Therapeutic implications of diazepam in patients with elevated left ventricular filling pressure.

Diazepam (0.1 mg. per kilogram) was given intravenously to 12 patients with hemodynamic left ventricular failure at the time of cardiac catheterization. Anxiety was effectively relieved in 10 patients. Systemic and coronary hemodynamic parameters were assessed before and 5 and 15 minutes after diazepam. Heart rate, cardiac index, and left ventricular stroke-work index did not change significantly. Mean aortic pressure decreased in all patients (average of 10 mm. Hg) and left ventricular end-diastolic pressure (LVEDP) decreased from a mean +/- S.E.M. of 24.3 +/- 3 mm. Hg at rest to 16 +/- 2.1 at 5 minutes (p less than 0.001) and 15.8 +/- 2.1 at 5 minutes (p less than 0.002). Left ventricular angiography performed 30 minutes after diazepam did not increase LVEDP above the pre-diazepam control value. Systolic ejection period and tension-time index also decreased significantly after diazepam. Coronary hemodynamics and myocardial metabolism were unaltered by diazepam. The fall in LVEDP induced by diazepam is probably secondary to a decrease in arterial pressure (afterload) possibly associated with a decrease in venous return (preload). Our data therefore suggest that diazepam exerts a beneficial action on depressed left ventricular function and, thus, may be a sedative agent of choice in patients with myocardial infarction and heart failure.     

Myocardial bridging and milking effect of the left anterior descending coronary artery: Normal variant or obstruction?

Of 5,250 patients undergoing coronary arteriography over a 5 year period, 27 (0.51 percent) had an intramyocardial segment of the left anterior descending coronary artery producing a milking effect or constriction of the artery during systole. Of these, 11 patients with otherwise normal coronary arteries were studied. Hemodynamic data, coronary sinus blood flow and myocardial lactate extraction were measured during atrial pacing at rates of 120 and 150 beats/min and during a 60 watt supine ergocycle exercise test. The degree of narrowing of the left anterior descending coronary artery during systole was graded 3 (greater than 75 percent), 5 patients; 2 (50 to 75 percent), 4 patients; and 1 (less than 50 percent), 2 patients. Four patients with a grade 3 milking effect had S-T depression in the electrocardiogram indicating anterior wall ischemia and lactate production during pacing at 149 ± 2 (mean ± standard error of the mean) beats/min. Three patients had severe angina during pacing. Two patients with a grade 2 milking effect had angina-like chest pain and electrocardiographic changes during pacing at 150 beats/min. However, lactate extraction was unchanged during pacing. Two patients with a grade 1 milking effect had no angina and no electrocardiographic or metabolic abnormalities. Coronary sinus blood flow increased significantly with pacing and ergocycle exercise in all patients (rest 118 ± 8 ml/min; pacing at 150 beats/min 219 ± 27 ml/min; ergocycle exercise 251 ± 17 ml/min) (P < 0.001). We conclude that a grade 3 milking effect observed at coronary arteriography can result in significant obstruction of the left anterior descending coronary artery with typical angina and anterior wall ischemia during tachycardia. Surgical periarterial muscle resection or bypass of the left anterior descending coronary artery might be considered in symptomatic patients with this rare anomaly.     

Ventricular arrhythmias during ergonovine-induced episodes of variant angina

Of 95 consecutive patients with active variant angina who underwent ergonovine testing in the coronary care unit while off treatment, 24 (25%) developed serious ventricular arrhythmias: ventricular tachycardia in eight, bigeminy in seven, pairs in five, and frequent ventricular extrasystoles in four. Ergonovine-induced arrhythmias were observed more often in patients with anterior than inferior ST segment elevation (p less than 0.05). ST segment elevation was significantly higher (10.3 +/- 8.1 vs 3.1 +/- 2.1 mm) in patients who developed arrhythmias. All ventricular arrhythmias began within 3 minutes after the onset of ST segment elevation. The intravenous administration of nitroglycerin eliminated arrhythmias in 22 of 24 cases; in only two patients did ventricular arrhythmias develop after the administration of nitroglycerin. Serious ventricular arrhythmias were found during spontaneous variant angina attacks in 14 of 24 patients with ergonovine-induced arrhythmias compared to 16 of 71 patients without ergonovine-induced arrhythmias (p less than 0.001). We conclude that arrhythmias during ergonovine testing are most often caused by ischemia and not reperfusion. Patients with arrhythmias during ergonovine-induced attacks are more likely to have arrhythmias during spontaneous attacks.     

