Early evolution of symptoms and long-term prognosis in variant angina: importance of the functional component of coronary arterial disease.

PURPOSE: Most investigations describing the long-term outcome of large groups of patients with variant angina pectoris have focused on such endpoints as myocardial infarction, coronary artery surgery, and death, and have asked how the risk of these events is related to the severity of existing organic coronary disease. It is also possible to ask what is the relative importance of organic and functional components in causation of symptoms and outcomes, as was done in this study. PATIENTS AND METHODS: The early and long-term clinical course was observed in a group of 80 patients with variant angina and a low prevalence of severe organic coronary disease (diameter stenosis greater than 70 percent of one vessel in 28.3 percent, of two or more vessels in 2.7 percent). Patients were seen at the UCLA Medical Center between July 1963 and June 1985. RESULTS: The following observations were made: Compared with those experiencing a first episode of angina at rest, subjects whose first episode of vasospastic angina occurred during strenuous effort were more likely subsequently to have a positive exercise test result and a more stable but long-term anginal course. A good initial response to vasodilator therapy indicated a likelihood of being alive and symptom-free without an intervening myocardial infarction by five years after diagnosis, which was twice the rate as if initial response to such treatment was poor. The presence or absence of severe coronary artery obstruction as detected by angiography could not be predicted from the nature or severity of angina, the historical presence of effort angina, or the occurrence of a positive result on an exercise test. The existence of severe coronary stenosis in at least one vessel was not associated with an increased incidence of myocardial infarction, cardiac arrest, or death in the first nine years after diagnosis. CONCLUSION: These findings are consistent with the hypothesis that manifestations of ischemic heart disease in these patients were more directly caused by coronary vasospasm than by the degree of organic coronary obstruction seen by coronary arteriography. In addition, the presence of severe organic stenosis in one coronary artery did not appear to be associated with measurably increased adverse effects on clinical course or survival over the first nine years after diagnosis.

Multiclinic controlled trial of diltiazem for Prinzmetal's angina.

To assess the efficacy of a new calcium entry blocker, diltiazem (Cardizem), for prophylaxis of Prinzmetal's angina, 48 patients were studied in randomized, multiple crossover multiclinic study (2 weeks single-blind, 8 weeks double-blind). Diltiazem dosage in one crossover phase was 120 mg per day; in the other, 240 mg per day. Therapeutic response was measured by patients' diary records of angina frequency and nitroglycerin tablet consumption. Treatment with 120 mg of diltiazem per day reduced angina by 41 percent from the entry placebo period and 20 percent from the paired placebo period (p less than 0.005). Treatment with 240 mg of diltiazem per day reduced angina frequency by 68 percent from the entry placebo period and 43 percent from the paired placebo period (p less than 0.01). There were similar reductions in nitroglycerin consumption. Adverse experiences that may have been related to the medication were noted in only 5 percent of patients. There were no alterations in blood pressure or heart rate. The PR interval increased 3 percent at the 240 mg dosage level. We conclude that diltiazem is an effective and safe agent for control of symptoms of Prinzmetal's angina.

Relation of coronary arterial spasm to sites of organic stenosis.

Among 63 patients with Prinzmetal's variant angina, coronary arterial spasm responsible for attacks of variant angina was documented arteriographically in 9 patients. In each observed episode (11 attacks in nine patients), coronary spasm producing myocardial ischemia occurred at and was superimposed on a site of preexisting organic stenosis. Measurements of normal portions of "spastic" and "nonspastic" vessels suggested a generalized uniform constriction of all major coronary arteries during attacks, with "spasm" limited to the site of an organic lesion in most cases. In two cases the magnitude of constriction in all vessels was consistent with generalized coronary hypercontractility or spasm. Among 104 patients with organic coronary artery disease and documented single vessel coronary spasm (foregoing 9 patients combined with 95 others from published reports), there were 70 patients with essentially single vessel organic coronary disease in 90 percent of whom the spasm involved the diseased vessel. Of 60 cases abstracted from the literature in which the relation of coronary spasm to the site of organic disease was described, 88 percent had the spasm causing ischemia localized to the site of an organic lesion. Hypotheses attempting to describe the pathophysiologic aspects of coronary spasm in variant angina must account for the intimate association of spasm with sites of organic stenosis in the majority of cases.

