Paul Adams

The developmental complex of "parachute mitral valve," supravalvular ring of left atrium, subaortic stenosis, and coarctation of aorta.

Abstract A developmental complex is described in which four obstructive anomalies of the left side of the heart and aorta coexist. These anomalies are (1) parachute mitral valve; (2) supravalvular ring of left atrium; (3) subaortic stenosis of either the muscular or membranous type; and (4) coarctation of the aorta. Eight cases form the basis of this report. In 2 cases, each of the four anomalies was present; all of the other 6 cases represent partial forms of the complex, or formes frustes, in that only two or three of the anomalies were present. The clinical picture is compounded of the effects of the several anomalies of the complex and of the frequent association with still other anomalies, including ventricular septal defect.

Diagnosis and Management of Hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Diseases

This guideline has been approved by the American Association for the Study of Liver Diseases (AASLD) and represents the position of the association.

Molecular medicine and hemochromatosis: At the crossroads

Abstract Summary of a conference sponsored by the Division of Digestive Diseases and Nutrition and the Division of Kidney, Urology and Hematology of the National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland GASTROENTEROLOGY 1999;116:193-207

Anomalous inferior vena cava with azygos continuation (infrahepatic interruption of the inferior vena cava). Report of 15 new cases.

Summary Fifteen new cases of anomalous inferior vena cava with azygos or hemiazygos continuation are presented, together with a review of 26 cases previously published. The incidence of this anomaly approximates 0.6 per cent in patients with congenital heart defects. The commonly encountered cardiac defects include cor biloculare, atrioventricular canal, anomalously connecting pulmonary veins, double outflow right ventricle, large atrial septal defect, pulmonary stenosis or atresia, or combinations of these. Abnormal positions of the heart and abdominal viscera are often present. An antemortem diagnosis can be established by cardiac catheterization or angiocardiography. A typical “candy cane” appearance of the anomalous venous pathway occurs when angiocardiography is performed from the leg veins. The most common pattern is azygos continuation with normal position of the heart and abdominal viscera. There is no evident relationship between the subtypes of this anomaly and the intracardiac defects that may be present. The embryologic development of the venous system is discussed, particularly in regard to the origin of the anomalies under discussion. Anomalous inferior vena cava with azygos or hemiazygos continuation is best interpreted as interruption or failure of fusion of the hepatic and prerenal segments of the inferior vena cava, combined with persistence of either the right lumbar azygos vein or left lumbar hemiazygos vein. Thus, a better term for the anomaly would be “infrahepatic interruption of the inferior vena cava with azygos (hemiazygos) continuation.”

SYNDROME OF CONGENITAL CARDIAC DISEASE WITH ASPLENIA. DISTINCTION FROM OTHER FORMS OF CONGENITAL CYANOTIC CARDIAC DISEASE.

Abstract The pathologic and clinical features in 17 patients with congenital cardiac disease in association with agenesis of the spleen have been presented. Pathologically, the cases fell into two groups as follows: those with two ventricles and a large ventricular septal defect (10 cases), and those with a common ventricle (7 cases). Conotruncal abnormalities were present in each case. These consisted of pulmonary stenosis or atresia (17 cases) and transposition of the great vessels (16 cases). Ventricular and infundibular inversion was common, occurring in 8 cases with two ventricles and 5 cases with common ventricle, respectively. “Endocardial cushion defects” were found in each of the 17 cases. Persistent common atrio-ventricular canal was present in 16, and an “ostium primum” atrial septal defect, in association with mitral atresia, was seen in the seventeenth case. Atrial septal defects were present in each case. In 13 instances, the only remnant of the atrial septum was a narrow strand of tissue between two large coexisting defects (the condition referred to herein as common atrium). The common occurrence of anomalies of the systemic and pulmonary veins was noted. Among the 17 cases, bilateral superior venae cavae with absent coronary sinus were found in 15 and anomalous pulmonary venous connections occurred in 12. Malposition of the viscera was represented by the finding of mirror-image dextrocardia in 1, dextroversion of the ventricles in 9 and abdominal heterotaxia in 13 cases. The finding of the cardiac apex and stomach on opposite sides was noted primarily in cases with common ventricle and may be helpful in the clinical diagnosis of this condition. There was a tendency toward bilateral symmetry of the organs characterized by the universal presence of bilateral three-lobed lungs, a large, transverse liver, absence of the spleen (the only unilateral organ in the body) and by the very frequent presence of common atrium, persistent common atrioventricular canal and bilateral superior venae cavae, and malrotation of the intestine. The patients presented, usually as young infants, with obvious cyanosis from birth. Electrocardiographically, the occurrence of left axis deviation and a counterclockwise QRS loop in the frontal plane suggesting the presence of an A-V commune defect, may help separate these patients with complicated cardiac malformations and asplenia from other patients with cyanotic congenital cardiac disease but with less complex malformations and without asplenia. In 5 cases of common ventricle and asplenia, the “A-V commune electrocardiogram” was absent, even though a complete form of persistent common atrioventricular canal was present in each. Routine thoracic and abdominal roentgenograms, as well as angiocardiographic studies, have proved to be the most effective means of establishing the clinical diagnosis of the asplenic syndrome. The angiocardiogram may identify many of the intracardiac and associated vascular anomalies found in this condition. The clinical features which are most useful in identifying cases of cyanotic congenital cardiac disease associated with asplenia include: (1) hematologic signs of asplenia; (2) electrocardiographic features of persistent common atrioventricular canal; and (3) radiologic evidence of hepatic symmetry, evidence of diminished pulmonary blood flow, and transposed great vessels.

