Irene H. Lamb

Efficacy of diltiazem for control of symptoms of coronary arterial spasm

To evaluate the efficacy of the calcium antagonist diltiazem for therapy of active coronary arterial spasm, 13 patients with clinical variant angina attributed to documented coronary arterial spasm completed a prospective randomized double-blind crossover trial of diltiazem (120 and 240 mg/day) versus placebo. Response was assessed with the diary technique measuring frequency of angina, consumption of nitroglycerin and percent of pain-free days. When 120 mg of diltiazem/day was compared with the paired placebo period there was a significant increase in percent of pain-free days (from 43 to 71 percent [p = 0.03]), but no significant decrease in frequency of angina (p = 0.06) or consumption of nitroglycerin (p = 0.32). When 240 mg of diltiazem/day was compared with the paired placebo period there was a significant increase in percent of pain-free days (from 50 to 79 percent [p = 0.03]) and a significant decrease in both frequency of angina (from 1.6 to 0.4 episodes/day [p = 0.03]) and consumption of nitroglycerin (from 1.3 to 0.4/day [p = 0.01]). Diltiazem was found to be a highly effective drug for control of symptoms of active coronary arterial spasm, without side effects and with excellent patient tolerance.

Do Patients in Whom Myocardial Infarction Has Been Ruled out Have a Better Prognosis after Hospitalization Than Those Surviving Infarction

To determine the prognosis after hospitalization of patients hospitalized with acute chest pain in a coronary-care unit, we undertook a prospective study of 211 consecutive admissions to the Stanford Coronary Care Unit. On the basis of predetermined criteria, 16 patients were found to have noncardiac chest pain, and myocardial infarction was ruled out in 89, one of whom died in the hospital. Infarction was documented in 84 others, six of whom died in the hospital. Prospective follow-up after hospitalization was carried out in the 88 patients in whom infarction was ruled out and in the 78 patients who survived infarction. The rate of myocardial infarction or death was 8.0 per cent at six months and 21.6 per cent at a mean of 27.8 months of follow-up for patients who had infarction ruled out, as compared with 7.7 per cent at six months and 21.8 per cent at a mean of 27.8 months of follow-up for those who had a documented infarction during the initial hospitalization. Cardiomegaly, congestive heart failure, and angina after discharge from the hospital tended to increase the risk of morbidity and mortality in both groups. The patient hospitalized with acute ischemic chest pain without evolution of a myocardial infarction has a six to 24-month prognosis similar to that of the patient hospitalized with an acute infarction, and therefore requires similar diagnostic and therapeutic assessment.

The prehospital course of patients with chest pain: Analysis of the prodromal, symptomatic, decision-making, transportation and emergency room periods

Abstract In order to determine whether prehospitalization characteristics of patients with chest pain are useful in predicting their subsequent course, we analyzed the precoronary care course in 211 consecutive patients admitted because of suspected myocardial infarction. On the basis of serial electrocardiograms and enzymes, 61 patients had a definite myocardial infarction on admission, 30 patients evolved criteria for an infarction during hospitallzation, 102 patients had cardiac pain without infarction, and 18 patients were judged to have noncardiac pain. The mean patient delay from onset of chest pain to arrival at the hospital was 456 ± 703 minutes (median 210 minutes). The decision to seek medical help consumed a mean 307 ± 575 minutes of this delay, whereas transportation to the hospital required only a mean of 17 ± 49 minutes. Known heart disease, known stable angina and progressive unstable angina tended to prolong the patients decision to seek medical help. Of 140 patients who contacted a physician, 67 (48 per cent) were sent to the emergency room; whereas 71 had an additional mean 180 ± 436 minutes (median 38 minutes) of physician-advised delay consisting of office visits (59 patients), house call (five patients) and other attempted therapy (seven patients). The presence of prodromas or chest pain consistent with unstable angina was not significantly different in any patient group. We conclude that prodromas, although common, are not helpful in differentiating those with infarction from those without infarction among the patients hospitalized because of chest pain. Furthermore, the mean patient delay of over 6 hours and median delay of 3 12 hours indicates that this delay is the most immediate problem to be solved in order to decrease out of hospital mortality.

Randomized double-blind comparison of nifedipine and isosorbide dinitrate therapy in variant angina pectoris due to coronary artery spasm

Twelve patients were entered prospectively into a randomized double-blind study comparing the efficacy of nifedipine and isosorbide dinitrate (ISDN) in the treatment of variant angina pectoris due to coronary artery spasm. Using the diary technique, both anginal episodes and nitroglycerin tablets consumed were recorded during the pretrial, no drug period, and both active drug phases. During the baseline pretrial period, an average of 1.1 anginal episodes/day occurred with reduction to 0.28/day during nifedipine treatment and 0.39/day during ISDN treatment. Headache was the major side effect during ISDN treatment, occurring in 9 of 11 (81%) patients; and nonheart failure related pedal edema during nifedipine treatment, occurring in 4 of 12 (33%) patients. Intolerable side effects necessitating cessation of treatment occurred in two patients during nifedipine treatment and in three patients during ISDN treatment. Patients preferred nifedipine over ISDN because of increased efficacy and fewer uncomfortable side effects. We conclude that both nifedipine and ISDN are effective therapy for coronary spasm, but that nifedipine was more effective and was preferred by the majority of patients.

