Richard F. Leighton

Alterations in left ventricular diastolic function with doxorubicin therapy

To determine whether impaired diastolic function may be an early sign of doxorubicin cardiotoxicity, a retrospective study was performed in 12 patients who had undergone serial radionuclide angiography and were found to have a left ventricular ejection fraction of 55% or more before doxorubicin (Adriamycin) treatment and during follow-up. Average rapid filling velocity and slow filling velocity were both significantly reduced after doxorubicin treatment. Rapid filling velocity decreased from 5.17 +/- 1.52 to 4.18 +/- 0.96 units/s (p less than 0.01), and slow filling velocity decreased from 2.20 +/- 1.32 to 1.42 +/- 0.62 units/s (p less than 0.05). There were no significant changes in filling volume ratio, total diastolic time or diastolic time ratio. Because a change in left ventricular diastolic function can occur before ejection fraction falls to subnormal levels, diastolic function as well as systolic function should be examined for the early detection of doxorubicin cardiotoxicity. The clinical implications of our observations can only be established by a longer-term prospective analysis of left ventricular function in patients receiving doxorubicin therapy.

Effectiveness of three models for comprehensive cardiovascular disease risk reduction

Cost and accessibility contribute to low participation rates in phase 2 cardiac rehabilitation programs in the United States. In this study, we compared the clinical effectiveness of 2 less costly and potentially more accessible approaches to cardiovascular risk reduction with that of a contemporary phase 2 cardiac rehabilitation program. Low- or moderate-risk patients (n = 155) with coronary artery disease (CAD) were randomly assigned to 12 weeks of participation in a contemporary phase 2 cardiac rehabilitation program (n = 52), a physician supervised, nurse-case-managed cardiovascular risk reduction program (n = 54), or a community-based cardiovascular risk reduction program administered by exercise physiologists guided by a computerized participant management system based on national clinical guidelines (n = 49). In all, 142 patients (91.6%) completed testing at baseline and after 12 weeks of intervention. For patients with abnormal (i.e., not at the goal level) baseline values, statistically significant (p < or =0.05) improvements were observed with all 3 interventions for multiple CAD risk factors. No statistically significant risk factor differences were observed among the 3 programs. For patients with a baseline maximal oxygen uptake < 7 metabolic equivalents, cardiorespiratory fitness increased to a greater degree in patients in the cardiac rehabilitation program and the community-based program versus the physician-supervised, nurse- case-managed program. These data have important implications for cost containment and increasing accessibility to clinically effective comprehensive cardiovascular risk reduction services in low- or moderate-risk patients with CAD.

Adherence to exercise interventions in the treatment of hypercholesterolemia

The goals of this study were to determine the rate of adherence to exercise treatment of hypercholesterolemia and to identify personality and demographic factors associated with adherence. Of the 31 subjects entering the 26-week program, 12 attended 80% or more of the scheduled sessions. Adherence was positively associated with the perceived seriousness of hypercholesterolemia, the expectation of benefit from treatment, and depressed feelings of helplessness and hopelessness. Negative associations were identified between adherence and the perception of health status being under the control of chance or of powerful others. Older subjects were more likely to be adherers at 8 and 16 weeks but not at 26 weeks.

Mild mitral regurgitation. Its characterization by intracardiac phonocardiography and pharmacologic responses.

Abstract Fifteen patients with apical or peri-apical systolic murmurs without accompanying conventional roentgenologic or electrocardiographic evidence of cardiac enlargement were studied. All were shown to have mild mitral regurgitation. Investigative technics included intracardiac, esophageal and external phonocardiography coupled with pharmacologic responses and left ventricular angiography. The murmurs were of high frequency and low intensity. Their configuration varied from pansystolic to entirely late systolic. Typical responses to phenylephrine and amyl nitrite are reported. The value of transseptal intracardiac phonocardiography in making this diagnosis is emphasized. Intracardiac recordings suggest that the position of the regurgitant jet in relation to the chest wall is a factor in the configuration of the murmur as appreciated externally. Evidence is presented that associated mid- to late systolic clicks and whoops are mitral valvular in origin. Despite the evident longevity of patients with mild mitral regurgitation, arrhythmia, embolization and endocarditis may occur.

The Toledo Exercise and Diet Study: Results at 26 Weeks

This study was designed to test whether an exercise program is additive to diet counseling in lowering elevated blood cholesterol levels. From a screened population of 1024 subjects, we randomized 66 predominantly female subjects to two intervention groups: diet counseling and diet counseling with exercise. Subjects were selected who had elevated levels of serum low-density lipoprotein cholesterol, an average or low fitness level, and a diet high in saturated fat and cholesterol. After 26 weeks of intervention, 51 subjects exhibited significant decreases in serum levels of cholesterol, high-density lipoprotein cholesterol, triglycerides, and low-density lipoprotein cholesterol. The addition of exercise to diet counseling resulted in improved aerobic capacity, losses of body fat and weight, and further nonsignificant decreases in serum cholesterol and low-density lipoprotein cholesterol levels. Since these results differ from data acquired in individuals with normal to borderline serum cholesterol levels, further studies appear indicated in hypercholesterolemic subjects, especially in women.

