Showing papers by "Eugene Braunwald published in 1983"

Studies of experimental coronary artery reperfusion. Effects on infarct size, myocardial function, biochemistry, ultrastructure and microvascular damage.

Abstract: The present report is a review of recent experimental studies in a canine model of acute coronary occlusion. The questions addressed were: (1) Does coronary reperfusion reduce myocardial infarct size? (2) What is the relationship between microvascular damage and hemorrhage and the development of myocardial necrosis? (3) What are the biochemical, functional and ultrastructural characteristics of reperfused tissue salvaged from necrosis? Coronary occlusion followed by reperfusion in the dog resulted in significant subepicardial salvage of myocardium if reperfusion was instituted before 6 hours of ischemia. Because ultrastructural evidence of microvascular damage was found only after irreversible damage to myocytes, and because gross hemorrhage after coronary reperfusion was confined to zones of myocardium that were already necrotic, it does not appear that hemorrhage should serve as a deterrent to reperfusing reversibly injured myocytes. Severely ischemic myocardium that had been salvaged by coronary reperfusion required several days before it returned to normal from biochemical, functional and ultrastructural standpoints.

Evaluation of a New Bipyridine Inotropic Agent — Milrinone — in Patients with Severe Congestive Heart Failure

Abstract: Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone. In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure. Significant increases occurred in cardiac index (from 1.9 +/- 0.1 to 2.9 +/- 0.2 liters per minute per square meter) and the peak positive first derivative of left ventricular pressure, with a slight increase in heart rate. Hemodynamic improvement was sustained during a 24-hour continuous infusion. Nineteen of the 20 patients subsequently received oral milrinone (29 +/- 2 mg per day) for up to 11 months (mean, 6.0 +/- 0.8), with sustained improvement in symptoms of heart failure. In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug. Four patients died after a mean of 4.8 months of therapy, and three patients with severe underlying coronary-artery disease and angina pectoris required additional antianginal therapy. No patient had fever, thrombocytopenia, gastrointestinal intolerance, or aggravation of ventricular ectopy. We conclude that milrinone shows promise for the longterm treatment of congestive heart failure.

Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based on analysis of 3,697 patients.

Abstract: Over a 34.5-month period, all admissions to 5 university hospital coronary care units were screened for eligibility for the Multicenter Investigation of the Limitation of Infarct Size (MILIS), an ongoing study of the effects of hyaluronidase, propranolol and placebo on myocardial infarct (MI) size. Of 3,697 patients with greater than or equal to 30 minutes of discomfort that was thought to reflect myocardial ischemia who were assessed for the presence or absence of certain electrocardiographic abnormalities at the time of hospital admission, the electrocardiogram was considered predictive of acute MI if greater than or equal to 1 of the following abnormalities was present: new or presumably new Q waves (greater than or equal to 30 ms wide and 0.20 mV deep) in at least 2 of the 3 diaphragmatic leads (II, III, aVF), or in at least 2 of the 6 precordial leads (V1 to V6), or in I and aVL; new or presumably new ST-segment elevation or depression of greater than or equal to 0.10 mV in 1 of the same lead combinations; or complete left bundle branch block. In the screened population, the diagnostic sensitivity of the electrocardiographic criteria was 81%, whereas the overall infarct rate in the total population screened was 49%. The diagnostic specificity of these entry criteria was 69% and the predictive value 72%.(ABSTRACT TRUNCATED AT 250 WORDS)

The contractile state as the major determinant in the evolution of left ventricular dysfunction in the spontaneously hypertensive rat.

