The quality of cine angiography is excellent in our days, and as a consequence some of the pitfalls encountered in previous randomized trials are not currently present. An example can be found in the CASS analysis of the reproducibility of coronary arteriographic reading by the Quality Control Committee Sessions: "There is an indication that different clinics" involved in the CASS trial "can reduce the variability between their readings by concerted effort to improve both the quality and the completeness of the angiographic examination." The introduction of electronic calipers to judge the severity of the obstruction can eliminate human errors. The computerized protocol has the disadvantage that it takes longer to tabulate cine coronary angiography and it will depend on its pattern, but it certainly will not be as long as filling in the CASS protocol. However, this effort is justified because it will enrich our knowledge of coronary arteriosclerosis. As a result, patients will be divided into proximal (1, 2, 12, 13, and 19), middle (mainly, 3, 14, and 20), and distal (remainder) segments. Sometimes midsegments can be important. For example, in the report from CASS related to the left main equivalent lesions, the 5-year survival rate was 48% if the obstruction on the left anterior descending was proximal and increased to 71% if it was more distal. Several randomized studies to compare PTCA with CABG as suggested by Gruentzig et al in 1979 are underway, and it is hoped that the data will be properly analyzed. However, if cine coronary angiography and the status of the left ventricle are not carefully tabulated (classification of patients into left main trunk or one-, two-, or three-vessel disease is not sufficient), the results of the randomized trials comparing PTCA with CABG will add more confusion instead of clarifying proper therapeutic implications.

To determine the antihypertensive efficacy of aerobic exercise training in mild essential hypertension, a prospective randomized controlled trial was conducted comparing an aerobic exercise regimen to a placebo exercise regimen, with a crossover replication of the aerobic regimen in the placebo exercise group. The study took place in an outpatient research clinic in a university-affiliated Veterans Administration medical center. Twenty-seven men with untreated diastolic blood pressure (DBP) of 90-104 mm Hg were randomized to the two exercise regimens. Ten patients completed the aerobic regimen. Nine patients completed the control regimen, seven of whom subsequently entered and completed the aerobic regimen. The aerobic regimen consisted of walking, jogging, stationary bicycling, or any combination of these activities for 30 minutes, four times a week, at 65-80% maximal heart rate. The control regimen consisted of slow calisthenics and stretching for the same duration and frequency but maintaining less than 60% maximal heart rate. DBP decreased 9.6 +/- 4.7 mm Hg in the aerobic exercise group but increased 0.8 +/- 6.2 mm Hg in the placebo control exercise group (p = 0.02). Systolic blood pressure (SBP) decreased 6.4 +/- 9.1 mm Hg in the aerobic group and increased 0.9 +/- 9.7 mm Hg in the control group (p = 0.11). Subsequently, seven of the nine controls entered a treatment crossover and completed the aerobic regimen with significant reductions in both DBP (-6.1 +/- 3.2 mm Hg, p less than 0.01) and SBP (-8.1 +/- 5.7 mm Hg, p less than 0.01). BP changes were not associated with any significant changes in weight, body fat, urinary electrolytes, or resting heart rate. This randomized controlled trial provides evidence for the independent BP lowering effect of aerobic exercise in unmedicated mildly hypertensive men.