Echocardiographic diagnosis of a mobile, pedunculated tumor in the left ventricular cavity.

A mobile left ventricular tumor was detected by echocardiography. The tracing showed a cluster of echoes in the left ventricular cavity corresponding to the location of the tumor as seen in angiograms. At surgery the tumor was attached to the interventricular septum by a thin fibrous stalk.

Echocardiographic manifestations of infiltrative cardiomyopathy. A report of seven cases due to amyloid.

Echocardiography has been useful in the evaluation of congestive and hypertrophic cardiomyopathies. We present echocardiographic findings in seven patients with infiltrative cardiomyopathy due to amyloid. Cardiac amyloidosis was documented at autopsy in two patients, and the diagnosis was suggested by clinical, echocardiographic, tissue, or hemodynamic findings in the other five. Hemodynamic findings in three patients mimicked constrictive pericarditis; and autopsy was performed on one of the three and showed a normal pericardium. Underlying disorders were multiple myeloma (five patients), ankylosing spondylitis (one patient), and an unknown disorder (one patient). The basic echocardiographic findings in infiltrative cardiomyopathy due to amyloid were (1) symmetrically increased left ventricular wall thickness (in the absence of hypertension or aortic valvular disease), (2) hypokinesia and decreased systolic thickening of the interventricular septum and left ventricular posterior wall, and (3) small to normal size of the left ventricular cavity. Two patients also had small pericardial effusions. Thus, in a patient with congestive heart failure, these echocardiographic findings should suggest infiltrative cardiomyopathy.

A comparison of area-equivalent phases of systole and diastole as a method for evaluation of left ventricular movement.

A method of left ventricular motion evaluation is described that does not use the end-diastolic contour as a reference point. The systolic outline in the RAO view was divided into four equal time periods. The systolic outline at the end of each period was paired to the diastolic outline with approximately the same area. Index values were calculated in order to elucidate any existing asymmetry of movement between the anterior and diaphragmatic left ventricular wall. In a group of 14 patients with coronary artery disease without obvious local left ventricular contractility disturbances, pathological asymmetry index values were found in 10. In a group of 16 patients with local left ventricular contractility disturbances, abnormal asymmetry index values were found in eight. This index of assymmetry demonstrated pathological changes of left ventricular motion in spite of a normal appearance of local left ventricular contractility during visual evaluation.

Angiographic determination of disease-produced alterations of vasomotor tone in large coronary arteries.

Quantitative coronary arteriography was done before and after ergonovine and/or nitroglycerin in 24 patients. After nitroglycerin there was an average 18.6 +/- 3.9% increase in diameter of normal vessels over 2 mm in diameter, and a similar 19.3 +/- 8.7% increase in diameter of the same sized, normal appearing segments in subjects with coronary disease. In individual cases the luminal response to the drug was significantly more variable in "normal" segments of diseased vessels than in entirely normal arteries. Twenty-eight of thirty seven coronary stenoses dilated an average of 18 +/- 10.8% (range 3 to 43%) after nitroglycerin. Unequal dilation of stenosis and normal reference segment caused a 10% or greater change in calculated percent diameter stenosis in 16 lesions. Because they dilated less than would be predicted using a hypothetical geometric model to assess vessel reactivity, most of the lesions could be considered hyporeactive. Ergonovine predictably constricted normal coronary vessels in a relatively uniform fashion. Response of diseased arterial segments was more variable in a limited number of observations. Ergonovine partially antagonized the vasodilating effect of subsequently administered nitroglycerin, and larger than average or intracoronary doses of nitroglycerin had to be used to achieve the same degree of dilation seen with smaller doses in the absence of ergonovine. Disease of large coronary arteries focally alters their vasomotor tone and reactivity as gauged by responsiveness to nitroglycerin and ergonovine. Some implications of this are discussed.

Coronary ostial embolus and mitral vegetation simulating a left atrial myxoma: a case of probable cryptococcal valvulitis.

A 56 year old man died with disseminated cryptococcosis after immunosuppressive therapy for a hematologic disorder of unknown etiology. The immediate cause of death was cardiogenic shock, probably resulting from a large right coronary ostial embolus and subsequent ischemic myocardial injury. The embolus originated from a bulky mitral vegetation (possibly cryptococcal) demonstrated ante mortem by echocardiography and cardiac angiography, and at autopsy. The differential diagnosis of such an echocardiographic pattern is discussed.