Abstract: Female spontaneously hypertensive and normotensive rats were studied at 6, 12, 18, and 24 months of age to determine which characteristics of myocardial performance herald the onset of left ventricular dysfunction. Peak ejection fraction index was derived from measurements of peak stroke volume (in vivo volume loading) and passive pressure-volume relations. The myocardial stiffness constant (km, slope of the incremental modulus-stress relation, EINC = km sigma), chamber stiffness constant (kc, slope of the chamber stiffness-pressure relation, dP/dV = kcP), and left ventricular cavitary volume-to-wall volume ratio at 10 mm Hg) were calculated from the pressure-volume data and the contractile state was assessed from the ejection fraction index-afterload relations. In the normotensive rats, the myocardial stiffness constant was not affected by age, whereas, in the spontaneously hypertensive rats, the myocardial stiffness constant remained within normal limits until 18 months, at which time a significant increase in this index of myocardial stiffness occurred. Baseline and maximal cardiac indices and ejection fraction index of spontaneously hypertensive rats were normal from 6 to 18 months, but were markedly reduced at 24 months. This reduction in cardiac performance was associated with a decrease in the left ventricular chamber stiffness constant, i.e., kc. This decreased chamber stiffness, which occurred at a time when myocardial stiffness was increased, was due to a greater increase in cavity size than in myocardial stiffness. The left ventricular cavity-to-wall volume ratio of normotensive rats was not affected by age, whereas, in the spontaneously hypertensive rats, this ratio markedly declined by 18 months. The ejection fraction index-afterload relations i.e., a measure of the contractile state, of the 6- and 12-month-old spontaneously hypertensive rats were similar to those of the normotensive rats of all ages. However, a depression in the contractile state of the spontaneously hypertensive rats occurred at 18 months and was further depressed at 24 months. This abnormality of the contractile state was evident before the deterioration of cardiac performance, as reflected in a decrease in baseline and maximal cardiac indices, and dilation of the left ventricle occurred. The contractile state (ejection fraction index-afterload relation) is thus the most sensitive indicator of left ventricular dysfunction in spontaneously hypertensive rats.

Dose-dependent effects of short-term methylprednisolone on myocardial infarct extent, scar formation, and ventricular function.

Abstract: Etude faite chez le chien. Les doses eleves de methylprednisolone, mais pas les doses faibles, provoquent une cicatrice nettement moins epaisse, avec reduction de la fonction regionale, sans modification du contenu en collagene

Scar thinning due to ibuprofen administration after experimental myocardial infarction.

Abstract: Although much attention has been directed toward interventions which reduce myocardial infarct size, the effect of such agents on the healing phase of myocardial infarction is not well understood. The present study examines the effect of the nonsteroidal anti-inflammatory agent ibuprofen, previously demonstrated to be able to reduce infarct size, and of aspirin on the healing of experimentally produced myocardial infarcts. Thirty-nine anesthetized, open-chest dogs were subjected to proximal left anterior descending coronary artery occlusions for 6 weeks. Four groups of dogs were studied: (1) a control (untreated) group: (2) ibuprofen, 12.5 mg/kg intravenously 15 minutes and 6, 12, 18, and 24 hours after occlusion (high dose); (3) ibuprofen, 12.5 mg/kg intravenously 15 minutes and 3 hours after occlusion (low dose); (4) aspirin, 30 mg/kg intravenously 15 minutes and 3 hours after occlusion. The average thickness of the transmural scar and of the noninfarcted left ventricular wall was determined from multiple measurements of formalin-fixed left ventricular slices. The ratio of transmural scar to noninfarcted wall thickness was determined. In control animals the ratio was 0.87 with only 1 of 15 animals having a ratio

Cardiovascular reflexes stimulated by reperfusion of ischemic myocardium in acute myocardial infarction.