To assess the value and timing of percutaneous transluminal coronary angioplasty (PTCA) after thrombolytic therapy for acute myocardial infarction (AMI), 586 patients in the Thrombolysis in Myocardial Infarction Study Phase II-A were randomized among three treatment strategies, one using immediate coronary arteriography followed by PTCA if appropriate (immediate invasive strategy group, n = 195), a second that deferred angiography and PTCA for 18-48 hours (delayed invasive strategy group, n = 194), and a third, more conservative, approach in which PTCA was used only if ischemia occurred spontaneously or at the time of predischarge exercise testing (conservative strategy group, n = 197). Predischarge contrast left ventricular ejection fraction, the primary study end point, was similar among the patients in all three treatment groups and averaged 49.3%. The finding of a patent infarct-related artery at the time of predischarge arteriography was equally common among the patients in the three groups (mean, 83.7%); however, the mean residual infarct artery stenosis was greater in the patients in the conservative strategy group (67.2%) as compared with the patients in the immediate invasive (50.6%) and the delayed invasive strategy groups (47.8%) (p less than 0.001). Immediate invasive strategy led to a higher rate of coronary artery bypass graft surgery (CABG) after PTCA (7.7%) than did delayed invasive and conservative strategies (2.1% and 2.5%, respectively; p less than 0.01). Furthermore, among patients not undergoing CABG during the first 21 days, blood transfusion of more than 1 unit was used in 13.8% of the patients in the immediate invasive strategy group, 3.1% of the patients in the delayed invasive strategy group, and 2.0% of the patients in the conservative strategy group (p less than 0.001). At 1-year follow-up, the three treatment groups had similar cumulative rates of mortality (8.7%, pooled over all groups), fatal and nonfatal reinfarction (8.5%), combined death and reinfarction (14.5%), and CABG (17.2%), although the cumulative performance rate of PTCA remained higher in the invasive groups (immediate invasive strategy group, 75.8%; delayed invasive strategy group, 64.3%; and conservative strategy group, 23.9%; p less than 0.001). Thus, because conservative strategy achieves equally good short- and long-term outcome with less morbidity and a lower use of PTCA, it seems to be the preferred initial management strategy.

We studied separately the effects of weight loss by calorie restriction (dieting) and by calorie expenditure (primarily, running) on lipoprotein subfraction concentrations in sedentary, moderately overweight men assigned at random into three groups as follows: exercise without calorie restriction (n = 46), calorie restriction without exercise (n = 42), and control (n = 42). Plasma lipoprotein mass concentrations were measured by analytic ultracentrifugation for flotation rates (F0(1.20), S0f) within high density lipoprotein (HDL) (F0(1.20) 0-9), low density lipoprotein (LDL) (S0f 0-12), intermediate density lipoprotein (IDL) (S0f 12-20), and very low density lipoprotein (VLDL) (S0f 20-400) particle distributions. Particle diameter and flotation rate of the most abundant LDL species were determined by nondenaturing polyacrylamide gradient gel electrophoresis and analytic ultracentrifugation, respectively. During the 1-year trial, the exercisers ran (mean +/- SD) 15.6 +/- 9.1 km/wk, and the dieters ate 340 +/- 71 fewer kilocalories per day than at baseline. Total body weight was reduced significantly more in dieters (-7.2 +/- 4.1 kg) and exercisers (-4.0 +/- 3.9 kg) than controls (0.6 +/- 3.7 kg). As compared with mean changes in controls, the exercisers and dieters significantly increased HDL2 mass (48.6% and 47.1%, respectively), decreased VLDL mass (-23.9% and -25.5%), and increased LDL peak particle diameter (2.4 and 3.2 A). When adjusted to an equivalent change in body mass index by analysis of covariance, 1) exercise-induced and diet-induced weight loss produced comparable mean changes in the mass of small LDL and VLDL, and in LDL peak particle diameter; 2) the exercisers versus control group difference in HDL2 was attributed to the exercisers' reduced body mass index; and 3) HDL2 increased significantly less in dieters than in exercisers. In dieters, low calorie intake might mitigate the effects of weight loss on HDL2.

Despite large gains in the medical and surgical treatment of angina pectoris in the past two decades, many patients are refractory to conventional medical therapy and are unsuitable for a first or, more commonly, repeat coronary revascularization procedure. We evaluated the efficacy of perhexiline maleate, a drug with an antianginal mechanism of action in humans that is as yet unknown, by using a randomized double-blind placebo-controlled crossover design in 17 patients with refractory angina who continued to receive maximal antianginal therapy, typically including nitrates, a beta-blocker, and a calcium channel antagonist. In view of perhexiline's potential for hepatic and neurological toxicity, plasma drug levels were monitored and maintained in the 150-600 ng/ml range. Sixty-three percent of patients were judged perhexiline responders by objective exercise testing criteria, as compared with 18% of patients on placebo (p less than 0.05). By blinded review of subjective measures of anginal frequency and severity, 65% of patients noted an improvement while on perhexiline, whereas no patient identified the placebo phase with improvement. Side effects observed in 29% of patients were minor and related to transient elevations of blood levels of more than 600 ng/ml; no patient suffered hemodynamic or cardiac conduction abnormalities attributable to perhexiline. With attention to the pharmacokinetics of perhexiline's elimination in individual patients, this novel antianginal agent seems to be safe and effective and deserves further evaluation in patients already receiving maximal antianginal therapy who are not candidates for revascularization procedures.

