Abnormal regional myocardial flow in myocardial bridging of the left anterior descending coronary artery

A patient with angina pectoris, myocardial bridging of the left anterior descending coronary artery and otherwise normal coronary arteries is presented. Regional myocardial blood flow was studied with the thermodilution technique. Atrlal pacing of the heart at a rate of over 140/min reproduced the anginal syndrome, with S-T segment depression in the electrocardiogram. There was a transient decrease in great cardiac vein flow during rapid pacing with a simultaneous increase in total coronary sinus flow. The study demonstrates that in this patient, a myocardial bridge was associated with decreased blood flow to the area perfused by the bridged artery with a concomitant increase in coronary sinus flow as the pacing rate was increased from 96 to 150 and 180/min.After administration of nitroglycerin, the bridging effect was more accentuated on angiography; pacing-induced tachycardia was associated with similar changes in great cardiac vein and coronary sinus flows with less S-T segment depression in the electrocardiogram and chest pain of milder intensity.     

Spectrum of exercise thallium-201 myocardial perfusion imaging in patients with chest pain and normal coronary angiograms.

Twenty-seven consecutive patients with chest pain and no significant obstructive coronary lesions on arteriography were studied with thallium-201 myocardial imaging during exercise and at rest. Fifteen of the patients had typical and 12 atypical angina pectoris. All underwent treadmill exercise electrocardiographic testing; the results were abnormal in 10 patients (37 percent), normal in 14 (52 percent) and uninterpretable in 3 (11 percent). The exercise and resting thallium-201 myocardial images were normal in 23 patients (85 percent); the results of exercise testing were normal in 12 of these patients, abnormal in 8 and uninterpretable in 3. Four patients had a perfusion defect on exercise thallium-201 myocardial imaging; the defect filled in by 4 hours in two patients but persisted in the other two. In contrast, when thallium-201 myocardial imaging was performed in 28 consecutive patients with angiographic coronary artery disease, only 5 patients (16 percent) had normal exercise and resting thallium-201 myocardial images. Therefore, thallium-201 myocardial imaging offers a more effective means of identifying patients with chest pain and no obstructive coronary artery disease than the clinical history or the exercise electrocardiographic test, or both. However, 15 percent of these patients will have abnormal exercise thallium-201 myocardial images because of factors that have not yet been identified.     

Provocation of myocardial ischemic events during initiation of vasodilator therapy for severe chronic heart failure: Clinical and hemodynamic evaluation of 52 consecutive patients with ischemie cardiomyopathy

Although hydralazine provokes myocardial ischemie events in hypertensive patients not in heart failure by producing reflex tachycardia, the frequency of and mechanisms underlying ischemie events when this drug is administered as a vasodilator agent to patients with heart failure is unknown. The responses to hydralazine in 52 consecutive patients with severe chronic heart failure secondary to coronary artery disease were reviewed. Twelve patients (23 percent) had 16 ischemie events during the initial administration of hydralazine (angina at rest in 12 and myocardial infarction in 4); these generally occurred in the absence of significant tachycardia and hypotension. Thirty-five of the 52 patients received nitroprusside (8 of whom had ischemie events with hydralazine), but this drug provoked ischemia in only 1 of the 35 although it resulted in greater decreases in systemic arterial pressure than occurred with hydralazine. In patients with an ischemie event only with hydralazine, left ventricular filling pressure decreased 14.6 mm Hg with nitroprusside but only 3.9 mm Hg with hydralazine (probability [p] < 0.01). Provocation of ischemia with hydralazine may therefore be due to the relative preservation of elevated left ventricular preload with this drug, since ischemie events are not common with nitroprusside despite greater decreases in systemic pressures.     

