialized tissues rather than in myocardium. Involvement is relatively specific, primarily assigned to the His-Purkinje system. The cardiac muscle disorder takes the form of dystrophy rather than myotonia, and is not selective, appearing with approximately equal distribution in all 4 chambers. Myocardial dystrophy seldom results in clinically overt ventricular failure, but may be responsible for atrial and ventricular arrhythmias. Since myotonic dystrophy is genetically transmitted, a primary biochemical defect has been proposed with complete expression of the gene toward striated muscle tissue, whether skeletal or cardiac. Specialized cardiac tissue and myocardium have close, if not identical, embryologic origins, so it is not surprising that the genetic marker affects both. Cardiac involvement is therefore an integral part of myotonic dystrophy, targeting particularly the infranodal conduction system, to a lesser extent the sinus node, and still less specifically, the myocardium.

Anomalous origin of the left main pulmonary artery from the ascending aorta associated with DiGeorge syndrome.

We place on record 2 infants with the DiGeorge syndrome and anomalous origin of the left pulmonary artery from the ascending aorta. We postulate that: (1) embryogenesis of anomalous origin of the left pulmonary artery from the ascending aorta might be due to the persistent fifth aortic arch connecting both arterial systems; (2) an anomalous pulmonary artery arising from the ascending aorta is part of the aortic arch abnormality accompanied by normal conotruncal septation; and (3) in the DiGeorge syndrome, cardiac anomalies that originate from the conotruncus or aortic arch, or both, may have the same embryologic mechanisms.

Mitral valve E point to ventricular septal separation in infants and children.

This investigation establishes heretofore unavailable norms that permit clinical application of mitral valve E point to ventricular septal separation (EPSS) as an ejection phase index in infants and children. The study consisted of 105 normal subjects (1 day through 15 years of age, mean 7.4 years) and 67 patients of comparable age. Fifty-seven patients had increased left ventricular (LV) volume with normal function (ventricular septal defect or patent ductus arteriosus) and 10 patients had increased LV volume with depressed function (dilated cardiomyopathy). In normal subjects, EPSS was 2.5 +/- 1.7 mm and "normalized" EPSS, that is, the ratio of EPSS to end-diastolic dimension (EPSS/EDD), was 0.08 +/- 0.06 (mean +/- standard deviation); there was no correlation between either of these indexes and age, body surface area, height or weight. In patients with ventricular septal defect or patent ductus arteriosus, or both, the EPSS and EPSS/EDD were similar to those of normal subjects (3.2 +/- 2.3 mm and 0.09 +/- 0.06 mm, respectively). In patients with dilated cardiomyopathy, these indexes were significantly increased (p greater than 0.05) (EPSS 16.5 +/- 5.1 mm; EPSS/EDD 0.39 +/- 0.09). The data provide normal values for EPSS and EPSS/EDD in infants and children and show that these indexes are independent of age, body surface area, height or weight. Mitral valve EPSS and EPSS/EDD can now be used in pediatric echocardiography as a simple, practical and accurate means of separating normal from abnormal LV function.

Primary hemochromatosis: anatomic and physiologic characteristics of the cardiac ventricles and their response to phlebotomy.

M-mode and 2-dimensional echocardiography and gated equilibrium blood pool imaging (rest and exercise) were used in 10 patients with primary hemochromatosis to characterize the spectrum of pathophysiologic abnormalities of the cardiac ventricles and to determine the response to chronic therapeutic phlebotomy. Dilated and restrictive cardiomyopathic patterns were identified in 1 patient each, but our data do not permit conclusions on when in the natural history a given pattern becomes overt. On entry into study, 3 patients had normal ventricles and 7 had ventricular abnormalities on echocardiography and blood pool angiography. In 2 of the latter patients, biventricular dysfunction and increased left ventricular (LV) mass normalized after phlebotomy; 1 patient achieved a normal LV response to exercise. Of the 4 patients with isolated abnormal LV ejection fraction responses to exercise, the EF normalized in 2 after phlebotomy. In 1 patient, isolated right ventricular enlargement and dysfunction (echocardiographic and radionuclide imaging) normalized after phlebotomy. Thus, primary hemochromatosis can effect LV and RV size and function; clinically occult cardiac involvement can be identified by echocardiography and equilibrium blood pool imaging; therapeutic phlebotomy can ameliorate or reverse the deleterious effects of excess cardiac iron deposition which appears to exert its harm, at least in part, by a mechanism other than irreversible connective tissue replacement.

Experience with the Fontan procedure.

From 1975 to the present, 45 patients have undergone modifications of the Fontan procedure for complex congenital heart disease. There were 30 males and 15 females ranging in age from 2 to 38 years (mean 13 years). Primary diagnoses were tricuspid atresia in 19, univentricular heart in 24, and pulmonary atresia with intact ventricular septum in two. Right atrial-pulmonary arterial connections were performed in 32 patients, 11 with conduits (seven with valves and four without) and 21 by direct anastomosis with patch augmentation. Right atrial-right ventricular connections were made in 13 patients, six with valved conduits and seven without conduits. Follow-up ranged from 0.1 to 9 years, with a mean of 2.3 years. There were three early deaths (less than 30 days) (7%) and two late deaths (5%) in this series, all in patients with a univentricular heart. The late deaths were both related to venous hypertension. A venous assist device was used in eight patients in the immediate postoperative period and was effective in improving cardiac output and reducing fluid accumulation. Postoperative Doppler flow studies in 15 patients revealed biphasic pulmonary artery flow in all without distinction between the type of connection or the presence of a valve. Cardiac catheterization was performed in 16 patients a mean of 14 months postoperatively (range 1 to 42 months) and revealed a reduced cardiac index at rest. Exercise testing in eight patients demonstrated a marked rise in right atrial pressure with a reduced rise in the cardiac index, even in those without functional limitations. With a mean follow-up of 2.3 years, 78% of patients were in New York Heart Association Class I, 17% in Class II, and 5% in Class III. We conclude that the Fontan procedure is an excellent operation in carefully selected patients with tricuspid atresia and other forms of complex congenital heart disease.