Dynamic characterization of premature ventricular beats and ventricular tachycardias

The contraction patterns induced by ectopic ventricular premature beats and ventricular tachycardias occurring in man during left ventriculography were analyzed. These were compared with contraction patterns induced by ventricular premature beats and tachycardias produced in five dogs by epicardial left ventricular apical or basilar stimulation. Two patterns of contraction observed in the animals corresponded to two patterns observed in man. Apically stimulated left ventricular beats produced an “hourglass” type of contraction pattern and were hemodynamically more effective than beats arising from basilar stimulation, which produced an inverse “teardrop” pattern. The same patterns were reproduced by experimental ventricular tachycardias. These observations stress the importance of a normal sequence of ventricular contraction to optimal cardiac function in man and warn against the hazards of misinterpretation of the left ventricular contraction pattern if the beat originates ectopically during ventriculography.     

Therapy of coronary vasoconstriction in patients with coronary artery disease

Patients with obstructive coronary artery disease and stable, exertional angina respond to the alpha adrenergic stimulus of the cold pressor test with an inappropriate increase in coronary vascular resistance. The clinical significance of this abnormal response and its possible role in the pathogenesis of ischemic heart disease are discussed. Comparison of the anti-anginal agents currently in use of undergoing investigation suggests that the calcium antagonists may be the most effective therapy for coronary vasoconstriction. Nifedipine, 10 mg buccally, successfully prevented the increase in coronary vascular resistance during the cold pressor test in 10 of 10 patients, whereas the response in placebo-treated patients was unaltered. This dose of nifedipine was without effect on systemic hemodynamics or myocardial oxygen consumption, suggesting a selective antivasoconstrictor effect on the coronary vasculature.     

"Silent" myocardial ischemia during and after exercise testing in patients with coronary artery disease

Although many patients with coronary artery disease (CAD) have a positive exercise test without pain, the frequency and significance of this "silent" ischemia is unclear. Therefore, we studied 122 consecutive clinically stable patients with angiographically defined CAD (greater than 75 per cent luminal stenosis) and a positive exercise test. Seventy-eight patients had pain or anginal equivalent during or after a positive exercise test; 44 did not, including 32 (26 per cent) with no symptoms at all. Patients were evaluated as to age, sex, prior myocardial infarction, congestive failure, hypertension, diabetes mellitus, and digoxin or propranolol therapy--in addition to anginal symptoms before, during, or after the exercise itself. Extent of CAD, presence of collaterals, and left ventricular ejection fraction were also determined. All exercise tests were evaluated for evidence of ST-T abnormalities or prior infarction on the control ECG as well as peak heart rate during exercise and post-exercise degree of ST segment depression. There were no significant differences between patients with and without exercise-induced pain in regard to any of the clinical and angiographic features noted above, demonstrating that "silent" myocardial ischemia during or after exercise testing is not uncommon and is not readily attributable to any obvious clinical or catheterization findings. Further studies are necessary to determine if patients with evidence of "silent" myocardial ischemia are especially prone to sudden death.     

Inappropriate coronary vasoconstriction in patients with coronary artery disease: A role for nifedipine?

Coronary arterial vasoconstriction, well recognized in Prinzmetal's variant angina, may participate in the pathogenesis of classic angina as well. Several recent studies in patients with obstructive coronary artery disease suggest that apparently spontaneous reductions in coronary blood flow can result in myocardial ischemia and even infarction. Evidence supporting the alpha adrenergic nervous system as a cause of such coronary vasoconstriction is reviewed, particularly the results of provocative testing with the cold pressor stimulus. Upon exposure of the skin to cold, patients with coronary artery disease demonstrate an inappropriate coronary vasoconstrictor response, often sufficient to produce angina. Normal patients, by contrast, show no change in coronary vascular resistance. In patients with a diseases coronary circulation, inappropriate vasoconstriction further restricts myocardial perfusion and appears to be little affected by beta adrenergic blocking agents or nitrates in the usual dosages. Nifedipine has proved effective in preventing coronary arterial spasm in patients with Prinzmetal's angina. Studies currently in progress suggest that it is also effective in blocking inappropriate coronary vasoconstriction in patients with typical angina. Nifedipine may thus be a useful addition to the treatment of ischemic heart disease.     

Electrocardiographic, arteriographic and ventriculographic correlations in transmural myocardial infarction

To determine if significant interrelations exist between the electrocardiographic diagnosis of transmural myocardial infarction, sites of coronary arterial obstruction, and left ventricular asynergy, 235 patients with angiographically documented coronary artery disease were subdivided according to the electrocardiographic location of the myocardial infarction, the coronary arterial system involved and the site of ventricular asynergy. Of 82 instances of anterior myocardial infarction, the left anterior descending artery demonstrated significant disease in 79 (96 percent). Of 100 instances of inferior myocardial infarction, the right coronary artery was significantly diseased in 87 and the left circumflex in 55. When multiple infarctions were present, multivessel disease was found in 93 percent of patients. Left ventricular asynergy was present in 81 percent, including 84 percent of those with anterior infarction, 74 percent of those with inferior infarction, and 93 percent of those with multiple infarctions. The results of our study suggest that the electrocardiogram is often of value in indicating sites of coronary arterial obstruction and ventricular asynergy in patients with coronary artery disease and transmural myocardial infarction.     

