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Biomedical subjects

S E Epstein

Publications and source records attributed to S E Epstein.

At least 163 records · Page 9Linked to original sources
PubMed1985

Combination therapy with calcium-channel blockers and beta blockers for chronic stable angina pectoris.

Combination therapy using calcium-channel blockers and beta blockers in patients with refractory chronic stable angina has gained much popularity, but remains highly controversial because of the potential for serious additive deleterious hemodynamic or electrophysiologic reactions. In studies involving patients with preserved left ventricular function receiving chronic oral beta blockers, short-term administration of intravenous verapamil has been shown to cause a further lowering in heart rate and blood pressure while prolonging atrioventricular node conduction; additive cardiodepressant effects were noted, including a tendency toward increased left and right heart filling pressures. Nifedipine, on the other hand, when added acutely to beta blockers, causes an increase in heart rate, a decrease in blood pressure and either no change or a slight improvement in most cardiac performance variables. Controlled, double-blind clinical trials have demonstrated that combinations of calcium-channel blockers and beta blockers result in augmented symptom benefit compared with either drug class alone. The predominant mechanism responsible for such improvement is increased lowering of myocardial oxygen demand by virtue of additive diminution in heart rate, blood pressure and, consequently, pressure-rate product both at rest and during exercise. Verapamil (and possibly diltiazem) plus beta blockers appears to have the greatest therapeutic efficacy but also the highest frequency of harmful adverse cardiac effects, whereas nifedipine plus beta blockers is generally safer but also less efficacious. Factors that should be carefully considered by clinicians contemplating combination therapy are the choice of calcium-channel blocker, the dose of calcium-channel blocker and beta blocker, the presence of antecedent left ventricular dysfunction or conduction system disease and the possibility of drug interactions. Concomitant calcium-channel blocker and beta-blocker therapy is an important contribution to the pharmacologic management of resistant patients who remain symptomatic during single drug treatment. However, the possibility of additive adverse cardiac effects mandates careful patient selection and close clinical monitoring.

Adrenergic beta-Antagonists↗
PubMed1985

Use of calcium-channel blocking drugs in hypertrophic cardiomyopathy.

Verapamil exerts a wide spectrum of hemodynamic effects in patients with hypertrophic cardiomyopathy (HC), and its administration offers an important alternative to beta-receptor blocker therapy in such patients. The intravenous administration of verapamil to 62 patients in the catheterization laboratory decreased systolic blood pressure from 118 +/- 17 to 102 +/- 17 mm Hg (p less than 0.001). It had no significant effect on heart rate, mean pulmonary artery wedge pressure, left ventricular (LV) end-diastolic pressure or cardiac output; however, LV outflow gradient in the basal state decreased from 62 +/- 34 to 29 +/- 34 mm Hg (p less than 0.05). These findings demonstrate a decrease in LV outflow tract obstruction. Radionuclide angiography indicated the major action responsible for the reduction in obstruction appears to be an improvement in LV diastolic function. Short-term nifedipine administration to patients with HC produced no significant effect on LV outflow tract gradients and early diastolic filling. Short-term double-blind studies showed that verapamil improved exercise time by 26 +/- 35% (p less than 0.005) compared with placebo, whereas propranolol improved it by 21 +/- 35% (p less than 0.025). In a separate study, verapamil improved exercise duration by 38 +/- 58% (p = 0.02) compared with placebo, whereas nifedipine improved it by 20 +/- 47% (difference is not significant). Verapamil resulted in a more beneficial subjective symptomatic response than propranolol or nifedipine when compared with placebo. Long-term verapamil therapy was instituted in 227 patients; 133 of these patients have continued taking the medication for an average of 25 +/- 13 months because their quality of life improved compared with what they experienced with their former therapy (usually beta blocker). Improved exercise capacity of 40% has been maintained in 32 patients for 2 years. A decrease in ventricular septal thickness of 1.5 +/- 2.6 mm was also found in 32 patients studied after 39 +/- 8 months of verapamil therapy. Nine patients died during follow-up study, but it is unclear whether the drug increased survival or, conversely, whether any of the deaths could be attributed to verapamil administration. Significant adverse electrophysiologic and hemodynamic effects were seen in 59 instances. The electrophysiologic events, atrioventricular block and sinus arrest, were definitely verapamil-related, but it is uncertain how many of the hemodynamic problems of hypotension and pulmonary congestion were drug-related.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Secondary prevention and lipid lowering: results and implications.

