James H. Moller

Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study

BACKGROUND Ventricular arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot are devastating complications in adult survivors of early surgery, but their prediction remains difficult. METHODS We examined surgical, electrocardiographic, and late haemodynamic data, and their relation to clinical arrhythmia and sudden death occurring over 10 years, in a multicentre cohort of patients with repaired tetralogy, who were alive in 1985. RESULTS Of 793 patients (mean age at repair 8.2 years [SD 8], mean time from repair 21.1 years [8.7]) who entered the study, 33 patients developed sustained monomorphic ventricular tachycardia, 16 died suddenly, and 29 had new-onset sustained atrial flutter or fibrillation. Electrocardiographic markers (QRS duration, QRS rate of change between 1985 and 1995) were significantly greater in the ventricular tachycardia and sudden-death groups. Older age at repair was associated with a higher risk of sudden death and atrial tachyarrhythmia. Pulmonary regurgitation was the main underlying haemodynamic lesion for patients with ventricular tachycardia and sudden death, whereas tricuspid regurgitation was for those with atrial flutter/fibrillation. Despite adverse haemodynamics, no patient who died suddenly had undergone late reoperation. CONCLUSION Arrhythmia and sudden death are important late sequelae for patients after repair of tetralogy of Fallot. The electrophysiological and haemodynamic substrate of sudden death resembled that of sustained ventricular tachycardia, with pulmonary regurgitation being the predominant haemodynamic lesion. Preservation or restoration of pulmonary valve function may thus reduce the risk of sudden death. Furthermore, electrocardiographic markers can help to identify patients at risk.

Long-Term Follow-Up of Patients After Coarctation of the Aorta Repair

Late cardiovascular complications after operative repair of coarctation of the aorta include systemic hypertension, premature coronary artery disease, aortic valve abnormalities, aortic aneurysm, and recoarctation. We report the outcome in 274 subjects greater-than-or-equal50 years after coarctation repair. Operative repair of simple coarctation was performed on 274 patients at the University of Minnesota Hospital between 1948 and 1976. Twenty patients (7%) died in the immediate postoperative period. Of the 254 survivors, 2 were lost to follow-up, 45 (18%) died at a mean age of 34 years, and 207 (81%) were alive greater-than-or-equal50 years after the original operation. Coronary artery disease and perioperative deaths at the time of a second cardiac operation accounted for 17 of the 45 late deaths. Predictors of survival were age at operation and blood pressure at the first postoperative visit. Of the 207 long-term survivors, 92 (48%) participated in a clinical cardiovascular evaluation. Thirty-two of the 92 subjects had systemic hypertension that was predicted by age at operation, blood pressure at the first postoperative visit, and paradoxic hypertension at operative repair. New cardiovascular abnormalities detected at follow-up evaluation included evidence of a previous myocardial infarction, cardiomyopathy, atrial fibrillation, moderate to severe left ventricular outflow tract obstruction, moderate aortic valve regurgitation, recoarctation, and ascending aortic dilation. Thus, long-term survival is significantly affected by age at operation, with the lowest mortality rates observed in patients who underwent surgery between 1 and 5 years of age. More than 1/3 of the survivors developed significant late cardiovascular abnormalities.

Polysplenia: A review of 146 cases

SummaryThe types of cardiac and visceral anomalies of 146 autopsied cases of polysplenia are described. One hundred and five of these cases were from the literature and the other 41 cases were specimens we personally reviewed. The anomalies found support the previous description of this condition as bilateral leftsidedness. Each lung had 2 lobes in 55% of patients, and abdominal heterotaxia was present in 56%. Cardiac anomalies occurring in at least half of the patients include bilateral superior vena cava, interruption of the inferior vena cava with azygos continuation, ventricular septal defect, ostium primum defect, and morphologic left ventricular outflow obstruction. Not all patients with polysplenia have cardiac anomalies, and in many patients the cardiac anomalies are not complex. Fifty percent of the 146 patients died by 4 months of age and 75% before 5 years of age.

Congenital Cardiac Disease Associated with Polysplenia A Developmental Complex of Bilateral "Left-Sidedness"

The well-recognized association of congenital cardiac disease with asplenia has been termed “bilateral right-sidedness” or dextro-isomerism, since the spleen is absent, the liver is symmetrical, and each lung has three lobes and an epiarterial bronchus. In a study of pathological material from 12 patients with congenital cardiac disease associated with multiple spleens (as contrasted to accessory spleen), we found a definite tendency for the symmetrical development of organs but with a tendency for bilateral left-sidedness or levo-isomerism.The abnormalities assumed one of three forms as follows: (1) absence of a normal right-sided structure, (2) bilateral organs, each with the structure of a left-sided organ, or (3) excessive tissue of a left-sided organ. Thus, in polysplenia we observed a tendency for (1) absence of the hepatic segment of the inferior vena cava and absence of the gallbladder, (2) two lobes in each lung with hyparterial bronchi, and (3) multiple spleens. Other noncardiac abnormalities were partial or complete abdominal heterotaxia and partial malrotation of the bowel. The cardiac malformations included dextrocardia, bilateral superior venae cavae, anomalous pulmonary venous connection with malposition of the atrial septum, and defects in the atrial septum and in the ventricular septum.Our study suggests that the developmental complex of multiple spleens is closely related to the asplenic syndrome, with the important difference being left-sided symmetry rather than right-sided symmetry.

