Alan G. Wasserman

Acute arrhythmogenicity of doxorubicin administration

The magnitude of acute arrhythmogenicity of doxorubicin administration has not been characterized. In this study the type and frequency of cardiac arrhythmia is determined in the first hour and first 24 hours following doxorubicin given as a 10‐minute infusion. Twenty‐nine patients with diverse malignancies were studied with Holter monitors on 33 postdoxorubicin days. Control recordings were made on days remote from doxorubicin treatment. The frequency of arrhythmia that could be attributed to doxorubicin was low: 3% of studies in the first hour postinfusion and 24% of studies in 1 to 24 hours postinfusion. The most commonly seen arrhythmia was an increased frequency of ventricular premature beats. Arrhythmia following doxorubicin infusion is rare in the first hour and more common in the remainder of the first 24 hours postinfusion. There are no acute or long‐term adverse consequences related to the appearance of arrhythmia due to doxorubicin.

Doppler guide wire flow-velocity indexes measured distal to coronary stenoses associated with reversible thallium perfusion defects

A Doppler guide wire was used to measure phasic coronary blood flow velocity distal to coronary stenoses in 17 symptomatic patients with corresponding positive exercise or adenosine thallium scintigrams. Distal average peak velocity and diastolic/systolic flow-velocity ratio were obtained in 16 vessels with stenoses (55% to 85% diameter stenosis) and a corresponding reversible thallium defect and in 11 control vessels with no stenosis or thallium defect. Coronary flow-velocity reserve was obtained with intracoronary adenosine. Coronary flow reserve (2.3 +/- 0.4 vs 1.2 +/- 0.3, p < 0.01) and diastolic/systolic flow-velocity ratio (1.95 +/- 0.56 vs 1.44 +/- 0.59, p < 0.04) were significantly different between normal vessels and distal to stenoses, respectively. Excellent concordance between distal coronary flow reserve and diastolic/systolic flow-velocity ratio to thallium scintigraphy was noted. A coronary flow reserve of < 1.8 and a diastolic/systolic flow-velocity ratio of < 1.7 predicted a reversible thallium perfusion scintigram (concordance 96% and 88%, respectively). Distal coronary flow velocity indexes may provide an alternative means of physiologic assessment of lesion severity during coronary angiography.

Lipoprotein and apolipoprotein levels in angiographically defined coronary atherosclerosis

Recent studies suggest that apolipoproteins and subfractions of high-density lipoprotein (HDL) cholesterol may be better predictors of atherosclerotic coronary artery disease (CAD) than are plasma cholesterol and total HDL cholesterol. To examine this hypothesis, plasma cholesterol and triglyceride, cholesterol of low-density lipoprotein, HDL and its subfractions 2 and 3, apolipoprotein A-I, the apolipoprotein B of low-density lipoprotein, the ratio of apolipoprotein EII to EIII, and ratios of several of these variables were measured in a selected series of 126 patients (83 men and 43 women) who underwent coronary angiography for suspected CAD. Mean values of many of these variables differed significantly between the men with CAD and the men without significant CAD, when controlled for age, use of beta blockers and diuretic drugs. Using multivariate logistic regression analysis, the only variable that made a significant independent contribution in predicting CAD in men was the ratio of HDL cholesterol to total plasma cholesterol (p less than 0.0001). The mean of this ratio was 0.17 +/- 0.01 mg/dl in the men with CAD and 0.23 +/- 0.02 mg/dl in the male controls. All men with ratios of less than 0.15 mg/dl had significant CAD, defined as 50% or greater luminal diameter narrowing of 1 or more of the major coronary arteries. No measurement was a significant univariate or multivariate predictor of CAD in the women, but the power to detect such predictors was reduced because of small group sizes. In conclusion, the ratio of HDL cholesterol to plasma cholesterol may be superior to many of the more recently described lipoprotein and apolipoprotein-derived predictors of CAD.

Anterior ST segment depression during acute inferior myocardial infarction: Evidence for the reciprocal change theory☆

We evaluated the recently proposed concern that ECG anterior ST segment depression in patients with acute inferior wall myocardial infarction represents an additional area of ischemia and therefore implies worsened prognosis. We studied patients enrolled in the Aspirin Myocardial Infarction Study (AMIS), ages 30 to 69 years, who sustained an inferior myocardial infarction within 6 months from the start of the study. Two hundred nineteen patients who met those criteria were followed for an average of 38.2 months. One hundred ten patients had significant anterior lead ST depression (greater than or equal to 0.1 mV) during their acute inferior infarction and their 3-year mortality rate was 9.1%. One hundred nine patients had no anterior ST abnormality and a mortality rate of 10.1% (p = ns). Only one patient with significant depression had a subsequent anterior wall myocardial infarction. Anterior ST depression correlated closely with the magnitude of inferior ST segment elevation. Since ST depression does not alter long-term mortality but relates to magnitude of ST elevation, it probably represents a reciprocal change.

