A randomized study was performed on 104 patients undergoing elective coronary artery bypass grafting to examine whether the infusion of nifedipine (n = 53) reduces the incidence of perioperative myocardial ischemia and necrosis in the early postoperative period. Continuous hemodynamic and three-channel Holter monitoring was performed for 24 hours and serial assessment of serum enzymes and 12-lead electrocardiography were performed for 36 hours postoperatively. Nifedipine (minimum dose, 10 micrograms/kg/hr for 24 hours) was applied from the onset of extracorporal circulation. The control group (n = 51) received nitroglycerin (minimum dose, 1 micrograms/kg/min for 24 hours). Using the combined analyses of electrocardiography and Holter recordings, myocardial ischemia was defined as being either a transient ischemic event (TIE), transient coronary spasm (TCS), or myocardial infarction (MI). The two groups did not differ with respect to preoperative New York Heart Association classification, age, history of myocardial infarction, extracorporal circulation and aortic cross-clamp time, number of distal anastomoses, or systemic and pulmonary hemodynamics. The incidence of perioperative myocardial ischemia was substantially lower in the nifedipine than in the nitroglycerin group [TIE: three of 53 patients (6%) versus nine of 50 patients (18%), p less than 0.001; MI: two of 53 patients (4%) versus six of 50 patients (12%), p less than 0.001; and TCS: none of 53 patients (0%) versus two of 50 patients (4%), p = NS].(ABSTRACT TRUNCATED AT 250 WORDS)

In the Thrombolysis in Myocardial Infarction, Phase II pilot and clinical trial, 908 patients [326 (35.9%) in the pilot study and 582 (64.0%) in the randomized study] were treated with 150 mg recombinant tissue-type plasminogen (rt-PA) activator in combination with heparin and aspirin, and 3,016 patients [64 (2.1%) in the pilot study and 2,952 (97.9%) in the randomized study] were treated with 100 mg rt-PA in combination with heparin and aspirin. Adverse neurological events occurred in 23 patients treated with 150 mg rt-PA (2.5%) [nine cerebral infarctions (1.0%), 12 intracerebral hemorrhages (1.3%), and two subdural hematomas (0.2%)] and in 33 patients treated with 100 mg rt-PA (1.1%) [20 cerebral infarctions (0.7%), 11 intracerebral hemorrhages (0.4%), and two subdural hematomas (0.1%)]. The difference in adverse neurological events observed comparing the two rt-PA regimens was primarily due to a higher frequency of intracerebral bleeding among patients treated with 150 mg rt-PA (1.3% versus 0.4%, p less than 0.01). Patients with recent (within 6 months) histories of stroke were not eligible for the study, and patients with any history of cerebrovascular disease were declared ineligible early in the study. The small number of patients (89, or 2.3%) with any history of neurological disease, intermittent cerebral ischemic attacks, or stroke who were enrolled before the stricter eligibility criteria were imposed or on the basis of incomplete baseline information experienced an increased frequency of intracerebral hemorrhage compared with patients without such histories (3.4% versus 0.5%). Mortality at 6 weeks after presentation among 23 patients who had intracerebral hemorrhage was 47.8%. Intracerebral hemorrhage is a severe but infrequent complication of rt-PA therapy for acute myocardial infarction. The combined frequency of intracerebral hemorrhage, subdural hematoma, and cerebral infarction after treatment with 100 mg rt-PA is comparable to that observed in other trials with thrombolytic agents in acute myocardial infarction.

