Arthur S. Pickoff

Effect of Body Size, Ponderosity, and Blood Pressure on Left Ventricular Growth in Children and Young Adults in the Bogalusa Heart Study

BACKGROUND The measurement of left ventricular mass (LVM) is important because individuals with increased LVM are at increased risk for cardiovascular diseases, including myocardial infarction and congestive heart failure. There are limited longitudinal data on the acquisition of LVM in children and young adults and the relative importance of sex, growth, excess body weight, and blood pressure (BP) on change in LVM. METHODS AND RESULTS The study cohort consisted of a cross section of 160 healthy children and young adults 9 to 22 years of age at first exam in the biracial community of Bogalusa, La. All had stable BP levels recorded over a 2- to 3-year period. Repeated examinations were performed 4 to 5 years apart. At each exam, 6 BPs were obtained with a mercury sphygmomanometer by trained examiners. The mean of the observations was used, with the fourth Korotkoff phase serving as the measure of diastolic BP. Anthropometric data, including height (HT), weight (WT), and triceps skin fold thickness (TSF), were also obtained, and M-mode echocardiograms were performed. Ponderal index (PI = WT/HT3) was used as a measure of weight-for-height. Tracking of HT (r = .68 to .76), WT (r = .73 to .82), PI (r = .77 to .89), TSF (r = .70 to .80), BP (r = .47 to .60), and LVM (r = .40 to .70) was strong in both sexes (P < .0001). LVM indexed for linear growth (LVM/HT2.7) tracked in females (r = .56, P < .0001) but not in males. In univariate cross-sectional analyses, LVM/HT2.7 correlated with WT, PI, and TSF in both sexes (r = .21 to .60, P < .05) and with systolic BP (SBP) in females (r = .23, P < .05). WT was the only independent correlate of LVM/HT2.7 in both sexes in multivariate cross-sectional analysis in a model containing age, SBP, WT, and TSF as independent variables (r2 = .08 to .28, P < .02). In longitudinal univariate analyses, initial measurements of WT, PI, and TSF predicted final LVM/HT2.7 in both sexes (r = .28 to .56, P < .01), and SBP was significant for females (r = .27, P < .05). In multivariate analyses, initial WT was associated with final LVM and LVM/HT2.7 in both sexes (r2 = .27 to .54, P < .01). Finally, baseline LVM correlated with final SBP in both sexes (r = .21 to .27, P < .05), and initial LVM/HT2.7 correlated with final SBP in females (r = .26, P < .05) with a trend for males (r = .17). CONCLUSIONS These data indicate that linear growth is the major determinant of cardiac growth in children and that excess weight may lead to the acquisition of LVM beyond that expected from normal growth. Increased mass may also precede the development of increased BP. The development of obesity may therefore be a significant, and possibly modifiable, risk factor for developing left ventricular hypertrophy and hypertension, risk factors for cardiovascular morbidity and mortality.

Plasma Homocysteine Distribution and Its Association With Parental History of Coronary Artery Disease in Black and White Children The Bogalusa Heart Study

BACKGROUND Elevated homocysteine is associated with increased risk for coronary artery disease (CAD) in adults, but its distribution in children is not well documented. We examined the distribution of homocysteine in children and its relation to parental history of CAD. METHODS AND RESULTS A subsample of 1137 children (53% white, 47% black) aged 5 to 17 years in 1992 to 1994 examined in the Bogalusa Heart Study (n=3135), including all with a positive parental history of CAD (n=154), had plasma homocysteine levels measured. Homocysteine correlated positively with age (r=0.16, P=0.001). No race or sex differences in homocysteine levels were observed; geometric mean (GM) levels were 5.8 micromol/L (95% CI, 5.6 to 6.1) among white males, 5.8 micromol/L (95% CI, 5.5 to 6.0) among white females, 5.6 micromol/L (95% CI, 5.4 to 5.8) among black males, and 5.6 micromol/L (95% CI, 5.4 to 5.9) among black females. Children with a positive parental history of CAD had a significantly greater age-adjusted GM homocysteine level (GM, 6.7 micromol/L; 95% CI, 6.4 to 7.1) than those without a positive history (GM, 5.6 micromol/L; 95% CI, 5.4 to 5.7); this relation was observed in each race-sex group. CONCLUSIONS Higher homocysteine levels were observed among children with a positive family history of CAD. Additional studies should elucidate the contribution of genetic, dietary, and other factors to homocysteine levels in children.

Dual atrioventricular nodal pathways: A benign finding in arrhythmia-free children with heart disease

The incidence and significance of dual atrioventricular (A-V) nodal pathways are described in 78 children with associated congenital or acquired heart disease. None of these patients had clinical or electrocardiographic evidence of arrhythmia. Dual A-V nodal pathways were observed in 35 percent of the preoperative group and in 33 percent of the postoperative group. Despite this substrate for A-V nodal reentry, supraventricular tachycardia was neither induced during electrophysiologic evaluation nor did it develop clinically over a follow-up period of 1 month to 15 years. It is concluded that dual A-V nodal pathways are common and may be a benign finding in arrhythmia-free children with heart disease.