Safety of immediate treadmill testing in selected emergency department patients with chest pain: A preliminary report

To determine the feasibility and safety of an immediate, symptom-limited, treadmill test on selected emergency department (ED) patients, a convenience sample of 28 patients underwent an exercise treadmill test (ETT) within the first several hours after hospital arrival using the modified Bruce protocol. Patients were included in the study if they presented with otherwise unexplained chest pain consistent with (but not characteristic for) angina pectoris and had a normal electrocardiogram. A negative ETT was seen in 23 of 28 patients, and five of 28 patients had a positive ETT. No patients had serial enzyme or electrocardiogram evolution suggestive of myocardial ischemia, and all patients with a negative ETT were discharged after a full inpatient evaluation designed to rule out unstable coronary disease. At a mean follow-up period of 6.1 months there has been no cardiac morbidity or mortality in the patients with negative ETTs. It was concluded that early ETTS of selected ED patients with chest pain is safe, and an exercise test administered during the ED visit which is negative can preclude unnecessary hospitalization.

Alterations in Serum Levels of Lipids and Lipoproteins with Indinavir Therapy for Human Immunodeficiency Virus—Infected Patients

Alterations in lipid metabolism have been associated with the use of protease inhibitors. Sequential lipid analyses were performed on serum samples from human immunodeficiency virus-infected antiretroviral-naive patients who received indinavir in combination with two nucleoside reverse transcriptase inhibitors. Serum levels of cholesterol, triglycerides, high-density lipoproteins (HDLs), and low-density lipoproteins (LDLs) were measured at baseline and at periodic intervals. After 48 weeks of indinavir therapy, mean serum levels +/- SD rose as follows: cholesterol, from 167.2 +/- 36.0 to 206.3 +/- 32.4 mg/dL (P < .0005); triglycerides, from 110.4 +/- 47.5 to 158.4 +/- 72.5 mg/dL (P < .0101); and LDLs, from 106.6 +/- 35.1 to 136.1 +/- 31.6 mg/dL (P = .0029). There was no significant change in the serum HDL fraction. Mean serum lipoprotein (a) levels +/- SD rose from 6.5 +/- 1.4 to 9.6 +/- 2.0 mg/dL after 30 weeks (P = .0695). Potential mechanisms for the noted increases include alterations in serum lipoprotein lipase activity or changes in hepatic lipid metabolism. The clinical significance of these changes remains to be determined.

Arteriographic predictors of spontaneous improvement in left ventricular function after myocardial infarction.

To better characterize the changes in left ventricular ejection fraction after myocardial infarction, we compared radionuclide ventriculograms obtained acutely and 2 weeks after acute myocardial infarction in 40 patients. These patients underwent angiography within a mean of 4 hr and 20 min after the onset of symptoms of infarction and either received no therapy (32 patients who were control subjects in a thrombolysis trial) or did not experience reperfusion (eight patients) despite receiving streptokinase infusions. In all 40 patients, the change in left ventricular ejection fraction over 2 weeks was small (+2.6%). Patients were then grouped according to the presence or absence of residual flow on their angiograms. Residual flow was considered to be present in 21 patients, in 12 by virtue of subtotal occlusion of the artery supplying the area of infarct and in nine because of well-developed coronary collaterals to the distal infarct artery. Mean change in ejection fraction for patients with residual flow was +6.9 +/- 2.3% vs -2.2 +/- 1.7% for patients without residual flow (p less than .01). Fourteen of 21 (67%) patients with residual flow had a spontaneous rise in ejection fraction of greater than 5%, as compared with two of 19 (11%) patients without residual flow (p less than .01). Time to peak level of creatine kinase (CK) was significantly shorter in the residual flow group (15 vs 23 hr, p less than .01), while the peak level of CK was lower (1550 vs 2220 IU) in these patients. This latter difference did not reach statistical significance (p = .10).(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive Detection of Multivessel Disease After Myocardial Infarction by Exercise Radionuclide Ventriculography