Studies in animals have shown that drug-induced action potential prolongation with class III antiarrhythmic agents increases with slow pacing rates. We studied the physiological rate dependence of sotalol effects on ventricular repolarization, measured as QT interval duration on the surface electrocardiogram at rest and during a maximal exercise test, in 10 normal volunteers. In a randomized, crossover study, three dosages of sotalol (160 mg/24 hr, 320 mg/24 hr, and 640 mg/24 hr) were administered during 4 days to each subject. In a control period, no drug was administered. During each period, 50-100 QT intervals were measured over a wide range of RR intervals recorded at rest and during the course of a maximal exercise test. Plasma sotalol concentration and beta-adrenoceptor blockade (percent reduction in peak exercise heart rate from control) were also measured. The QT-versus-RR relation was fitted to several formulas, and the overall best fit was used to calculate QT interval duration normalized for a heart rate of 60 beats/min (QTc) and to analyze the rate dependence of QT prolongation with sotalol. Sotalol-induced beta-adrenoceptor blockade and QTc prolongation were dose and concentration dependent. Sotalol reduced peak exercise heart rate by 13.8 +/- 7% at the dosage of 320 mg/24 hr and by 25.4 +/- 8% at the dosage of 640 mg/24 hr (both p less than 0.01). Sotalol prolonged QTc interval by 5.8 +/- 3.7% and 11.8 +/- 3% at these respective dosages (both p less than 0.01). The concentration of sotalol required to produce minimal (mean QTc prolongation, 5.6%; confidence interval, 0-11.2%) QTc prolongation (680 ng/ml) tended to be lower than that required for minimal (mean percent reduction in maximal exercise heart rate, 13.9%; confidence interval, 0-27.8%) beta-blockade (840 ng/ml). QT prolongation with sotalol increased with increasing RR intervals (i.e., decreasing heart rate) at all dosages. QT prolongation became statistically significant for RR of 800 msec or more at all dosages and for RR intervals of 600 msec or more at the dosage of 640 mg/24 hr. This rate dependence altered the relation between QT interval duration and sotalol plasma concentrations. These results suggest that sotalol prolongs QTc interval in humans at dosages and concentrations similar to those required to produce beta-adrenoceptor blockade, QT prolongation with sotalol is more pronounced when heart rate decreases and is not apparent during exercise-induced tachycardia, and the relation between QT prolongation with sotalol and plasma concentrations of the drug depends on the heart rate at which measurements are made.

In the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial, patients received intravenous recombinant tissue-type plasminogen activator (rt-PA) and were randomized to either a conservative or an invasive strategy. Within this study, the effects of immediate versus deferred beta-blocker therapy were also assessed in patients eligible for beta-blocker therapy, a group of 1,434 patients of which 720 were randomized to the immediate intravenous group and 714 to the deferred group. In the immediate intravenous group, within 2 hours of initiating rt-PA metoprolol was given (5 mg intravenously at 2-minute intervals over 6 minutes, for a total intravenous dose of 15 mg, followed by 50 mg orally every 12 hours in the first 24 hours and 100 mg orally every 12 hours thereafter). The patients assigned to the deferred group received metoprolol, 50 mg orally twice on day 6, followed by 100 mg orally twice a day thereafter. The therapy was tolerated well in both groups and the primary end point, resting global ejection fraction at hospital discharge, averaged 50.5% and was virtually identical in the two groups. The regional ventricular function was also similar in the two groups. Overall, there was no difference in mortality between the immediate intravenous and deferred groups, but in the subgroup defined as low risk there were no deaths at 6 weeks among those receiving immediate beta-blocker therapy in contrast to seven deaths among those in whom beta-blocker therapy was deferred. These findings for a secondary end point in a subgroup were not considered sufficient to warrant a recommendation regarding clinical use. There was a lower incidence of reinfarction (2.7% versus 5.1%, p = 0.02) and recurrent chest pain (18.8% versus 24.1%, p less than 0.02) at 6 days in the immediate intravenous group. Thus, in appropriate postinfarction patients, beta-blockers are safe when given early after thrombolytic therapy and are associated with decreased myocardial ischemia and reinfarction in the first week but offer no benefit over late administration in improving ventricular function or reducing mortality.