The effects of desmopressin acetate (DDAVP) on platelet aggregation and the von Willebrand factor antigen (vWF:Ag) were studied in 19 patients undergoing cardiac surgery with extracorporeal circulation. The patients represented one of five blocks in a randomized double-blind placebo-controlled parallel group trial on the effects of DDAVP on postoperative bleeding after uncomplicated coronary artery bypass operations. After termination of extra-corporeal circulation, DDAVP (0.3 microgram/kg body wt) or its vehicle was infused into a peripheral vein throughout 15 minutes. The increase in factor VIII coagulant activity after infusion did not differ between the groups but there was a significantly larger increase in vWF:Ag levels in DDAVP-treated patients. The aggregatory response to adenosine-diphosphate (ADP) and ristocetin showed a normal pattern and was not significantly different between the two groups. As compared with placebo, DDAVP did not decrease the bleeding time or the postoperative blood loss. We conclude that DDAVP causes an increase in vWF:Ag levels but does not alter platelet aggregation, bleeding time, or blood loss in uncomplicated coronary artery bypass patients.

The appearance of impaired left ventricular diastolic function in chronic ischemic heart disease often precedes systolic dysfunction. Myocardial ischemia and increased calcium loading have been implicated in the genesis of increased left ventricular stiffness. We have assessed the effects of long-term therapy with different classes of calcium channel-blocking drugs on left ventricular peak filling rate in patients with chronic stable angina and congestive heart failure secondary to ischemic heart disease. Therapeutic effects of nicardipine (30 mg t.i.d.), nisoldipine (10 mg b.i.d.), and verapamil (120 mg t.i.d.) (4 weeks) have been assessed on radionuclide left ventricular diastolic filling parameters in patients with chronic stable angina using placebo-controlled studies. All three drugs significantly improved exercise capacity as compared with placebo. Verapamil produced significant improvements in peak filling rate (p less than 0.005), time to peak filling rate (p less than 0.01), and first one-third filling fraction (p less than 0.005), whereas nicardipine only improved peak filling rate (p less than 0.005); neither drug altered the mean ejection fraction (n = 20). Nisoldipine did not significantly alter diastolic filling parameters or ejection fraction (n = 10). Nisoldipine and digoxin were also assessed in congestive heart failure (New York Heart Association [NYHA] classes II and III) associated with ischemic heart disease (n = 26) (open parallel design). Neither produced significant alterations in peak filling rate and ejection fraction after 3 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients with atherosclerotic peripheral arterial disease (PAD) of the lower extremities have impaired walking ability due to exercise-induced muscle ischemia and the resultant pain of intermittent claudication. To evaluate the benefit of exercise training as a treatment for patients with PAD, as well as possible mechanisms associated with improvement, we randomly assigned 19 men with disabling claudication to treated and control groups. Treatment consisted of supervised treadmill walking (1 hr/day, 3 days/wk, for 12 weeks) with progressive increases in speed and grade as tolerated. Graded treadmill testing was performed to maximal toleration of claudication pain on entry and after 12 weeks of training to define changes in peak exercise performance. After 12 weeks, treated subjects had increased their peak walking time 123%, peak oxygen consumption 30%, and pain-free walking time 165% (all p less than 0.05). Control subjects had no change in peak oxygen consumption, but after 12 weeks, peak walking time increased 20% (p less than 0.05). In treated subjects, maximal calf blood flow (measured by a plethysmograph) increased 38 +/- 45% (p less than 0.05), but the change in flow was not correlated to the increase in peak walking time. Elevated plasma concentrations of acylcarnitines have been associated with the functional impairment of PAD and may reflect the metabolic state of ischemic skeletal muscle. In treated subjects, a 26% decrease in resting plasma short-chain acylcarnitine concentration was correlated with improvement in peak walking time (r = -0.78, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A within-group risk factor analysis was conducted to predict angiographic change in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled trial of colestipol plus niacin therapy in men with previous coronary bypass surgery. Global angiographic change, including both native coronary arteries and bypass grafts after 2 treatment years, was the end point. Risk factors included on-trial clinical measures, plasma lipids, lipoproteins, and apolipoproteins. Univariate analysis indicated that risk factors previously observed by others in epidemiologic investigation of ischemic heart disease--total cholesterol, LDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein B, and diastolic blood pressure--had significant effects in the placebo-treated group. Univariate analysis indicated significant effects of apolipoprotein C-III in drug- and placebo-treated groups. Multivariate analysis indicated the predominant risk factor predicting the probability of global coronary progression was non-HDL cholesterol in placebo-treated subjects and the content of apolipoprotein C-III in high density lipoproteins of drug-treated subjects. Both drug- and placebo-treated group findings point to an important role for triglyceride-rich lipoproteins in progression and regression of human atherosclerosis.

