Martin J. Frank

Relation among impaired coronary flow reserve, left ventricular hypertrophy and thallium perfusion defects in hypertensive patients without obstructive coronary artery disease

Abstract Invasive Doppler catheter-derived coronary flow reserve, echocardiographic measurements of left ventricular hypertrophy and intravenous dipyridamole-limited stress thallum-201 scintigraphy were compared in 48 patients (40 were hypertensive or diabetic) with clinical ischemic heart disease and no or coronary artery disease. Abnormal vasodilator reserve (ratio The decrement in flow reserve was not linearly related to the of left ventricular hypertrophy. Abnormal vasodilator reserve subsets found in hypertensive patients were defined on the basis of basal flow velocity, indexed left ventricular mass and clinical factors. In this series, diabetes did not cause a detetable additional decrement in flow reserve above that found with hypertension alone. These findings demonstrate that thallium perfusion defects are associated with depressed coronary vasodilator reserve in hypertensive patients without obstructive coronary artery disease, Left ventricular hypertrophy by indexed mass criteria is predictive of which hypertensive patients are likely to have thallium defects. Depressed coronary reserve is typically found in hypestensive patients with hypertrophy and increased basal coronary flow velocity, but less typical presentations including hypertrophy and normal or low coronary low velocity are found in advanced hypertensive disease.

Ventricular function in noncardiacs with alcoholic fatty liver: role of ethanol in the production of cardiomyopathy

Since many patients with cardiomyopathy have a history of chronic ethanolism often associated with malnutrition, we have evaluated left ventricular (LV) function in alcoholics with fatty liver, who had no clinical evidence of cardiac or nutritional disease. During an afterload test of LV function the pressor response to angiotensin evoked a threefold rise of enddiastolic pressure in the alcoholic group which was substantially greater than the 4 mm Hg rise in control subjects. The stroke volume and stroke work response in the noncardiac alcoholic was significantly less than in controls. Diminished LV function was corroborated in the noncardiac alcoholic at rest, using a contractility index. To evaluate the dose-response relationship of ethanol in the production of cardiac malfunction, two groups of noncardiac alcoholic subjects were studied acutely at low and moderate dose levels. After 6 oz, ventricular function, myocardial blood flow, and metabolism were not significantly affected. After 12 oz, there was a progressive rise of end-diastolic pressure and decrease of stroke output at a mean blood alcohol level of 150 mg/100 ml, reverting toward control by 4 hr. The coronary effluent transiently evidenced leakage of cell constituents, despite an increase of coronary blood flow, suggesting a direct but reversible cardiac injury. Myocardial extraction of triglyceride was enhanced, whereas FFA uptake was reduced. A possible role of myocardial triglyceride accumulation in heart muscle was considered in pathogenesis. Chronic ingestion of 16 oz of Scotch daily by an alcoholic subject while on a normal diet produced, after 12 wk, a progressive increase of heart rate and size, circulation time, and venous pressure, and a ventricular diastolic gallop. Normal values were restored within 7 wk after interrupting alcohol. These several studies suggest that the cumulative effects of repeated ingestion of ethanol in intoxicating doses can produce diminished LV function before clinical evidence of cardiac abnormality, or heart disease not necessarily related to malnutrition.

Long-term medical management of hypertrophic obstructive cardiomyopathy.

Abstract Twenty-two patients, aged 15 to 61 years, with hypertrophic obstructive cardiomyopathy documented at catheterization were followed up prospectively for 2 to 8 years (mean 5) while receiving “complete” beta receptor blocking doses of propranolol (average dose 462 mg/day). Hypertension, fluid retention, pulmonary disease and arrhythmias were treated as required. Dyspnea, angina, syncope, presyncope and palpitations were graded from 0 to 3 based on severity, and the scores were added to obtain a total score. This group was compared with 14 nonrandomized control patients, aged 17 to 78 years, who were not receiving propranolol and were evaluated retrospectively for a mean follow-up period of 5 years (range 2 to 13). The average total score for the protocol group was initially 7.9 and is now 1.9. No patient died; the condition of all patients is improved, with an average improvement in dyspnea of 58 percent. Eighteen patients are currently asymptomatic during usual daily activities. In contrast, symptoms increased in severity in 13 of the 14 control patients. Their mean score increased from 2.9 to 5.4, and dyspnea increased by 133 percent. Of the 10 control patients treated only medically, 4 died suddenly. Improvement in protocol patients was independent of the severity of subvalve obstruction. Potentially life-threatening arrhythmias were found in 11 of the 22 protocol patients, including the 3 patients without obstruction at rest. Rhythm disturbance responded to propranolol alone in four patients, but antiarrhythmic drugs or pacemaker insertion, or both, was required in the remaining seven patients. Thus, “complete” beta blockade supplemented by control of arrhythmia is optimal management for hypertrophic obstructive cardiomyopathy. Most patients do not require surgery.

