Robert J. Luchi

Comparison of medical and surgical treatment for unstable angina pectoris: results of a veterans administration cooperative study

We conducted a multicenter, randomized, prospective study comparing medical therapy alone with coronary-artery bypass surgery plus medical therapy in 468 men with unstable angina pectoris. Patients were entered in the study from June 1, 1976, to June 30, 1982. Among those assigned to surgery who received bypass grafts, operative mortality was 4.1 percent. Arteriography performed after one year of follow-up revealed that 74.8 percent of the grafts studied were patent. The cumulative rate of crossover from medical to surgical therapy after two years was 34 percent; the operative mortality among patients crossed over was 10.3 percent. Nonfatal myocardial infarction occurred in 11.7 percent of the patients treated surgically and 12.2 percent of those treated medically (no significant difference). Most of the nonfatal myocardial infarctions in the surgical group occurred in the perioperative period. Overall, the two-year survival rate computed by life-table analysis did not differ between the two groups. However, the curves reflecting mortality as a function of left ventricular ejection fraction were significantly different (P = 0.03); surgery was associated with a significantly reduced mortality among patients with lower ejection fractions. We conclude that patients with unstable angina pectoris have a similar outcome after two years whether they receive medical therapy alone or coronary bypass surgery plus medical therapy. However, patients with reduced left ventricular ejection fractions may have a better two-year survival rate after coronary bypass surgery.

Provocation of coronary artery spasm by the cold pressor test. Hemodynamic, arteriographic and quantitative angiographic observations.

In this study we attempted to determine if the cold pressor test, a known sympathetic reflexogenic stimulus, could precipitate coronary artery spasm. Thirty-five patients undergoing coronary arteriography for evaluation of chest pain syndromes were given the cold pressor test. During 1 minute of cold pressor stimulation, aortic systolic pressure increased 18.1 ± 9.7 mm Hg (mean ± SD) and heart rate did not change significantly. Focal coronary artery spasm was provoked in seven patients, each of whom had an atheromatous plaque at the site of spasm. Four of six patients with a precatheterization clinical diagnosis of variant angina (group 1) had coronary artery spasm, and two of the four had associated ischemic manifestations. Of 14 patients in whom classic angina (group 2) was diagnosed before cardiac catheterization, two manifested focal coronary spasm. One of 15 patients thought to have atypical chest pain (group 3) manifested spasm. There were no significant differences in baseline variables (aortic systolic or diastolic pressure, heart rate, double product and left ventricular end-diastolic pressure) or hemodynamic response (aortic systolic pressure, heart rate or double product) to cold pressor stimulation between patients in each group and between those who manifested spasm and those who did not. Ventricular ectopy and ventricular tachycardia developed in one patient but were readily reversed with intravenous nitroglycerin. Quantitative angiography showed that the luminal diameter of normal coronary segments significantly decreased in each group of patients in response to cold pressor stimulation, but this response was most pronounced in the variant angina group (-12.7 ± 11.5% from control in group 1, −5.1 ± 10.2% in group 2, and −7.9 ± 9.6% in group 3; p < 0.001 for each group). Patients who are prone to coronary spasm may represent one extreme of a spectrum of reactivity to a coronary vasoconstrictive stimulus. The cold pressor test can provoke focal coronary artery spasm in certain patients and may be a useful nonpharmacologic provocative screening test to aid in the diagnosis of this phenomenon.

The incidence and clinical implications of coronary artery spasm.

The total incidence of coronary artery spasm during coronary angiography has been reported to be between 0.26% and 0.93%. The rarity of this phenomenon has been invoked to minimize its clinical significance. Review of a one-year experience in our catheterization laboratory showed that coronary spasm occurred in eight of 274 coronary angiograms (2.93%). In three instances, spasm could not be ascribed to catheter tip irritation, and was considered to be spontaneous. Since multiple factors during coronary arteriography might inhibit the occurrence of coronary spasm, it is believed that the incidence of spontaneous spasm may be higher than can be documented during angiography. Coronary spasm may have important clinical significance in various chest pain syndromes and greater methodical attention should be directed toward this phenomenon.

