5-fluorouracil cardiotoxicity is a rare, dose and schedule-dependent adverse event: a prospective study.

PURPOSE: Cardiotoxicity associated with 5-fluorouracil (5FU) administration is infrequently reported in the literature, albeit case reports of acute coronary syndromes have been published. In the present study, patients undergoing 5FU chemotherapy were tested for the development of cardiac-related symptoms during its administration. PATIENTS AND METHODS: Five hundred twenty-two patients entered the study. Those experiencing any cardiac-related symptoms during 5FU infusion were subjected to electrocardiogram (ECG) and serum cardiac enzymes determination. If cardiotoxicity was confirmed, 5FU infusion was interrupted, sublingual nitrates administered and cardiac monitoring initiated, while patients with >2-fold enzyme elevation were admitted into a coronary care unit for at least 72 hours. Cases with acute myocardial infarction had to discontinue 5FU treatment. RESULTS: Overall 20 (3.8%) patients developed symptoms and/or ECG abnormalities due to 5FU. Patients with continuous 5FU infusion had a trend for higher incidence of cardiotoxicity (13/205, 6.3%) than the remaining (7/317, 2.2%; p=0.067). More specifically, increased toxicity was encountered in patients with continuous 24 h 5FU+ leucovorin (LV) infusion for 5 days compared to patients with the same schedule without LV (p <0.027) and patients with short 5FU+LV administration as well (p=0.024). Seven out of the 20 patients suffered acute myocardial infarction, 6 developed only ischemia, while ECG findings consistent with coronary vasospasm were detected in 4 patients and conduction disturbances in 3 patients (one subsequently died). CONCLUSION: The present study indicates a toxic effect of 5FU on myocardium, which is largely schedule-dependent. High level of alert is required when using this drug, while its toxic effect on the coronary endothelium and myocardium merits further investigation.

Intraerythrocytic 2,3-diphosphoglycerate concentration in hypertensive subjects before and following control by anti hypertensive treatment.

METHODS: We measured the 2,3-diphosphoglycerate inraerythrocytic concentration in 24 normal controls and in 24 hypertensives before and following drug therapy. RESULTS: In hypertensives the 2,3-diphosphoglycerate concentration was higher than that of the controls (14.96 mumol/g Hb vs 13.26 mumol/g Hb respectively); the difference is statistically significant (p < 0.001). Following control of the hypertension by drug therapy, the 2,3 DPG levels in the patients studied do not seem to differ statistically from those of the controls. CONCLUSIONS: This may be a consequence of lower cardiac output in hypertension which results to a lower tissue perfusion, leading to an increased concentration of deoxygenated haemoglobin in the vein blood. Measurement of 2,3-diphosphoglucerate may prove of value in estimating tissue perfusion in hypertension.

The relationship of anticoagulation level and complications after successful percutaneous transluminal coronary angioplasty.

The degree of anticoagulation and its effect on the frequency of abrupt coronary artery closure, coronary ischemia, bleeding complications requiring transfusion, and death were examined in 336 patients after elective percutaneous transluminal coronary angioplasty (PTCA). All patients received a bolus of 10,000 U of heparin at the beginning of the procedure followed by a continuous infusion of 2000 U/hr. At the conclusion of the procedure the infusion was reduced to 1000 U/hr and continued for 18 to 24 hours at which time the heparin infusion was suspended to allow removal of arterial and venous access sheaths. Partial thromboplastin time (PTT) was examined while patients continued to receive the heparin infusion. There was a variable degree of PTT prolongation in response to a standard dose of heparin with a range of 34 seconds to "greater than 150 seconds." Patients were divided into two groups according to the degree of heparin-induced PTT prolongation: group A included 271 patients with PTT greater than or equal to 3 times the control value, and group B comprised 65 patients with PTT less than 3 times the control value. Ischemic complications were analyzed on day 1 after PTCA and at hospital discharge. Bleeding complications and mortality were examined only at hospital discharge. There was a significant reduction in the incidence of abrupt coronary artery closure in group A on day 1 (1.5% vs 10.7%, p less than 0.001) and at hospital discharge (2.6% vs 10.7%, p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary angiographic assessment of left posterior hemiblock.