Measurement of left ventricular mass in hypertrophic cardiomyopathy using MRI : comparison with echocardiography

Left ventricular mass (LVM) is an important consideration in the management of cardiac hypertrophy associated with hypertrophic cardiomyopathy (HCM), systemic hypertension, and other diseases. A brief MRI cardiac imaging procedure used to monitor regression of LVM during treatment would be beneficial in management of these patients, since echocardiograms cannot be obtained in all patients and since the volume of a hypertrophic heart can straightforwardly be assessed from a series of tomographic slices. The present study was designed to evaluate a brief cardiac MRI procedure for measurement of LVM in HCM and compare it to echocardiography. MRI images acquired in a simulated transverse body plane were used to evaluate the mass of the left ventricle in 6 ex vivo human hearts obtained at autopsy. The estimates of LVM by MRI in the ex-vivo hearts were within 8% of the actual LVM. MRI images were acquired to evaluate LVM in 5 normal subjects and 12 patients diagnosed with HCM. Echocardiography was accomplished on 4 of the normal subjects and 10 of the patients having HCM. There were no significant differences in LVM by MRI and echocardiographic techniques in normal subjects. Transverse MRI images acquired on normal subjects demonstrated that estimates of LVM are reproducible when repeated over 3-w to 3-mo intervals. Images selected for analysis represented the heart in an early diastolic phase. MRI and echocardiographic techniques demonstrated significant differences in LVM in HCM patients. Estimates of LVM in normal subjects and patients diagnosed with HCM were normalized for body weight. The LVM estimates for HCM patients were very significantly different than normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic effects of staged hematocrit reduction in patients with stable cor pulmonale and severely elevated hematocrit levels

Patients with cor pulmonale and high hematocrit levels are often subjected to phlebotomy in the belief that the adverse effects of high viscosity may outweigh the benefit of increased oxygen carrying capacity. To evaluate this, 12 patients with stable cor pulmonale and hematocrit values greater than 55 per cent were studied before and after a series of venesections. Right heart and aortic pressures, cardiac output and blood gases were measured at three mean hematocrit levels, 61 per cent (stage I), 50 per cent (stage II) and 44 per cent (stage III), with blood volume unchanged. From stages I to II, there were significant decreases in both man pulmonary artery pressure and total pulmonary resistance. Oxygen transport fell but not oxygen consumption. Right ventricular end-diastolic pressure and cardiac output did not change. Right ventricular work either fell or was maintained by increased output. Frank-Starling performance (supine exercise) improved. No significant changes occurred with further reduction in hematocrit to normal levels (stage III). The findings of this study support the concept of overcompensating erythrocytosis in cor pulmonale, and the effects of moderate hematocrit reduction should not be overlooked in these severely ill patients.

Rhythm disturbances in hypertrophic cardiomyopathy: Prevalence, relation to symptoms and management

Abstract The prevalence of arrhythmias, associated symptoms and the effect of antiarrhythmic therapy were studied in 33 patients with hypertrophic obstructive cardiomyopathy (mean follow-up period 4.7 years). Arrhythmias were found in 29 patients (88 percent) and were potentially life-threatening in 13 (39 percent). Most patients had more than one type of arrhythmia. All patients were symptomatic at Initial evaluation: A history of syncope was noted in 12 patients, of presyncope in 27 and of palpitations in 23. All patients received large doses of propranolol (more than 240 mg/day or more than 3.5 mg/kg per day; average 460 mg/day or 6.7 mg/kg per day) for treatment of hypertrophic obstructive cardiomyopathy. In addition, pacemaker insertion or additional antiarrhythmic therapy was required in 10 patients; these patients underwent repeated Holter monitoring until arrhythmia control was documented, and at least at yearly intervals thereafter. Although some patients had arrhythmias, including short runs of ventricular tachycardia, in the absence of symptoms during ambulatory monitoring and others had symptoms in the absence of rhythm disturbances, the relation between suppression of potentially life-threatening arrhythmias and symptomatic improvement was striking: potentially life-threatening arrhythmias were suppressed in all but one patient, palpitations and episodes of presyncope have decreased in most, syncope has been eliminated in all and there have been no deaths. In addition, atrial fibrillation appears to have been prevented. Symptomatic improvement was independent of the severity of left ventricular outflow tract obstruction. It is concluded that Holter monitoring and stress testing should be a routine part of the evaluation of all patients with hypertrophic cardiomyopathy and that aggressive therapy of potentially life-threatening arrhythmias results in a lessening of palpitations and episodes of presyncope and syncope and appears to prevent sudden death in these patients when combined with large doses of propranolol.