Impact of Laboratory Molecular Diagnosis on Contemporary Diagnostic Criteria for Genetically Transmitted Cardiovascular Diseases: Hypertrophic Cardiomyopathy, Long-QT Syndrome, and Marfan Syndrome A Statement for Healthcare Professionals From the Councils on Clinical Cardiology, Cardiovascular Disease in the Young, and Basic Science, American Heart Association

Over the last several years, substantial progress has been achieved in defining the molecular basis for several genetically transmitted, nonatherosclerotic cardiovascular diseases. These advances in molecular biology have enhanced our understanding of the primary defects and basic mechanisms responsible for the pathogenesis of these conditions and their phenotypic expression, and in the process, new perspectives on cardiac diagnosis have been formulated. In the course of this scientific evolution, a certain measure of uncertainty has also arisen regarding the implications of genetic analysis for clinical diagnostic criteria. New subgroups of genetically affected individuals without conventional clinical diagnostic findings have been identified solely by virtue of access to molecular laboratory techniques, creating a number of medical and ethical concerns regarding the possible clinical implications. Indeed, the extent to which such individuals should receive sequential evaluations and/or therapy or be subjected to employment or insurance discrimination, psychological harm, loss of privacy, or unnecessary withdrawal from competitive athletics is uncertain but remains a legitimate source of concern. It is therefore particularly timely and appropriate to analyze these issues in detail, specifically the extent to which molecular biology has revised traditional diagnostic criteria. The role of genetic testing in assessing prognosis and identifying high-risk subgroups or in defining basic disease mechanisms and pathophysiology is, however, largely beyond the scope of this scientific statement. As models for the present critique, we selected the 3 most common familial cardiovascular diseases for which gene defects have been identified, each of which is associated with autosomal dominant inheritance and a risk for sudden cardiac death: hypertrophic cardiomyopathy (HCM), long-QT syndrome (LQTS), and Marfan syndrome (MFS).

Anomalies of the pulmonary veins

Abstract Eighty pathologic specimens with anomalies of pulmonary veins were reviewed for the type of lesions encountered. These were classified on an anatomic basis into five groups, characterized by (1) stenotic lesions; (2) accessory veins; and (3) anomalous connection of pulmonary veins (a) either partial or total, to a systemic vein or right atrium (the most common condition found), (b) to a systemic vein while connection to the arterial atrium was also present and (c) to a pulmonary artery (arteriovenous fistula). Combinations may occur, since pulmonary veins involved in anomalous connection may also be stenotic. The latter combination effects an adverse course on the patient with total anomalous pulmonary venous connection. The clinical manifestations of these malformations are dependent on the anatomic structure and in general result in one of three clinical pictures: (1) pulmonary venous obstruction, (2) bidirectional shunt and (3) cyanosis without abnormal cardiac signs.

The first open heart corrections of tetralogy of Fallot: a 26-31 year follow-up of 106 patients

Tetralogy of Fallot became a correctable malformation on August 31, 1954, and from that date through 1960, 106 patients (ages 4 months-45 years) who underwent open repairs at the University of Minnesota and were discharged, have been followed (99% complete) until death or for 26–31 years (mean: 23.7 years, 2424 patient years). The purposes of this study were to determine survival, morbidity, hemodynamics, educational/employment attainments, and relation of these to surgical technics. Operations were done by cross circulation (6 patients) and bubble oxygenator (100 patients). This group had the first uses of patch ventricular septal defect closure, outflow root, infundibuloplasty, atresia correction, ischemic arrests, and pacemakers among other innovations. Twenty-one (of 105 patients) have died during the followup: eight deaths in the first 10 years, 12 between 10 and 20 years, and 1 >20 years. The causes of death were sudden (5), accidental (4), congestive failure (2), reoperation (2), suicide (2), and other (2). Actuarial survival at 30 years was 77%. Late complications were ten reoperations, five arrhythmias, and one endocarditis. Actuarial freedom from reoperations at 30 years was 91%. Cardiac recatheterizations in 62 patients disclosed only 10 with residual shunts. Peak right ventricular systolic pressures were < 40 mmHg (34 patients), 41–60 mm (2 patients), 61–70 mm (4 patients), >71 mm (4 patients). Thirty-four patients (32%) completed college, ten of these completed graduate school (5 masters degrees, 2 M.D.S, 2 Ph.D.s, 1 lawyer). Fifteen others attended college, and nine received technical school diplomas. Forty patients (18 men, 22 women) had progeny, with 82 (93%) live births and six major cardiac defects (7.3%). In summary, complete repair gave excellent late results in this group cared for very early in the open heart era. Survivors led productive lives without restrictions in education and employment. Many of the deaths/complications that occurred are now easily preventable, which augurs extremely well for this generation.