QT interval measurement by a computer assisted program: a potentially useful clinical parameter

The duration of electrical systole (QT interval) was measured in 72 subjects (48 women and 24 men) who had normal coronary arteries and left ventricular function at cardiac catheterization (group 1). The same measurements were obtained in 100 patients with a normal ECG (from 40 women and 60 men referred to our institution and found normal on a noninvasive clinical basis) and compared to a double independent manual calculation (group 2). The computer assisted program was found reliable in QT interval measurements. In both study groups women showed longer QTc. No difference in QTc duration was seen in subjects taking beta-blockers prior to angiography. As compared to group 1, subjects of group 2 showed similar average QTc values. However, 9 out of 100 subjects of group 2 had abnormal QTc as compared with none of group 1 (p less than 0.05). QTc calculations may improve the usefulness of computer assisted programs in ECG interpretation. Present data can be used as reference values for normality. They stress in addition the necessity of introducing the heart rate correction for the interpretation of QT interval. This can help in stimulating prospective clinical studies to assess the value of QTc as an index of risk for cardiac dysrhythmias.     

Influence of aortocoronary saphenous vein bypass surgery on left ventricular volumes and ejection fraction. Comparison before and one year after surgery in 51 patients

Ventricular volumes and ejection fraction were studied by single plane cineventriculography before and one year after vein bypass graft surgery in 51 patients. Selective opacification of the grafts was performed two to three weeks and one year after surgery. In 23 patients with patent grafts without stenosis or with ≤50 per cent stenosis, left ventricular end-diastolic volume, end-systolic volume and ejection fraction were unchanged (p always < 0.3). Unchanged ventricular volume and ejection fraction were also observed in nine patients with double grafts of which one was occluded and the other patent. However, in 19 patients with occluded or severely stenosed grafts, a significant increase in end-diastolic volume (p < 0.05) and end-systolic volume (p < 0.01), and a decrease in ejection fraction (p < 0.05) were found. The variation in ejection fraction was different between patients with grafts to the left anterior descending and to the right coronary artery (p < 0.025). In conclusion, there was no significant improvement in ventricular volume and ejection fraction in patients with patent grafts whereas deterioration was evident after unsuccessful surgery but only to the left anterior descending coronary artery. This lack of improvement in ventricular performance in the presence of patent grafts and the deleterious effect of graft occlusion should promote continuing objective and critical evaluation of this type of surgery.     

Long term follow-up of aneurysmectomy for recurrent ventricular tachycardia or fibrillation.

The success of aneurysmectomy in abolishing recurrent ventricular tachycardia or ventricular fibrillation has not been clearly defined. Ten patients who underwent aneurysm resection to control ventricular arrhythmias were studied before and an average of 19 (4 to 42) months following operation. All patients had moderate to large aneurysms and four had asynergy in adjacent segments. Of four patients with significant stenosis in vessels not supplying the aneurysm, three had aortocoronary bypass grafts in addition to their resection. Ambulatory Holter monitoring and a graded exercise test were performed in all patients postoperatively. There was no operative mortality. Two patients who did not have associated revascularization procedures died suddenly 1.5 and 7 months postoperatively. Of the eight survivors, despite clinical improvement, the Holter ECG revealed runs of ventricular tachycardia in three patients and frequent multifocal ventricular extrasystoles in the other five patients. No correlation was found between recurrence of the ventricular arrhythmias and aneurysm size, contraction pattern of other myocardial segments, extent of coronary disease, or the presence of congestive heart failure. In conclusion, aneurysmectomy does not abolish ventricular tachyarrhythmias and probably should be reserved for patients who remain symptomatic despite an adequate medical trial. The persistence of complex arrhythmias following operation warrants a close follow-up in these patients.     