Verapamil Pharmacodynamics and Disposition in Young and Elderly Hypertensive Patients: Altered Electrocardiographic and Hypotensive Responses

We studied verapamil pharmacodynamics and disposition in seven young, ten elderly, and seven very elderly hypertensive males. Maximal decrease in mean (+/- SD) blood pressure tended to be greater in the elderly (-13.5 +/- 5.9 mm Hg) and the very elderly patients (-15.9 +/- 9.6 mm Hg) compared with that in young patients (-7.3 +/- 4.2 mm Hg). Disparate effects on heart rate responses were noted with reflex tachycardia in young patients compared with decreases in heart rate among the elderly and very elderly. Sensitivity to verapamil-induced prolongation in electrocardiographic P-R interval was less in the very elderly, and maximal prolongation in P-R interval induced by verapamil was less in the elderly and very elderly. Verapamil disposition was also age related. Total verapamil clearance was decreased in elderly (10.5 +/- 3.5 mL/min X kg; p less than 0.05) and very elderly (8.0 +/- 4.1 mL/min X kg; p less than 0.01) when compared with that in young patients (15.5 +/- 4.5 mL/min X kg). Elimination half-life was prolonged in the elderly (7.4 +/- 3.3 h; p less than 0.01) and very elderly (8.0 +/- 1.2 h; p less than 0.01) compared with that in young patients (3.8 +/- 1.1 h). Our data indicate age- and hypertension-related physiologic changes result in predictable pharmacokinetic changes. However, the complex alterations in verapamil pharmacodynamic responses indicate an interaction between direct drug effects and age- and disease-related changes in hemodynamic and autonomic nervous system function.

Abnormal biochemistry in myocardial failure

The important subcellular systems involved in the regulation of intracellular calcium were studied in normal and in diseased heart muscle. These include mitochondria, fragments of sarcoplasmic reticulum, sodium, potassium adenosine triphosphatase and the tropomyosin-troponin system. Normal and pathologic tissues were obtained from human and animal models. In all specimens taken from areas in which a significant diminution of contractility was measured, one of the earliest defects was found in isolated fragments of sarcoplasmic reticulum. The rate of calcium released from the sarcoplasmic reticulum was decreased, compared to that in control preparations. When the severity of failing process increased, the rate of calcium binding by isolated fragments of sarcoplasmic reticulum was also attenuated. Alterations of intracellular pH may play a role in these early aberrations. Mitochondria isolated from severely failing hearts were defective with respect to respiration control and calcium accumulation. During “nonfailing” compensatory cardiac hypertrophy, mitochondria exhibited increased rates of respiration and no defect in oxidative phosphorylation. Another significant, albeit preliminary observation of an early defect in “pump failure” involved the tropomyosin-troponin system. Isolated, purified actomyosin from cardiac muscle exhibited a significant diminution in calcium sensitivity due to a defect in the tropomyosin-troponin system.

Hearing impairment in older adults: new concepts.

OBJECTIVE: To review present information about the epidemiology, etiologies, pathogenesis, evaluation, and quality of life aspects of hearing loss and to present an approach to rehabilitation for hearing loss in older adults.

Exercise-induced coronary arterial spasm: angiographic demonstration, documentation of ischemia by myocardial scintigraphy and results of pharmacologic intervention

Exercise-induced coronary arterial spasm is an infrequently recognized phemonemon whose mechanism and management are not well established. In two patients with reproducible exercise-induced S-T segment elevation and angina pectoris thallium-201 scintigraphy showed areas of reversible anteroapical hypoperfusion, and gated radionuclide ventriculography revealed anteroapical hypokinesia with a decrease in left ventricular ejection fraction at peak exercise. During coronary arteriography supine exercise provoked occlusive spasm of the left anterior descending coronary artery, which at rest had only minimal plaques. Consequently, treadmill testing was performed with five different pharmacologically provoked interventions: direct vasodilatation (nitrates), alpha adrenergic blockade (phenmoxybenzamine), beta adrenergic blockade (propranolol), calcium flux blockade (verapamil), and prostaglandin inhibition (indomethacin). Exercise-induced coronary arterial spasm, manifested as S-T segment elevation and angina, was prevented by nitrates, but was not eliminated by short-term oral administration of an alpha or beta blocking agent, a calcium antagonist or a prostaglandin inhibitor. Further, beta adrenergic blockade appeared to be detrimental. Thus, this study demonstrates (1) that coronary arterial spasm may be the underlying mechanism of at least some cases of exertional angina associated with transient perfusion deficits and left ventricular dysfunction, and (2) that it may be prevented by oral nitrates.