Prognostic importance of anginal symptoms in angiographically defined coronary artery disease

To evaluate the prognostic importance of anginal symptoms, 44 patients with angiographically defined coronary artery disease and no anginal symptoms at time of cardiac catheterization were selected from the Duke Harvard Collaborative Data Bank. They were “matched” with 127 symptomatic patients in the Data Bank who had similar coronary anatomy and ventricular function. Follow-up data indicated that the patients without anginal symptoms had a significantly better prognosis over a 7 year period than did those with symptoms: Annual mortality in the asymptomatic group was 2.7 percent compared with 5.4 percent in the group with angina (p 0.05). Although the patient population was a highly selective one and the matching categories were relatively broad, these results suggest that the presence of anginal symptoms may be an important independent correlate of prognosis in patients with coronary artery disease. The absence of angina did not preclude the presence of multivessel disease and did not necessarily imply a benign prognosis, because the yearly mortality rate was nearly 5 percent in the subgroup of asymptomatic patients with three vessel disease.     

Effect of coronary collateral vessels on regional myocardial blood flow in patients with coronary artery disease: Relation of collateral circulation to vasodilatory reserve and left ventricular function

The effect of radiographically graded coronary collateral vessels on regional myocardial blood flow was evaluated with intracoronary injection of xenon-133 at rest and during contrast agent-induced coronary hyperemia in 24 patients with coronary artery disease. Eleven patients had no coronary collateral vessels demonstrated radiologically, whereas 13 had such vessels. In 7 of the 13 these were high grade and noncompromised, whereas in 6 they were of lesser grade. Regional myocardial blood flow at rest in patients with and without collateral channels was similar and increased during hyperemia. However, the increase in flow was significantly greater in the patients with high grade noncompromised collateral vessels than in those with lesser grade collateral vessels (80 ± 16 versus 31 ± 9 percent, p <0.05). To evaluate the functional significance of the high grade noncompromised collateral vessels against that of vessels of lesser grade, various indexes of global and regional ventricular function were compared in the 13 patients in the present study, as well as in 24 patients whose collateral vessels had been subjected to similar grading systems in previous studies of regional myocardial blood flow. There were no significant differences in degree of regional asynergy, ejection fraction or left ventricular end-diastolic pressure between the patients with high and lower grades of collateral vessels. Thus, high grade noncompromised collateral vessels do not appear to have a beneficial effect on resting left ventricular function despite their enhanced vasodilatory reserve.     

Noninvasively induced postextrasystolic potentiation of ischemic and infarcted myocardium in patients with coronary artery disease.

To evaluate noninvasively-induced postextrasystolic potentiation (PESP) of ischemic or apparently infarcted regions of myocardium, an external mechanical cardiac stimulator (develoepd by Zoll) was used to induce ventricular extrasystoles during M-mode echocardiography in 29 patients with coronary artery disease and in four control subjects. Twenty-five patients had > 75 per cent stenosis of the left anterior descending artery including 13 with ECG evidence of anteroseptal myocardial infarction; 21 patients had > 75 per cent stenosis of the right coronary and/or left circumflex arteries, including 11 with ECG evidence of inferior and/or posterior myocardial infarction. Twenty-four regions with reduced wall excursion showed varying effects of PESP: eight regions improved to the normal range, while 16 did not. Twelve of the latter had ECG evidence of prior infarction. Similarly, regions of asynergy that did not respond at all to PESP were usually, but not always, seen in patients with infarctions. Based on prior ventriculographic-histopathologic correlates, non-responding regions are probably totally scarred with irreversible contraction abnormalities, whereas regions with evidence of contractile reserve are potentially viable. Because the ECG and resting echocardiogram are not totally accurate predictors of contractile reserve, noninvasively induced PESP may be a useful adjunct technique in delineating local contractile reserve in patients with echocardiographic evidence of hypocontractile myocardium of uncertain viability.     

