Julien I. E. Hoffman

The incidence of congenital heart disease.

This study was designed to determine the reasons for the variability of the incidence of congenital heart disease (CHD), estimate its true value and provide data about the incidence of specific major forms of CHD. The incidence of CHD in different studies varies from about 4/1,000 to 50/1,000 live births. The relative frequency of different major forms of CHD also differs greatly from study to study. In addition, another 20/1,000 live births have bicuspid aortic valves, isolated anomalous lobar pulmonary veins or a silent patent ductus arteriosus. The incidences reported in 62 studies published after 1955 were examined. Attention was paid to the ways in which the studies were conducted, with special reference to the increased use of echocardiography in the neonatal nursery. The total incidence of CHD was related to the relative frequency of ventricular septal defects (VSDs), the most common type of CHD. The incidences of individual major forms of CHD were determined from 44 studies. The incidence of CHD depends primarily on the number of small VSDs included in the series, and this number in turn depends upon how early the diagnosis is made. If major forms of CHD are stratified into trivial, moderate and severe categories, the variation in incidence depends mainly on the number of trivial lesions included. The incidence of moderate and severe forms of CHD is about 6/1,000 live births (19/1,000 live births if the potentially serious bicuspid aortic valve is included), and of all forms increases to 75/1,000 live births if tiny muscular VSDs present at birth and other trivial lesions are included. Given the causes of variation, there is no evidence for differences in incidence in different countries or times.

Blood flow measurements with radionuclide-labeled particles.

When appropriately and correctly applied, the microsphere technique is relatively simple and extremely accurate. Distribution patterns, both of total systemic arterial blood flow or venous return as well as within specific organs, can be measured. Several techniques have been applied to quantitate flow using microspheres; the reference sample method is extremely simple and by far the most accurate of all. Collection of venous effluent is perhaps more accurate but requires extensive surgery and is almost certainly the least physiologic. Other methods used for quantitation, such as bolus injections of indocyanine green dye or in fusions of diffusable indicators, are considerably less accurate and therefore significantly reduce the reliability of the microsphere technique. Selection of the appropriate size microspheres allows for definition of arteriovenous anastomoses as well as the measurement of organ blood flows and distribution of blood flow within those organs. In most instances, smaller microspheres (15mu diameter or 8-10mu diameter) have significant advantages over larger ones. They are distributed more like red cells, obstruct less of the vascular bed, are less variable in size, and can be given in significantly greater numbers. This latter point is important, since the statistical criteria need to be satisfied and the use of small spheres allows for the more reliable measurement of blood flow to small organs or to small regions of organs.

Task force 1: the changing profile of congenital heart disease in adult life.

The extraordinary advances in cardiac surgery, intensive care, and noninvasive diagnosis over the last 50 years have led to an enormous growth in the U.S. and throughout the world in the number of adults with congenital heart disease (CHD). Approximately 85% of babies born with cardiovascular

Experimental Subendocardial Ischemia in Dogs with Normal Coronary Arteries

Subendocardial ischemia without anatomic coronary artery obstruction may result from a discrepancy between metabolic needs and available blood supply. We studied this in open-chest anesthetized dogs and measured pressures in aorta and left ventricle (LV), phasic left coronary arterial blood flow (CBF) by electromagnetic flowmeter, total CBF and LV subendocardial (endo) and subepicardial (epi) flow with radioactive microspheres 8−10μ, in diameter. Since LV Subendocardial flow is mainly or entirely diastolic, it should depend on coronary driving pressure and duration of diastole (i.e., the area between aortic and left ventricular diastolic pressures). This diastolic pressure time index (DPTI) was varied by opening arteriovenous fistulas to lower aortic diastolic pressure, constricting the ascending aorta to raise LV diastolic pressure and pacing to shorten diastole. Myocardial oxygen needs were estimated from the tension time index (TTI). Normal endo-epi flow ratios per gram (1:1) fell to 0.1:1 with these procedures and paralleled a fall in diastolic flow fraction (often nearly zero) and postischemic coronary reactive hyperemic responses. These changes occurred despite normal or raised mean CBF and 300−500% increase in systolic CBF. The altered flow ratios were best predicted by relating them to the ratio of DPTI (supply) to TTI (demand).

Incidence of congenital heart disease: I. Postnatal incidence

The incidence of congenital heart disease (CHD) in the Western industrialized world has varied from a low value of about 3 to 5 per 1000 live births to about 12 per 1000 live births. Most of the lower incidence figures were obtained before there were sufficiently well trained pediatric cardiologists and before the success of cardiac surgery put a premium on early and correct diagnosis of CHD. The advent of echocardiography with Doppler color flow measurements has made it possible to diagnose lesions that are asymptomatic, minor, and even without murmurs. Given these differences, there does not appear to have been a significant increase in the incidence of CHD over the last 20–30 years. The incidence of CHD in underdeveloped countries is not known, but the distribution of different lesions is fairly similar to those in developed countries except perhaps for fewer with aortic stenosis and coarctation of the aorta.

Total and regional coronary blood flow measured by radioactive microspheres in conscious and anesthetized dogs.