The inside-out electrocardiographic stress test: a view from the left ventricular cavity.

A new method is described for measuring the unipolar left ventricular cavitary electrogram by means of a standard pigtail ventriculography catheter. Experiences with this technique in 30 patients are described with particular reference to changes in the S-T segment of the cavitary electrogram during cardiac stress by atrial pacing. This method allows convenient recording of His bundle potentials from the left ventricular outflow tract in most patients.

Contribution of dynamic vascular wall thickening to luminal narrowing during coronary arterial constriction.

Available estimates of the ratio of wall thickness to luminal radius of human coronary arteries and certain geometrical assumptions were used to calculate the amounts of vascular smooth muscle shortening required to produce specific changes in luminal diameter for hypothetical "normal" and stenotic arteries. The results indicate that even modest mural thickening due to disease may act as a "lever" in translating physiologic degrees of medial smooth muscle shortening into critical luminal obstructions, providing the diseased segment maintains some pliability. The possibility of acute luminal occlusion occurring at stenotic sites as the result of "normal" vasomotion is illustrated. The appropriate use of the term coronary arterial "spasm" is discussed in light of these observations.

Cardiac arrest and sudden unexpected death in variant angina: complications of coronary spasm that can occur in the absence of severe organic coronary stenosis.

Experiences in 81 patients with variant angina were reviewed with the goal of determining which clinical features were associated with the greatest risk of angina-linked cardiac arrest (13 patients) or sudden unexpected death (9 patients). The risk of occurrence of one of these actually or potentially fatal events was approximately tripled by the presence of either a history of angina-linked syncope or documentation of serious arrhythmia complicating attacks. An unexpected finding was that the risk was increased 1.5-fold by the absence of high-grade organic coronary stenosis. Cardiac arrest and sudden death are important risks of variant angina, which can occur without the presence of severe organic coronary stenosis. These risks can be reduced by adequate vasodilator therapy that includes a calcium channel blocker.

Absent septal Q waves in otherwise normal electrocardiograms--a variant of normal?

Absence of septal Q waves can be defined as the simultaneous absence of Q waves from all of leads I, V(5), and V(6). This has been considered abnormal by some investigators, but whether this is true of tracings lacking other abnormalities is uncertain. In electrocardiograms (ECGs) from 4,174 patients, 95 were found that were normal except for absence of septal Q waves. Clinical characteristics of these were compared to those of age- and gender-matched patients having normal ECGs with septal Q waves. The ratio of the number of patients with normal ECGs except for absent septal Q waves to the number of patients with entirely normal ECGs was independent of age. Most patients having normal ECGs except for absent septal Q waves had clinically normal hearts, and they were not significantly more likely to have apparent cardiovascular disease than age- and gender-matched controls with septal Q waves. It is concluded that absence of septal Q waves in otherwise normal ECGs may be a variant of normal.

Adaptation to exercise in angina pectoris. The electrocardiogram during treadmill walking and coronary angiographic findings.

Twelve patients with angina pectoris manifested an ability to adapt to exercise during treadmill stress testing with electrocardiographic monitoring. Three patterns of adaptation were seen. Nine subjects had the ability to continue walking after the onset of angina with eventual disappearance or lessening of anginal pain and the associated ischemic ST-segment depression; anginal pain and ST depression began to diminish during a steady state of blood pressure and heart rate in those cases in which these factors were measured. Four subjects were able to continue walking for long periods of time during a state of angina and ischemic ST depression. Three subjects demonstrated an increase in exercise capacity after being warmed up by a preceding bout of exercise-induced angina; blood pressures and heart rates during the initial, "warming-up" effort tended to be higher than those during the early stages of the second effort. In three subjects more than one of these patterns of adaptation were demonstrated. Five of the subjects showed striking subjective and objective improvement in exercise tolerance while on a program of regular walking exercise. Selective coronary cineangiography was performed in eight of these patients and two patterns of coronary disease were seen: (1) occlusion of a major coronary vessel with good collateral channels circumventing the obstruction; (2) strategically placed, proximal, stenotic lesions in major coronary vessels without frank occlusion and without discernible collateral development. Some diagnostic and therapeutic implications of these findings are discussed.