Abstract: Acute myocardial infarction (AMI), especially of the inferior left ventricular wall, where most cardiac receptors with vagal afferents that are stimulated during coronary occlusion are located, is commonly associated with reflex hypotension and sinus bradycardia. To determine whether reperfusion of an acutely ischemic area can activate cardiac reflexes, changes in the heart rate, arterial pressure and rhythm were correlated with the time course and location of intracoronary thrombolytic therapy in 41 patients with AMI. Of the 27 patients with successful reperfusion, 17 developed significant transient bradycardia and hypotension and one became tachycardic and hypertensive at the time of recanalization. Spontaneous reversion of the bradycardia and hypotension occurred definitely in six patients and possibly in more (nine reverted after atropine and two after fluids). A positive correlation existed between the changes in heart rate and blood pressure, in contrast to the usual inverse relationship when baroreceptors are stimulated. Two of the three patients in whom reperfusion was transient also developed hypotension and bradycardia. In contrast, all 11 patients with persistent occlusion demonstrated no reflex cardiovascular changes during intracoronary thrombolytic therapy. Thus, successful reperfusion in AMI stimulates cardioinhibitory and vasodepressor (Bezold-Jarisch) reflexes. These findings raise the possibility that the transient hypotension and bradycardia observed during AMI, particularly inferior MI, may sometimes reflect the occurrence of spontaneous reperfusion of the acutely ischemic myocardium.

Indomethacin-induced scar thinning after experimental myocardial infarction.

Abstract: We investigated the effect of indomethacin, a widely used nonsteroidal antiinflammatory drug, on the healing of myocardial infarction (MI). Experimental MI was produced in anesthetized, open-chest dogs by occluding the left anterior descending coronary artery. Ten dogs received indomethacin, 10 mg/kg i.v., and 11 received saline, 15 minutes and 3 hours after occlusion. After 6 weeks, the dogs were killed and their hearts were subjected to morphologic and biochemical analysis. The average thickness of the transmural scar and the noninfarcted left ventricular wall was measured at multiple sites in formalin-fixed left ventricular slices and the ratio of the thickness of the transmural scar to the noninfarcted wall determined. The average thickness of the noninfarcted wall was 8.80 +/- 0.19 mm (mean +/- SEM) in the control group and 8.44 +/- 0.26 mm in the indomethacin group (NS). The scar thickness was 7.24 +/- 0.64 mm in the control group and 3.56 +/- 0.40 mm in the indomethacin group (p less than 0.001). The ratio of scar to noninfarcted wall thickness was 0.83 +/- 0.07 in the control group and 0.43 +/- 0.04 in the indomethacin group (p less than 0.001). Scars in treated dogs did not differ from controls either by light microscopic histologic analysis or by analysis of hydroxyproline content per unit weight. We conclude that indomethacin results in marked scar thinning when given early after experimental MI.

Effects of coronary-artery bypass grafting on survival. Implications of the randomized coronary-artery surgery study.

Abstract: IN 1977 the Journal published the results of the Veterans Administration randomized trial of coronary-artery bypass grafting (CABG).1 In an accompanying editorial2 I stated: "This report confirms the widely held impression that CABG reduces the incidence and severity of angina, but finds no difference in the survival of almost 600 patients with chronic stable angina (excluding those with obstructive disease of the left main coronary artery) randomized into medically and surgically treated groups. . . ." Concern was also expressed about the steeply rising frequency with which the procedure was being performed (approximately 70,000 in 1977) and that despite the . . .

First ultra-short-acting beta-adrenergic blocking agent: its effect on size and segmental wall dynamics of reperfused myocardial infarcts in dogs.