Progression of atherosclerosis in coronary arteries and bypass grafts: Ten years later

Progression of atherosclerosis in aortocoronary saphenous vein grafts is frequent and is the predominant cause of late graft closure after CABG. Only approximately 60% of grafts remain patent between 10 and 12 years after surgery. Of patent grafts, 45% show angiographie evidence of atherosclerosis between 10 and 12 years after surgery and 70% of the atherosclerotic lesions reduce the graft lumen diameter by 50% or more. Atherosclerosis of saphenous vein grafts does not appear to be related to age, sex or cigarette smoking, but is associated with abnormalities of cholesterol lipoprotein fractions. Progression of atherosclerosis in the native coronary arteries is also very significant after CABG. Progression of CAD between 10 and 12 years after surgery occurs in approximately 50% of nongrafted arteries. Between 10 and 12 years after surgery, the rate of progression of disease in nongrafted arteries is not different from that of grafted arteries with patent grafts; however, progression is more frequent in grafted arteries with occluded grafts. The rate of progression is not related to age, sex, risk factors or extent of disease at baseline coronary arteriography. Progression of preexisting stenoses is more frequent than appearance of new stenosis. Progression is related to the severity of the preexisting stenosis only in nongrafted arteries. Finally, progression is related to alterations of left ventricular function during follow-up.

Because of these progressive late changes, CABG should probably remain limited to patients with incapacitating anginal symptoms or to those with severe lesions for whom surgery might enhance long-term survival, such as patients with severe left main CAD and 3-vessel CAD.     

Failure of transdermal nitroglycerin to improve chronic stable angina: a randomized, placebo-controlled, double-blind, double crossover trial

We assessed the effect of transdermal nitroglycerin (NTG-TTS), releasing 5 mg/24 hr, in 11 patients with chronic stable angina during a randomized, placebo-controlled, double-blind, double crossover trial of four 1-week periods. All patients had a positive exercise test and coronary artery disease prior to entry into the study. Efficacy was assessed weekly by anginal diaries, ambulatory ST segment recordings, and computerized exercise testing 2 to 4 hours after renewal of NTG-TTS. One patient withdrew in the first week (placebo) and was excluded from all analysis. The weekly frequency of anginal attacks was 9 +/- 11 (mean +/- SD) and 9 +/- 10 during the 2 placebo weeks and 11 +/- 14 and 9 +/- 11 during NTG-TTS; the time to 1 mm ST segment depression (seconds) was 268 +/- 178 and 303 +/- 217 with placebo and 228 +/- 221 and 285 +/- 178 with NTG-TTS; exercise duration (seconds) was 375 +/- 230 and 467 +/- 254 during placebo and was 394 +/- 233 and 412 +/- 236 during NTG-TTS. The weekly number of episodes of ST depression was 11 +/- 9 and 8 +/- 5 during placebo and 8 +/- 5 and 9 +/- 7 during NTG-TTS. Our study failed to show any consistent differences in patients treated with placebo or NTG-TTS.     

Clinical and angiographic assessment 6 months after double vessel percutaneous coronary angioplasty

Percutaneous transluminal coronary angioplasty is an accepted treatment for selected patients with single vessel disease but has not been rigorously evaluated in patients with double vessel disease. Among 769 patients undergoing transluminal coronary angioplasty between 1980 and 1984, 74 with double vessel stenosis of 50% or more underwent double vessel coronary angioplasty. Primary success was obtained for both lesions in 63 patients (85%), for one lesion in 11 patients (15%) and for 137 (93%) of 148 segments overall. Except for myocardial infarction in one patient, no serious complication occurred. Before coronary angioplasty, 15 patients had unstable angina, 14 had Canadian Cardiovascular Society class III and 32 class I to II effort angina and only 2 were asymptomatic. Six months after coronary angioplasty, 27 were asymptomatic, 27 had class I to II and 5 had class III effort angina and 2 had sustained an episode of unstable angina. During the follow-up study, two patients had an infarction and one had coronary artery bypass surgery. Coronary arteriography was performed at a mean of 5.5 +/- 2.1 months after coronary angioplasty in all but three patients. Restenosis was found in 30 (23%) of 132 segments with angiographic control. Restenosis was present in one vessel in 17 patients and in both vessels in 4; 40 patients (66%) had no restenosis. Of the 34 patients with definite or probable angina, 50% had restenosis and 19% of patients with restenosis were symptom free.(ABSTRACT TRUNCATED AT 250 WORDS)     