The Multicenter Diltiazem Postinfarction Trial (MDPIT) reported no consistent diltiazem effect on new or worsened congestive heart failure (CHF) during 12-52 months' follow-up after acute myocardial infarction. This was puzzling in light of the observation that patients with findings suggesting left ventricular dysfunction (LVD) at baseline on diltiazem had more cardiac events (cardiac mortality or recurrent nonfatal infarction) than such patients on placebo. We hypothesized that diltiazem increased the frequency of late CHF as well as of cardiac events, but only in patients predisposed by LVD. Using the same characterizing variables as the primary MDPIT analysis, we found that patients with pulmonary congestion, anterolateral Q wave infarction, or reduced ejection fraction (EF) at baseline were more likely to have CHF during follow-up than those without these markers of LVD. CHF was particularly frequent in the patients with LVD who were randomized to diltiazem. Among those with a baseline EF of less than 0.40, late CHF appeared in 12% (39/326) receiving placebo and 21% (61/297) receiving diltiazem (p = 0.004). Life table analysis in patients with an EF of less than 0.40 confirmed more frequent late CHF in those taking diltiazem (p = 0.0017). In addition, the diltiazem-associated rise in the frequency of late CHF was progressively greater with increasingly severe decrements in baseline EF. This diltiazem effect was absent in patients with pulmonary congestion at baseline but an EF of 0.40 or more, suggesting a unique association between diltiazem-related late CHF and systolic LVD.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolytic therapy has been shown to improve clinical outcome when administered early after the onset of symptoms of acute myocardial infarction; the mechanism of benefit is believed to be reestablishment and maintenance of coronary artery patency. Anistreplase is a second generation thrombolytic agent that is easily administered and has a long duration of action. To compare anistreplase (30 units/2-5 min) and therapy with the Food and Drug Administration-approved regimen of intravenous streptokinase (1.5 million units/60 min), a randomized, double-blind, multicenter patency trial was undertaken in 370 patients less than 76 years of age with electrocardiographic ST segment elevation who could be treated within 4 hours of symptom onset. Coronary patency was determined by reading, in a blinded fashion, angiograms obtained early (90-240 minutes; mean, 140 minutes) and later (18-48 hours; mean, 28 hours) after beginning therapy. Early total patency (defined as Thrombolysis in Myocardial Infarction grade 2 or 3 perfusion) was high after both anistreplase (132/183 = 72%) and streptokinase (129/176 = 73%) therapy, and overall patency patterns were similar, although patent arteries showed "complete" (grade 3) perfusion more often after anistreplase (83%) than streptokinase (72%) (p = 0.03). Similarly, residual coronary stenosis, determined quantitatively by a validated computer-assisted method, was slightly less in patent arteries early after anistreplase (mean stenosis diameter, 74.0%) than streptokinase (77.2%, p = 0.02). In patients with patent arteries without other early interventions, reocclusion risk within 1-2 days was defined angiographically and found to be very low (anistreplase = 1/96, streptokinase = 2/94). Average coronary perfusion grade was greater, and percent residual stenosis was less, at follow-up than on initial evaluation and did not differ between treatment groups. Enzymatic and electrocardiographic evolution was not significantly different in the two groups. Despite rapid injection, anistreplase was associated with only a small (4-5 mm Hg), transient (at 5-10 minutes) mean differential fall in blood pressure. In-hospital mortality rates were comparable for anistreplase and streptokinase (5.9%, 7.1%). Stroke occurred in one (0.5%) and three (1.6%) patients, respectively; one stroke was hemorrhagic. Other serious bleeding events and adverse experiences occurred uncommonly and with similar frequency in the two groups. Thus, for the end points of our study (patency, safety), anistreplase and streptokinase showed overall favorable and relatively comparable outcomes, with a few differences.(ABSTRACT TRUNCATED AT 400 WORDS)