Abstract: Beta-adrenergic blocking agents have an established role in the treatment of myocardial ischemia, but precipitation of cardiac failure or bronchospasm may restrict their use in some patients with acute myocardial infarction or in those undergoing coronary bypass surgery. ASL-8052 is a new cardioselective ultra-short-acting beta blocker which allows abolition of beta blockade within 16 minutes on termination of an intravenous infusion. An investigation was made of the effect of ASL-8052 on myocardial infarct size, regional myocardial wall function, and hemodynamic features during a 3-hour experimental occlusion of the left anterior descending coronary artery followed by 3 hours of reperfusion in dogs. Twenty-two dogs (10 control, 12 treated) were instrumented for the measurement of left ventricular (LV) pressure, the first derivative of left ventricular pressure (LV dP/dt), systolic and diastolic aortic pressure, and heart rate. Two pairs of ultrasonic crystals were inserted into a nonischemic segment and an ischemic marginal zone segment to obtain percent segment shortening. The area of necrosis was determined by tetrazolium staining and expressed as a percentage of the in vivo area at risk obtained by autoradiography. Dogs in the control group received saline solution; in treated dogs, a continuous infusion of ASL-8052 was begun 15 minutes after occlusion with a dose “titrated” to reduce the heart rate by approximately 20% (100 to 150 μg/kg/min). After 3 hours of reperfusion, the amount of myocardial tissue necrosis, as a function of the in vivo area at risk, was significantly lower in ASL-8052-treated (48 ± 7%) than in control (73 ± 6%) dogs (p

Cardiorenal hemodynamics and sodium excretion in rats with myocardial infarction

Abstract: The relation between left ventricular function and renal excretion of sodium (Na+) was studied in rats with myocardial infarction (MI) and varying degrees of left ventricular dysfunction. Three groups of rats were defined: 1) control sustained no infarct, 2) small to moderate infarcts involved 10-40% of the left ventricular circumference, and 3) large infarcts involved greater than 40%. In conscious rats, Na+ excretion was measured after administration of saline load by gavage. Four hours after the load, rats with large MI excreted less than one half the amount of Na+ excreted by control rats, whereas rats with small to moderate MI excreted an intermediate amount. In a second group of anesthetized rats, Na+ excretion, renal hemodynamics, and ventricular performance were determined before and after acute intravenous volume expansion with a balanced salt solution. Rats with small to moderate MI demonstrated minimal impairment in ventricular pumping ability but excreted less Na+ after volume expansion than did control rats. However, rats with large MI demonstrated marked impairment in left ventricular performance and exhibited the least natriuretic response to volume loading. Glomerular filtration rate and renal plasma flow failed to increase with volume expansion in both groups of rats with MI. Thus Na+ excretion in response to acute volume loading was diminished in rats with large MI and markedly impaired cardiac performance but was also reduced in rats with small to moderate MI and minimal changes in ventricular pumping capacity.

Coronary Reperfusion for the Treatment of Acute Myocardial Infarction: Postischemic Ventricular Dysfunction

Abstract: There has been recent interest in treating acute myocardial infarction with coronary reperfusion by fibrinolytic therapy. Experimental studies have shown that myocardial infarct size can be reduced by

A flow- and time-dependent index of ischemic injury after experimental coronary occlusion and reperfusion

Abstract: The purpose of the present study was to determine whether an ischemic index--expressed as the product of flow deprivation (FD) and the duration of occlusion (T), FD X T--correlated with biochemical and early morphologic alterations of the subendocardial myocardium and could predict ultimate development of irreversible injury after coronary reperfusion. Myocardial biopsy specimens for measurement of ATP and other purines and for ultrastructure studies were obtained in vivo during coronary occlusion in a canine model and were considered relative to development of necrosis after coronary reperfusion. FD X T correlated negatively with ATP content [ATP, nmol/mg of cardiac protein = 23.6 - 0.24(FD X T) + 0.0007(FD X T)2; r = -0.81] and with a semiquantitative early histologic index of damage (r = 0.70). Values of (FD X T) less than 18 were associated with reversible injury--i.e., complete salvage after coronary reperfusion. (FD X T) greater than 18 was associated with varying degrees of necrosis; necrosis was severe (78 +/- 12% of subendocardial biopsy specimens) when ATP less than 10 nmol/mg of protein and total purine pool was decreased by 50%. FD X T correlated with the eventual percentage of subendocardial necrosis (r = 0.85). Accordingly, as an index of ischemic injury, FD X T may be useful in assessing whether ischemic myocardial tissue will benefit from early restoration of blood flow to the ischemic area.