Total and regional coronary blood flow were measured in dogs by left atrial injection of carbonized microspheres labeled with different radioactive isotopes (mean diameter 14 to 61μ). Simultaneously blood was collected at 20 ml/min from a catheter tied into a peripheral artery. The ratios of flow to radioactivity in myocardium and arterial blood should be equal if microspheres are well mixed in the aortic root and are distributed regionally in proportion to flow. This was proved in seven right heart by-pass experiments where coronary venous drainage was measured directly. Also, less than 0.1% of total myocardial radioactivity appeared in coronary venous blood, even with hypoxemia and small microspheres. Total coronary flow in seven conscious dogs averaged 95 to 150 ml/min/100 g heart; and flow to the left ventricle was 111 to 169 ml/100 g. Although not validated independently, there was evidence that values for flow to each ventricle, the atria and the septum were correct. The radioactivity per gram of left ventricular subendocardial muscle was 2.5 times that of subepicardial muscle using microspheres 51 to 61μ in diameter, but the ratios were 1.4 and 1.3 using microspheres of mean diameters 20 to 23μ and 14μ, respectively. It is unlikely that any of these microspheres measure blood flow to small portions of the ventricle.

The pathophysiology of failure in acute right ventricular hypertension: hemodynamic and biochemical correlations.

SUMMARY Acute right ventricular (RV) hypertension and failure occur clinically. In this study we examined the mechanism of RV failure. Adult dogs were studied acutely under anesthesia; dogs were instrumented for measurement of pressures and right coronary artery blood flow. Myocardial blood flow and cardiac output were determined with radionuclide-labeled microspheres, and the presence of ischemia was determined by biochemical analysis of ventricular biopsies. RV hypertension was produced by constricting the pulmonary artery and was increased until RV failure occurred, as evidenced by decreased aortic pressure and cardiac output and increased RV end-diastolic pressure. With increasing RV systolic pressure, RV myocardial blood flow failed to increase in proportion to demand. At the onset of RV failure, there was no reactive hyperemia of right coronary flow compared with control, indicating the absence of further coronary vascular reserve; biochemical analysis demonstrated that the RV free wall was ischemic; the LV free wall was not. Infusion of phenylephrine raised aortic pressure and hence, myocardial perfusion pressure; RV failure reversed as shown by decreased RV end-diastolic pressure and increased cardiac output and RV systolic pressure; reactive hyperemia of right coronary flow was restored and the biochemical indexes of ischemia were reversed, demonstrating that ischemia is the cause of failure in acute RV hypertension.

Incidence of congenital heart disease: II. Prenatal incidence

The incidence of congenital heart disease appears to be about 1 per 100 liveborn infants. In infants who die before term, however, there is a much higher incidence of congenital heart disease, with a tendency for an excess of complex lesions. Some but not all of these lesions are associated with gross chromosomal abnormalities, which occur frequently in first-trimester abortions. Most of these chromosomal abnormalities are associated with such maldevelopment of many organ systems that fetal death occurs in utero. Monosomy X (45, XO), has a high association with congenital heart disease. Most fetuses with this abnormality die in utero, but because the abnormality is not inevitably lethal a small increase in survival of these fetuses would cause a large increase in the total incidence of congenital heart disease.

Physiological Basis of Clinically Used Coronary Hemodynamic Indices

In deriving clinically used hemodynamic indices such as fractional flow reserve and coronary flow velocity reserve, simplified models of the coronary circulation are used. In particular, myocardial resistance is assumed to be independent of factors such as heart contraction and driving pressure. These simplifying assumptions are not always justified. In this review we focus on distensibility of resistance vessels, the shape of coronary pressure-flow lines, and the influence of collateral flow on these lines. We show that (1) the coronary system is intrinsically nonlinear because resistance vessels at maximal vasodilation change diameter with pressure and cardiac function; (2) the assumption of collateral flow is not needed to explain the difference between pressure-derived and flow-derived fractional flow reserve; and (3) collateral flow plays a role only at low distal pressures. We conclude that traditional hemodynamic indices are valuable for clinical decision making but that clinical studies of coronary physiology will benefit greatly from combined measurements of coronary flow or velocity and pressure.

Cardiac mechanics revisited: the relationship of cardiac architecture to ventricular function.

The keynote to understanding cardiac function is recognizing the underlying architecture responsible for the contractile mechanisms that produce the narrowing, shortening, lengthening, widening, and twisting disclosed by echocardiographic and magnetic resonance technology. Despite background knowledge of a spiral clockwise and counterclockwise arrangement of muscle fibers, issues about the exact architecture, interrelationships, and function of the different sets of muscle fibers remain to be resolved. This report (1) details observed patterns of cardiac dynamic directional and twisting motions via multiple imaging sources; (2) summarizes the deficiencies of correlations between ventricular function and known ventricular muscle architecture; (3) correlates known cardiac motions with the functional anatomy within the helical ventricular myocardial band; and (4) defines an innovative muscular systolic mechanism that challenges the previously described concept of “isovolumic relaxation.” This new knowledge may open new doors to treating heart failure due to diastolic dysfunction.