Aorticopulmonary septal defect.

Abstract The anatomic, clinical, hemodynamic, roentgenographic and surgical problems in six cases studied and in sixty cases found in the literature of aorticopulmonary septal defect are analyzed. Anatomically, the lesion is characterized by an abnormal communication between the ascending aorta and pulmonary arterial trunk. In the aggregate of sixty-six cases, associated anomalies were as follows: (1) patent ductus arteriosus, eight cases; (2) coarctation of aorta, three cases; (3) ventricular septal defect, two cases; (4) right aortic arch, two cases; and (5) atrial septal defect, two cases. Clinically, the picture in each of the six patients studied resembled the findings of a large ventricular septal defect. The most striking clinical feature was the absence of a continuous murmur, and this finding was noted in 80 per cent of cases reviewed in the literature. The electrocardiogram is not specific and may show left, right or biventricular hypertrophy, depending on the degree of pulmonary vascular resistance. In general, hemodynamic findings are similar to those in cases of large patent ductus arteriosus. Pulmonary arterial pressure was equal or nearly equal to systemic arterial pressure in the four cases in which data for this comparison existed. A left to right shunt was demonstrated in each of the five cases subjected to cardiac catheterization. The diagnostic importance of the position of the catheter during catheterization is emphasized and illustrated. The radiologic features of the malformation are nonspecific but the diagnostic value of selective aortography is of high order. Five of the six patients underwent corrective surgical procedures, and three survived. Closure of the defect during conditions of cardio-pulmonary bypass is recommended.

Screening in liver disease: Report of an AASLD clinical workshop

This report summarizes an AASLD Clinical Workshop that was presented at Digestive Diseases Week 2003 on screening in liver diseases. As newer diagnostic tests become available, many liver diseases and complications of liver disease can be detected at an early asymptomatic stage. In many cases, early detection can lead to earlier treatment and an improved outcome. However, screening for liver diseases in asymptomatic persons has the potential for adverse consequences, including discrimination and stigmatization. The cost of screening programs is significant, and access to screening tests varies in different countries. Future screening programs require careful planning and implementation to balance the benefits, risks, and cost‐effectiveness. This review outlines the concepts of screening and their application to a broad range of liver diseases. (HEPATOLOGY 2004;39:1204–1212.)

HFE C282Y homozygotes have reduced low-density lipoprotein cholesterol: the Atherosclerosis Risk in Communities (ARIC) Study