Relation between serum sodium concentration and the hemodynamic and clinical responses to converting enzyme inhibition with captopril in severe heart failure

The relation between pretreatment serum sodium concentration and the early and late effects of captopril was examined in 77 consecutive patients with severe chronic heart failure, in whom cardiac catheterization was performed during initiation of treatment and after 2 to 8 weeks. Two groups of patients were defined: 37 patients had hyponatremia (serum sodium less than 135 mEq/liter, group A) and 40 patients had a normal serum sodium concentration (greater than or equal to 135 mEq/liter, group B). With first doses of captopril, patients in group A showed more marked hemodynamic responses than did patients in group B (p less than 0.02). The changes in mean arterial pressure and left ventricular filling pressure seen with first doses of the drug varied linearly and inversely with the pretreatment serum sodium concentration (r = -0.58 and r = -0.53, respectively); this was likely related to the finding that, before administration of captopril, the serum sodium concentration varied linearly and inversely with the logarithm of the plasma renin activity (r = -0.78). However, the pretreatment serum sodium concentration did not predict the long-term hemodynamic or clinical responses to converting enzyme inhibition. Symptomatic hypotension occurred early in the course of therapy (within 24 hours of initiating captopril therapy) in 9 (12%) of the 77 patients; 8 of these 9 had severe hyponatremia (serum sodium less than 130 mEq/liter) and comprised 53% of the 15 patients in our study with such low serum sodium concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Verapamil-induced polymorphous ventricular tachycardia

A 31 year old woman who developed an atypical ventricular tachycardia after administration of intravenous verapamil for control of a recurrent supraventricular tachycardia is presented. Possible explanations for the observed arrhythmia, polymorphous ventricular tachycardia, are discussed. Verapamil must be considered one of the pharmacologic agents that can cause this arrhythmia.     

Failure of low doses of amrinone to produce sustained hemodynamic improvement in patients with severe chronic congestive heart failure

Although amrinone produces acute hemodynamic improvement in patients with severe chronic congestive heart failure (CHF), it has not produced clinical benefits in long-term controlled trials. To determined if the administration of subtherapeutic doses of amrinone may account for its lack of efficacy in these studies, the dose requirements of the drug were investigated in 30 patients with severe CHF. Doses of 100 mg of oral amrinone produced moderate increases in cardiac index (0.35 liters/min/m2) and decreases in pulmonary capillary wedge pressure (6.8 mm Hg) and systemic vascular resistance (16%) (all p less than 0.01); these effects, however, were short-lived (less than 2.5 hours). Doses of 200 mg of oral amrinone produced marked increases in cardiac index (0.56 liters/min/m2) and substantial decreases in left ventricular filling pressure (9.9 mm Hg) and systemic vascular resistance (30%) (all p less than 0.01), and these effects persisted for longer than 4 hours. Only 4 patients showed hemodynamic responses with 100 mg of the drug that were sufficiently marked and long-lasting to merit chronic therapy, whereas 28 patients had such a response with the 200-mg dose. When 200 mg of amrinone was administered orally every 8 hours, sustained hemodynamic benefits were seen for 48 hours. However, 16 of 22 patients who received 600 mg of the drug daily for more than 1 week had intolerable adverse reactions that required drug withdrawal. In conclusion, hemodynamically effective doses of amrinone (600 mg/day) cannot be tolerated for long periods by most patients with severe chronic CHF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrocardiographic and coronary arteriographic correlations during acute myocardial infarction