The ECGs of 1,095 patients with coronary angiographic evidence of significant coronary artery disease (greater than or equal to 50% obstructive lesion in at least one major coronary artery) were reviewed. Five patients had left posterior hemiblock (LPHB), an incidence of 0.5%. Three of five patients also had a right bundle branch block (RBBB). Of the five patients with LPHB, all had significant right coronary artery (RCA) disease (four complete occlusions, one 90% obstructive lesion). All five patients having LPHB also had evidence of critical disease (greater than or equal to 75% obstruction) of at least one of the major branches of the left coronary artery; four of the five had complete occlusion of the left anterior descending coronary artery (LAD). The left circumflex coronary artery (CFx) was critically diseased in three patients. The ECGs of four patients showed evidence of only one myocardial infarction while one patient had evidence of an anterior and an inferior infarction. It is concluded that the presence of LPHB in patients with coronary artery disease is an ominous electrocardiographic finding, and is associated with extensive coronary artery disease.

Lactate metabolism as a prognostic index in unstable angina.

Fifty patients evaluated because of unstable angina were followed up for a mean period of 63.7 months. Analysis of transmyocardial lactate metabolism was performed in all patients in addition to coronary angiography and ventriculography. All patients had at least one coronary lesion of great than 75%. Although technically feasible, aortocoronary bypass surgery was not performed on initial hospitalization and all patients were treated medically. Patients were divided into two groups on the basis of lactate metabolism; group A lactate production great than 15%, group B lactate production less than 15% or lactate extraction. There was no difference in left ventricular end-diastolic pressure or ejection fraction between the two groups. A coronary score index was higher in group A than group B (5.45 +/- 2.2 vs 3.13 +/- 1.2) (p less than 0.05). The incidence of myocardial infarction was higher in group A than group B in hospital (44.4% vs. 4.3%, p less than 0.05), and long term (70.3% vs. 17.3%, p less than 0.05). Mortality was higher in group A than group B in hospital (25.9% vs. 0%, p less than 0.05) and long term (66.7% vs. 13%, p less than 0.05). Analysis of lactate metabolism thus provides a prognostic index in unstable angina which complements information obtained by coronary angiography and ventriculography.

Improved survival after coronary bypass surgery in patients with poor left ventricular function: role of intraaortic balloon counterpulsation.

The operative mortality rate of aortocoronary bypass surgery in 23 patients with poor left ventricular function (ejection fraction 0.30 or less) operated on in 1973-74 was 34.7 percent. The incidence rate of operative myocardial infarction was 30.4 percent. In an attempt to improve survival, intraaortic balloon counterpulsation was used therafter in 25 similar patients. Counterpulsation was instituted preoperatively and continued intra- and postoperatively for 2 to 5 days. Preoperative studies revealed an "unloading" effect of the left ventricle, with significant reductions of systolic arterial blood pressure, end-diastolic pulmonary arterial pressure and end-diastolic left ventricular volume and pressure. Metabolic improvement was demonstrated by the lesser production of myocardial lactate after pacing-induced tachycardia when the ventricle was balloon-assisted. Intraoperatively, blood flow through the vein graft was found to increase with counterpulsation. The rate of operative myocardial infarction was reduced to 4 percent and the mortality rate to 8 percent. In patients who have sustained a significant loss of functioning myocardium, the beneficial hemodynamic and metabolic effects of intraaortic balloon counterpulsation appear to prevent furhter, possibly critical, myocardial damage in the perioperative period.

Cardiac work demands and left ventricular function in end-stage renal disease.

Cardiac hemodynamics were assessed by right and left heart catheterizations in nine patients on hemodialysis. Results showed increased stroke work index and left ventricular work indices. Left ventricular end-diastolic pressure was elevated in all patients (markedly so in five) and did not fall with occlusion of arteriovenous communications. Cardiac output was significantly elevated, but fell to normal postocclusion. Myocardial oxygen consumption, indirectly assessed by tension time and pressure rate indices, appeared increased. Six patients died: four from complications attributed to myocardial failure without infarction, one from transplant-related complications, and one from bacterial meningitis. Five had increased cardiac weights at autopsy, but none showed infarction. This study suggests that increased cardiac work is present in chronic renal failure. Myocardial mass increases result in increased myocardial oxygen demand; however, the increased oxygen requirements may not be met because of reduced erythrocyte mass. Persistance of pressure-volume overload and severe anemia are conducive to myocardial failure.

Spectrum of coronary arterial spasm. Clinical, angiographic and myocardial metabolic experience in 29 cases.