Recent studies have raised questions about the long-term health risks for individuals with mutations in the HFE gene, although previous studies may have been plagued by selection bias or lack of population-based comparison groups. We examined cardiovascular disease risk factors and iron and liver biomarkers, as well as morbidity and mortality associated with the C282Y and H63D variants of HFE in the Atherosclerosis Risk in Communities (ARIC) study, which is a population-based cohort of nearly 16,000 U.S. white and black men and women who were 45-64 years old at baseline. Subjects were followed for an average of 15 years for death, incident coronary heart disease, stroke, and heart failure, and an average of 8 years for incident diabetes. The prevalence of C282Y homozygosity was 0.42% (45/10,800) in whites, which is similar to other North American population-based studies. C282Y homozygotes had significantly lower mean low-density lipoprotein (LDL) cholesterol and fibrinogen as well as higher mean levels of iron (ferritin, transferrin saturation) and liver biomarkers (alanine aminotransferase, Hepascore) compared with HFE wild-type subjects. Rates of all-cause mortality, cardiovascular disease, and diabetes were similar across HFE genotypes. These prospective, population-based data indicate higher serum iron indices and possible mild liver dysfunction or disease in some C282Y homozygotes, but they provide little evidence that HFE C282Y or H63D mutations are related to all-cause mortality, cardiovascular disease, or diabetes. Reduced LDL in C282Y homozygotes may be because of effects of excess iron on cholesterol metabolism and lipoprotein formation in the liver.

Congenital corrected transposition of the great vessels: Correlation of electrocardiograms and vectorcardiograms with associated cardiac malformations and hemodynamic states☆

Abstract An electrocardiographic and vectorcardiographic analysis of 37 cases of corrected transposition revealed that characteristic findings were uniformly present in those cases (group I) in which the cardiac apex was on the expected or correct side in relation to the atrial chambers (on the left in situs solitus; on the right in situs inversus). When dextroversion was present (group II), however, many of these features were absent. The findings typical of the 30 cases in group I were initial QRS vectors directed to the left, anteriorly and superiorly; corresponding electrocardiographic findings of Q waves in the right precordial leads (V 4 R and/or V 1 ) and in lead III with absence of the Q wave in lead V 6 ; and corresponding vectorcardiographic findings of absence of the Q loop (represented by a leftward, straight initial efferent limb of the QRS loop in the horizontal plane). Comparative vectorcardiographic analysis of 25 cases in group I (study group) and 78 control cases without corrected transposition but with comparable associated malformations and hemodynamic states, revealed that the aforementioned characteristic vectrocardiographic findings in the study group were effective in distinguishing between the two groups. Otherwise, the patterns of ventricular hypertrophy in the cases with corrected transposition were, in most cases, similar to those of the control cases. The electrocardiographic and vectorcardiographic findings in the 7 cases with dextroversion (group II) were more variable, depending, in part, on the degree of dextroversion. There were, however, such findings as absence of the normal Q loop in the vectorcardiogram in 4 cases and absence of the Q waves in the left precordial leads in 5 cases, which may represent characteristic features of corrected transposition when dextroversion is present. In the over-all approach to the diagnosis of corrected transposition with or without associated cardiac anomalies, the vectorcardiogram proved to be a valuable adjunct to the electrocardiogram in characterizing the electrical events which produce the unusual electrocardiographic features of this condition.

Is there a threshold of hepatic iron concentration that leads to cirrhosis in C282Y hemochromatosis

OBJECTIVE:The relationship between the degree of iron overload and the presence of cirrhosis has not been clearly established in hemochromatosis. Severe iron overload occurs without cirrhosis and moderate iron overload can occur with cirrhosis. Previous estimates may have overestimated the problem because of the overdiagnosis of hemochromatosis in patients with alcoholic liver disease and chronic viral hepatitis. The objective of this study was to determine if a threshold for hepatic iron concentration leads to the development of cirrhosis in C282Y hemochromatosis.METHODS:This study included only hemochromatosis patients who were homozygotes for the C282Y mutation of the HFE gene and had undergone liver biopsy with hepatic iron concentration. Analysis of the thresholds for cirrhosis were determined using receiver operating characteristic (ROC) curve analysis.RESULTS:Data were available on 100 C282Y homozygotes (62 men, 38 women; mean age 51, range 18–74 yr). ROC curve analysis showed an area under the curve for hepatic iron concentration versus cirrhosis of 0.85 (95% CI = 0.75–0.96). The threshold for the prediction of cirrhosis was 283 μmol/g. At that threshold, the sensitivity was 85% and specificity 84%.CONCLUSIONS:From this analysis, it appears that a hepatic iron concentration >283 μmol/g is associated with cirrhosis. However, the low sensitivity of this threshold suggests that other cofactors contribute to the development of cirrhosis in hemochromatosis. Early diagnosis is encouraged to initiate iron depletion before the development of cirrhosis.