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Byline: Steven C. Cassidy, James J. McGovern, David P. Chan, Hugh D. Allen Abstract: This study compared the effects of high-dose infusions of various adrenergic agonists on cardiovascular function in piglets. We hypothesized that agonists would have different effects on systolic, diastolic, and vascular functions. Nine anesthetized 3-week-old piglets underwent cardiac catheterization. Manometric and conductance catheters measured pressures and volumes. Data were acquired at rest and during infusions of epinephrine, norepinephrine, dopamine, dobutamine, isoproterenol, and phenylephrine. End-systolic elastance, preload-recruitable stroke work, cardiac output, the maximum and minimum derivatives of left ventricular pressure, the relaxation constant I, peak filling rate, and end-diastolic stiffness were obtained. Contractile efficiency and the cardiac output/pressure-volume area ratio were calculated. Regression was used for analysis of variance; p < 0.05 was considered significant. All agonists increased indexes of contractility. [beta]-Adrenergic agonists enhanced relaxation. Isoproterenol and dopamine increased efficiency. No drug changed diastolic stiffness. Therefore both [alpha]-adrenergic and [beta]-adrenergic agonists have inotropic effects in the 3-week-old piglet. Some beneficial effects of [beta]-agonists on cardiac output may be due to enhancement of relaxation and to afterload reduction. Various agents exert different effects on the cardiovascular system, and these differences may be clinically important. (Am Heart J 1997; 133:174-83.) Author Affiliation: Columbus, Ohio Article History: Received 22 April 1996; Accepted 20 May 1996 Article Note: (footnote) [star] Supported in part by the Bremer Foundation., [star][star] Reprint requests: Steven C. Cassidy, MD, Section of Cardiology, Children's Hospital, 700 Children's Dr., Columbus, OH 43205., a E-mail: scassidy@magnus.acs.ohio-state.edu., aa 4/1/75878

Congenital heart defects affect approximately one of every one thousand infants born each year. Coupled with acquired heart diseases, such as rheumatic fever, AIDS myocarditis (AIDS-related inflammation of the heart), arrythmias (abnormal heart rhythms), and cardiomyopathies (diseases of heart muscle), up to one-half million children may suffer some degree of cardiac impairment. Of this total, approximately one-third have the added burden of poverty. Each child will require frequent visits for medical treatment and follow-up care; some will require invasive diagnostic procedures, and about 40 percent will require reparative surgery. The risks attendant on children who live in poverty add to the burden. Environmental challenges, lack of participation in the support system, and inadequate insurance (including lack of insurance) further complicate the situation. The cardiac services needed by poor children with heart disease are difficult to acquire, because of parental ignorance or lack of insurance coverage. The age of the grown child with heart disease adds to the problem. The 21-year-old previously insured dependent who received Crippled Children's Services is unable to obtain insured care because of the 'pre-existing condition'. Care and treatment are expensive, usually beyond the financial reach of young parents who lack adequate resources. Without a compassionate system, physician, clinic or other resource, their children do not get the care they need. Health and educational services for children with heart disease need to be expanded and made more readily available. Prevention and intervention strategies should be developed. Pediatric cardiologists must be the voice for children with heart and they must speak out in the political arena. (Consumer Summary produced by Reliance Medical Information, Inc.)

Fetal echocardiography is an ultrasound technique for examining the heart of a fetus. It can identify abnormal cardiac conditions such as congenital heart disease, structural anomalies, and cardiac dysrhythmia (abnormal heart beat). A four-year clinical study evaluated the accuracy of diagnosis, frequency of fetal heart defect, and the overall effects of the fetal echocardiogram on prenatal care and fetal outcome. The study demonstrated that fetal echocardiography can be a valuable diagnostic tool. Some patients were referred because of a family history of congenital heart disease (CHD); three percent of these cases showed abnormalities on the echocardiogram. Five percent of the patients referred because of a history of diabetes mellitus had abnormalities. The highest rate of abnormalities, 31 percent, was detected in patients referred for dysrhythmia, which was followed closely by patients suspected to have CHD (29 percent). The most serious condition detected was sustained fetal bradycardia (abnormally slowed heart rate). Five of the nine infants diagnosed with this condition died in utero (in the uterus) or soon after birth. When patients are referred for suspected major fetal defects, fetal echocardiography should be conducted in conjunction with amniocentesis or fetal blood sampling. It is estimated that 32 percent of fetuses with CHD may have associated chromosomal abnormalities. (Consumer Summary produced by Reliance Medical Information, Inc.)

Long QT syndrome (LQTS) is a genetic disease resulting in a prolonged QT interval on a resting electrocardiogram, predisposing affected individuals to polymorphic ventricular tachycardia and sudden death. Although a number of genes have been implicated in this disease, nearly one in four individuals exhibiting the LQTS phenotype are genotype‐negative. Whole‐exome sequencing identified a missense T223M variant in TBX5 that cosegregates with prolonged QT interval in a family with otherwise genotype‐negative LQTS and sudden death. The TBX5‐T223M variant was absent among large ostensibly healthy populations (gnomAD) and predicted to be pathogenic by in silico modeling based on Panther, PolyPhen‐2, Provean, SIFT, SNAP2, and PredictSNP prediction tools. The variant was located in a highly conserved region of TBX5 predicted to be part of the DNA‐binding interface. A luciferase assay identified a 57.5% reduction in the ability of TBX5‐T223M to drive expression at the atrial natriuretic factor promotor compared to wildtype TBX5 in vitro. We conclude that the variant is pathogenic in this family, and we put TBX5 forward as a disease susceptibility allele for genotype‐negative LQTS. The identification of this familial variant may serve as a basis for the identification of previously unknown mechanisms of LQTS with broader implications for cardiac electrophysiology. [ABSTRACT FROM AUTHOR]