To assess the effect of bypass surgery on outcome from unstable angina, 468 patients were randomized to medical treatment (237 patients) or surgery plus medical treatment (231 patients) and have been followed for comparison of survival, cardiac end points, and quality of life; the latter end point is discussed in the present report. Data were available at 3 and 5 years for 80% and 82% of patients in the medical group, respectively, and 77% and 80% of patients in the surgery group, respectively. At 3 months after randomization to therapy, 79.8% of patients in the surgery group reported subjective improvement, compared with 58% of the medical group, 12.6% of the surgery group reported no change compared with 24.5% of the medical group, and 5.5% of the surgery group reported worsening compared with 24.5% of the medical group (p less than 0.01 by chi 2). Similar data were found for chest pain status, and the benefit to the surgery group remained statistically significant through 5 years of follow-up. Crossover rate to surgery was 43% by 5 years. Treadmill duration was increased in the surgery group compared with the medical group (6.5 +/- 0.25 versus 5.3 +/- 0.25 minutes at 6 months, p less than 0.01), and a significant difference was again demonstrated at 3 and 5 years. A trend toward decreased recurrence of unstable angina was present in the surgery group at 1 year (six of 168 [3.6%] versus 13 of 187 [6.9%] in the medical group, p = 0.158), but the two groups were similar at 3 and 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether there are differences in responses to thrombolytic therapy in certain populations, the data for the Thrombolysis and Angioplasty in Myocardial Infarction (phase 1) study were analyzed for black and white patients. Baseline variables including risk factors and extent of coronary artery disease were similar in the 352 white and 24 black patients. The time from onset of chest pain to recombinant tissue-type plasminogen activator (rt-PA) therapy and rt-PA dosing regimens were the same in the two groups. The patency rate of the infarct-related artery at 90 minutes was 91% for blacks and was 72% for whites (p = 0.051). Blacks displayed significantly lower nadir fibrinogen levels (0.57 +/- 0.62 versus 1.3 +/- 0.76 g/l, p less than 0.0001), greater delta fibrinogen (baseline-nadir) (2.7 +/- 1.1 versus 1.7 +/- 1.1 g/l, p less than 0.0001), and increased peak levels of fibrin(ogen) degradation products (837 +/- 865 versus 245 +/- 475 micrograms/ml, p less than 0.0001). rt-PA antigen levels tended to be higher in blacks than in whites (2.8 +/- 2.2 versus 2.2 +/- 3.2 micrograms/ml [p = 0.10] at the peak and 1.6 +/- 1.3 versus 0.99 +/- 1.4 micrograms/ml [p = 0.06] at the end of the maintenance infusion). Major clinical outcomes including survival until time of hospital discharge (92% black versus 93% white, p = 0.68) were not significantly different. However, despite undergoing fewer angioplasty procedures (25% versus 46.3%, p = 0.047), blacks received more transfusions (58.8% versus 19.5% were administered greater than or equal to 2 units packed erythrocytes, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Oral flecainide acetate was administered to 34 patients with documented symptomatic paroxysmal supraventricular tachycardia (PSVT) with a double-blind, placebo-controlled, 8-week crossover trial design. PSVT was defined as a regular tachycardia of at least 120 beats/min without evidence of atrioventricular dissociation. The study required considerable patient cooperation. Patients first entered a 4-week qualifying phase followed by a 3-week, open label, flecainide dose-ranging phase. They were then randomized in a blind fashion to receive either placebo or tolerated flecainide dose for an 8-week treatment period and then crossed over after four symptomatic documented episodes of PSVT or at the end of the treatment period. By all efficacy parameters analyzed, flecainide was superior to placebo. Flecainide was associated with an actuarial 79% freedom from symptomatic PSVT events compared with only 15% on placebo at 60 days (p less than 0.001). Of the 34 patients, 29 had recurrence of symptomatic PSVT at least once during the placebo phase; only eight patients had a recurrence during the flecainide phase (p less than 0.001). The median time to the first symptomatic PSVT event was 11 days in the placebo group and greater than 55 days in the flecainide group (p less than 0.001). Likewise, the interval between attacks was a median of 12 days on placebo compared with more than 55 days on flecainide (p less than 0.001). Finally, the flecainide slowed symptomatic PSVT heart rates to 143 +/- 12 beats/min from 178 +/- 12 on placebo (p less than 0.02) in the seven patients who had events in the placebo and flecainide treatment phases.(ABSTRACT TRUNCATED AT 250 WORDS)

In 167 patients with complete occlusion (greater than 3 cm) of the femoropopliteal artery, percutaneous transluminal laser angioplasty (PTLA) was performed after an unsuccessful attempt at crossing with a guide wire and was immediately followed by balloon dilatation. An Nd-YAG laser and an optical fiber delivery system with a sapphire tip serving as a contact probe were used for PTLA. In 132 of 167 (79%) patients, the occluded segment was successfully reopened. Clinical symptoms improved in 126 of 167 (75%) patients. PTLA was unsuccessful in 35 patients, and in 15 of these, injury of the vessel wall occurred. In one patient, surgical drainage of a large hematoma became necessary. All patients in whom recanalization had been achieved were randomized to receive long-term treatment with either phenprocumarol or acetylsalicylic acid (ASA) plus dipyridamole to prevent rethrombosis. At 36 months of follow-up, the cumulative patency rate (CPR) was 63%. A complete reobstruction in 32 patients (24%) and a partial reobstruction in 15 patients (11%) were found angiographically. The CPR after 36 months was significantly lower (p less than 0.05) in patients younger than 60 years of age (54%) than in patients older than 60 (68%); it was also significantly lower (p less than 0.05) in patients with reduced peripheral runoff (55%) due to obstructed arteries of the lower leg than in patients with unaffected runoff (73%). The CPR was 65% in recanalized segments shorter than 7 cm and was 62% in recanalized segments longer than 7 cm.(ABSTRACT TRUNCATED AT 250 WORDS)