Topographic changes in the left ventricle after experimentally induced myocardial infarction in the rat

Abstract: The factors that determine the thickness of transmural myocardial infarcts are unknown. Therefore, the relation between the size and thickness of transmural infarcts in 67 rats 21 days after occlusion of the left main coronary artery was studied. On examination of histologic sections, infarct size was determined by planimetry and expressed as a percentage of the left ventricular (LV) area, and thickness was expressed as a percentage of noninfarcted ventricular septal wall thickness. The circumferential length of the infarcted ventricle was measured in millimeters, as well as the circumferential length of the noninfarcted ventricular septum. Septal wall thickness was similar in rats with transmural infarcts and in sham-operated rats. No significant correlation was observed between infarct size and thickness (r = 0.10) or between circumferential length of the infarct and infarct thickness (r = 0.17). However, large (greater than or equal to 20% of the left ventricle, n = 37) and small (less than 20% of the left ventricle, n = 30) infarcts which were similarly thin (37 +/- 1% and 34 +/- 2% of septal wall thickness, respectively) affected LV topography differently. Large infarcts resulted in a 23% greater loss of myocardium (p less than 0.001), greater expansion of the LV cavity (18 +/- 9 mm2 compared with 14 +/- 1 mm2 in small infarcts, p less than 0.005), and lengthening of the septal wall (7.2 +/- 1.1 mm and 6.7 +/- 1.0 mm in large and small infarcts, respectively [p less than 0.05], and 6.3 +/- 0.1 mm in shams). Increase in cavity area and septal length in infarcted ventricles suggested a volume overload hypertrophy, which at 3 weeks was nonetheless inadequate to provide as much normal muscle as was present in sham-operated rats. In an additional 9 rats with subendocardial infarctions (involving less than 75% of the LV wall from endocardium to epicardium), the LV walls were thicker (94 +/- 5% of septal wall thickness, compared with 35 +/- 1% for transmural infarcts, p less than 0.001) and an inverse correlation was observed between infarct size and thickness. In conclusion, neither the size of a transmural infarct in rat nor the circumferential length of infarction determines the thickness of the infarct; however, infarct size does affect LV topography by increasing LV cavity area and the length of the noninfarcted septal wall. Subendocardial infarcts result in less myocardial thinning than do transmural infarcts.

Systemic hemodynamic effects of leukotrienes C4 and D4 in the rat

Abstract: Although local administration of the sulfidopeptide leukotrienes into cutaneous and coronary vascular beds indicates that these naturally occurring metabolites of arachidonic acid are vasoconstrictors, their systemic administration has produced both pressor and depressor responses. The systemic hemodynamic effects of intravenous leukotriene C4 (LTC4) and leukotriene D4 (LTD4) were assessed in ether-anesthetized rats and compared with the effects produced by equimolar doses (2 X 10(-10) to 4 X 10(-8) mol/kg) of norepinephrine and angiotensin. Mean arterial pressure, right atrial pressure, and cardiac output (electromagnetic flowmetry) were recorded during bolus administrations of these vasoactive compounds. LTC4 and LTD4 had similar hemodynamic effects that were characterized by moderate pressure elevations produced by dose-dependent increases in total peripheral resistance, since cardiac output declined. Although the peak mean arterial pressure levels produced by LTC4 and LTD4 (135 +/- 7 and 129 +/- 5 mmHg, respectively) were less than those by norepinephrine (157 +/- 3 mmHg) and angiotensin (174 +/- 5 mmHg), the peak total peripheral resistance values of LTC4 and LTD4 (2.23 +/- 0.32 and 1.86 +/- 0.17 mmHg X ml-1 X min-1, respectively) were between those of the well-known vasopressors, norepinephrine (1.50 +/- 0.09) and angiotensin (2.72 +/- 0.41). The pressor response to LTC4 and LTD4 was less marked than that to norepinephrine and to angiotensin because of the concomitant reduction in cardiac output. These results indicate that LTC4 and LTD4 are systemic vasoconstrictors with potencies similar to those of norepinephrine and angiotensin.