Significance of positive or negative thallium-201 scintigraphy in hypertrophic cardiomyopathy

Myocardial ischemia, fibrosis and infarction may occur in patients with hypertrophic cardiomyopathy (HC) in the absence of epicardial coronary artery disease. To determine their prevalence and relation with common characteristics, stress thallium-201 scintigraphy was performed in 28 patients. Eleven (39%) had positive scans despite normal epicardial coronary arteries (7 patients) or a pretest risk of coronary disease less than or equal to 5% (4 patients). There was no relation between thallium defects and age, sex, chest pain or outflow tract gradients at rest. However, the mean left ventricular ejection fraction was significantly lower in those with perfusion abnormalities compared with those without (64 +/- 15 vs 75 +/- 11%, respectively, p less than 0.05). Also, the mean ventricular septal thickness was greater in patients with positive scans (27 +/- 7 vs 21 +/- 6 mm, p less than 0.05), and there was a nonparametric relation between increasing septal thickness and the frequency of positive scans (p less than 0.025). Seven of 11 patients with positive scans had ventricular tachycardia compared with none among those who had negative scans (p less than 0.001), and 5 of these 11 patients had conduction system disease requiring permanent pacemaker insertion compared with 1 of 17 with negative scans (p less than 0.025). It is concluded that thallium perfusion abnormalities are common in patients with HC in the absence of epicardial coronary disease, and are strongly associated with potentially lethal arrhythmias. Thallium scintigraphy appears to identify a subset of patients with HC at increased risk for sudden death, who therefore require closer follow-up.

Left Ventricular Function, Metabolism, and Blood Flow in Chronic Cor Pulmonale

Left ventricular function, oxidative metabolism, and coronary blood flow were evaluated in 11 patients with chronic cor pulmonale (mean age 53 years) at rest and during stress, and compared with 11 normal subjects (mean age 29 years) studied under similar conditions. The left ventricles of patients with chronic cor pulmonale were normal in regard to contractile state, preload, afterload, coronary blood flow, and myocardial oxidative metabolism. However, the mean cardiac index, stroke volume, stroke work, and left ventricular ejection fraction were below normal, and end-systolic volume was elevated. These differences in performance are consistent with the older mean age of the patients. An alternative explanation is the limit placed on right ventricular stroke volume by the increased afterload (pulmonary vascular resistance). Allowance for these factors permits the conclusion that the left ventricles of patients with chronic cor pulmonale are normal unless involved by a second disease process.

An index of the contractile state of the myocardium in man

There is a profound need, on both clinical and physiologic grounds, for a measure of the contractile state of the intact ventricle. Such a measure can be obtained by evaluating the force-velocity relationship with a correction for myocardial fiber length. The force-velocity relation can be expressed as the ratio of maximum rate of pressure rise to maximum isovolumetric pressure, a quantity which was described by Hill as the maximum rate of proportional rise of pressure and which is similar to the velocity constant of a chemical reaction. Division of this ratio by an estimate of ventricular circumference corrects for variations due to differences in initial fiber length. This index was evaluated in 11 normal subjects and 46 patients with cardiac disease during left heart catheterization. Maximum rate of pressure rise was obtained by electronic differentiation of the ventricular pressure pulse, and ventricular circumference, assuming a spherical ventricle, was calculated from volumes measured by indicator washout. The contractility index of normal subjects did not differ from that of patients with mitral stenosis, atrial septal defect, or chronic pulmonary disease (patients without left ventricular overloading). In contrast, in patients with left ventricular failure, the indices were more than two standard deviations below the mean value for normal subjects. Such a reduction was not noted in patients with pressure or volume overloading of the left ventricle before the onset of myocardial failure. During exercise, the index rose uniformly in patients without left ventricular disease, responded variably in compensated patients with volume or pressure overloading, and was virtually unchanged in patients with left ventricular decompensation. The administration of isoproterenol or digitalis resulted in increased contractility regardless of the patients status. It is concluded that the use of this index in physiologic studies of the ventricle and in diagnostic and therapeutic decisions is justified.

Studies of Cardiopulmonary Blood Volume Measurement of Left Ventricular Volume by Dye Dilution

The measurement of ventricular end-diastolic volume from washout of an indicator requiring blood sampling was studied in a heart model and in dogs and applied to the left ventricle in 34 human subjects. The model, under the ideal conditions of constant ejection fraction, uniform cycle length, and complete or nearly complete mixing, demonstrated that dye dilution accurately measures chamber volumes if the distorting effects of catheter sampling are obviated by clearance of the sampling system at least once per two cardiac cycles. The studies in dogs and in human beings demonstrated that the required sampling conditions are achievable.In 11 normal human subjects, left ventricular end-diastolic volume ranged from 72 to 99 with a mean of 82 ± 12 ml/m,2 end-systolic volume, from 22 to 60 with a mean of 37 ± 11 ml/m,2 and ejection fraction, from 0.39 to 0.71 with a mean of 0.55 ± 0.08. These measurements are in substantial agreement with results by radiocardiography and thermal dilution and are systematically, but only slightly, higher than results by quantitative angiocardiography.In six considerably older patients with chronic pulmonary disease, cardiac output was normal for the age group but ejection from a ventricle of normal size was reduced. In 12 subjects with pure mitral stenosis and in five with atrial septal defect, end-diastolic volume and ejection fraction were significantly reduced.End-diastolic volume correlated with stroke volume in all groups and in the series as a whole, but a correlation between end-diastolic volume and cardiac output was demonstrated only in the patients with mitral stenosis or atrial septal defect. This suggests that chronic restriction to ventricular filling results in decreased end-diastolic volume. The absence of a significant correlation between end-diastolic volume and end-diastolic pressure indicates that variation in ventricular compliance precludes reliance on end-diastolic pressure as a valid index of end-diastolic fiber length.