In a secondary prevention trial conducted by the National Heart, Lung, and Blood Institute, the effect of lipid lowering by drug intervention on the progression of existing coronary artery disease (CAD) was evaluated in type II hyperlipidemic patients. This first randomized, secondary prevention trial compared the effect of cholestyramine and diet with that of placebo and diet in 143 patients over a 5-year period. End points evaluated were progression or regression of CAD, as demonstrated by angiographic changes compared with baseline angiograms. The cholestyramine-treated group demonstrated a significant reduction in total cholesterol and in low-density lipoprotein cholesterol (LDL) levels as compared with placebo, and an 8% increase in high-density lipoprotein cholesterol (HDL). A statistically significant result supporting the use of cholestyramine treatment was found in one category of CAD progression.

Angiocardiography↗
PubMed1985

Cost-effective application of the Centers for Disease Control Guideline for Prevention of Catheter-associated Urinary Tract Infections.

To decrease UTIc in a cost-efficient manner, efforts should be concentrated in areas that have been shown to be beneficial. These include the following measures: have an established infection control program; catheterize patients only when necessary, by using aseptic technique, sterile equipment, and trained personnel; maintain a closed sterile drainage system; do not disconnect the catheter and drainage tubing unless absolutely necessary; remove the catheter as soon as possible; and follow and reinforce good handwashing technique. Changing indwelling catheters at arbitrary fixed intervals and regular bacteriologic monitoring of catheterized patients are not cost-effective practices and should not be performed. Other measures should be avoided until further data are available. New products that appear to be questionable or gimmicky probably are and should also be avoided.

Centers for Disease Control and Prevention, U.S.↗
PubMed1985

Dynamic subaortic obstruction in hypertrophic cardiomyopathy: analysis by pulsed Doppler echocardiography.

To determine whether true obstruction to left ventricular ejection exists in patients with hypertrophic cardiomyopathy and a subaortic gradient, pulsed Doppler echocardiography was used to analyze the patterns of left ventricular emptying in 50 patients with hypertrophic cardiomyopathy (20 with and 30 without evidence of obstruction) and in 20 normal subjects. In obstructive hypertrophic cardiomyopathy, left ventricular ejection was characterized by early and rapid emptying (76 +/- 14% of aortic flow velocity in the initial one-third of systole). The proportion of forward flow velocity occurring before initial mitral-septal contact (and hence, by inference before the onset of the subaortic gradient) was variable, but averaged 58%. In contrast, the proportion of forward flow velocity occurring after mitral-septal contact (and, therefore, concomitant with the gradient and increased intraventricular pressure) was considerable, averaging over 40%. Mid-systolic impedance to left ventricular outflow was suggested by the rapid deceleration in aortic flow velocity concomitant with mitral-septal contact and premature partial aortic valve closure. Furthermore, left ventricular ejection was prolonged (384 +/- 40 ms) and the ventricle continued to empty and shorten during the period when both the pressure gradient and markedly increased intraventricular pressures were present. In 16 of 20 patients, a relatively small second peak in flow velocity appeared in late systole. Since marked systolic anterior motion of the mitral valve was still present, the late systolic portion of forward flow velocity also appeared to be largely ejected during imposition of a mechanical impediment to outflow. In contrast, patients with nonobstructive hypertrophic cardiomyopathy showed no evidence of impedance to left ventricular ejection. Aortic flow velocity waveforms were similar to those of normal subjects, with flow persisting to aortic valve closure; significant mitral systolic anterior motion and partial mid-systolic aortic valve closure were absent, and the systolic ejection period was normal (303 +/- 27 ms).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Effect of verapamil on pH of ischemic canine myocardium.

Verapamil has been shown to depress the contractility of ischemic myocardium. The present study was designed to determine whether that effect is due to an increase in ischemic injury caused by the drug or whether it might reflect a protective effect. A critical partial occlusion was effected on the left anterior descending coronary artery of 16 open chest foxhounds. A fiberoptic pH probe was implanted in the subendocardium of the ischemic zone, and coronary blood flow was reduced by 79% from a control value of 38 +/- 4 ml/min and held constant. Mean coronary perfusion pressure was decreased 48% from its control value of 90 +/- 6 mm Hg and remained constant. Eight animals were treated with intravenous verapamil, beginning 20 to 30 minutes after the onset of ischemia, in incremental doses (5, 10 and 20 micrograms/kg per min) and eight were treated with placebo. The pH of the ischemic zone increased after institution of treatment in the verapamil group (+ 0.04 +/- 0.05 pH unit) whereas it decreased in the placebo group (- 0.06 +/- 0.4 pH unit) during the first dose (p less than 0.05). Although the difference in pH between the two groups was marked at all doses (p less than 0.03) compared with control partial occlusion, verapamil caused no significant change in heart rate (+ 0.1 +/- 1 beat/min in the verapamil group versus + 0.6 +/- 4.5 beats/min in the placebo group), mean arterial pressure (- 7.5 +/- 4 versus - 4.3 +/- 3 mm Hg, respectively) or cardiac output (- 0.2 +/- 0.07 versus - 0.02 +/- 0.04 liters/min, respectively) comparing control with the first or the second dose of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve.

