This paper provides guidelines for the optimal, rather than minimal, performance of ultrasonic examination of the heart for current clinical applications using conventional echocardiographic equipment. Since the original report of this Inter-Society Commission on Heart Disease Resources Committee in 1975, M-mode echocardiography has continued to be a valuable clinical tool, and two-dimensional echocardiography has been developed. Guidelines are presented for optimal physician and cardiac sonographer training, case loads, space and support systems, equipment design features and performance testing, and administrative considerations. The developing area of Doppler ultrasound and the competitive technologies are noted.

Angina pectoris results from a deficiency in myocardial oxygen supply. The rate-pressure product is an important predictor of myocardial oxygen requirements in patients with ischemic heart disease and in normal persons. The rate-pressure product at the onset of angina pectoris is reproducible under a variety of circumstances with a suitable protocol. In some patients, coronary artery spasm may reduce myocardial blood flow and contribute to the development of angina pectoris. Lidoflazine is a synthetic drug that appears to be a calcium-entry blocker and results in symptomatic improvement in patients with angina pectoris. Lidoflazine reduces the exercising rate-pressure product by its effect on heart rate and by decreasing systemic vascular resistance. It decreases coronary vascular resistance and antagonizes processes leading to an increase in coronary vasomotor tone.

Calcium-entry blockers depress the myogenic activity and the responsiveness to vasoconstrictor stimuli of the smooth muscle cells of the precapillary vessels. Thus, they can reduce the afterload of the heart and have antihypertensive properties. Their inhibitory effect on the contractile responses of the vascular smooth muscle cells of large arteries also results in the reduction or the abolition of vasospastic episodes. By inhibiting the constrictor responses of the splanchnic capacitance vessels to the sympathetic nervous outflow, they reduce the preload of the heart. However, different calcium-entry blockers differ in their ability to affect different cardiovascular variables and in the onset and duration of their effect; they also have different degrees of tissue selectivity. This variability must reflect differences in pharmacodynamic and pharmacokinetic properties.

The membranes that separate the myocardial cell interior from the extracellular space and delimit compartments within the myocardial cell represent ion-impermeable phospholipid barriers. Embedded in these phospholipid membranes are intrinsic membrane proteins, some of which serve as ion channels. The voltage-sensitive ion channels that control the sarcolemmal action potential appear to be highly regulated intrinsic membrane proteins that contain "gates" that respond to changing membrane potential by opening and closing an ion-selective "pore" that allows specific ions to cross the membrane. Pharmacologic blockade of the sarcolemmal ion channels is selective, not only for individual classes of ion channels, but also for specific states of a given type of channel. The basis for this selectivity remains unclear, but may derive from a preferential interaction between a given drug and a specific type of ion-channel protein, or a selective drug action on a structurally specific region of the membrane phospholipid that is in intimate contact with the ion-channel protein.

Many basic concepts of cardiac output and arterial pressure control have changed considerably in the past few years. In general, each tissue controls its own local resistance and blood flow regardless of the level of arterial pressure; the sum of the local flows then determines the venous return and cardiac output. However, the arterial pressure is normally controlled by separate mechanisms that do not significantly alter the cardiac output. During acute circulatory stresses, such as exercise, the arterial pressure is controlled almost entirely by nervous reflex mechanisms; but over long periods, there reflex mechanisms fade away because they adapt. The arterial pressure is then controlled mainly by a renal-volume-endocrine pressure control system, in which the blood volume and total peripheral resistance are manipulated slowly to adjust the pressure.