Angiographic evaluation of the natural history of normal coronary arteries and mild coronary atherosclerosis

Between September 1966 and September 1976, a group of 48 patients with normal coronary arteries or nonsignificant coronary atherosclerosis documented in a first coronary arteriogram underwent a second angiogram because of persistent or recurrent chest pain. The interval between studies was 13 to 108 months (mean 42 months). The indication for the first angiogram was typical or atypical anginal pain. The patients were separated into two groups according to the results of the first angiogram. Group I included 22 patients, 9 men and 13 women, with normal coronary arteries (mean age 49 years, range 28 to 62). Group II included 26 patients, 18 men and 8 women, with coronary stenosis of less than 50% of intraluminal diameter (mean age 49 years, range 38 to 63). The second angiogram revealed normal coronary arteries in all 22 patients in Group I but showed progression of diseases in 7 (27%) of the 26 patients in group II. The coronary arterial narrowings were greater than 50% in four patients and greater than 70% in only two patients. The clinical course, coronary risk factors and interval between angiograms were not useful predictors of progression of disease. The data suggest that coronary artery disease is unlikely to developed in adults with normal coronary arteries and that roughly 75% of adults with nonsignificant atherosclerosis will not show progression of disease over a 3 to 4 year period.     

Long-term prognosis of patients with incomplete bilateral bundle branch block complicating acute myocardial infarction. Role of cardiac pacing

During a 40 month period, 27 patients with acute myocardial infarction complicated by incomplete bilateral bundle branch block were treated with temporary transvenous pacemakers. Twelve of the 27 patients (44 percent) died in the hospital, 7 of cardiogenic shock, 3 of ventricular fibrillation and 2 of other causes. Progression to complete heart block occurred in 9 of the 12 patients who died but was not a direct cause of death. Of the 15 patients who survived, 6 manifested transient complete heart block, and 3 of these 6 were treated with permanent pacemakers although sinus rhythm later returned. Serious ventricular arrhythmias were common in the group as a whole. One of the 15 survivors died of congestive heart failure 15 months after infarction. The other 14 have survived an average of 16.7 months (5 to 35 months) after infarction, and none have manifested complete heart block. Four have no electrocardiographic evidence of intraventricular conduction disturbance and five have evidence of unifascicular block only.We conclude that (1) prophylactic temporary transvenous pacemaker insertion in patients with acute myocardial infarction complicated by incomplete bilateral bundle branch block is of little value; (2) such patients generally do not require a permanent pacemaker; (3) survival is often followed by regression of the intraventricular conduction disturbances; and (4) the prognosis appears to be good for paients who survive the acute phase.     

Circadian variation in variant angina

Thirteen hospitalized patients with variant angina were studied to assess circadian variation in disease activity. Over 48 hours, all angina attacks were noted, a continuous Holter electrocardiogram was recorded and 2 ergonovine tests were performed 12 hours apart, 1 at 4 AM and the other at 4 PM. Only 2 patients gave a clearcut history of more frequent nocturnal or early morning attacks. During the study period, 1.8 +/- 1.6 AM and 0.62 +/- 1.2 PM angina episodes per patient were reported (p less than 0.02), but a circadian pattern was apparent in only 4 patients. However, Holter analysis revealed 5.3 +/- 13.8 AM and 2.6 +/- 8.5 PM episodes of ST elevation per patient (p less than 0.05) and 8.1 +/- 13.9 AM and 3.2 +/- 8.5 PM episodes of ST elevation, ST depression or T-wave pseudonormalization (p less than 0.01). Ten of 11 patients with Holter abnormalities had more frequent AM than PM attacks (p less than 0.01). ST elevation developed during all 13 of the 4-AM and 12 of 13 of the 4-PM ergonovine tests. In 10 cases the ergonovine threshold at which the attack occurred was lower in the morning, in no case was it lower in the afternoon, and in 3 patients the morning and afternoon doses were identical (p less than 0.01). Thus, circadian variation in disease activity both for spontaneous and provoked attacks is present in most patients with variant angina, even though it is often not clinically apparent.     

