Addition of angiotensin II receptor blockade to maximal angiotensin-converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure.

BACKGROUND: Incomplete suppression of the renin-angiotensin system during long-term ACE inhibition may contribute to symptomatic deterioration in patients with severe congestive heart failure (CHF). Combined angiotensin II type I (AT1) receptor blockade and ACE inhibition more completely suppresses the activated renin-angiotensin system than either intervention alone in sodium-depleted normal individuals. Whether AT1 receptor blockade with losartan improves exercise capacity in patients with severe CHF already treated with ACE inhibitors is unknown. METHODS AND RESULTS: Thirty-three patients with severe CHF despite treatment with maximally recommended or tolerated doses of ACE inhibitors were randomized 1:1 to receive 50 mg/d losartan or placebo for 6 months in addition to standard therapy in a multicenter, double-blind trial. Peak aerobic capacity (V(O2)) during symptom-limited treadmill exercise and NYHA functional class were determined at baseline and after 3 and 6 months of double-blind therapy. Peak V(O2) at baseline and after 3 and 6 months were 13.5+/-0.6, 15.1+/-1.0, and 15.7+/-1.1 mL. kg-1. min-1, respectively, in patients receiving losartan and 14.1+/-0.6, 14.3+/-0.9, and 13.6+/-1.1 mL. kg-1. min-1, respectively, in patients receiving placebo (P<0.02 for treatment group-by-time interaction). Functional class improved by at least one NYHA class in 9 of 16 patients receiving losartan and 1 of 17 patients receiving placebo. CONCLUSIONS: Losartan enhances peak exercise capacity and alleviates symptoms in patients with CHF who are severely symptomatic despite treatment with maximally recommended or tolerated doses of ACE inhibitors.

Hemodynamic and hormonal response to transdermal nitroglycerin in normal subjects and in patients with congestive heart failure.

The hemodynamic and hormonal responses to nitroglycerin administered transdermally in a gel-like matrix were evaluated in nine patients with severe congestive heart failure and in nine normal subjects. In normal subjects, peripheral vasodilation was accompanied by reflex sympathetic stimulation as reflected by an increase in heart rate and plasma norepinephrine. In patients with heart failure, nitroglycerin produced sustained hemodynamic effects that began 30 minutes after the application and fully persisted for at least 6 hours. A significant decrease in right and left ventricular filling pressures was associated with an increase in stroke index and a significant decrease in forearm and pulmonary vascular resistances. There was no change in heart rate and systemic arterial pressure or in plasma norepinephrine or plasma renin activity. After 24 hours, pressures had partially returned to control levels, but mean pulmonary artery pressure was still significantly lower than in the control period. After removal of the nitroglycerin, each patient exhibited a decrease in cardiac index and an increase, above the control values, in pulmonary and systemic arterial pressures and pulmonary, systemic and forearm vascular resistances. This transient rebound appeared to be unrelated to stimulation of the sympathetic or renin-angiotensin systems. Thus, transdermal absorption of this new form of nitroglycerin appears to provide a nitrate vascular effect that is sustained for 24 hours, but an endogenous vasoconstrictor effect may influence the hemodynamic response over the first 24 hours.

Abnormal neurohumoral response to nitroprusside infusion in congestive heart failure.

Vasodilator drugs produce tachycardia and an increase in circulating plasma norepinephrine in normal subjects. In contrast, heart rate does not change when the same drugs are given to patients with congestive heart failure. To assess if this difference could be related to a different reflex activation of the sympathetic nervous system, the response of plasma norepinephrine to nitroprusside infusion and to head-up tilt was studied in 5 normal subjects and in 46 patients with chronic congestive heart failure. Norepinephrine and heart rate increased significantly during both stimuli in normal subjects but were unchanged during nitroprusside infusion for the entire group of patients with heart failure, with considerable variability in individual responses. In 21 patients (Group I) norepinephrine increased during nitroprusside infusion, while in the remaining 25 (Group II) norepinephrine decreased. The hemodynamic response to nitroprusside was similar in the two groups, thus suggesting that the different changes in plasma norepinephrine could not be explained on the basis of a different hemodynamic response to the drug. Plasma norepinephrine also did not change significantly in Group II during tilt, although the decrease in intracardiac pressure and the increase in peripheral resistance were similar to those in Group I who increased norepinephrine normally by 56%. These data indicate that a subset of patients with severe ventricular dysfunction have an abnormal humoral, reflex sympathetic response to changes in arterial or intracardiac pressure, or both. The higher mortality in Group II suggests that this alteration in the sympathetic response may be a marker of the severity and prognosis of heart failure.