A relationship of coronary arterial spasm to variant angina pectoris, subendocardial ischemia, major ventricular arrhythmias and myocardial infarction has been demonstrated. In 29 patients, spasm was angiographically observed in normal-appearing coronary arteries (7 patients) as well as superimposed on various degrees of coronary atherosclerotic obstruction (22 patients). All patients experienced an atypical anginal syndrome;16 patients also experienced typical exertional angina. Coronary spasm appeared to be a major contributory factor in eight occurrences of myocardial infarction and in 11 incidents of ventricular tachycardia, ventricular fibrillation and heart block. Coronary spasm in the 29 cases was distributed in the following fashion: left main trunk, 6 cases; right main trunk, 12 cases; proximal left anterior descending artery, 13 cases; proximal circumflex artery, 1 case; distal left anterior descending artery, 1 case; and distal circumflex artery, 2 cases. In 5 cases coronary spasm was noted at multiple sites.

Correlation of abnormal Q waves, coronary pathology, and ventricular contractility.

Four hundred and ninety-two patients with coronary artery disease underwent analysis of their electrocardiograms, coronary arteriograms, and ventriculograms. Significant Q-waves were correlated with critical coronary occlusions (greater than or equal 75 per cent obstruction) and ventricular contractility. It was found that Q-waves correlate equally well with ventriculographic abnormalities and critical coronary occlusions. The Q-wave correlation varied from 77 to 87 per cent, depending on the area of myocardium under consideration, except for true posterior myocardial infarction, which correlated 55 per cent with ventriculographic abnormalities and 55 per cent with critical coronary occlusions. Significant Q-waves in Leads II, III, and aVF are better indicators of ventriculographic abnormality than in Leads III and aVF alone, whereas Q-waves in the latter two leads are more definitive than in Lead III alone. Patients who have critical coronary occlusions and normal electrocardiograms have normal ventriculograms in 71 to 78 per cent of the cases, again depending on the area of the myocardium under consideration. Thus, the normal electrocardiogram correlates better with the ventriculogram than with coronary pathology. The abnormal electrocardiogram correlates equally well with both.

Comparative hemodynamic effects of placebo and oral isosorbide dinitrate in patients with significant coronary artery disease.

Comparative hemodynamic effects of placebo and 10 mg of oral isosorbide dinitrate were studied in patients with significant coronary artery disease (larger than or equal to 75 per cent lumen narrowing) proved angiographically. Isosorbide dinitrate or placebo was given to eight and 10 patients, respectively, in a double-blind fashion. Cardiac performance at rest and during supine leg exercise was evaluated before and 60 minutes after drug administration. In the resting state, isosorbide dinitrate compared to placebo significantly reduced the left ventricualr (systolic and diastolic), mean pulmonary artery and mean aortic pressures, cardiac index, stroke index, left ventricular work index, stroke work index, and mean systolic ejection rate. Isosorbide dinitrate also significantly reduced left ventricular (systolic and diastolic and mean pulmonary artery pressures during exercise. This study indicates that 10 mg of isosorbide dinitrate has a significant influence on ischemic left ventricular dysfunction 60 minutes after its oral administration.

Interpreting cardiac catheterization data. Part 2.

Data obtained by cardiac catheterization, properly interpreted, are an extremely useful supplement to information obtained from the medical history, physical examination, electrocardiography, chest x-ray examination, and other noninvasive diagnostic techniques. Elevations of pressure in the cardiac chambers and great vessels and corresponding patterns of pressure curves are discerned in the presence of various pathologic conditions affecting the heart. Blood samples are taken during cardiac catheterization for measurement of cardiac output and to detect intracardiac shunting. Attempts have been made to estimate the magnitude of shunts from abnormal dye-dilution curves. Exercise stress is often used during cardiac catheterization to evaluate overall cardiovascular performance. Angiocardiography gives a permanent graphic record of structural abnormalities. Myocardial lactate metabolism provides a means of evaluating the adequacy of coronary blood flow.

Coronary arteriography in patients with impending and evolving myocardial infarction.

To determine whether characteristic pathologic alterations in coronary arteries are associated with impending and complicated evolving myocardial infarction, the angiographic and hemodynamic findings in 47 acute coronary patients were compared to those of 49 patients with chronic stable angina. Subtle differences in angiographic and hemodynamic alterations were found in these two groups of patients. These differences were more pronounced in patients with evolving myocardial infarction with less than--15 per cent lactate extraction. The risk of coronary arteriography was surprisingly low. Myocardial metabolic function studies demonstrating less than--15 per cent lactate extraction were considered an indication for emergency coronary arteriography in preparation for contemplated coronary bypass surgery.