Thirty-three patients with chest pain despite angiographically normal coronary arteries underwent both coronary flow studies during pacing and resting and exercise gated blood pool scintigraphy. During atrial pacing after administration of ergonovine, those patients developing their typical chest pain demonstrated significantly lower great cardiac vein flow (97 +/- 31 vs 150 +/- 33 ml/min, p less than .001), higher coronary resistance (1.27 +/- 0.43 vs 0.77 +/- 0.18 mm Hg/ml/min, p less than .005), and less lactate consumption (30.5 +/- 22.0 vs 69.7 +/- 41.1 mM . ml/min, p less than .005) and a higher left ventricular end-diastolic pressure after pacing (20 +/- 4 vs 12 +/- 1, p less than .001) compared with those without pain and in the absence of significant luminal narrowing of the epicardial coronary arteries. The 26 patients with abnormal vasodilator reserve demonstrated reduced left ventricular ejection fraction during exercise (58 +/- 8%) compared with the seven patients with appropriate vasodilator reserve (66 +/- 4%, p less than .05) and with a group of 52 control patients of similar age and sex distribution and free of known heart disease (66 +/- 10%, p less than .001). In addition, 12 of the 26 patients with abnormal vasodilator reserve demonstrated exercise-induced regional wall motion abnormalities. Many of these patients also manifested impaired left ventricular diastolic filling at rest compared with the control subjects (peak filling rate 2.6 +/- 0.7 vs 3.2 +/- 0.7 end-diastolic volume/sec, p less than .005). Thus, patients with chest pain resulting from abnormal vasodilator reserve demonstrate abnormalities of left ventricular systolic and diastolic function suggestive of myocardial ischemia.

Adult↗
PubMed1985

Myocardial ischemia in patients with hypertrophic cardiomyopathy: contribution of inadequate vasodilator reserve and elevated left ventricular filling pressures.

To study the mechanism and hemodynamic significance of myocardial ischemia in hypertrophic cardiomyopathy, 20 patients (nine with resting left ventricular outflow tract obstruction greater than or equal to 30 mm Hg) with a history of angina pectoris and angiographically normal coronary arteries underwent a pacing study with measurement of great cardiac vein flow, lactate and oxygen content, and left ventricular filling pressure. Compared with 28 control subjects without hypertrophic cardiomyopathy, their resting coronary blood flow was higher (91 +/- 27 vs 66 +/- 17 ml/min; p less than .001) and their coronary resistance was lower (1.13 +/- 0.38 vs 1.55 +/- 0.45 mm Hg/ml/min; p less than .001). Left ventricular end-diastolic pressure (16 +/- 6 vs 11 +/- 3 mm Hg; p less than .001) and pulmonary arterial wedge pressure (13 +/- 5 vs 7 +/- 3 mm Hg; p less than .001) were significantly higher in patients with hypertrophic cardiomyopathy. During pacing, coronary flow rose in both groups, although coronary and myocardial hemodynamics differed greatly. In contrast to the linear increase in flow in control subjects up to heart rate of 150 beats/min (66 +/- 17 to 125 +/- 28 ml/min), patients with hypertrophic cardiomyopathy demonstrated an initial rise in flow to 133 +/- 31 ml/min at an intermediate heart rate of 130 beats/min. At this point, 12 of 20 patients developed their typical chest pain. With continued pacing to a heart rate of 150 beats/min, mean coronary flow fell to 114 +/- 29 ml/min (p less than .002), with 18 of 20 patients experiencing their typical chest pain and metabolic evidence of myocardial ischemia. This fall in coronary flow was associated with a substantial rise in left ventricular end-diastolic pressure (30 +/- 9 mm Hg immediately after peak pacing). In the 14 patients whose coronary flow actually fell from intermediate to peak pacing, the rise in left ventricular end-diastolic pressure in the same interval was greater than that of the six patients whose flow remained unchanged or increased (11 +/- 8 vs 2 +/- 2 mm Hg; p less than .01). In addition, despite metabolic and hemodynamic evidence of myocardial ischemia, the arteriovenous O2 difference actually narrowed at peak pacing. Thus most patients with hypertrophic cardiomyopathy achieved maximum coronary vasodilation and flow at modest increases in heart rate. Elevation in left ventricular filling pressure, probably related to ischemia-induced changes in ventricular compliance, was associated with a decline in coronary flow.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1985

Effects of sublingual nifedipine on hemodynamics and systolic and diastolic function in patients with hypertrophic cardiomyopathy.