One hundred fifty-two patients underwent cardiac catheterization and coronary arteriography within 6.3 ± 6.0 hours from the onset of acute myocardial infarction (AMI). All had standard 12-lead electrocardiograms recorded within 1 hour of cardiac catheterization. The electrocardiographic abnormalities present were correlated with the infarctrelated artery as determined by coronary arteriography. ST-segment elevation was the most common finding in patients with the left anterior descending (LAD) or right coronary artery as the infarct-related artery. ST-segment depression was the most common abnormality in patients with the left circumflex (LC), artery as the infarct-related artery. A classic pattern of anteroseptal AMI was seen in 93% of all patients with the LAD as the infarct-related artery. A classic pattern of inferior AMI was seen in 53% of patients with right or LC narrowing taken as 1 group. The pattern of true posterior and isolated lateral wall AMI in the absence of classic changes in the inferior leads was highly specific and predictive of LC narrowing. In contrast, the pattern of an inferior wall AMI, in the absence of true posterior or lateral wall changes, was highly specific and predictive of right coronary artery narrowing. Fifty-six percent of patients with LC artery as the infarct-related artery presented with non-classic electrocardiographic abnormalities. The electrocardiographic patterns in patients with subtotal occlusions were similar to those of patients with total occlusions. Thus, the electrocardiogram obtained in the first few hours of AMI is reliable in localizing the LAD as the infarct-related artery. Certain patterns are specific but not sensitive in localizing the right coronary artery as opposed to the LC artery as the infarct-related artery. Presentation with signs and symptoms of AMI and a nonclassic electrocardiogram is suggestive of LC narrowing.     

Septal myocardial perfusion imaging with thallium-201 in the diagnosis of proximal left anterior descending coronary artery disease

The use of myocardial perfusion imaging (MPI) to identify obstructive coronary disease of the left anterior descending coronary artery proximal to the first septal perforator (prox LAD) was studied in 60 patients. Perfusion of the septum and anteroapical areas with thallium-201 injected during exercise was compared to results of coronary arteriography. Septal MPI defect was found in 92.3% of patients with obstruction of the proximal LAD, 27.7% of patients with obstruction of LAD distal to first septal perforator, 0% in patients with obstructions involving right or circumflex arteries, and in 10.5% of patients without coronary disease. Anteroapical MPI defects were found with similar frequency in the three groups with obstructive coronary disease. Septal MPI defect had a sensitivity of 92.3% and specificity of 85.4% in the diagnosis of proximal LAD disease. Normal septal perfusion with thallium-201 virtually excluded proximal LAD disease.     

Efficacy of captopril in low-renin congestive heart failure: importance of sustained reactive hyperreninemia in distinguishing responders from nonresponders

To determine the efficacy of converting-enzyme inhibition in patients with low-renin congestive heart failure (CHF), the long-term hemodynamic and clinical responses to captopril were evaluated in 26 consecutive patients with severe, chronic CHF whose pretreatment plasma renin activity (PRA) was less than 2 ng/ml/hour. After 2 to 8 weeks of continuous treatment with captopril, 14 patients (54%) showed long-term hemodynamic benefits, of whom 13 (50%) improved clinically by at least 1 New York Heart Association functional class. To distinguish responders from nonresponders, patients were grouped based on the presence or absence of sustained reactive hyperreninemia (PRA during chronic therapy greater than 4 ng/ml/hour). After 2 to 8 weeks of therapy with captopril, 14 patients had sustained reactive hyperreninemia. Their cardiac index increased by 0.33 liters/min/m2 (p less than 0.01), left ventricular filling pressure decreased by 12.6 mm Hg (p less than 0.001), mean right atrial pressure decreased by 4.9 mm Hg (p less than 0.001) and systemic vascular resistance decreased by 529 dyne s cm-5 (p less than 0.001). Twelve of these 14 patients improved clinically. Twelve other patients had no reactive increase in PRA, and these patients showed no significant improvement in any hemodynamic variable after 2 to 8 weeks of treatment with captopril; only 1 of the 12 patients improved clinically (p less than 0.001 between groups). The 2 groups were otherwise similar with regard to pretreatment demographic, hemodynamic and hormonal variables.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic and clinical significance of the pulmonary vascular response to long-term captopril therapy in patients with severe chronic heart failure

