Despite a decade of experience with aortocoronary bypass grafting embracing 300,000 or more operations, indications for its use remain controversial. The controversy persists because of a lack of adequate controls with which to compare the clinical course of operated patients; only 1248 have been reported who have been studied in a carefully controlled and random manner. Benefit has been claimed frequently by comparing the course of patients treated surgically with medically treated patients followed the decade before. Such comparisons are not valid in view of the well documented changes in the natural history of coronary artery disease that have been occurring during the last decade. Despite a low operative mortality and rate of graft closure, available data in the literature do not indicate that initial symptomatic improvement necessarily persists, or that myocardial infarctions, arrhythmias, or congestive heart failure will be prevented, or that life will be prolonged in the vast majority of operated patients.

The presentation, management, and follow-up of 31 patients with discrete membranous subaortic stenosis (DMSS) is presented. DMSS comprised 16% of 185 patients with congenital left ventricular (LV) obstruction. Only one patient was older than 40 years. The rarity of DMSS in older patients in both our population and in the literature is noted, and possible explanations are discussed. One-quarter of these patients had dyspnea, chest pain, or syncope combined with electrocardiographic left ventricular hypertrophy (LVH) and strain, and these all had peak LV outflow gradients (PSG) greater than 85 mm Hg. One-quarter had neither symptoms nor electrocardiographic abnormalities and all had PSG less than 90 mm Hg. Bacterial endocarditis was found in 13%, and in 13% an immediate family member also had congenital LV obstruction. Following surgical resection (25 patients), 18 were asymptomatic, two had residual fibromuscular obstruction, and four developed new fibromuscular obstruction after from one to six years (leading in one to late sudden death). Thus, even after resection, these patients require continued re-evaluation for residual or new LV obstruction.

Electrocardiograms and cardiac electrograms now frequently are measured for both clinical and experimental purposes by direct digital sampling, with no recording of the signal in analog form. This study examined the question of what sampling rates were required to measure accurately the continuous waveforms from the digital samples. Body surface waveforms and intracellular and extracellular waveforms measured directly from cardiac tissues were evaluated. Cardiac measurements included waveforms from the atrium, ventricle, atrioventricular transmission system and individual Purkinje strands. Sampling rates as high as 15,000 samples/sec were required to record accurately extracellular waveforms of the ventricular conduction system. Decreasing sampling rates were required as the recording site shifted through the ventricle to the body surface, where sampling rates as high as 1500 samples/sec were necessary.

Recently, the availability of a number of specific inhibitors of the renin-angiotensin system has made it possible to address certain critical questions concerning the role of angiotensin II in physiologic homeostasis and in a number of pathologic states. These studies indicate that angiotensin II does not have an obligatory role in blood pressure maintenance in the normal, sodium replete individual, but it is essential following sodium depletion. The role of angiotensin II in feedback control of renin secretion is confirmed as is its importance in aldosterone stimulation both in relation to posture and sodium depletion. Angiotensin II is responsible for the initial pressor response of experimental renovascular hypertension and appears to be important in the initiation of chronic renovascular hypertension. Converting enzyme blockers and competitive inhibitors of angiotensin II are helpful in the diagnosis of clinical renovascular hypertension and in the identification of renin dependent hypertensives. Homeostatic mechanisms leading to maintenance of blood pressure and accumulation of edema in experimental congestive heart failure appear to be dependent on angiotensin II.

For half a century the systolic click and late systolic murmur lay dormant as innocent auscultatory curiosities. The thirteen years since Barlow related these phenomena to mitral leaflet prolapse have witnessed an astonishing information explosion. We have sought to bring together the accumulated data in this review. An Historical Perspective traces the evolution from the now abandoned "pericardial" or "extracardiac" phases, through the leafletchordal phase (redundancy), the myocardial phase (segmental left ventricular contraction abnormalities), to the anular phase (dilatation and faulty systolic contraction). Functional Anatomy is dealt with in terms of pathology, pathophysiology, hemodynamics, angiocardiography, echocardiography, and physical and pharmacological interventions. Clinical Manifestations are concerned with prevalence, natural history, symptoms, physical signs, electrocardiographic abnormalities and roentgen fingings. The four Major Complications- sudden death, infective endocarditis, spontaneous rupture of chordae tendineae, and progressive mitral regurgitation- are examined. Associated Cardiac Diseases, i.e., Marfan's syndrome, ostium secundum atrial septal defect and atherosclerotic coronary artery disease, are discussed, and a section on Treatment deals chiefly with prophylaxis for infective endocarditis and the management of arrhythmias and chest pain. A final section on Evolving Information considers etiologic concepts, the nature of left ventricular contration abnormalities, the cause of chest pain, the relationship to Marfan's syndrome and ostium secundum atrial septal defect, and the effect of aging and sex differences on leaflet chordal redundancy.