The hemodynamic effects of sublingual nifedipine were examined in 36 patients with hypertrophic cardiomyopathy. Twenty-one patients were initially given 20 mg and 15 patients were given 10 mg of the drug; 30 min after this first dose 26 patients received 10 mg and one patient 20 mg as a second dose. Hemodynamic findings in patients who received different doses of the drug were similar. Peak effects included an increase in heart rate from 79 +/- 12 to 91 +/- 14 (mean +/- 1 SD) beats/min (p less than .01), and a decrease in mean blood pressure from 89 +/- 12 to 77 +/- 10 mm Hg (p less than .01). Cardiac index increased after nifedipine (2.8 +/- 0.6 to 3.3 +/- 0.8 liters/min/m2; p less than .01); stroke volume index, however, did not change (36 +/- 7 to 36 +/- 8 ml/beat/m2; NS). Peripheral vascular resistance index fell significantly from 822 +/- 261 to 610 +/- 197 dynes X sec X cm-5 (p less than .01). Overall, left ventricular outflow tract gradient (LVOTG) did not change in patients with significant (greater than or equal to 30 mm Hg) basal LVOTG (75 +/- 22 to 83 +/- 22 mm Hg; NS), but it increased significantly in those six patients in whom peripheral vascular resistance fell by 25% or more (73 +/- 28 to 99 +/- 22 mm Hg; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function.

Recent studies suggest that preoperative left ventricular function may no longer be an important determinant of survival or functional results after operation for aortic regurgitation because of improved operative techniques. To assess the effect of left ventricular function on prognosis in the current surgical era, we performed echocardiographic and radionuclide angiographic studies in 80 consecutive patients undergoing valve replacement from 1976 to 1983. No patient had associated coronary artery disease. For all patients, 5 year survival was 83 +/- 5%, significantly better than the 62 +/- 9% 5 year survival in our patients operated on from 1972 to 1976. Preoperative resting left ventricular ejection fraction (p less than .001), fractional shortening (p less than .001), and end-systolic dimension (p less than .01) were the most significant predictors of survival (univariate life-table analysis). Five year survival was 63 +/- 12% in patients with subnormal ejection fraction (n = 50) compared with 96 +/- 3% in those with normal ejection fraction (n = 30). Patients with subnormal left ventricular ejection fraction and poor exercise tolerance or prolonged duration of left ventricular dysfunction (greater than 18 months) comprised the high-risk subgroup (5 year survival 52 +/- 11%). Patients in this subgroup also had persistent left ventricular dysfunction after operation, with greater left ventricular end-diastolic dimensions and reduced ejection fraction (both p less than .001) compared with patients with normal preoperative left ventricular ejection fraction or a brief duration of left ventricular dysfunction (less than 14 months). Cold hyperkalemic cardioplegia was used for myocardial preservation in 46 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1985

Indications for coronary artery bypass surgery in patients with chronic angina pectoris: implications of the multicenter randomized trials.

The three major randomized studies of medical vs surgical therapy in patients with coronary artery disease have had a major impact in the management of patients with this disease. For the most part, these multicenter trials have provided concordant information regarding the influence of surgery on survival in asymptomatic or mildly symptomatic patients. It has been demonstrated that coronary artery bypass surgery improves survival in patients with stenosis of the left main coronary artery. Bypass surgery probably should be performed in most patients with this lesion, although studies have identified low-risk subgroups in whom surgery may not improve survival. There are also concordant data that survival is not enhanced by surgery in mildly symptomatic patients with either one- or two-vessel disease. The important discrepancies regarding the role of surgery in three-vessel disease have been resolved to a major extent. Long-term follow-up studies in the Veterans Administration Cooperative Study and the Coronary Artery Surgery Study (CASS) demonstrate improved survival with surgical management in patients with three-vessel disease and left ventricular dysfunction. The remaining controversy regards management of patients with three-vessel disease and normal left ventricular function; this may be resolved by studies indicating that inducible left ventricular ischemia in patients with three-vessel disease and preserved left ventricular function at rest identifies patients at higher risk during medical management. Different proportions of such patients entered into the multicenter studies may explain the discordant results in three-vessel disease and normal left ventricular function reported by the European trial and CASS.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗
PubMed1984

Mechanisms contributing to precipitation of unstable angina and acute myocardial infarction: implications regarding therapy.