Frequent occurrence of occult pulmonary embolism from venous sheaths during endomyocardial biopsy.

To determine the frequency of occult right heart thromboembolism during endomyocardial biopsy, 51 cardiac transplant recipients undergoing routine endomyocardial biopsy were studied echocardiographically. Patients were randomized to two groups. In Group 1, the venous sheath was flushed between each biopsy attempt; in Group 2, it was flushed only at the time of initial placement. Right heart thromboemboli were identified in 18 (35%) of 51 patients. Seventeen (94%) of these 18 patients were in Group 2. Patients requiring more than six biopsy attempts had a significantly higher incidence of embolism. Other variables such as antiplatelet therapy, operator experience and total time of the procedure did not correlate with occurrence of thrombus. All right heart emboli were asymptomatic. These data demonstrate a high incidence of occult pulmonary embolism during uncomplicated routine endomyocardial biopsy. Meticulous flushing of the introducer sheath significantly reduces the incidence of thrombus formation in intravenous sheaths.

Trends in patient selection for heart transplantation.

OBJECTIVES: The purpose of this study was to review specific outcomes of patient referrals and the utility of selection criteria for heart transplantation at a single transplant center and to assess important trends over a 5-year period. BACKGROUND: Although patient selection criteria are important for the clinical success of heart transplantation and the optimal utilization of the limited supply of donor organs, there are few data regarding actual outcomes and whether selection criteria are facilitating the identification of the most appropriate patients. METHODS: We retrospectively reviewed 511 consecutive referrals of adult patients with heart failure from January 1, 1987 to December 31, 1991. Patients were followed up to one of five end points: 1) acceptance onto the transplant waiting list, 2) rejection from the transplant waiting list, 3) death, 4) referral to another program, and 5) still pending evaluation. RESULTS: Of the 511 referred patients, 221 (43%) were accepted onto the waiting list, 222 (43%) were rejected, 39 (8%) died before the evaluation was completed, 15 (3%) were referred to another program and 14 (3%) are still pending evaluation. The rates for acceptance and rejection each year ranged between 30% and 51% and there were no consistent trends in the acceptance/rejection ratio from 1987 to 1991. Of the 221 patients accepted onto the waiting list, 115 (52%) underwent transplantation, 50 (22%) died, 12 (5%) were removed from the list because of clinical improvement, 9 (4%) were referred to another program and 35 (16%) are still on the waiting list. The continuing shortage of donor organs resulted in a marked increase in the size of the waiting list from 12.6 patients in 1987 to 36.5 in 1991, as well as a marked increase in the time on the waiting list before transplantation. Over 5 years, 50 patients were considered "too well" for transplantation (23% of all rejections). Of these 50 patients, 43 (86%) are alive and 7 were lost to follow-up during a mean period of 28.6 months (range 4 to 62). All 12 patients who were taken off the active transplant list because of improvement in symptoms, ejection fraction or peak exercise oxygen consumption are alive with a mean follow-up period of 27.7 months (range 11 to 61). CONCLUSIONS: These data confirm the fact that transplant referrals are a selected group of patients with a high mortality rate, as 8% died before the evaluation could be completed and 22% died while waiting for a suitable donor organ. Furthermore, patient selection criteria are able to identify a small subset of patients with a low mortality risk as patients who were rejected because they were too well or taken off the list for clinical improvement have a reasonably good prognosis.

Effectiveness and safety of diltiazem or lisinopril in treatment of hypertension after heart transplantation. Results of a prospective, randomized multicenter trail.