Quinidine Excretion in Aciduria and Alkaluria

Abstract Quinidine toxicity may develop unexpectedly when the urine becomes alkaline in disease or during alkalinizing therapy. Excretion of quinine, the optical isomer of quinidine, is known to be...

Medical compared with surgical management of unstable angina. 5-year mortality and morbidity in the Veterans Administration Study.

We evaluated medical in comparison to surgical plus medical (surgical) treatment of unstable angina using a prospective randomized protocol that stratified patients by clinical presentation and by invasive evaluation of left ventricular (LV) function. Clinical presentations were as follows--type 1: progressive or new onset angina relieved by medication; type 2: prolonged bouts of angina poorly or incompletely relieved by medication. Abnormal LV function was arbitrarily defined as ejection fraction less than 0.50 or LV end-diastolic pressure 16 mm Hg or more. Of 468 patients, 237 were assigned to medical and 231 to surgical therapy. There were 374 type 1 and 94 type 2 patients. LV function was normal in 334 and abnormal in 134 patients. Compared with results at 24 months, this 60-month follow-up study showed important differences in survival for patients with three-vessel disease: 75% for medical and 89% for surgical patients (p less than 0.02). The cumulative 5-year rate of repeat hospitalizations for cardiac reasons was less with surgical patients for either clinical presentation. For type 1, medical patients had a 56% rate, and surgical patients had a 42% rate (p = 0.004). For type 2, medical patients had a 62% rate, and surgical patients had a 43% rate (p = 0.05). Overall mortality did not differ between the two treatments, and this remained true in type 1 versus type 2 patients and in those with normal versus abnormal LV function. However, regression analysis of medical and surgical groups with ejection fraction as a continuous variable showed that mortality of medical patients depended on ejection fraction (p = 0.004), whereas the mortality of surgical patients did not (p = 0.76), and survival in the surgical group was higher in the lowest ejection fraction tercile-73% for medical and 86% for surgical patients, p = 0.03. We conclude that surgery improves survival in patients with three-vessel disease and leads to fewer subsequent hospitalizations for cardiac reasons. An impaired ejection fraction had an adverse impact on survival of medical patients but not on surgical patients, and mortality in surgical patients was improved compared with medical patients in the lowest ejection fraction tercile.

Congestive heart failure in the elderly

eart disease is a common cause of disability and death in older people. Of the various clinical syndromes with which heart disH ease presents, congestive heart failure (CHF) is one of the most familiar, so familiar indeed that for many physicians diagnosis and treatment are considered one of their simpler and more rewarding tasks. However, the diagnosis of CHF in its earliest stages is not always simple, and treatment, as measured by survival and frequency of recurrences, is far from satisfactory . CHF may be considered the result of a series of changes beginning with some form of cardiovascular stress (overload) which brings into play compensatory mechanisms, among which cardiac hypertrophy, activation of the sympathetic nervous system (SNS) and use of the Frank-Starling relationship are the most familiar. Continued employment of these compensatory mechanisms leads to another series of changes, “cardiomyopathy of overload,” which further compromises cardiac function and ultimately leads to the syndrome of CHF characterized by edema, dyspnea, limited exercise tolerance, reduced organ perfusion, systemic and pulmonary embolization, cardiac arrhythmias, and sudden death. In the older patient, agerelated changes in the cardiovascular system further impair cardiac compensatory mechanisms, thereby hastening the development of CHF. We will review the relationship between age and the incidence and prevalence of CHF to illustrate the importance of CHF in care of the elderly and discuss the implications of this relationship for the pathophysiology of CHF. Current recommendations for treatment will be discussed. Treatment is now directed against the individual components of the symptom complex and not the antecedent diseaseand age-related changes that produce CHF. Because these changes are still poorly understood, additional research is needed before treatment of CHF will be more effective.