Left ventricular ejection fraction as a prognostic guide in surgical treatment of coronary and valvular heart disease

The immediate and short-term prognostic values of increased left ventricular end-diastolic pressure, reduced cardiac index and depressed ejection fraction determined during preoperative evaluation were compared in 128 patients undergoing coronary revascularization and 44 patients undergoing cardiac valve replacement. A modification of the New York Heart Association (NYHA) functional classification was used to evaluate pre- and postoperative left ventricular decompensation. One hundred fifty-eight of the 172 patients did well postoperatively (NYHA classes I and II), including the majority of patients with either an abnormal left ventricular end-diastolic pressure (> 15 mm Hg), reduced cardiac Index (< 2.5 liters/min per m²) or depressed ejection fraction (< 0.50). However, of the 14 patients who did not survive surgery or had progressive postoperative deterioration, 10 had a depressed ejection fraction and 7 had combined abnormalities of left ventricular end-dlastolic pressure and cardiac index. Because these latter values may often be borderline, or occur as isolated abnormal findings, the ejection fraction is probably the most useful of the readily obtainable, single hemodynamic measurements in assessing the import of deranged left ventricular function on the outlook for patients undergoing cardiac surgery.     

Effects of hyaluronidase and hydrocortisone on myocardial necrosis after coronary occlusion.

In anesthetized open chest dogs, hydrocortisone (50 mg/kg body weight administered 30 minutes after occlusion and 25 mg/kg 12 hours later) substantially reduced the size of myocardial infarcts, as reflected by both myocardial creatine phosphokinase activity and histologic appearance 24 hours later. Similarly, hyaluronidase, which increases diffusion through the extracellular space and presumably facilitates delivery of substrate to ischemic cells, also reduced the extent of myocardial necrosis after coronary occlusion in the dog. In view of the salutary effects of hyaluronidase and the absence of serious side effects, this agent was administered clinically to two groups of patients, who were compared with two groups of untreated control subjects. Hyaluronidase (500 National Formulary units/kg X 8) was shown to result in a significantly more rapid reduction in the magnitude and the extent of precordial S-T segment elevations, and in patients treated within 4 hours a tendency to a lower incidence rate of Q waves and a smaller reduction of R waves.     

Clinical significance of coronary arterial ectasia.

In a study group of 2,457 consecutive patients undergoing cardiac catheterization, 30 patients had coronary arterial ectasia, an irregular dilatation of major vessels up to seven times the diameter of branch vessels. The frequency of hypertension, abnormal electrocardiogram and history of myocardial infarction was greater than that in a control group with obstructive coronary artery disease. Patients with ectasia did not differ from patients with obstructive disease in sex, age, prevalence of angina or presence of metabolic abnormalities. Six deaths occurred in the group with ectasia during a mean follow-up period of 24 months (annual rate of 15 percent). Extensive destruction of the musculoelastic elements was evident, resulting in marked attenuation of the vessel wall. The short-term prognosis in this group is the same as in medically treated patients with three vessel obstructive coronary artery disease.     

Natural history of S-T segment elevation after acute myocardial infarction

Clinical, electrocardiographic and cineventriculographic data in two patient groups were analyzed to define the natural history of S-T segment elevation after myocardial infarction. In sixteen of 22 patients (73 percent) with acute inferior myocardial infarction, S-T segment elevation was present on hospital admission, persisting in 1 (5 percent) by the 2nd week. S-T segment elevation was present on admission in 18 of 23 patients (78 percent) with acute anterior myocardial infarction and persisted in 13 after 1 week and in 9 of 14 (64 percent) during a follow-up period of 1 to 6 months. S-T segment elevation lasting more than 2 weeks after myocardial infarction did not resolve. Compared with patients with inferior myocardial infarction or anterior infarction without persistent S-T segment elevation, patients with anterior infarction and persistent S-T segment elevation had a higher level of mean maximal serum creatine phosphokinase (CPK), more severe left ventricular decompensation and a greater frequency of death in the early follow-up period. In a separate series of 95 patients with cineangiographically documented coronary artery disease, 40 of 65 patients (62 percent) with advanced anterior and apical asynergy had persistent S-T segment elevation. By contrast, only 1 of 30 (3 percent) with coronary disease and normal ventriculograms had persistent S-T segment elevation.We concluded that (1) the natural history of S-T segment elevation after myocardial infarction is resolution within 2 weeks in 95 percent of inferior but in only 40 percent of anterior infarctions; (2) S-T segment elevation persisting more than 2 weeks after myocardial infarction does not resolve; (3) persistent S-T segment elevation is associated with clinically more severe myocardial infarction; and (4) in patients with coronary artery disease, persistent S-T segment elevation after myocardial infarction is a specific but insensitive index of advanced asynergy.     

Effect of sublingually administered nitroglycerin on regional myocardial blood flow in patients with coronary artery disease.