OBJECTIVES: The purpose of this study was to determine the effectiveness and safety of diltiazem or lisinopril for treatment of hypertension after heart transplantation. BACKGROUND: Systemic hypertension is common after heart transplantation, and to date there are no randomized, prospective multicenter treatment trials. METHODS: Members of the Cardiac Transplant Research Database Group developed and implemented a prospective, randomized multicenter trial of the effectiveness and safety of diltiazem or lisinopril in the treatment of hypertension in cyclosporine-treated patients after heart transplantation. RESULTS: One hundred sixteen patients with hypertension (blood pressure > or = 140/90 mm Hg) after heart transplantation were randomized for > or = 3 months of treatment. Of 55 diltiazem-treated patients, 21 (38%) were responders (diastolic blood pressure < 90 mm Hg), 23 (42%) were nonresponders (diastolic blood pressure > or = 90 mm Hg), and 11 (20%) were withdrawn from the study. Of 61 lisinopril-treated patients, 28 (46%) were responders, 22 (36%) were nonresponders, and 11 (18%) were withdrawn. There was no difference in baseline characteristics or percent responders between the two groups. Systolic pressure decreased from 157 +/- 2.3 to 130 +/- 2.0 mm Hg (mean +/- 1 SEM) in the diltiazem-treated responders and from 153 +/- 2.1 to 127 +/- 2.7 mm Hg in the lisinopril-treated responders (p < 0.0001). Diastolic pressure decreased from 100 +/- 0.9 to 85 +/- 1.6 mm Hg in the diltiazem-treated responders and from 100 +/- 1.0 to 84 +/- 2.0 mm Hg in the lisinopril-treated responders (p < 0.0001). There were a total of 35 reported adverse events, 22 of which led to withdrawal of the patient from the study. All drug-related side effects were considered minor and resolved with discontinuation of the drug. CONCLUSIONS: These results indicate that both diltiazem and lisinopril are safe for treatment of hypertension after heart transplantation, although titrated monotherapy with either drug controlled the condition in < 50% of patients.

Stress-induced and sympathetically-mediated electrocardiographic and circulatory variations in the primary hyperkinetic heart syndrome.

As shown by the inotropic changes, the sympathetic discharge on the heart, is selectit syndrome. In the steady state the electrocardiogram shows flat, diphasic, or "tucked' T waves. Mental stimulation or isoproterenol, and, respectively, pain or beta blockade induce changes of the repolarization phase divergent from steady state. The former causes ST depression and deep T-wave inversion and the latter fully normalizes the repolarization phase. It is concluded that the electrical activity of the heart is directly influenced by the adrenergic drive in this disorder, and that different stressful factors can alter the repolarization phase in opposite ways in relation to the influence of the stimulus on the cardiac sympathetic tone.

Circulatory and renin responses in man to unilateral reduction of the renal perfusion pressure.

This study is concerned with the mechanisms of human renovascular hypertension. Unilateral partial occlusion of a renal artery was accomplished using a balloon-tipped catheter for occlusive angiography in seven normotensive and 17 primary hypertensive subjects. The renin and circulatory responses were studied during a 60 min reduction of the renal perfusion pressure (RPP) by 50% of control. This stimulus was considered to be safe and strong enough to produce a three to four-fold rise in plasma renin activity. It was observed that: a) systemic (arterial) renin was significantly raised at 5 min, reached a peak at 15 min and continued to be significantly higher than the baseline until the occlusion was removed; b) venous renin and venous arterial difference on the occluded side became elevated after the stimulus and remained so for the duration of the occlusion; c) renin release from the contralateral kidney became partially inhibited; d) in no case did systemic arterial pressure, heart rate or cardiac output change during the studies; e) renin and circulatory patterns were similar in normotensive and hypertensive subjects. It is concluded that in humans unilateral RPP reduction duplicates the renin pattern of the Goldblatt kidney, but does not duplicate the circulatory response. This evidence applies to a 1 h renal artery occlusion and does not exclude the possibility that renin may have a role in a rise in blood pressure following renal artery stenosis of longer duration.

Calcium uptake by cardiac sarcoplasmic reticulum in human dilated cardiomyopathy.

To determine the biochemical basis of abnormal diastolic properties in human dilated cardiomyopathy calcium uptake by the sarcoplasmic reticulum in ventricular homogenates of biopsy specimens from 21 patients with dilated cardiomyopathy was compared with that in nine normal controls. As a group, patients with cardiomyopathy had considerably lower calcium uptake rates (3.3(0.6) nmol.mg-1.min-1 vs 6.5(0.5) nmol.mg-1.min-1, p less than 0.01). Calcium uptake rates correlated modestly with resting haemodynamic values and significantly with plasma noradrenaline concentrations but not with plasma renin activity. These results show that sarcoplasmic reticulum function is impaired in human dilated cardiomyopathy and that this impairment is related both to the severity of haemodynamic dysfunction and to the extent of sympathetic nervous system activation.