Pulmonary vascular disease, a serious complication of many congenital heart lesions, has three major components: increased muscularity of small pulmonary arteries; intimal hyperplasia, scarring and thrombosis; and reduced numbers of intraacinar arteries. The muscularity is due to increased stress on the vessel wall, and is reversible. The intimal changes may be due to endothelial damage, causing an imbalance between prostacyclin and thromboxane A2 production and leading to local platelet aggregation. This, in turn, may stimulate migration and division of myointimal cells, which thicken the intima and lead to scarring and thrombosis. Extensive intimal changes are probably irreversible, but the possibility of preventing them by use of agents that inhibit platelet aggregation needs to be considered. The mechanism of a decrease in numbers of intraacinar arteries is unexplained. The potential for growth of new vessels after corrective surgery of the cardiac defect is an important factor in restoring pulmonary vascular resistance to normal. Available evidence suggests that this growth potential is reduced after 2 years of age and argues for early surgical relief of pulmonary vascular stresses.

The realization that bias in patient selection may influence the results of clinical studies has helped to establish the randomized controlled clinical trial in medical research. However, bias can be equally important at other stages of a trial, especially at the time of analysis. Withdrawing patients from consideration in the analysis because of ineligibility on account of study entry criteria, lack of compliance to the protocol, or data of poor quality may be a source of systematic error. Examples to illustrate the possible consequences are taken from trials in the cardiovascular field. We recommended that reported study results should include outcome data from all subjects randomized in the group to which they were originally assigned.

The cardiovascular reflexes, by regulating the traffic in the sympathetic nerves, govern the amount of norepinephrine released from the nerve endings. However, the final adjustments in the amount of neurotransmitter available to activate the beta 1 receptors in the heart and the alpha receptors in the blood vessels take place at the sympathetic neuroeffector junction. Thus, a decrease in pH, hyperosmolarity, moderate increases in the concentration of K+ ion, adenosine and adenine nucleotides depress the release of norepinephrine at any given level of sympathetic nerve activity. These metabolic changes, which occur in active tissues, and in particular in adenosine, have been proposed as mediators of the accompanying local hyperemia. In addition, they apparently facilitate this local dilatation by disconnecting the blood vessels in the active tissues from sympathetic control. Acetylcholine, histamine and 5-hydroxytryptamine are present in and around certain blood vessels and can activate specific receptors on the prejunctional fibers and cause vasodilatation by reducing the output of neutrotransmitter. Some of the norepinephrine released into the synaptic cleft may depress its continued release by activating prejunctional alpha receptors. In contrast, angiotensin II, by a local action on the nerve endings, can augment the release of transmitter. Decreases in local temperature reduce transmitter release but augment the affinity of the postjunctional alpha receptors for norepinephrine. The role of these local events at the neuroeffector junction, their physiologic significance and potential clinical importance are discussed in this review.

Excessive alcohol ingestion results in profound derangements of lipid and lipoprotein metabolism, reflecting the effects of ethanol on peripheral and hepatic lipid metabolism and its toxic effects on hepatic function. The alterations in plasma lipids and lipoproteins are secondary to complex abnormalities of lipoprotein synthesis, secretion and catabolism. The major effects of alcohol include fatty liver secondary to excessive triglyceride synthesis, resulting in an imbalance between synthesis and hepatic secretion; hypertriglyceridemia and hypercholesterolemia; defective plasma cholesterol esterification; and decreased high-density lipoprotein cholesterol. In patients with severe alcoholic hepatitis, the plasma lipoproteins have an abnormal structure and apoprotein composition. Although these changes are usually reversible with abstinence from alcohol (if liver function returns to normal), they indicate serious effects of alcohol on the liver, which may culminate in cirrhosis and hepatic insufficiency. These effects of alcohol on lipids and lipoproteins should be contrasted with the elevation in high-density lipoprotein cholesterol concentration produced by moderate alcohol intake and the possibility that this increase may protect against the development of atherosclerotic disease.

In this paper are summarized the implications of recent population studies in which drinking behavior is used to predict development of heart disease. A key inference is that the association of drinking behavior with mortality may be attributed as much to characteristic lifestyles as to the drinking itself. Increased emphasis on validation studies is needed to improve measurement of drinking behavior for greater precision in predicting mortality. A plan is presented for large-scale longitudinal studies to predict heart disease and other major health problems, calling for the joint efforts of agencies such as the National Center for Health Statistics and the Multiple Risk Factor Intervention Trial.