Congenital Pulmonary Stenosis Resulting from Dysplasia of Valve

A distinctive type of pulmonary valvular stenosis, termed “pulmonary valvular dysplasia,” is described from six necropsies and 10 living children. The anatomic features of the stenotic pulmonary valve are unique in that there are three distinct cusps and no commissural fusion. The obstructive mechanism is related to markedly thickened, immobile cusps, characterized by the presence of disorganized myxomatous tissue.Several clinical features tend to distinguish this form of pulmonary stenosis. In each of 16 patients studied, a pulmonary ejection murmur was present, but this was not associated with an ejection click. Other features suggestive of this type of pulmonary stenosis were slow body growth, abnormal facies, and a positive family history of pulmonary stenosis. The electrocardiogram showed a greater degree of right axis deviation than is found in most cases of dome-shaped pulmonary stenosis. Right ventriculography revealed distinctive features of the pulmonary valve which were characterized by lack of typical dome-shaped deformity and by the presence of thick cusps.Experience with simple incision-valvulotomy was associated with a high (38%) operative mortality and significant residual stenosis in survivors. The suggested operative procedures include excision of a valve cusp, placement of a right ventricular outflow patch, or replacement of the pulmonary valve.

Late results (30 to 35 years) after operative closure of isolated ventricular septal defect from 1954 to 1960.

This study was designed to determine the clinical status, cause of death, and effects of pulmonary vascular disease and conduction abnormalities 30 to 35 years after surgery in 296 consecutive surviving patients of closure of ventricular septal defect. Of the 296 patients, current status was determined by contact with patient and physician in 290 cases, with 6 (2%) lost to follow-up (7,912 patient years are included). Cardiac catheterization after surgery in 168 patients showed complete closure of the defect in 80%. Death occurred in 59 patients (20%), with higher mortality rates in those operated on after the age of 5 years, those with pulmonary vascular resistance greater than 7 units (51%), and those with complete heart block (78%). Of 37 patients with transient heart block after surgery, 8 (22%) have died (3 pulmonary vascular disease, 2 sudden death, 2 unknown causes and 1 complete heart block). Twenty other patients had a dysarrhythmia after surgery, and none of these died. Nine episodes of endocarditis occurred (11.4/10,000 patient years). Nine of 296 (3%) offspring had cardiac malformation. Most patients are in New York Heart Association class I, 57% attended college and 15% received an advanced degree. The data show good results for this group of patients operated on during an early era (1954 to 1960) of open cardiac surgery. They support the current trend toward operation in patients with ventricular septal defects at an early age and with low pulmonary vascular resistance.

Diseases of the Mitral Valve in Infancy: An Anatomic Analysis of 55 Cases

A pathologic study of mitral valvular lesions among 55 infants revealed 29 cases in which the mitral valve was the site of a primary congenital malformation and 26 cases in which the mitral lesion was an acquired infarction of papillary muscles secondary to some other malformation.Among the 29 cases with primary congenital anomalies of the mitral valve, there were 41 lesions represented. Congenital anomalies were identified according to the four components of the valve as follows: leaflets, commissures, chordae tendineae, and papillary muscles. The most common basis for primary congenital mitral valvular disturbance was an abnormality of the papillary muscles. In this group, parachute mitral valve and abnormal position of papillary muscles associated with endocardial fibroelastosis were most common (eight and 10 examples, respectively). Anomalous mitral arcade and obstructing papillary muscles were observed four and three times, respectively.Involvement of leaflets was the second most common type of congenital anomaly, being observed 11 times. In this group, in order of decreasing frequency, were supra-valvular ring (five cases), accessory mitral valvular tissue (three cases), “Ebsteins” malformation of the left atrioventricular valve in corrected transposition (two cases), and cleft mitral valve (one case).Commissural fusion was observed once and, in two cases, involvement of multiple components of the valve was observed.Among the 26 examples of infarction of papillary muscles, exclusive of 10 cases with endocardial fibroelastosis, the fundamental congenital anomalies included aortic stenosis (15 cases), coarctation of the aorta (six cases), and anomalous origin of the left coronary artery from the pulmonary trunk (five cases).