Cyclosporine impairs the ability of human platelets to mediate vasodilation.

Cyclosporine causes various platelet abnormalities. Whether it affects the ability of platelets to mediate vasodilation is unknown. Platelets were isolated from healthy volunteers and 13 heart transplant patients on cyclosporine. When perfused through preconstricted normal rabbit carotid arteries, activated platelets from transplant patients failed to cause vasorelaxation, whereas normal platelets produced significant vasodilation (-4.0 +/- 1.9% versus 30 +/- 3% [P < .0001] change in vessel diameter, respectively). When normal platelets were exposed to cyclosporine in vitro, they lost their ability to cause vasodilation in a dose- and time-dependent fashion. However, when activated and perfused through quiescent, N omega-nitro-L-arginine-pretreated arteries, platelets from transplant patients and normal platelets caused similar degrees of vasoconstriction. The amount of adenosine triphosphate in the supernatant from activated cyclosporine-exposed and control platelets was similar (1.7 +/- 0.4 versus 1.5 +/- 0.3 mumol/L [P = NS], respectively). However, concomitant perfusion of activated platelets from transplant patients impaired acetylcholine-mediated, endothelium-dependent vasodilation but perfusion of normal platelets did not. Although cyclosporine-exposed platelets showed an impaired ability to produce vasorelaxation, supernatant from the same platelets caused near normal vasodilation. Human platelets exposed to cyclosporine have an impaired ability to mediated vasodilation. This is not due to increased platelet-mediated vasoconstriction or a decrease in the release of platelet-derived nucleotides but rather to a short-acting compound released by cyclosporine-exposed platelets that interferes with endothelium-dependent vasodilation.

Antihypertensive action of propranolol in man: lack of evidence for a neural depressive effect.

The hypothesis that a neural depressive action is related to the antihypertensive effects of beta blockers has been evaluated in 14 essential hypertensive male patients through the circulatory response to noxious stimuli. The pressor reaction to mental arithmetic was primarily mediated by cardiac stimulation (beta receptors activation), that to cold by vasoconstriction (alpha receptors activation). Arithmetic and cold were tested to separate the effects of peripheral beta blackade from possible neural and other influences. After propanolol (320 mg per day for 3 wk): (1) The baseline pressure was reduced; (2) appearance, peak, and disappearance time of the circulatory reaction to either stimulus was not altered; (3) the pressor effect of arithmetic was decreased in an extent proportional to the reduced rise of cardiac output; and (4) pressure during cold reached the pretreatment levels through an augmented increase of vascular resistance. Our findings indicate that propranolol depresses only the circulatory reactions mediated through beta receptors activation and provide no evidence of effects other than beta blockade.

Nifedipine, a new antihypertensive with rapid action.

Oral (17 cases) or sublingual (9 cases) administration of nifedipine (10 mg), a new coronary dilator, induced a prompt and large pressure reduction in patients with severe primary hypertension. Pressure started to fall within 20 and 5 min after oral and sublingual administration, respectively, and reached the lowest levels in the next 10 min. Maximal mean arterial pressure reduction averaged 36 mm Hg; 120 min after the drug, mean arterial pressure was diminished by 19.5% of control. The hypotension was mediated through diminished peripheral resistance associated with rise of cardiac output and pulse rate. Nifedipine was also administered siblingually in 3 cases with hypertensive encephalopathy and acute left ventricular failure with average systemic and pulmonary arterial pressures from 307/164 and 91/55 mm Hg, respectively, which fell to 237/115 and 68/35 mm Hg 15 min after 10 mg of the drug, and were further reduced to 176/89 and to 47/19 mm Hg by an additional 10 mg.

Acute hemodynamic and hormonal response to indoramin in congestive heart failure.

Acute hemodynamic and hormonal responses to a single dose of indoramin, an alpha 1-antagonist, were evaluated in 11 subjects with severe chronic congestive heart failure. A hemodynamic effect began within 1 hr of indoramin and persisted during the 6 hr of hemodynamic monitoring. Decreased right and left ventricular filling pressures were associated with increased stroke index and decreased pulmonary and systemic vascular resistances. Heart rate did not increase despite a fall in systemic arterial pressure. Forearm blood flow, forearm venous capacitance, and plasma norepinephrine levels were unchanged, whereas plasma renin activity rose from 12.7 +/- 17.4 to 16.6 +/- 20.4 ng/ml/hr. The only side effect was drowsiness in five of the 11 subjects. Our data demonstrate the acute effectiveness of indoramin in reducing ventricular preload and systemic vascular resistance in heart failure.