To examine the manner in which changes in diastolic performance can contribute to the effect of vasodilation in patients with left ventricular (LV) systolic dysfunction, we examined the effect of acute inhibition of angiotensin converting enzyme with intravenous enalaprilat on early LV diastolic filling. We studied 43 patients with congestive heart failure and depressed LV systolic function (mean ejection fraction +/- SD, 0.24 +/- 0.06), performing radionuclide ventriculography before and after administration of 1.25 mg intravenous enalaprilat. We measured the effect of enalaprilat on the maximum rate of early LV diastolic filling normalized in four different ways and related these changes to both LV and right ventricular (RV) volumes. Enalaprilat induced a small but statistically significant reduction in LV end-systolic volume and increase in LV ejection fraction. For the entire patient group, there was no significant change in LV peak filling rate after enalaprilat administration. For individual patients, however, the effect of enalaprilat on peak filling rate was related to resting RV end-diastolic and end-systolic volumes. In patients with enlarged RV end-diastolic volumes (greater than or equal to 120 ml/m2), mean peak filling rate increased from 1.38 +/- 0.6 to 1.71 +/- 0.6 end-diastolic volumes (EDV)/sec and from 244 +/- 131 to 297 +/- 162 ml/sec/m2 after enalaprilat administration, whereas no change in mean peak filling rate was observed in patients with nondilated RVs. These observations were present regardless of the method of normalizing peak filling rate. Thus, the response of LV peak filling rate to enalaprilat is influenced by the presence of RV dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

A new cardioselective beta 1-adrenergic receptor agonist xamoterol (Corwin) has been developed for the treatment of heart failure. To study the acute hemodynamic effects of xamoterol, 24 patients, 39-70 years old, with mild-to-moderate postinfarction left ventricular dysfunction entered a double-blind, between-patient comparison of a single 5-minute intravenous infusion of xamoterol (0.2 mg/kg) and placebo. The acute hemodynamic effects of xamoterol were measured at rest and during two multistaged symptom-limited supine bicycle exercise tests (Ex-T), a control Ex-T followed by an Ex-T with either xamoterol or placebo. Compared with placebo, xamoterol significantly increased left ventricular contractility (Vmax and positive [+] dP/dt) and enhanced relaxation (dP/dt- and time constant relaxation) at rest and at the 25% and 50% levels of maximum exercise. The heart rate, the frequency and time to onset of anginal symptoms, the magnitude of exercise-induced ST segment depression, the left ventricular end-diastolic and peak systolic pressures, the mean pulmonary artery pressures, the cardiac index, the left ventricular stroke-work index, and the epinephrine and norepinephrine plasma levels at rest and during exercise did not differ significantly between placebo xamoterol groups. Thus, xamoterol can be a useful addition for the treatment of left ventricular dysfunction because of long-term ischemic heart disease.