Prevention of the development of heart failure and the regression of cardiac hypertrophy by captopril in the spontaneously hypertensive rat

Abstract: The spontaneously hypertensive rat (SHR) exhibits both a compensated phase of cardiac hypertrophy in which forward output is maintained despite persistently elevated systemic arterial pressures and a decompensated phase in which cardiac performance has deteriorated in spite of further hypertrophic growth. To determine whether chronic antihypertensive therapy prevents the development of heart failure and the progression of cardiac hypertrophy in SHR with advanced hypertension, captopril (2 g/l of drinking water), a converting enzyme inhibitor, was administered to 14 month old female SHR and normotensive American Wistar rats (NWR)for 10 months. The severe left ventricular hypertrophy of the 24 month old untreated SHR (4·37±0·2 mg/g v. 2·50 ± 0·06 mg/g, untreated NWR) was markedly reduced ( P <0·02) by captopril (3·01 ± 0· mg/g). Chronic therapy prevented the reduction of both baseline and maximal cardiac indices in SHR, but did not alter blood flow in NWR. Left ventricular dilatation was present in 24 month old SHR and, as peak stroke volume index was diminished, the ejection fraction index of the SHR was reduced. Captopril restored this index in SHR to normal. The relation of ejection fraction index and afterload (peak systolic wall stress) was depressed in untreated SHR, but was normal in treated SHR. Thus, chronic therapy with captopril prevented the development of severe cardiac dysfunction and produced a marked regression of cardiac hypertrophy in SHR with advanced hypertensive heart disease.

The Use of β-Blockers After Myocardial Infarction

Abstract: Several beta-blockers have now been shown to be effective in reducing total mortality during the extended recovery period after myocardial infarction. The rate of occurrence of reinfarction and sudden death is also reduced. While the exact mechanisms of this beneficial effect are unknown, it appears to result from a "class" effect, ie, secondary to beta-blockade, since neither cardioselectivity, intrinsic sympathomimetic activity, nor membrane-stabilizing activity appears to be requisite. The reduction in mortality is seen in all age groups, for all types of infarction, and in all risk groups. On the basis of presently available evidence, in patients without contraindication to beta-blockade, prophylactic treatment with beta-blockers should be initiated between one and four weeks after myocardial infarction. The dosage should be sufficient to blunt the heart rate response to exercise, and therapy should be continued for at least two years. The positive results of several well-designed and conducted studies have proved that the concept of secondary prevention is a valid one and should help to save thousands of lives in the coming decade. It is expected that ongoing investigations will determine the efficacy and safety of earlier institution of beta-blockade, including IV administration in the peri-infarction period. The effectiveness of secondary prevention with other agents, including calcium channel blockers, antiplatelet agents, anticoagulants, lipid-lowering drugs, antiarrhythmics, prostacyclin analogues, and thromboxane synthetase inhibitors, should be investigated further. Additional information is needed on the mechanisms by which beta-blockers reduce mortality, sudden death, and reinfarction, on whether specific beta-blockers and/or specific types of beta-blockers have the greatest benefit, and, as a result of further analysis from some of the studies already published, the effect of beta-blockade after myocardial infarction on angina, rhythm disturbances, lipid profile abnormalities, and the quality of life.

Enzymatic estimation of myocardial infarct size when early creatine kinase values are not available.