Abstract The ability of exercise radionuclide ventriculography to detect multivessel coronary artery disease in patients who survived a single myocardial infarction was assessed. Seventy-four patients who had had myocardial infarction at least 8 weeks earlier underwent cardiac catheterization and exercise radionuclide ventriculography. Thirty-eight patients had had an inferior infarction: 25 with multivessel disease and 13 with single vessel disease of the right coronary artery. Thirty-six patients had had an anterior infarction: 26 with multivessel disease and 10 with single vessel disease of the left anterior descending coronary artery. Among patients with anterior infarction there was no significant difference between patients with single vessel disease and patients with multivessel disease with regard to resting ejection fraction, exercise ejection fraction, and the mean change from rest to exercise. Patients with single vessel disease had a decrease in ejection fraction from rest to exercise of 2.2 ± 2.7% units (mean) ± standard error [SE]), compared with a decrease of 5.4 ±1.3% units in those with multivessel disease (p = not significant [NS]). Seventeen of 26 (65%) patients with multivessel disease and 6 of 10 (60%) with single vessel disease had a decrease in ejection fraction of at least 5 percentage units (p = NS). In patients with inferior infarction there was no difference in the mean resting ejection fraction in those with single vessel disease (53 ± 2%) compared with those with multivessel disease (50 ±2%); however, the mean exercise ejection fraction in patients with single vessel disease (57 ± 3%) was significantly higher (p p A new wall motion abnormality developed in 8 patients with anterior infarction and 11 with inferior infarction with multivessel disease and none with single vessel disease. The sensitivity and specificity in predicting multivessel disease using the criteria of the development of a new wall motion abnormality or a decrease in ejection fraction with exercise of at least 5 percentage units were 80 and 92% for the patients with inferior infarction, but only 69 and 40% for the patients with anterior infarction. These results suggest that exercise radionuclide angiography can be used to discriminate between single and multivessel disease after inferior myocardial infarction. For patients with anterior infarction, only a new abnormality in wall motion accurately predicts multivessel disease, but this occurred in only one third of such patients.

Prognostic implications of diagnostic Q waves after myocardial infarction.

The long-term prognostic implications of the electrocardiographic location of a myocardial infarction and the subsequent retention or disappearance of diagnostic Q waves were examined in patients enrolled in the Aspirin Myocardial Infarction Study (AMIS). The 4524 participants, ages 30-69 years, had sustained a myocardial infarction 8 weeks to 60 months before randomization to aspirin and placebo groups. Subjects were followed for at least 3 years (average 38.2 months). Using the Minnesota Code, myocardial infarctions were classified according to three electrocardiographic locations: lateral, inferior and anterior, with further subdivision into major, moderate and minor criteria based on Q-wave duration and Q/R rations. Total mortality was not significantly different among patients with single infarct sites: lateral 11.8%, inferior 8.0% and anterior 9.4%. Patients with multiple electrocardiographic infarct locations had a significantly higher mortality (14.6%, p less than 0.0002). Participants with Minnesota Code major criteria of infarction also had a significantly higher mortality (10.6%) than those with moderate (7.2%) or minor (7.4%) criteria (p less than 0.01). Loss of a previously documented diagnostic Q wave occurred in 14.2% of participants. Mortality among patients who lost Q waves (6.5%) was not significantly different from that among those with persistent Q waves in a single infarct location (8.7%). No long-term prognostic significance can be attributed to the site of infarction or loss of Q wave on the resting ECG. However, major Q-wave criteria and extent of infarction based on multiple coded sites are associated with a higher 3-year mortality.

Intravenous digital left ventriculography at rest and with atrial pacing as a screening procedure for coronary artery disease

Digital subtraction left ventriculography using intravenous contrast injection was evaluated as a screening diagnostic method for coronary heart disease. Intravenous ventriculography was performed in 61 patients with 35 cc of contrast medium injected into a central vein (usually the inferior vena cava). Recognition of regional wall motion abnormalities by this technique was shown to be comparable with direct left ventriculography in 40 patients who underwent both imaging modalities at rest. If the rest digital ventriculogram was normal, it was repeated after incremental atrial pacing to the onset of chest pain or to a maximal heart rate of 150 beats/min. Forty-four of the 61 patients had significant coronary artery disease, of whom 10 had a wall motion abnormality at rest on intravenous ventriculography. With pacing, 28 of the 34 remaining patients developed a new wall motion abnormality. Thus, 38 (86%) of 44 patients with coronary heart disease were identified by wall motion abnormalities. One of the 17 patients without coronary artery disease had an abnormal rest study and was incorrectly assigned a diagnosis of coronary disease. Intravenous digital ventriculograms approximate those obtained by direct ventriculography. When combined with atrial pacing they are a sensitive and specific means of detecting coronary artery disease.