Patients admitted to the coronary care unit for chest pain: High risk subgroup for subsequent cardiovascular death

Approximately 300 persons a year who are admitted to the Stanford University Hospital coronary care unit because of prolong ischemic chest pain and transient S-T changes do not manifest evidence of a myocardial infarction during their hospital stay. In a retrospective study carried out in 170 such patients, follow-up data obtained during a mean of 17.9 months revealed rates of mortality from cardiovascular causes of 4.2 percent for 1 month, 10.1 percent for 1 year and 19.7 percent for the entire follow-up period. Ten (40 percent) of the 23 deaths that occurred were sudden and 13 were due to acute myocardial infarction or its complications. Another 21 patients had a nonfatal myocardial infarction during this follow-up period. The data confirm the impression that patients with suspected myocardial infarction who do not have an infarction in the coronary care unit are at high risk for cardiovascular deaths after hospital discharge. Efforts are under way to define further a high risk subgroup on the basis of clinical indications before discharge.

Prevention of cardiovascular events in variant angina by long-term diltiazem therapy

In 43 patients with variant angina, the cardiovascular event rate during diltiazem therapy was compared with that in an equal time period before initiation of therapy. Cardiovascular events, that is, myocardial infarction, sudden death and hospitalization for prolonged angina, were decreased significantly (p less than 0.01) during the initial 6 months and mean 19.6 months of therapy. Based on the binomial principle, there were 22 events during the mean 19.6 months before therapy and 2 events during the equal time period on therapy. No patient died during follow-up. The frequency of angina was decreased by 94%. Diltiazem was well tolerated by all patients and no patient had to discontinue therapy because of adverse effects. It is concluded that long-term diltiazem therapy reduces cardiovascular events in patients with variant angina.

Diltiazem for long-term therapy of coronary arterial spasm

The first 36 patients with coronary arterial spasm treated with diltiazem and followed up at the Stanford University Coronary Artery Spasm Clinic for 6 months or longer are described. There were 13 men and 23 women with a mean age of 50.2 years; the mean duration of angina was 36.1 months. All patients had angina at rest with a good or fail response to sublingual nitroglycerin. During a mean of 17.5 months of diltiazem therapy, the frequency of angina was reduced from a mean of 21.5 to 1.3 attacks/week. This 94 percent reduction in pain frequency occurred when either 240 or 360 mg of diltiazem was administered daily. Sixteen patients required the addition of isosorbide dinitrate to achieve a painfree state. Pain breakthrough occurred a mean of 1.7 times during the 17.5 month follow-up period but tended to be of short duration. Six patients had trace to 1+ pedal edema and no other adverse effects occurred. It is concluded that diltiazem is highly effective and well tolerated for the long-term prophylaxis and treatment of angina in patients with coronary spasm.

Long-term transtelephonic electrocardiographic monitoring in the detection and evaluation of variant angina

To facilitate the outpatient diagnosis of variant angina by documenting transient ST segment evaluation during chest pain, we studied the feasibility of transtelephonic ECG monitoring during angina episodes. Eight patients with known coronary artery spasm underwent simultaneous continuous ambulatory and transtelephonic ECG monitoring during a 24-hour period. Five patients (62%) had transient diagnostic ST segment shifts on both continuous ambulatory and transtelephonic monitoring. Another eight patients with coronary spasm underwent 24-hour continuous ambulatory monitoring and separate 14-day period of transtelephonic monitoring. The addition of this longer monitoring period provided diagnostic ST segment shifts in three patients. We conclude that transtelephonic monitoring in patients with suspected coronary artery spasm can provide important additional diagnostic information to continuous ambulatory monitoring, particularly in the patient with infrequent or predictable chest pain.

Application and safety of outpatient ergonovine testing in accurately detecting coronary spasm in patients with possible variant angina

We analyzed the results of 61 consecutive outpatient ergonovine provocation tests to determine the safety and efficacy of such outpatient testing for detecting coronary artery spasm (CAS). Criteria for outpatient testing included: clinical history suggestive of variant angina, noncritical coronary artery disease documented by coronary arteriography, normal exercise treadmill test, no symptomatic arrhythmias, and no history of recent myocardial infarction. All antianginal medications were tapered and stopped. Ergonovine maleate was given as a bolus at 3-minute intervals in consecutive doses of 0.05, 0.10, and 0.25 mg. A positive test was defined as chest pain accompanied by greater than 0.1 mV ST segment elevation of 12-lead ECG. If pain and ST-segment elevation occurred, intravenous and sublingual nitroglycerin were immediately administered for relief of myocardial ischemia. Of the 61 patients studied, 10 had positive tests; there were no complications. Follow-up the 51 patients with negative studies has not revealed cardiac etiology for their chest pain. We conclude that outpatient ergonovine testing is a safe and accurate diagnostic test for identifying CAS in a highly selected population of patients with possible variant angina when performed under carefully controlled conditions.

Long-term results of coronary artery bypass surgery for unstable angina: incidence of mortality, myocardial infarction, and angina resumption†

To determine if routine treadmill testing would be helpful in identifying patients at high risk for subsequent events, the first 81 patients to undergo coronary artery bypass0 surgery for unstable angina pectoris at Stanford University Medical Center were reevaluated at four intervals after surgery. Evaluations, including assessment of angina pectoris and a treadmill test, were done at mean times of 18,40, and 72 months after surgery. At a mean time of 90 months postoperatively, angina status was determined in survivors. The prevalence of angina rose from 19% during the first year to 53% during the fourth and fifth postoperative years. Cardiac deaths and myocardial infarctions were frequent during the first postoperative year, and were more frequent in patients with three‐vessel disease and those with one or more severely narrowed coronary arteries which were not bypassed. Cardiac events were rare between 12 and 36 months after operation; clinical and treadmill variables did not predict these events. During the fourth and subsequent postoperative years, the incidence of cardiac events increased. While the presence of stable angina pectoris was the clinical variable most useful prognostically, treadmill testing added additional independent prognostic information (p<0.0001). During the intervals between visits 1 and 2, and visits 2 and 3, cardiac events were ten times more frequent in persons with a maximal heart rate of 130 beats/min or less on the treadmill at 18 and 40 months.