Associations between alcohol intake and levels of high-density lipoprotein (HDL) cholesterol were examined in 2473 men and 1530 women seen as part of the random sample at visit 2 of the Lipid Research Clinics Prevalence Study. More men than women reported alcohol intake. The alcoholic beverage preference differed by age and sex. The levels of HDL cholesterol were higher in drinkers than in nondrinkers. The statistically significant associations varied somewhat by age; however, the average correlation coefficient was 0.21 for men and 0.25 for women. HDL cholesterol levels were lower in those who reported never drinking alcohol than in occasional drinkers.

The association between reported alcohol intake and plasma high-density lipoprotein (HDL) cholesterol concentration is examined in an effort to establish whether it was a cause-and-effect basis. A cross-sectional descriptive study of several populations reveals a strong and consistent dose-response pattern: Social drinkers have mean HDL cholesterol levels that are higher than those of teetotalers by as much as 33%. Cross-sectional analyses in another epidemiological study reveal the association to be independent of potential confounding factors such as smoking and body weight, and longitudinal analyses suggest that it is also not a result of certain unmeasured sources of confounding. A small experiment reveals a 15% reduction in HDL cholesterol levels among social drinkers who abstain from alcohol from a 2-week period. The evidence supports the conclusion that alcohol habits are probably one of the determinants of plasma HDL cholesterol level. A clarification of the relevance of this phenomenon to clinical medicine awaits future clinical efforts.

The relationship of alcohol intake to plasma lipids and lipoproteins was assessed in 1603 white children, ages 12-19 years, from six Lipid Research Clinics as part of the Lipid Research Clinics Collaborative Population Studies. Of the 1603 children, 933 came from a randomly recalled group and 660 from a group recalled because of elevated cholesterol or triglyceride or both (the hyperlipidemic recall group). Using multiple regression analysis, the relationships of lipoproteins (as dependent variables) to alcohol, smoking, age and body mass (as explanatory variables) are assessed in both recall groups. In the random recall group, high-density lipoprotein (HDL) cholesterol was positively related to alcohol intake, independent of the other variables considered; for every ounce of alcohol intake, HDL cholesterol was 0.55 mg/dl higher in males and 1.04 mg/dl higher in females. HDL cholesterol was strongly and inversely related to smoking and body mass in both males and females and was inversely related to age in males. In females, plasma low-density lipoprotein (LDL) cholesterol, triglycerides and very low density lipoprotein (VLDL) cholesterol were all positively related to alcohol intake. In the hyperlipidemic recall group of children, alcohol intake had a weak positive relationship with HDL cholesterol in males; in the females, for every ounce of alcohol intake, HDL cholesterol was higher by 1.5 mg/dl. Alcohol intake was positively related to triglyceride levels in hypertriglyceridemic male children. In each recall group, alcohol intake had a small, significant, positive association with HDL cholesterol levels in 12--19-year-old children, and a less consistent positive association with triglyceride and VLDL cholesterol. If low HDL cholesterol concentrations in children are undesirable, attention should first be focused reduction of smoking (inversely associated with HDL cholesterol) and weight (inversely associated with HDL cholesterol, positively associated with LDL cholesterol, triglyceride and VLDL cholesterol), as measures that may modify HDL cholesterol levels.

Most epidemiologic studies suggest that alcohol consumption is associated with increased blood pressure levels and an increased prevalence of hypertension. A review of experimental studies of the blood pressure effects of acute alcohol administration to man and acute and chronic administration to animals does not clearly support the epidemiologic findings, which suggest that other direct or indirect factors besides a simple pharmacologic effect of alcohol may be operative. Several endocrine and renal mechanisms have been postulated, and indirect factors related to both alcohol use and blood pressure pathogenesis cannot be firmly excluded. Preliminary data from the Lipid Research Clinics (LRC) population studies generally show a positive association between alcohol and blood pressure, although women and young men reporting no alcohol use had higher systolic pressures than those reporting low levels of alcohol intake. LRC findings also suggest that the blood pressure elevations associated with use of oral contraceptives appear to be independent of those associated with alcohol. Some preliminary epidemiologic findings and circumstantial evidence suggest that the alcohol-blood pressure relationship may be due in part to the timing of blood pressure measurement during physiologic alcohol withdrawal. Although further verification is needed, this hypothesis implies that the pattern of alcohol consumption and the interval between last use and blood pressure measurement may be as important as the amount of alcohol consumed in explaining the relationship between alcohol and blood pressure.