The effect of sublingually administered nitroglycerin on regional myocardial specific blood flow (in ml/min per 100 g tissue) was evaluated with a xenon-133 washout technique in 31 patients in a resting nonstressed state. Eight patients had normal coronary arteriograms (Group 1), 12 had coronary artery disease without collateral vessels (Group 2) and 11 had coronary artery disease with collateral vessels (Group 3). Although nitroglycerin caused a similar decrease in mean arterial blood pressure and blood pressure-heart rate product in all three groups, the decrease in regional myocardial blood flow was significantly less in Group 3 (-8+/-6% [mean+/-standard error of the mean]) than in Group 1 (-31+/-5%), P less than 0.05); an intermediary decrease occurred in Group 2 (-23+/-5%). Within Group 3, there was a mean increase in regional myocardial blood flow after nitroglycerin in the five patients whose collateral vessels were of a higher angiographic grade and arose from non-stenosed coronary arteries, whereas a reduction was observed in the six patients with none or only one of these findings (+10+/-7% versus -23+/-3%, P less than 0.001). This study suggests that even in the resting state, in some patients with coronary artery disease enhancement of regional myocardial blood flow can occur after sublingual administration of nitroglycerin and is probably mediated through well functioning collateral vessels. It is possible that the drug's effects on both the coronary and systemic circulation may relieve angina in some patients with coronary artery disease.     

Reproducibility of the angiographic left ventricular ejection fraction in patients with coronary artery disease

Quantitative analysis of the single and repeated cine left ventriculogram was performed in 20 patients with coronary artery disease to determine both the intrinsic variance of individual beats separated by different time intervals and variance between analyses of different observers. In addition, ventriculograms obtained from left ventricular injections of contrast medium prior to coronary arteriography were compared to ventriculograms obtained from either left ventricular or pulmonary artery injections after arteriography. The time period between studies varied from 30 minutes to 90 minutes to four days. Analysis of the same ventriculogram by different observers resulted in an average difference in ejection fraction of 0.05 (pNS). The average difference in ejection fraction was 0.02 between two early beats of the same ventriculogram (pNS). The average difference between sequential ventriculograms was 0.07 (pNS), but individual variations greater than 0.10 were not uncommon, particularly between studies done before and after arteriography, or several days apart. Patients exhibiting wide variance in ejection fractions between two studies either had wide variance in other hemodynamic measurements or degree of asynergy, or both. This study provides a frame of reference for analysis of sequential ventriculograms in patients with coronary artery disease, especially in evaluating changes in the state of the disease or the effects of therapy. It is especially important that: (1) standard hemodynamic measurements be made before ventriculography, (2) the same radiographic techniques repeated whenever possible, and (3) the same person analyze the two ventriculograms.     

Dissection of the thoracic aorta: Medical or surgical therapy?

Both medical and surgical therapy are available for the treatment of aortic dissection. To help determine which form of treatment is indicated for which patients, all cases of aortic dissection at the Peter Bent Brigham Hospital from 1963 to 1973 were reviewed. The most important feature in determining the patient's clinical status and response to therapy was the site of dissection, that is, the ascending or descending aorta.

Of 31 patients with dissection of the ascending aorta, 26 had one or more of the following contraindications to medical therapy: congestive heart failure (8 patients), hemopericardium (8 patients), new aortic insufficiency (13 patients) or jeopardized carotid or coronary arteries (4 patients). Medical therapy was successful in only 1 of 9 patients with dissection of the ascending aorta; 17 of 22 patients having surgical correction of this lesion did well and were discharged.

The clinical status of the 14 patients with dissection limited to the descending aorta was quite different. None had a contraindication to medical therapy. Medical therapy was instituted in all 14, and was successful in 6; dissection progressed in 8 patients despite medical therapy, and subsequent surgery was successful in only 2.

We conclude that the treatment of choice for dissection of the ascending aorta is prompt surgical therapy. In patients with dissection limited to the descending aorta, medical therapy is usually feasible and often successful.     

Right ventricular diastolic pressure in coronary artery disease

Right ventricular hemodynamics were evaluated in 179 patients with coronary artery disease to determine the effects of chronic ischemia on right ventricular diastolic pressure. Abnormal right ventricular filling pressures occurred only in patients with an abnormal right ventricular systolic pressure or an abnormal left ventricular end-diastolic pressure. Of the 63 patients whose right ventricle was stressed by an increased systolic load secondary to passive pulmonary hypertension, 44 (72 percent) had an abnormal right ventricular end-diastolic pressure. In this group obstruction of vessels serving the right ventricular free wall or septum, or both, was almost universal (43 of 44, 98 percent) and a significantly increased incidence of inferior infarction (P < 0.05) was noted. Such obstruction was significantly less frequent in patients with normal filling pressures (10 of 17, 59 percent; P < 0.001). Compared with patients with coronary artery disease, patients with passive pulmonary hypertension due to aortic stenosis or mitral stenosis had significantly greater degrees of pulmonary hypertension (P < 0.05) yet slightly lesser elevations of right ventricular end-diastolic pressure. These data suggest that in patients with ischemic heart disease the right ventricle exhibits diastolic dysfunction at lower levels of afterload stress than it would with normal coronary blood flow.