Ethnic (black-white) contrasts in heart rate variability during cardiovascular reactivity testing in male adolescents with high and low blood pressure. The Bogalusa Heart Study

Heart rate variability (HRV) is used to study autonomic effects on the heart. The time domain PNN50 (percentage of consecutive RR intervals differing by > 50%) measures high frequency in HRV primarily reflecting parasympathetic activity. The ratio of low to high frequency power (LF/HF) measured by fast Fourier analysis is used to measure sympathetic to parasympathetic balance. In adults, increased sympathetic tone has been found in hypertensive individuals. The present study was performed to look for differences in HRV by race and between subjects with high and low blood pressure (BP). Heart rate variability data was analyzed from Holter monitor recordings in 39 healthy male subjects aged 13 to 17 years (50% white). Half were selected with Korotkoff fourth sound (K4) DBP > 85th percentile for height measured twice, 3 to 5 years apart (average 116/75 mm Hg). Half had DBP < 15th percentile for height (average 101/57 mm Hg). Subjects underwent a physical examination including BP, height, and weight before cardiovascular reactivity testing including measurements taken while supine and standing, and during 20% maximal isometric hand grip, Valsalva maneuver, and immersion of the hand in water at 4 degrees C. The LF/HF ratio was significantly higher and the PNN50 was significantly lower in whites compared with ratios for blacks during all CV reactivity tests (all P < .05). There was a trend for higher LF/HF ratio and lower PNN50 in blacks and whites with higher levels of BP, although this did not reach statistical significance. It was concluded that healthy white adolescents exhibit increased sympathetic tone compared with that of blacks during CV reactivity tests. A trend towards sympathetic predominance during reactivity testing was demonstrated in children with higher levels of DBP.

Preventive Cardiology and Its Potential Influence on the Early Natural History of Adult Heart Diseases: The Bogalusa Heart Study and the Heart Smart Program

Observations from pediatric epidemiology studies over the past 20 years document that atherosclerosis and essential hypertension begin in childhood. Evidence of coronary artery disease and hypertensive cardiovascular renal disease is found and relates strongly to clinical cardiovascular risk factors. Obesity, especially central obesity, and hyperinsulinemia are commonly found, and these cluster with other risk factors. Lifestyles, such as poor eating behavior and tobacco usage, also begin early and influence cardiovascular risk. The implication from these pediatric observations is that intervention should begin early to prevent unhealthy lifestyles and encourage adoption of healthy behaviors. Where adult heart diseases pervade the major part of the United States population and other industrialized cultures, various epidemiologic strategies of prevention are needed. A high-risk, clinical approach can be applied to individuals with heart disease or to individuals with underlying risk factors and their families. Primary and secondary prevention are both important and should be implemented by primary care physicians. A population approach is also needed because of the widespread occurrence of heart disease. A public health approach to prevention can occur through health education and health promotion programs. Physicians should play a role in encouraging prevention for the general population. The future direction of Preventive Cardiology for our nation rests on educating children to adopt and maintain healthy lifestyles. The Bogalusa Heart Study has made a major contribution in providing the background information for that direction.

Left isomerism and complete atrioventricular block: A report of six cases☆

Six children, aged 12 days to 13 years, with left isomerism and complete atrioventricular (A-V) block are presented. In all six patients the diagnosis of left isomerism was suggested by an interrupted inferior vena cava found during cardiac catheterization and angiocardiography; four patients had complex heart disease consisting of endocardial cushion defect, five had a common atrium, three had pulmonary stenosis, three had patient ductus arteriosus and two had dextrocardia. Further anatomic abnormalities included situs inversus of the viscera (four patients) as well as partial malrotation of the bowel. Of the six patients, four had congenital complete A-V block, whereas the remaining two had A-V conduction disturbances documented during early infancy that progressed to complete A-V block later in life. All six patients required pacemaker implantation and five of the six patients died. This report discusses the clinical presentation of complete AV block and left isomerism and reviews the literature.

The fast-slow form of atrioventricular nodal reentrant tachycardia in children.