The evidence supporting the thesis that hypertension can be prevented by eliminating salt from the diet is based on four principal sources: (1) epidemiological studies in unacculturated peoples showing that the prevalence of hypertension is inversely correlated with the degree of salt intake; (2) hemodynamic studies suggesting that the development of chronic experimental hypertension is a homeostatic response to a maintained increase in extracellular fluid volume (ECF); (3) evidence that the ECF of "salt eaters" is expanded in comparison to that of "no-salt eaters"; and (4) investigations in hypertensive patients receiving either diets greatly restricted in salt or continuous diuretic therapy which correlate the fall in blood pressure with a reduction in ECF. Although this mechanism of essential hypertension is still obscure the evidence is very good if not conclusive that reduction of salt in the diet to below 2 g/day would result in the prevention of essential hypertension and its disappearance as a major public health problem.

The ST segments of the electrocardiogram (ECG) become elevated within 20 to 30 seconds after the onset of acute coronary occlusion and, when persistent, such changes offer a possible indirect marker of the extent and severity of myocardial ischemic injury and of eventual cell death. When ST-segment elevation on the epicardial ECG is measured 15 minutes after an acute coronary occlusion in the dog, a general correlation exists with biochemical changes, regional myocardial blood flow, and myocardial electrolyte alterations measured at 15 minutes, although when an effort is made to correlate the degree of such alterations with the magnitude of the ST-segment change there is considerable scatter. On the other hand, when the ST-segment elevation at 15 minutes is correlated with myocardial blood flow, histologic changes, and creating phosphokinase (CPK) depletion 24 hours later, the correlation is good. Possible mechanisms underlying ST-segment elevation are discussed, and data are reviewed which indicate that the epicardial ECG my be relatively insentive to subendocardial injury; in the experimental setting this problem may be partially corrected by the use of intramyocardial ECG leads. The extension of direct epicardial ECG maps to precordial ST-segment mapping poses additional problems that include reduced sensitively, problems due to reciprocal changes in the ECG at the body surface, surface contact of the electrodes, pericarditis, and individual variability in the rate of spontaneous regression of ST-segment changes. Such mapping appears reliable only for infarctions of the anterior and lacteral wall. Further research is necessary on analysis of the QRS complex, and use of vector leads. Despite these problems experimental and clinical studies indicate that precordial electrocardiographic analysis may be useful for detecting acute changes in the severity of ischemic injury over relatively short periods of time (2 to 4 hours). This indirect measure clearly will require correlation with specific markers of ischemic damage, but with further improvements it seems likely that analysis of serial ECG changes will evolve into a valuable and reliable nonivasive clinical tool for characterizing myocardial ischemia and infarction.

From many observations made at autopsy it is apparent that thrombosis in a coronary artery is usually, if not always, associated with rupture of an atheromatous plaque. The sequelae of such rupture include hemorrhage into the plaque with further narrowing of the lumen, formation of an occlusive thrombus or of a non-occlusive thrombus. A developing thrombus in an artery undergoes fragmentation with showering of the distal microcirculation by aggregates of platelets possibly with some admixture of fibrin. In many cases of sudden cardiac death associated with severe atherosclerotic stenosis of the coronary vessels, an occlusive thrombus is not found and the myocardium shows no morphological lesion or else focal patchy early damage in the subendocardial region. One possible mechanism that might explain these findings is microembolism from mural nonobstructing coronary thrombus. Such a mechanism is well established in transient ischemia of the brain and retina related to ulcerated atheroma of the internal carotid artery. Experimental observations indicate that platelet aggregates in the myocardial circulation cause arrhythmias, sudden death, vasculitis, and myocardial ischemic damage. Induction of an occlusive coronary artery thrombus is associated with development of an infarct involving the full thickness of the myocardium. A nonocclusive thrombus is associated with either no myocardial damage or focal subendocardial ischemic injury. It is possible that further aggregation of platelets may facilitate the extension of infarction subsequent to an occlusive event, although there is little evidence on this point. A number of clinical studies show increased platelet reactivity to agents causing aggregation, such as norepinephrine or collagen, in subjects experiencing thromboembolic episodes. It seems unlikely, however, that in vitro tests of platelet function can identify or predict clinical arterial thrombotic disease, although studies of platelet survival and turnover may be more helpful. There is also evidence that platelet survival may be prolonged by drugs having a therapeutic benefit in coronary artery disease and arterial thromboembolism. There is a need for better designed and coordinated clinical trials and for better experimental approaches to explore the relationships among coronary thrombosis, embolsim of the myocardial microcirculation, myocardial ischemia, and sudden death.