Earlier studies of Kaiser-Permanente data have indicated that regular use of alcohol is associated with a reduced risk of major coronary events and that regular use of three or more drinks is associated with an increased prevalence of hypertension. A new study of hospitalizations in relation to alcohol use confirms this disparity in relations between alcohol use and cardiovascular disease and suggests that alcoholic cardiomyopathy has a relatively low incidence. An inverse relation between alcohol use and hospitalizations for cholelithiasis raises the possibility of a common pathogenic mechanism linking alcohol to coronary events and cholelithiasis. Overall risk of cardiovascular disease seems lower among users of two or fewer drinks daily than among either nondrinkers or heavier drinkers.

The toxic effects of chronic ethanol abuse on cerebral and hepatic function have long been recognized. The role of ethanol abuse as an etiologic factor in heart disease is less clear and is often attributed to coexistent malnutrition. However, malnutrition has been dissociated from ethanol use in many patients with congestive cardiomyopathy. Studies in various animals provide major support for the role of ethanol as a toxic agent when used in large amounts for a prolonged period. Abnormalities that result from ethanol in test animals include depression of left ventricular performance and metabolic and morphologic changes that parallel the changes in human alcoholics with subclinical mechanical dysfunction of the heart, such as symptomatic cardiac arrhythmias, particularly during intensive alcohol ingestion. What causes the progression to heart failure or arrhythmias is not known, but several factors may be involved. These include, particularly in males, the cumulative effects of ethanol alone or after intensified drinking episodes, excessive exposure to trace metals or superimposed infection. The low prevalence of clinical nutritional deficiency in patients with alcoholic cardiomyopathy and the apparent infrequency of heart failure in patients with cirrhosis or neuropathy supports the view that the cardiac abnormality is often not dependent on malnutrition. Clinical data indicate that the cessation of alcohol intake may reverse the disease or interrupt its progression in many patients. However, the pathogenetic process may continued unabated in some who become abstinent.

Forty-one patients with postinfarction ventricular septal rupture were cared for in our hospital during 1971-1975. Cardiogenic shock developed after septal rupture in 55% of these patients. Shock was unrelated to site of infarction, extent of coronary artery disease, left ventricular ejection fraction, or pulmonary-to-systemic flow ratio, but mean pulmonary artery pressure was lower in shock than in nonshock patients. These observations suggest that shock was produced mainly by right ventricular impairment. Perioperative survival was much higher in patients who did not have shock preoperatively (14 of 17 [82+]) than in those who did (three of 11 [27%]). Magnitude of shunt, left ventricular ejection fraction, extent of coronary artery disease, and performance of aortocoronary bypass grafting were not distinctly correlated with perioperative survival. After a minimum 4-year follow-up, 76% of the perioperative survivors are alive, and none suffer more than New York Heart Association functional class II disability. All 13 unoperated patients (11 in shock) died within 3 months.

A panel of biomedical and behavioral scientists were charged with the task of critically evaluating all available research and theory linking behavior to coronary heart disease. The task was divided into five topic areas: (1) association of coronary-prone behavior and coronary heart disease; (2) assessment of the "type A" behavior pattern; (3) physiologic mechanisms linking behavior to coronary heart disease; (4) cultural and developmental factors; and (5) intervention strategies. The review panels developed summary statements which delineated the perceived strengths and short-comings of the theory and data for their respective sections and provided recommendations to the National Heart, Lung, and Blood Institute concerning future research.