An unusual form of atrioventricular (A-V) nodal reentry is described as the underlying mechanism for incessant tachycardia in two children. During tachycardia a fast pathway was utilized for anterograde conduction and a slow pathway for retrograde conduction. This is the reverse of the usual form of A-V nodal reentrant tachycardia, in which the slow pathway is utilized for anterograde conduction and the fast pathway for retrograde conduction. One patient had a smooth ventriculoatrial (V-A) conduction curve demonstrating exclusive utilization of the slow pathway for retrograde conduction. The other had a discontinuous V-A conduction curve demonstrating failure of retrograde fast pathway conduction with resultant slow pathway conduction. In both cases the retrograde effective refractory period of the fast pathway was longer than that of the slow pathway, resulting in the establishment of this unusual reentry circuit. Both patients had a superior P axis with a P-R interval shorter than the R-P interval during tachycardia, features described in a significant number of children with incessant tachycardia. This unusual form of reentrant tachycardia can be suggested by its electrocardiographic pattern and is another mechanism for reentrant tachycardia not previously documented in children.

High-dose propranolol therapy in the management of supraventricular tachycardia

Five patients, age 3 weeks to 11 years, presented with supraventricular tachycardia that remained uncontrolled following adequate digitalization. Four of these patients underwent invasive electrophysiologic studies to determine the mechanism of the arrhythmias. Of these four patients, three had concealed Wolff-Parkinson-White syndrome, and one patient had evidence of dual A-V nodal pathways. Propranolol was added to the medical treatment and was administered orally in doses ranging from 7 to 14 mg/kg/day (average 9 mg/kg/day). All five children remain free of their tachycardia except for one patient who occasionally has supraventricular tachycardia with febrile illnesses. No adverse reactions to these high doses of propranolol were encountered.

Electrophysiologic effects of Tween 80 in the myocardium and specialized conduction system of the canine heart

Amiodarone, a wide spectrum antiarrhythmic agent, has been associated with hypotensive reactions in man as well as in dogs after intravenous use. This hypotensive effect has been attributed to Tween 80, the diluent in the commercially available form of amiodarone. We studied the electrophysiologic effects of Tween 80 in the cardiac conduction system of the dog. Electrophysiologic studies were conducted in anesthetized adult dogs before and after the administration of 10 and 20 mg/kg of Tween 80, equivalent to the amount of diluent in 5 and 10 mg/kg respectively of commercial intravenous amiodarone. In addition to a drop of 60% in systolic blood pressure and 66% in diastolic blood pressure (p less than 0.005), 10 mg/kg of Tween 80 induced a decrease in heart rate (sinus cycle length increased from 523 +/- 57 msec to 662 +/- 27 msec, p less than 0.025), prolongation of sinus node recovery time (652 +/- 77 msec to 804 +/- 45 msec, p less than 0.05), depression of AV nodal function manifested by induction of Wenckebach at longer cycle length (from 208 +/- 18 msec to 266 +/- 14 msec, p less than 0.005), and increase in atrial ERP (from 138 +/- 7 msec to 176 +/- 14 msec, p less than 0.025) and FRP (from 180 +/- 14 msec to 209 +/- 12 msec, p less than 0.025). No further significant changes were observed after the second Tween 80 dose. The ventricular ERP increased significantly (from 168 +/- 18 msec to 20 +/- 16 msec, p less than 0.025) following the 20 mg/kg dose. It is demonstrated that Tween 80 is a potent depressant of the cardiac conduction system in the dog, capable of causing electrophysiologic changes similar to those produced by amiodarone in humans and dogs.

Electrophysiological effects of high cocaine concentrations on intact canine heart. Evidence for modulation by both heart rate and autonomic nervous system.

BackgroundPrevious clinical reports have suggested that cocaine intoxication may produce severe ventricular arrhythmias due to a direct effect on the heart. However, the effects of high plasma levels of cocaine on the electrophysiology of the heart have not been well characterized and remain poorly understood. Methods and ResultsThe purpose of this study was to characterize the electrophysiological effects of high doses of cocaine on the in situ dog heart. In dogs anesthetized with morphine and a-chloralose, cocaine (2-11 pg/mL) increased both atrial and ventricular refractory periods and produced rate-dependent increases in atrial, atrioventricular, His-Purkinje, and ventricular conduction intervals. The time constant for the onset of cocaines conduction slowing effect following a reduction in pacing cycle length from 400 to 260 msec was approximately two beats, and the time constant for diastolic recovery from conduction slowing was -200 msec, which are similar to values reported for several class Ib antiarrhythmic drugs. Cocaine produced a rate-dependent increase in QT interval that was greatest at high heart rates yet produced no change in the ST (QT-QRS) interval. This suggests that high plasma levels of cocaine delay repolarization primarily via slowing of conduction. Cocaines effects on both atrioventricular and intraventricular conduction were significantly larger in autonomically blocked than in autonomically intact animals. ConclusionsWe conclude that high plasma levels of cocaine, similar to those reported in autopsy reports following fatal cocaine overdose in humans, produce significant rate-dependent conduction slowing effects on atrial, atrioventricular, and ventricular conduction in the in situ heart. These rate-dependent effects are intensified following autonomic blockade.