Abstract: Estimates of myocardial infarct (MI) size based on plasma creatine kinase (CK) are used widely for prognosis and in the assessment of therapy designed to salvage ischemic myocardium. However, if the initial plasma CK activity is elevated, MI size will be underestimated. To determine the impact of loss of early CK values on estimates of MI size and to develop a procedure to compensate for it, estimates of MI size based on complete and incomplete MB and total CK time-activity curves from 120 patients (experimental group) were compared. Estimates of MI size based on data inclusion intervals beginning at 24, 12, 8, and 4 hours before peak CK were 11, 14, 23, and 47% smaller than values based on complete CK curves, but the correlation was good between complete and incomplete estimates of MI size at any given interval, with r values ranging from 0.91 to 0.98. The derived correction factors were then prospectively applied to a new population (n = 25) with complete CK curves to compensate for purposely omitted early CK values. The corrected estimates of MI size were within 7% of those based on the complete CK curves. Similar results were obtained for transmural and nontransmural and anterior or inferior MI. Thus, if peak plasma CK is known, underestimation of MI size can be compensated for despite the unavailability of early CK values. Since greater than 90% of patients present before plasma CK has reached its peak (24 hours), MI size can be obtained in nearly all patients. Thus, being able to correct for unavailable early CK values makes MI size a more widely applicable endpoint for use in clinical trials and patient management.

Congestive heart failure: A propitious time for intensified research

Abstract: Chronic congestive heart failure is one of the most common serious illnesses, affecting an estimated 3 to 4 million Americans. Because the prognosis in most patients with heart failure is poor, life expectancy being measured in months or a few years, not only the prevalence but also the incidence of this condition is high. Heart failure causes great personal suffering and places enormous economic burdens on the patient, the family, and society at large. Cognizant of the importance of congestive heart failure as a medical problem, the Cardiology Program of the Division of Heart and Vascular Diseases of the National Heart, Lung and Blood Institute sponsored a Workshop on Congestive Heart Failure in Bethesda, Maryland in April 1981. The objective of the Workshop was to review important recent advances and to identify opportunities for research in this field. The Workshop was divided into 6 sections: Section I, Clinical Definitions and Current Clinical Studies, chaired by Jay N. Cohn, MD; Section II, Diagnostic Procedures for Evaluating Heart Failure, chaired by Arthur J. Moss, MD; Section III, Etiology, Biochemical, and Structural Changes in Heart Failure, chaired by L. Maximilian Buja, MD; Section IV, Research on the Physiology of Congestive Heart Failure, chaired by A. Clifford Barger, MD; Section V, Assessment of Clinical Treatment, Monitoring, and Surgical Intervention in Advanced Congestive Heart Failure, chaired by Benedict R. Lucchesi, MD; Section VI, Future of Clinical Investigation in Evaluating Treatment of Congestive Heart Failure, chaired by Michael B. Mock, MD. AIthough the proceedings of this Workshop were recently published, 1 it was considered desirable to summarize some of the major points that emerged.

Efficacy of nifedipine therapy in patients with refractory angina pectoris: significance of the presence of coronary vasospasm.

Abstract: Nifedipine is an effective antianginal agent, but its efficacy in patients with angina refractory to maximally tolerated conventional therapy has not been well studied. We reviewed the experience using nifedipine in an unblinded manner in 716 patients with refractory angina, all of whom underwent cardiac catheterization. Patients were treated with nifedipine when maximally tolerated conventional therapy was inadequate to control angina. Patients were divided into three mutually exclusive clinical groups based on the presumed pathophysiologic mechanism responsible for angina. Group I consisted of 389 patients with Prinzmetal's angina and coronary vasospasm documented by the observation of spontaneous angina with ST segment elevation and/or vasospasm observed during coronary angiography. Group II was composed of 292 patients with “mixed angina,” defined as those patients who exhibited evidence of both classic exertional angina as well as possible superimposed coronary vasospasm. None of these patients had documented coronary vasospasm or ST segment elevation with angina. Group III included 35 patients with classic stable exertional angina, without rest pain or ST segment elevation associated with episodes of ischemia. Angina frequency and nitroglycerin use were compared on conventional therapy before and after the addition of nifedipine. Mean duration of nifedipine therapy was 6.5 months. The addition of nifedipine (median dose 60 mg/day, range 10 to 200 mg) significantly decreased the mean frequency of angina attacks/week in group I from 14.4 to 3.0 (p