Clinical use of a calcium antagonistic agent (nifedipine) in acute pulmonary edema.

Nifedipine induces vascular smooth muscle relaxation through a calcium antagonistic action. The possibility of clinical use of the drug as a ventricular unloading agent has been explored in this study. In patients with hypertensive (seven cases), primary (seven cases) or rheumatic (aortic insufficiency five cases, mitral regurgitation five cases) cardiac disease, nifedipine, administered in a single sublingual dose (10 mg), relieved acute pulmonary edema. Circulatory variations from control were the following: decrease of systemic and pulmonary arterial pressures, and of vascular resistances, of pulmonary wedge pressure, of left ventricular diastolic and systolic dimensions (echocardiography); increase of cardiac and stroke index, of left ventricular mean rate of circumferential fiber shortening, of left and right mean pre-ejection delta P/delta t and mean rate of ejection; improvement of forward output in primary and rheumatic disease. Nifedipine benefits acute congestive heart failure by sustained fall of both preload and afterload and, possibly, by an enhanced contractility. It seems to have an appropriate indication in cases in which left ventricular afterload reduction is desirable.

Negative influences of ascites on the cardiac function of cirrhotic patients.

Right and left ventricular function was evaluated in 21 men with cirrhosis and tense ascites during staged removal of ascitic fluid. During paracentesis it was observed (1) that there was a significant increase in cardiac output, stroke volume, right and left ventricular stroke work and mean rate of systolic ejection; (2) that up to a certain stage of drainage (about 5,000 ml), there was a relationship between the amount of fluid removed and the intraabdominal and right atrial pressures and (3) that there was a direct relationship between improvement of cardiac function and normalization of right atrial pressure. It is believed that the increased intra-abdominal hydrostatic pressure acting upon the diaphragm affects the intrathoracic pressure to such an extent that the transmural filling pressure of the heart is reduced, and the mean pressure and respiratory pulsations of the right atrium increased, all of which impede venous return. Improved cardiac function during paracentesis appears to be due to an augmented filling of the heart and to a larger venous return.

Hemodynamic and regional blood flow response to captopril in congestive heart failure.

In 19 patients with moderate to severe congestive heart failure the over-all hemodynamic response to captopril was compared with its effect on regional blood flow. Ninety minutes after administering a single dose of captopril (25 to 150 mg), right atrial pressure decreased from 6.1 +/- 6.1 to 3.2 +/- 5.1 mm Hg (p less than 0.001), pulmonary artery pressure from 33.1 +/- 8.3 to 26.5 +/- 9.1 mm Hg (p less than 0.001), pulmonary capillary wedge pressure from 22.4 +/- 6.2 to 15.2 +/- 7.4 mm Hg to (p less than 0.001), mean arterial pressure from 77.2 +/- 8.0 to 66.5 +/- 13.7 mm Hg (p less than 0.001), and systemic vascular resistance from 1,630 +/- 503 to 1,233 +/- 443 dyne-s-cm-5 (p less than 0.001), and cardiac index increased from 2.0 +/- 0.6 to 2.4 +/- 0.7 l/minute/m2 (p less than 0.001). Despite the significant increase in cardiac index there was no increase in either hepatic blood flow (203 +/- 212 to 142 +/- 101 units, N.S.) or forearm blood flow (2.2 +/- 0.9 to 2.2 +/- 1.0 ml/100 g per minute, N.S.) after captopril. Similarly, the global reduction in systemic vascular resistance was not accompanied by a reduction in either hepatic vascular resistance (0.93 +/- 0.90 to 0.83 +/- 0.69 units, N.S.) or forearm vascular resistance (41.3 +/- 18.4 to 34.9 +/- 12.4 mm Hg/ml/100 g per minute, N.S.). The over-all improvement in hemodynamics that is seen when captopril is given to patients with severe heart failure does not apply uniformally to all vascular beds. The heterogeneous response reflects the variable vasoconstrictor part played by the renin-angiotensin system in regulating flow to individual regional circulations.