To reduce myocardial ischemia effectively, mechanical or surgical interventions must achieve either augmentation in coronary blood flow, a reduction in myocardial oxygen demand, or a combination of both. Coronary bypass graft procedures can achieve an immediate augmentation in coronary blood flow distally through the involved vessel and thereby improve myocardial perfusion and oxygen delivery and thus have the potential for reversing myocardial ischemia both acutely and for the long term. Although myocardial revascularization may resolve the ventricular functional alterations associated with acute myocardial ischemia it remains uncertain whether revascularization can reverse ischemic myocardial cellular injury and in what time framework, as related to reversible vs. irreversible ischemic cellular changes. Mechanical circulatory assistance (MCA) using diastolic counterpulsation effectively reduces myocardial ischemia by the physiologic mechanisms of 1) decrease in left ventricular after-load and left ventricular wall tension, 2) improvement is cardiac output by diastolic counterpulsation and 3) augmentation of coronary blood flow by diastolic pressure augmentation. The most effective indication for either MCA or myocardial revascularization is for interruption of myocardial ischemia prior to the development of infarction. Clinical sudies have demonstrated that acute myocardial ischemia can be effectively interrupted by intraaortic balloon pumping (IABP) including reversal of left ventricular dysfunction associated with acute myocardial ischemia. In most instances, cessation of IABP resulted in recurrence of myocardial ischemia indicating the need for urgent revascularization surgery. In the management of medically refractory myocardial ischemia. IABP has been effective in complete suppression of ischemia in 80 percent and resulted in marked improvement in all, allowing safe revascularization surgery with an operative mortality in the range of 5% and perioperative myocardial infarction incidence of 2%. In patients with acute myocardial infarction and cardiogenic shock (AMI-CS), IABP can resolve CS in 75 percent. The combination of IABP and surgery has resulted in survival approaching 45 percent indicative of a significant improvement in salvage in this group of patients where expected mortality approaches 100 percent.

A number of hemodynamic, pharmacologic, and metabolic interventions were found to change the extent of acute ischemic injury of the myocardium and subsequent necrosis following experimental coronary artery occlusion. Reduction in myocardial damage occurred by decreasing myocardial oxygen demands (beta-adrenergic blocking agents, intra-aortic balloon counterpulsation, nitroglycerin, decreasing afterload in hypertensive patients, inhibition of lipolysis, and digitalis in the failing heart); by increasing myocardial oxygen supply either directly (coronary artery reperfusion or elevating arterial pO2), or through collateral vessels (evevation of coronary perfusion pressure by alpha adrenergic agonists, intra-aortic balloon counterpulsation); or by increasing plasma osmolality (manitol, hypertonic glucose); presumably by augmenting anaerobi metabolism (glucose-insulin-potassium, hypertonic glucoxe insulin potassium, hypertonic glucose); by enhancing transport to the ischemic zone of substrates utilized in energy production (hyaluronidase); by protecting against autolytic and heterolytic damage (hydrocortisone, cobra venom factor, aprotinin). Augmentation of myocardial ischemic damage occurred as a consequence of increasing myocardial oxygen requirements (isoproterenol, glucagon, ouabain, bretylium tosylate, tachycardia); by decreasing myocardial oxygen supply either directly (hypoxia, anemia), through reduction of collateral flow (hemorrhagic hypotension, minoxidil), or by decreasing substrate availability (hypoglycemia). Pilot studies have been carried out in patients with hyaluronidase, nitroglycerin intra-aortic balloon counterpulsation, beta-blocking agents and Arfonad and have shown that these interventions may also reduce myocardial damage, which suggests that the concept of reduction in infarct size following coronary occlusion is applicable clinically.

Radionuclide techniques that assess regional myocardial perfusion and detect acute myocardial infarction promise to provide critical information in the detection and evaluation of coronary artery disease and in the assessment of therapies aimed at limiting the degree of ischemia and the extent of tissue necrosis. Radioindicators such as 99mTc-tetracycline and 99mTc-pyrophosphate which are sequestered by acutely infarcted myocardium provide a direct method to detect an infarct and to determine its size. Regional alterations in myocardial perfusion can be assessed by myocardial scintigraphy performed after the injection of radiopotassium or one of its analogues with the patient either at rest or at exercise. A somewhat more accurate evaluation of the extent of altered perfusion can be obtained after the intracoronary injection of macro-aggregated particles. A quantitative index of altered perfusion can be obtained after the intracoronary injection of an inert gas such as 133Xe.

Sudden death, known since antiquity, is almost always due to cardiovascular disorder, but not exclusively to coronary artery disease. It is postulated that two processes, action of pre-existing risk factors (enlarged heart, abnormal conduction, extra systoles, ischemia) and new, untoward events (acute infarction or ischemia) culminate in the catastrophic event. Sudden death is apparently most likely during waking hours; sleep is a lesser risk. Which subjects are at greatest risk and which circumstances are most dangerous remain unknown and are important topics for further investigation.