Exercise capacity in patients with left heart failure is closely related to the performance of the right ventricle and the pulmonary circulation. To determine the significance of changes in pulmonary resistance during long-term vasodilator therapy, hemodynamic studies were performed before and after 1 to 3 months of treatment with captopril in 75 patients with severe chronic left heart failure. Patients were grouped according to the relative changes in pulmonary and systemic resistances during long-term therapy: patients in Group I (n = 24) showed greater decreases in pulmonary arteriolar resistance (PAR) than in systemic vascular resistance (SVR) (% delta PAR/% delta SVR greater than 1.0), whereas patients in Group II showed predominant systemic vasodilation (% delta PAR/% delta SVR less than 1.0). Despite similar changes in systemic resistance, patients in Group I showed greater increases in cardiac index, stroke volume index and left ventricular stroke work index (p less than 0.01 to 0.001) but less dramatic decreases in mean systemic arterial pressure (p less than 0.02) than did patients in Group II. Despite similar changes in left ventricular filling pressure, patients in Group I showed greater decreases in mean pulmonary artery and mean right atrial pressures (p less than 0.02 to 0.01) than did patients in Group II. Pretreatment variables in Groups I and II were similar, except that plasma renin activity was higher (8.7 +/- 2.1 versus 3.0 +/- 0.6 ng/ml per h) and serum sodium concentration was lower (133.1 +/- 0.9 versus 137.1 +/- 0.6 mEq/liter) in Group II than in Group I (both p less than 0.05). Both groups improved clinically after 1 to 3 months, but symptomatic hypotension occurred more frequently in Group II than in Group I (36 versus 8%) (p less than 0.005). These findings indicate that changes in the pulmonary circulation modulate alterations in both right and left ventricular performance during the treatment of patients with left heart failure. Hyponatremic patients are likely to experience symptomatic hypotension with captopril because they are limited in their ability to increase cardiac output as a result of an inadequate pulmonary vasodilator response to the drug.     

Hemodynamic and clinical effects of combined verapamil and propranolol therapy in angina pectoris

Because of their common negative chronotropic and inotropic effects, combined therapy of beta-adrenergic blocking drugs and calcium channel antagonists has long been feared to produce synergistic cardiodepressant effects. To evaluate whether such fears are justified when such therapy is used in patients with angina pectoris, five hemodynamic and clinical studies were reviewed. These studies indicated that in patients with preserved ventricular function treated with low or moderate doses of propranolol, verapamil produced little change in cardiac performance; this finding was not significantly different from the effects of verapamil in the absence of beta-blockade. In patients receiving large doses of propranolol, verapamil produced modest but significant cardiodepressant effects; these could be avoided by withdrawal of propranolol for 24 hours. Adverse reactions, when they occurred, were primarily hemodynamic rather than electrophysiologic.Short-term (48 hours) and long-term (4 weeks) randomized controlled trials, which objectively evaluated exercise tolerance in patients with angina pectoris, demonstrated that combined therapy of verapamil and propranolol was superior not only to placebo but also to either drug alone. In patients with preserved left ventricular function, the incidence of adverse effects with combined therapy was small (less than 10%) but increased to 25% in patients with poor left ventricular performance (ejection fraction less than 30%). Combined therapy of nifedipine and propranolol also produced adverse hemodynamic and clinical reactions.Combined therapy of beta-adrenergic and calcium channel antagonists can provide substantial clinical benefits for patients with angina pectoris who remain symptomatic with either agent used alone. Because adverse effects can occur, however, patients being considered for such treatment need to be carefully selected and observed.     

Quantitative differences in the hemodynamic effects of captopril and nitroprusside in severe chronic heart failure