Comparison of thrombolytic therapy for acute myocardial infarction in rural and urban settings

In this study, a tertiary care hospital served as a registry and information source to rural hospitals in northwestern Ohio where thrombolytic therapy had not previously been used. The study was designed to compare the safety and efficacy of intravenous thrombolytic therapy for acute myocardial infarction in the two settings. Fifty-five patients in eight rural hospitals and 36 patients in the urban tertiary care center received intravenous streptokinase. Of the 87 patients whose symptoms first occurred out of the hospital, 63 percent were treated within three hours. There were no significant differences in rates of clinically determined coronary artery recanalization (63 percent versus 69 percent for rural and tertiary hospitals, respectively), in-hospital mortality (5.4 percent versus 11 percent), bleeding complications (3.6 percent versus 5.5 percent), or time from the onset of pain to infusion of streptokinase (3.4 hours versus 2.9 hours). There were also no differences in the completeness of collection of serial coagulation data and cardiac enzyme values, or in the documentation of chest pain onset and cessation. Major differences between rural centers and the tertiary care center involved the use of serial electrocardiography (58 percent versus 89 percent, respectively), subsequent cardiac catheterization (49 percent versus 86 percent), and the timing of catheterization, when performed (30.4 days versus 4.6 days) (p less than 0.005 for all values). Thrombolytic therapy for acute myocardial infarction can be administered quickly, safely, and effectively in rural hospital settings even by physicians previously unfamiliar with this form of treatment.

Quantification of thallium-201 scintigrams in acute myocardial infarction

A method has been developed for measurement of myocardial infarct size from thallium-201 scintigrams that depends on computer measurement of levels of radioactivity in the myocardium. In 16 dogs, thallium-201 scintigrams were obtained in the left lateral and left anterior oblique projections 48 hours after ligation of the left anterior descending coronary artery. Scintigraphic results were obtained by two independent observers and were compared with tissue measurements of infarct volume calculated from thallium autoradiograms and nitro-blue tetrazolium (NBT)-stained tissue slices. Infarct volumes derived from tissue measurements were used to develop criteria for the computer scintigraphic technique. There was no significant difference in the scintigraphic measurements made by the two observers. Scintigraphic infarct size in the left lateral and left anterior oblique projections correlated with tissue infarct size with r values of 0.88 and 0.75, respectively, for thallium autoradiography and 0.71 and 0.70, respectively, for NBT tissue staining. The range of infarct volume was 3.3 to 14.8 percent of the left ventricular mass. Results of this study suggest that scintigraphic quantitation of infarct size is feasible in this dog model.

Prediction of dietary adherence in cholesterol reduction: Relative contribution of personality variables and health attitudes

Abstract The purpose of this study was to identify personality and health attitude variables that might predict adherence to a cholesterol-reducing diet. After taking a battery of psychological inventories, 66 subjects entered a 26 week diet program. Adherence indices included attendance rate at scheduled appointments, changes in diet, and changes in serum cholesterol levels. Of the 55 subjects with complete data, 7 dropped out, 7 attended inconsistently, and 41 completed the program. Drop-outs scored significantly lower on the Health Belief measures of seriousness, susceptibility, and benefits. Improvement in serum cholesterol was positively correlated with the Health Belief Benefits Scale and negatively correlated with the Health Locus of Control chance scale. Dietary reduction in saturated fat was positively associated with the Health Belief Seriousness and Benefits Scales. Health attitudes and beliefs were better predictors of adherence than personality trait measures.

Subtle Left Ventricular Asynergy with Completely Obstructed Coronary Arteries

The phenomenon of apparently normal angiographic left ventricular wall motion in the presence of greater than or equal to 1 completely obstructed coronary artery was investigated in 16 patients with coronary artery disease (CAD) by quantitative phasic biplane cineangiography. Angiographic contours were digitized at quarterly intervals throughout ejection and 9 areas of motion were measured in both right and left anterior oblique planes. Normal values were derived from 18 other patients who had normal coronary arteries and normal left ventricular function. Areas of asynergy undetected when quantitative analysis was applied only at end-systole in the right anterior oblique plane were found in 12 of the 16 patients with CAD: in 2 patients by end-systolic analysis in the left anterior oblique plane and in 10 patients by phasic analysis of both planes. Of 19 asynergic areas 18 corresponded to sites of high-grade CAD. All patients had angina pectoris, but only 5 had clinical or electrocardiographic evidence of prior infarction.

Hyponatremia in patients treated with lorcainide, a new antiarrhythmic drug

The effects of lorcainide, a new antiarrhythmic drug, on serum electrolytes and osmolality are described in a series of 33 patients with organic heart disease and complex ventricular arrhythmias treated with lorcainide. In eight patients, a mean decrease in serum Na+ of 8.25 +/- 3.2 mEq/L was observed after a single 200 mg intravenous dose of lorcainide. Sixteen of 33 patients developed significant hyponatremia and hypoosmolality during oral treatment with lorcainide. In all except two patients, serum Na+ returned to normal values within 3 to 12 months of continued lorcainide therapy. Low serum Na+ and hypoosmolality in the absence of volume depletion, clinically manifest edema, and unaltered renal, adrenal, cardiac, or thyroid function suggest that this antiarrhythmic drug produced the syndrome of inappropriate antidiuretic hormone secretion (SIADH). SIADH appeared to be transient and asymptomatic in our patients. One patient developed severe hyponatremia with serum Na+ of 108 mEq/L when hydrochlorothiazide was given to control hypertension. It is concluded that SIADH is an important side effect of lorcainide therapy. We recommend that serum Na+ be carefully monitored in patients started on lorcainide therapy, and extreme caution should be exercised in prescribing diuretics to patients with persistent hyponatremia.