Patency of aortocoronary vein grafts and serum triglycerides. Three year follow-up study

Fasting blood lipid levels were determined before operation and 1 and 3 years after operation in 36 patients to verify the hypothesis that hypertriglyceridemia plays a role in the fate of aortocoronary vein grafts. Graft patency was evaluated with use of arteriography 2 weeks, 1 year and 3 years after operation. Results of these studies show that patients with hypertriglyceridemia have a higher risk of occlusion or stenosis of vein grafts. Serum cholesterol levels do not appear to affect the fate of the grafts.     

Clinical characteristics of patients with variant angina complicated by myocardial infarction or death within 1 month

Of 132 consecutive patients hospitalized during a 5 year period because of active variant angina, 18 died or had a myocardial infarction within 1 month. In 4 patients an episode of pain and S-T elevation unrelieved by calcium antagonist drugs and intravenous nitroglycerin persisted for more than 1 hour, inducing cardiogenic shock and death before the appearance of Q waves and elevated serum enzyme levels. In the other 14 patients myocardial infarction developed in the electrocardiographic leads in which S-T elevation had occurred during attacks of variant angina.Clinical features were not helpful in distinguishing the 18 patients with complications from the other 114. Angina at rest had been present for less than 1 month in 7 of the 18 patients with infarction compared with 31 of 114 in the other group (probability [p] not significant [NS]). Before infarction the artery presumed to be perfusing the involved territory contained a fixed stenosis of 70 percent or more of luminal diameter in 8 of the 14 patients with complications who had coronary arteriograms compared with 50 of 112 in the other group (p = NS). In 13 of the 18 patients, complications occurred in spite of large doses of calcium antagonist drugs. In 11 of these 13, attacks of variant angina were monitored for 3 to 17 days both before and during treatment. All 11 had fewer attacks with treatment and 5 had no attacks. Daily attacks per patient decreased from 4.6 ± 4.3 to 0.5 ± 0.7 (mean ± standard deviation) (p < 0.01). It is concluded that in variant angina of recent onset myocardial infarction occurs frequently and unpredictably. Myocardial infarction may occur in the absence of severe fixed lesions and in spite of apparent clinical improvement with administration of calcium antagonist drugs.     

Ergonovine testing to detect spontaneous remissions of variant angina during long-term treatment with calcium antagonist drugs

A subgroup of 22 patients with variant angina who had responded well to calcium antagonist drugs were studied to determine if ergonovine testing could help assess the need for continued therapy. Before treatment all 22 patients exhibited angina with S-T elevation during ergonovine testing done in the coronary care unit according to a previously described protocol with sequential ergonovine doses of 0.0125, 0.025, 0.05, 0.1, 0.2, 0.3 and 0.4 mg administered at 5 minute intervals. After 9.4 ± 4.7 (range 1 to 24) months of treatment (nifedipine 7 patients, diltiazem 3, verapamil 8, perhexiline 3, nifedipine and diltiazem 1), all patients were free from anginal attacks. Medication was discontinued and ergonovine testing repeated 24 to 48 hours later (3 weeks for perhexiline). In 12 of the 22 patiénts, angina or S-T segment shifts did not occur during the second ergonovine test to a maximal dose of 0.4 mg. Treatment was not restarted in these patients and all 12 remain free of variant anginal attacks 4.2 ± 2.9 (range 1 to 13) months later. In seven patients angina and S-T elevation occurred during the second ergonovine test, in the same electrocardiographic leads as during the test before treatment. In three patients the ergonovine test induced angina with S-T depression in the leads where S-T elevation had occurred during the previous test. Treatment was reinstituted in these 10 patients with a positive test. No complications resulted from ergonovine testing in any patient.We conclude that in many patients with variant angina, symptoms will disappear spontaneously and the ergonovine test will revert to negative. Treatment with calcium antagonist drugs can probably be safely discontinued in some patients with variant angina; ergonovine testing appears to be helpful in identifying such patients. Longer periods of follow-up are required to confirm that symptoms do not recur.