The hemodynamic effects of oral captopril and intravenous nitroprusside were compared in 15 patients with severe chronic congestive heart failure. At doses of both drugs titrated so as to produce similar decreases in systemic vascular resistance in each patient, nitroprusside produced substantially greater increases in cardiac index (+0.67 versus +0.31 liters/min/m2, p less than 0.01) but smaller decreases in mean arterial pressure (-18.4 versus -11.0 mm Hg, p less than 0.01) than did captopril. This finding was due to a significant decrease in heart rate with captopril (-7 beats/min, p less than 0.01) which was not seen with nitroprusside, since changes in stroke volume index with both drugs were similar. Nitroprusside produced a decrease in pulmonary arteriolar resistance quantitatively similar to the decrease in systemic vascular resistance, but the decrease in pulmonary arteriolar resistance with captopril was not significant. Despite similar decreases in systemic resistance, captopril produced a greater decrease in left ventricular filling pressure (-10.2 versus -6.9 mm Hg, p less than 0.01) but a smaller decrease in mean right atrial pressure (-3.1 versus -5.3 mm Hg, p less than 0.01) than did nitroprusside. Thus, captopril has actions independent of its systemic vasodilator effects which account for the quantitative differences observed in its hemodynamic responses compared with those of nitroprusside in patients with severe chronic heart failure. These differences support experimental evidence that angiotensin, in addition to its direct systemic arterial vasoconstrictor actions, exerts positive chronotropic effects and alters ventricular compliance but has minimal direct effects on the limb venous circulation and on the pulmonary vasculature.     

Coronary angiographic morphology in myocardial infarction: a link between the pathogenesis of unstable angina and myocardial infarction

It has previously been shown that analysis of coronary morphology can separate unstable from stable angina. An eccentric stenosis with a narrow neck or irregular borders, or both, is very common in patients who present with acute unstable angina, whereas it is rare in patients with stable angina. To extend these observations to myocardial infarction, the coronary morphology of 41 patients with acute or recent infarction and nontotally occluded infarct vessels was studied. For all patients, 27 (66%) of 41 infarct vessels contained this eccentric narrowing, whereas only 2 (11%) of 18 noninfarct vessels with narrowing of 50 to less than 100% had this lesion (p less than 0.001). In addition, a separate group of patients with acute myocardial infarction who underwent intracoronary streptokinase infusion were also analyzed in similar fashion. Fourteen (61%) of 23 infarct vessels contained this lesion after streptokinase infusion compared with 1 (9%) of 11 noninfarct vessels with narrowing of 50 to less than 100% (p less than 0.01). Therefore, an eccentric coronary stenosis with a narrow neck or irregular borders, or both, is the most common morphologic feature on angiography in both acute and recent infarction as well as unstable angina. This lesion probably represents either a disrupted atherosclerotic plaque or a partially occlusive or lysed thrombus, or both. The predominance of this morphology in both unstable angina and acute infarction suggests a possible link between these two conditions. Unstable angina and myocardial infarction may form a continuous spectrum with the clinical outcome dependent on the subsequent change in coronary supply relative to myocardial demand.     

Vasodilator and inotropic therapy for severe chronic heart failure: passion and skepticism

Although substantial progress has been made in the last 5 years in the development of vasodilator and inotropic drugs for the management of patients with severe chronic heart failure, much of the enthusiasm that surrounded the introduction of many of these agents has subsequently been tempered by reports of drug failure or adverse reactions. In this review and analysis, currently available vasodilator and inotropic agents are critically and comparatively evaluated to assess their respective advantages and limitations. It is apparent that the ability of most of these drugs to produce substantial clinical benefits in patients with severe heart failure has probably been overstated. Therapy fails to achieve the desired clinical results all too frequently, possibly as the result of: the choice of an ineffective drug; the administration of an effective drug in subtherapeutic doses; the administration of an effective drug to improperly selected patients; the failure of initial hemodynamic benefits to be sustained; the occurrence of severe or serious adverse reactions; and the failure to alter concomitant therapy appropriately. The present analysis indicates that there is no uniformly effective or safe vasodilator or inotropic drug for patients with severe heart failure; all agents have important limitations. Of the available therapeutic choices, however, long-term converting enzyme inhibition appears to produce more consistent hemodynamic and clinical benefits with an acceptable degree of adverse reactions than other pharmacologic approaches for the management of these severely ill patients.