Clinical and autopsy studies indicate that most patients who present with unstable angina or an acute myocardial infarction (AMI) have significant underlying coronary atherosclerosis. This review discusses 4 mechanisms that may contribute to the precipitation of these acute ischemic clinical syndromes: progression of atherosclerosis, acute coronary thrombosis, coronary artery spasm, and platelet aggregation. Numerous clinical trials using thrombolytic agents early during AMI have shown the incidence of thrombosis to be at least 60%. Other studies suggest that platelet aggregation frequently contributes to the evolution of AMI from unstable angina and that spasm may occasionally play a similar role. The therapeutic implications of these mechanisms are also considered in light of their potential to restore coronary artery blood flow (vs conventional methods thought mainly to reduce myocardial oxygen demand) and thereby limit the infarct process. The role of vasodilators, thrombolytic agents, antiplatelet drugs and beta-adrenergic blocking drugs are discussed. Finally, therapeutic guidelines for the treatment of acutely ill patients are constructed that emphasize the need for a comprehensive yet time-efficient treatment strategy that uses nitrates, calcium channel-blocking drugs, streptokinase, heparin, aspirin and, in selected patients in an unstable condition, emergency percutaneous transluminal coronary angioplasty and coronary artery bypass grafting.

Adrenergic beta-Antagonists↗
PubMed1984

Exercise-induced ischemia in mildly symptomatic patients with coronary-artery disease and preserved left ventricular function. Identification of subgroups at risk of death during medical therapy.

To determine prospectively whether the severity of reversible left ventricular ischemia provides prognostic information in mildly symptomatic patients with coronary-artery disease and preserved left ventricular function at rest (ejection fraction greater than 40 per cent), we studied 117 patients by means of exercise electrocardiography and radionuclide angiography. No patient had stenosis of the left main coronary artery. Mortality during subsequent medical therapy was significantly associated (by univariate life-table analysis) with three-vessel coronary-artery disease and the magnitude of the ejection fraction during exercise. In patients with three-vessel disease who had both ST-segment depression of 1 mm or more and a decrease in ejection fraction during exercise, in association with an exercise tolerance of 120 W or less, the probability of survival at four years was only 71 +/- 11 per cent (S.E.). All deaths occurred in this subgroup. Thus, objective evidence of left ventricular ischemia during exercise and exercise capacity identify one subgroup of minimally symptomatic patients with three-vessel disease with an excellent prognosis and another subgroup at relatively high risk of dying during subsequent medical therapy.

Adult↗
PubMed1984

Relation between marked changes in left ventricular outflow tract gradient and disease progression in hypertrophic cardiomyopathy.

Spontaneous and persistent changes in left ventricular (LV) outflow gradient have been observed occasionally in patients with hypertrophic cardiomyopathy (HC). However, the significance and frequency of such hemodynamic alterations have not been established. In this study, the serial preoperative hemodynamic status of 409 patients with HC was analyzed. Basal LV outflow tract obstruction either spontaneously appeared (or increased) or disappeared (or decreased) in 19 nonoperated patients (about 5%). Changes in hemodynamic state were shown by serial cardiac catheterization in 17 patients and by catheterization and M-mode echocardiography in 2 patients. In most patients (12 of 19), subaortic obstruction under basal conditions appeared or increased; 8 became more symptomatic and in 4 the condition remained stable. Reduction or loss of LV outflow gradient occurred in 7 patients; in 5 of these the condition deteriorated clinically and in 2 it did not change. Hence, in 13 of the 19 patients (70%), spontaneous changes in the magnitude of the basal LV outflow gradient were associated with symptomatic progression. The mechanism of the decrease or disappearance of subaortic obstruction in those patients who deteriorated clinically appeared to be related in 4 patients to impaired global and/or segmental LV function. Chronic atrial fibrillation probably contributed to the worsening clinical condition in 2 of these patients as well as in 2 others. In conclusion, substantial changes in the magnitude of basal subaortic obstruction may occur in a small proportion of patients with HC as part of the natural history of their disease, and such hemodynamic alterations are usually associated with clinical deterioration. It is exceedingly rare for the hemodynamic state of a patient with HC to change from totally nonobstructive to obstructive or vice versa, because such patients usually retain the capacity to generate gradients with provocative maneuvers.

Adult↗