We performed a prospective, randomized, double-blind, crossover study to compare the efficacy and safety of vasodilation with the calcium entry blocker nifedipine with that of isosorbide dinitrate (ISDN) and their combination as treatment for heart failure. Twenty-eight patients with New York Heart Association Functional class II or III chronic heart failure due to left ventricular systolic dysfunction were studied. All patients were maintained on a constant dose of digitalis and diuretics throughout the study. Eight weeks of therapy with nifedipine alone or in combination with ISDN resulted in a significantly higher incidence of heart failure deterioration necessitating hospitalizations and/or additional diuretics. Twenty-four percent of patients required hospitalization during nifedipine therapy and 26% required hospitalization during nifedipine-ISDN combination therapy in comparison to 0% requiring hospitalization during ISDN therapy alone. The total number of heart failure-worsening episodes was nine among patients on nifedipine, three among patients on ISDN (p less than 0.09 versus nifedipine), and 21 among patients on nifedipine-ISDN combination (p less than 0.001 versus nifedipine, p less than 0.0001 versus ISDN). Premature discontinuation of drug administration due to clinical deterioration or other side effects occurred in 29% of patients during nifedipine therapy, 5% of patients during ISDN therapy (p = 0.05 versus nifedipine), and 19% of patients during the combination therapy. A comparison of eight patients who demonstrated clinical deterioration on nifedipine with the remainder of the patients demonstrated no significant difference in left ventricular ejection fraction (0.24 +/- 0.06 versus 0.23 +/- 0.07) or maximal oxygen uptake during exercise (13 +/- 3 versus 14 +/- 2 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

This open, parallel-group study compares quinidine and sotalol treatment for maintenance of sinus rhythm after direct current conversion of patients with chronic atrial fibrillation. The patients from 15 centers in Sweden were randomized to sotalol (98 patients) or quinidine (85 patients) after 2 hours of sinus rhythm after direct current conversion. According to primary efficacy assessment, 52% of the patients in the sotalol group and 48% of the patients in the quinidine group remained in sinus rhythm during the following 6-month treatment period (NS). Furthermore, 34% of the patients treated with sotalol and 22% of the patients treated with quinidine relapsed into atrial fibrillation (NS). Heart rate after relapsing into atrial fibrillation was higher in the patients treated with quinidine (109 beats/min) than in the patients treated with sotalol (78 beats/min, p less than 0.001). Patients treated with sotalol were found to be less symptomatic at the time of relapse compared with relapsing patients in the quinidine group. In terms of safety, more patients were withdrawn from quinidine than from sotalol treatment (26% vs. 11%, p less than 0.05), and sotalol was generally better tolerated than quinidine. Twenty-eight percent of the patients treated with sotalol and 50% of the patients treated with quinidine reported side effects (p less than 0.01). The difference was primarily a result of early (within the first month of treatment) gastrointestinal and skin side effects in the group of patients treated with quinidine.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred ninety-nine patients with out-of-hospital cardiac arrest persisted in ventricular fibrillation after the first defibrillation attempt and were then randomly assigned to receive either epinephrine or lidocaine before the next two shocks. The resulting electrocardiographic rhythms and outcomes for each group of patients were compared for each group and also compared with results during the prior 2 years, a period when similar patients primarily received sodium bicarbonate as initial adjunctive therapy. Asystole occurred after defibrillation with threefold frequency after repeated injection of lidocaine (15 of 59, 25%) compared with patients treated with epinephrine (four of 55, 7%) (p less than 0.02). There was no difference in the proportion of patients resuscitated after treatment with either lidocaine or epinephrine (51 of 106, 48% vs. 50 of 93, 54%) and in the proportion surviving (18, 19% vs. 21, 20%), respectively. Resuscitation (64% vs. 50%, p less than 0.005) but not survival rates (24% vs. 20%) were higher during the prior 2-year period in which initial adjunctive drug treatment for persistent ventricular fibrillation primarily consisted of a continuous infusion of sodium bicarbonate. The negative effect of lidocaine or epinephrine treatment was explained in part by their influence on delaying subsequent defibrillation attempts. Survival rates were highest (30%) in a subset of patients who received no drug therapy between shocks. We conclude that currently recommended doses of epinephrine and lidocaine are not useful for improving outcome in patients who persist in ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Episodes of transient myocardial ischemia during ambulatory activities are common in patients with stable coronary artery disease and who are often asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is limited by a lack of direct comparative studies. To determine the most effective monotherapy for patients with stable angina and a high frequency of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293 mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose, 79 mg) were each compared with placebo, each for 2 weeks, in a randomized, double-blinded, crossover trial. Entry criteria were a positive exercise treadmill test during placebo therapy characterized by 1.0 mm or more ST segment depression and angina pectoris, and six or more episodes of transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory electrocardiogram. One hundred ninety-four patients were screened, 63 were eligible and received randomized therapy, of which 56 patients completed at least two of the four treatment periods and were included in an intent-to-treat analysis. Fifty patients completed all four treatment phases and were included in the protocol-completed analysis. Anti-ischemia efficacy was assessed by 48-hour ambulatory electrocardiographic monitoring, exercise treadmill tests, and anginal diaries. Ninety-four percent of all episodes of ambulatory ischemia were asymptomatic. Compared with placebo, only propranolol was associated with a marked reduction in all manifestations of asymptomatic ischemia during ambulatory electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less than 0.0001). Diltiazem's reduction of the frequency of episodes compared with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p = 0.08) in the protocol-completed analysis and with a significant reduction in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant effect on any measured variable of ambulatory ischemia. The dosages of medication used may have been excessive for some patients, and a more beneficial effect may have been evident at a lower dose. In contrast to the marked effects of the active agents on ambulatory asymptomatic ischemia, the effects on exercise performance and angina pectoris were slight. The active agents modestly improved treadmill exercise duration time until 1 mm ST segment depression (3%), and only propranolol and diltiazem had significant effects. Only diltiazem significantly prolonged the total exercise time. Anginal frequency was significantly decreased by both propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)

Although it is known that pressure gradients and calculated valve areas in bioprosthetic valves are highly flow dependent, no studies have compared bioprosthetic valve performances while adjusting for differences in flow rate. We therefore studied 75 patients undergoing mitral valve replacement who were randomized to receive either Hancock (n = 35) or Carpentier-Edwards (n = 40) bioprosthetic valves. Pressure gradients were measured using transducer-tipped catheters to record left ventricular and left atrial pressures and cardiac outputs by thermodilution. Repeated measurements were made in each patient after either pacing, fluid infusion, or pharmacological intervention to vary flow rates for a total of 239 measurements (mean, 3.2 measurements per patient). Using analyses of variance and covariance, mean valve gradients and the calculated Gorlin area were adjusted for flow rate, valve size, valve type, and interpatient differences to compare hemodynamics. Without flow and interpatient adjustment, the univariate analysis suggested higher mean gradients in the Carpentier-Edwards 29-mm valves (p = 0.038), with a trend toward higher gradients and smaller areas in the Hancock 33-mm valves (p = 0.057 and 0.059, respectively). After adjustment for flow rate and interpatient differences, however, there was no difference at any valve size in the mean pressure gradients (p = 0.13-0.89) or Gorlin valve areas (p = 0.34-0.96). Although measurements within a given patient were consistent, marked interpatient variabilities in gradients and areas were observed for identical valve types and sizes, which were as significant as flow-dependent or size-dependent changes. We conclude that comparisons of valve performance should adjust for variations in flow rate and for interpatient differences with the use of repeated-measures designs.(ABSTRACT TRUNCATED AT 250 WORDS)