Mary Allen Engle

Late Cardiac Complications of Chronic, Severe, Refractory Anemia with Hemochromatosis

Four fifths of 49 patients with chronic, severe anemia from birth have manifested, usually during the second decade, signs of hemochromatosis with cardiac involvement. Nineteen patients had 33 attacks of pericarditis. Congestive cardiac failure with arrhythmias developed in 26 patients, and all but one died with this complication. Four others died of sepsis before heart failure was evidenced. Postmortem examination showed hemochromatosis with severe myocardial involvement.

The Postpericardiotomy Syndrome

THE postpericardiotomy syndrome as described by Ito et al.1,2 is a febrile illness with pericardial and sometimes pleuropulmonary reaction that follows extensive pericardiotomy. This clinical entit...

Cardiac malformations in trisomy-18: A study of 41 postmortem cases

The cardiac malformations in 41 karyotyped and autopsy cases of trisomy-18 are presented in detail. The salient findings were a ventricular septal defect in all cases; tricuspid valve anomalies in 33 cases (80%); pulmonary valve anomalies in 30 (70%); aortic valve malformations in 28 (68%); mitral valve anomalies in 27 (66%); polyvalvular disease (that is, malformations of more than one valve) in 38 (93%); a subpulmonary infundibulum (conus) in 40 (98%); a bilateral conus with a short subaortic infundibulum in 1 case with double outlet right ventricle (this being the only documented case of bilateral infundibulum in trisomy-18); double outlet right ventricle in 4 cases (10%), three having a subpulmonary infundibulum only and all 4 having mitral atresia; tetralogy of Fallot in 6 cases (15%), 2 having pulmonary atresia; and a striking absence of transposition of the great arteries and inversion at any level (visceral or cardiac), findings that appear to be characteristic of all trisomies. These data suggest that excessive chromosomal material (as in trisomies) may result in situs solitus at all levels. The malformations of the atrioventricular and semilunar valves were characterized by redundant or thick myxomatous leaflets, long chordae tendineae and hypoplastic or absent papillary muscles. The ventricular septal defect was associated with anterosuperior conal septal malalignment in 25 cases (61%). On the basis of the characteristic valvular lesions, the type of ventricular septal defect and the absence of transposition or inversions, two-dimensional echocardiographic diagnosis of trisomy-18 in the fetus may become possible.

LONGITUDINAL STUDY OF CARDIAC FUNCTION IN THALASSEMIA MAJOR

Despite modifications in the management of /3 thalassemia major, the cardiac complications of hemochromatosis have continued to cause death in adolescence and early adulthood in patients with this disorder. From 1964 through 1977, 3 1 transfusion-dependent thalassemic patients have been followed at The New York Hospital-Cornell Medical Center until their death. In addition, 62 patients currently followed at this center have been investigated extensively prior to chelation therapy. These two patient groups form the basis of this report focusing on the natural history of cardiac disease and on cardiac function in thalassemia major.

Cardiac Involvement in Cooley's Anemia

Among patients who have had severe, refractory hypochromic anemia from infancy and have reached the second decade of life, four-fifths have cardiac involvement and in two-thirds serious cardiac complications have developed. One, acute pericarditis, appears benign but often recurs. The other, cardiac failure with arrhythmias and heart block, usually ends in death within a few months. Clinical and pathologic evidence indicates the presence of acquired hemochromatosis. The natural history of the development of cardiac hemochromatosis has been observed in this group of patients. Progressively deep skin pigmentation appeared in mid to late childhood, and retardation of growth and sexual maturation followed. Three of the seven patients who passed the age of 20 years developed diabetes. Asymptomatic but increasing cardiac enlargement and electrocardiographic abnormalities occurred in 39 out of 46 patients who passed the age of eight years. Nineteen patients had 33 recognized attacks of pericarditis, often with effusion. Cardiac failure developed in 24 patients, and 23 died despite therapy for the decompensation, arrhythmias, electrolyte disturbances, and anemia. The experience with the cardiac complications has been cumulative. Each year as a few more patients approach the second decade, the age of greatest risk, we observe a few more attacks of pericarditis and several more patients in congestive heart failure. In 1955, we had observed seven attacks in five patients.’ By 1960 12 patients had suffered 23 episodes.’ Now seven more patients have been affected, and the number of episodes is 33. With respect to congestive heart failure and arrhythmias, we saw the first three cases in the mid 1950’s and reviewed the previous experience a t the New York Hospital, which consisted of four other cases during the 1940’s.:’ By 1960, fifteen patients had developed the complication and 12 had died of it.’ The total now stands a t 24 patients with 23 deaths.