Angiotensin converting enzyme inhibitors in congestive heart failure. Overview in comparison of captopril and enalapril.

In this study, the use of enalapril and captopril is compared in the treatment of congestive heart failure. Although both drugs act on the renin-angiotensin system via converting enzyme inhibition, their different chemical structures may dispose them to different pharmacologic and physiologic activity. Both drugs exert a vasodilator effect, with reduction of left and right ventricular filling pressures and aortic impedance. In short-term hemodynamic studies, the onset of action and peak effect are earlier with captopril. Enalapril has a much more gradual onset and longer duration of action. Both drugs have a shallow dose-response curve and both produce comparable hormonal changes: an increase in plasma renin activity and a decrease in aldosterone levels. Captopril also increases prostaglandin production. Long-term efficacy trials have demonstrated symptomatic improvement in patients given captopril and those receiving enalapril who were also receiving digitalis and diuretics. Baseline hemodynamics may not predict long-term improvement. There are few adverse effects for the two drugs, but their incidences differ, suggesting a relationship to chemical structure. Recent studies in congestive heart failure suggest a reduction in mortality with various drug regimens.

Effects of orthotopic heart transplantation on sympathetic control mechanisms in congestive heart failure.

Abnormal sympathetic nervous system activity in severe congestive heart failure (CHF) was studied in 14 patients before and 3 to 6 months after orthotopic heart transplantation. Before transplantation plasma norepinephrine (NE) levels at rest were elevated (909 +/- 429 pg/ml, p less than 0.01 compared with normal, 185 +/- 60 pg/ml). No reflex activation of the sympathetic nervous system was seen with infusion of sodium nitroprusside despite a significant decrease in arterial pressure. The response to orthostatic tilt also was blunted in the patients before transplantation. Exercise capacity was reduced in these patients and plasma NE increased promptly at low exercise loads. After cardiac transplantation plasma NE levels returned to normal (319 +/- 188 pg/ml) and the sympathetic response to the stresses of orthostatic tilt (320 +/- 196 to 419 +/- 197, p less than 0.002) and nitroprusside infusion (255 +/- 94 to 555 +/- 130, p less than 0.001) normalized within 6 months after transplantation. Exercise capacity increased and the increase in plasma NE levels at various exercise loads was reduced for any given workload. Therefore, abnormal adrenergic activity in patients with severe CHF results mostly from the reduction in left ventricular pump function and is reversible if adequate pump function is restored.

Cardiac load and function in hypertension. Ultrasonic and hemodynamic study.

On the basis of echocardiographic measurements, 46 patients with established, uncomplicated primary hypertension (diastolic pressure = 100 mm Hg) were classified as: those with a normal-sized heart (Group I, 13 patients); those with left ventricular concentric hypertrophy (Group II, 19 patients); and those with left ventricular hypertrophy and enlargement (Group III, 14 patients). Eighteen age-matched healthy subjects were investigated as the controls. The function of both the left and right ventricle, evaluated by the stroke index-filling pressure relation and by the mean rate of ejection, was maintained in Group I, augmented in Group II and reduced in Group III, in comparison with the controls. Left ventricular mean rate of circumferential fiber shortening (Vcf) was normal in Group I, significantly augmented in Group II and definitely reduced in Group III. It could not be established whether the divergent variation from normal of the Vcf in Groups II and III reflected opposite changes in ventricular contractility or in afterload (wall stress during ejection), or both. However, the parallel functional pattern of the right and left ventricle in these two groups suggests a functional interdependence of the two sides which cannot be interpreted in terms of afterload but is best explained by changes in the contractile state of the whole heart.

Repetitive myocardial ischemia of Prinzmetal type without angina pectoris.

In a patient with a normal electrocardiogram, normal treadmill exercise test, normal coronary arteriogram and no symptoms to suggest angina pectoris, continuous monitoring during several days exhibited repetitive (one to two per hour) S-T segment elevations in the precordial electrocardiographic leads and hemodynamic changes typical of Prinzmetal's angina (reduction in arterial pressure and cardiac index and increase in systemic peripheral resistance and pulmonary wedge pressure). This case demonstrates that electrical and dynamic cardiac alterations of Prinzmetal's angina can occur even in the absence of angina pectoris.