The syndrome of apical systolic click, late systolic murmur, and abnormal T waves.

DEVELOPMENT of new diagnostic techniques often brings to our attention conditions previously described but rarely recognized and little understood. So it is with this syndrome, reported in bits about once every generation from 1887 till the past decade. Then the pieces began to fall into place, and now several articles are appearing every year, each with more information and larger numbers of subjects. The syndrome is characterized by distinctive auscultatory and electrocardiographic features. Typically in a healthy and asymptomatic young woman one hears at the apex a click near midsystole, followed by a late systolic murmur. The heart and lungs on roentgenograms appear normal; so it is a surprise to find inverted T waves in the left precordial leads, aVF, and leads II and III. What does it all mean? The diagnostic tests which combined to shed light on these findings were selective angiocardiography and phonocardiography, both extracardiac and intracardiac, with use of pharmacological agents, such as amyl nitrite and phenylephrine, and the Valsalva maneuver. The intracardiac phonocatheter localized the click and murmur to the left atrium and region of the mitral valve.1 The pharmacological and physiological maneuvers showed that the murmur behaves as does a murmur of mitral regurgitation.2 3 Selective

Prolonged survival in patients with beta-thalassemia major treated with deferoxamine

To determine whether survival of patients with beta-thalassemia major has been prolonged by management that utilizes hypertransfusion and chelation with deferoxamine, we analyzed longevity by the Kaplan-Meier product-limit method. Group 1 patients (n = 71) followed between 1960 and 1976 with a low-transfusion regimen (pretransfusion hemoglobin level 7 to 8 gm/dl) and no chelation had an estimated median age of survival of 17.4 years, whereas it was 31.0 years for group 2 subjects (n = 80), who began hypertransfusion between 1976 and 1978 (pretransfusion hemoglobin level 10.5 to 11.5 gm/dl) and chelation with deferoxamine (20 to 60 mg/kg per day) (p less than 0.0001). For 70 patients who were treated with hypertransfusion and deferoxamine, we had data to calculate the ratio of total milligrams of transfusional iron to cumulative grams of deferoxamine. The 24 patients who died had a total iron burden of greater than 1.05 gm/kg; the ratio for them exceeded 31. These patients were characterized by poor compliance with chelation or by late start of therapy, with inability to receive enough deferoxamine before death. Death was preceded by arrhythmia requiring therapy in all but one, and by cardiac failure in all. Of 41 similarly iron-loaded survivors, 33 had a ratio of less than 31; only three had an arrhythmia, and five had cardiac failure. We conclude that treatment with deferoxamine, when used in amounts proportional to iron burden, delayed cardiac complications and improved longevity.

The Postpericardiotomy Syndrome and Antiheart Antibodies

In a prospective, double-blind study, heart-reactive antibody in high titer was detected, using an indirect immunofluorescent technique, in the serum of patients in whom the postpericardiotomy syndrome developed after intrapericardial surgery. The syndrome occurred in 26 of 86 consecutive longterm survivors of such surgery, an incidence of 30%. Presence of antibody correlated closely with the clinical syndrome. Demonstration of this antiheart antibody in high titer appears to offer laboratory confirmation of the syndrome.

Regression after Open Valvotomy of Infundibular Stenosis Accompanying Severe Valvular Pulmonic Stenosis

Three patients operated upon under hypothermia for severe valvular pulmonic stenosis had right ventricular pressures in excess of 100 mm. Hg after open valvotomy. The residual obstruction, localized by pressure measurements to the subvalvular region, appeared to be due to greatly hypertrophied musculature in the outflow tract of the ventricle. Infundibular resection was not attempted. Electrocardiographic signs of right ventricular hypertrophy gradually disappeared, and cardiac catheterization about 1 year after surgery showed normal or nearly normal right ventricular pressures. Postoperative improvement is attributed to regression of hypertrophy of the right ventricle consequent to relief of obstruction at the valve.

Glycogen-Storage Disease of the Myocardium with Obstruction to Left Ventricular Outflow

A case of glycogen-storage disease of the myocardium with the clinical and hemodynamic picture of left ventricular outlet obstruction was presented. The concept of muscular subaortic stenosis is discussed and the diagnostic features are reviewed. In a survey of the literature 53 cases of cardiac-type glycogen-storage disease were found. The criteria for diagnosis, sex incidence, familial occurrence, symptomatology and physical signs, and laboratory studies including roentgenograms of the chest, electrocardiogram and muscle biopsy are discussed.