The sympathetic nervous system becomes activated in heart failure, and while this is initially beneficial, the consequences of prolonged raised levels of catecholamines can be counterproductive. Xamoterol, a partial agonist that acts on the cardiac beta 1-adrenergic receptor, modifies the response of the heart to variations in sympathetic activity. At rest, it produces modest improvements in cardiac contractility, relaxation, and filling without increase in myocardial oxygen demand. The improvements are maintained during exercise although the attendant tachycardia is attenuated. The beneficial effects of xamoterol on both systolic and diastolic function suggested that it would be effective in patients with mild-to-moderate heart failure, and this was demonstrated in small placebo-controlled studies where effort tolerance and symptoms were improved. A large multicenter study program comprised of four studies demonstrated that patients with mild-to-moderate heart failure randomized to xamoterol (n = 617) 200 mg b.i.d. for 3 months significantly (p less than 0.0001) improved exercise capacity by 37% as compared with the placebo group (n = 300) with an increase of 18%. The xamoterol group also showed significant improvements in symptoms of breathlessness, fatigue, and life values as compared with the placebo group. In one of the multicenter studies in which 433 patients were randomized to xamoterol (n = 220), placebo (n = 109), and a positive control, digoxin 0.125 mg b.i.d. (n = 104), the percentages of improvement in exercise work were 33%, 5%, and 17%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Episodic platelet activation has been shown to occur in unstable angina, and aspirin should have an important therapeutic role in the management of these patients. The response to aspirin alone or to aspirin in combination with vasodilators such as heparin and beta-blockers has been assessed in 41 patients with unstable angina. Therapy was added sequentially in the event of recurrence of transient myocardial ischemia. Patients were randomly assigned to two groups. Group 1 (21 patients) received an intravenous infusion of isosorbide dinitrate and oral diltiazem, and group 2 (20 patients) received intravenous aspirin (60 mg the first day and 20 mg on successive days). This dose of aspirin reduced serum thromboxane B2 from 160 +/- 88 ng/ml (mean +/- SD) to undetectable values (less than 6 ng/ml, p less than 0.01). If episodes of ischemic ST segment shift continued, the therapy of group 1 was added to that of group 2 or vice versa; if further ST segment changes were documented, intravenous heparin and oral beta-blockers were added; if episodes of myocardial ischemia persisted, urgent coronary arteriography and myocardial revascularization were performed. Nine patients in group 1 and six in group 2 (p = 0.8) had no further episodes of myocardial ischemia on their initial therapy; 12 additional patients had no further episodes when taking combined therapy of aspirin and vasodilators. Thus, the administration of aspirin alone was not superior to coronary dilators; 30% of all patients continued to have episodes of myocardial ischemia or had a myocardial infarction develop when heparin and beta-blockers were added. Myocardial infarction occurred in one patient on vasodilator therapy alone, in two on combined therapy, and in two on full therapy. These results suggest that in some patients, the stimulus to coronary thrombosis and vasoconstriction occasionally becomes so strong that it cannot be inhibited by certain antagonist drugs. The unstable tendency to continuation of ischemia or evolution to myocardial infarction is not related to the severity of the persisting stenosis. Those patients not promptly responding to combined therapy immediately from admission should have early coronary angiography and aggressive treatment.

Epinephrine and calcium possess both cardiac inotropic and vasopressor activity. In addition, epinephrine's cardiovascular effects are mediated via increases in intracellular calcium. As a result, many clinicians administer the two agents together in an attempt to augment their effects. Although this approach seems rational, it has never been proven effective. We evaluated the cardiovascular and hyperglycemic actions of epinephrine (10 and 30 ng/kg/min), with and without calcium chloride administration (10 mg/kg bolus followed by 2 mg/kg/hr infusion), in a prospective, randomized, blinded, crossover designed study. Twelve adult patients were studied 1 day after aortocoronary bypass surgery. Calcium chloride raised ionized calcium levels from 1.06 +/- 0.03 (mean +/- SEM) to 1.44 +/- 0.05 mM (p less than 0.05). Calcium raised mean arterial pressure from 85 +/- 1 to 94 +/- 2 mm Hg (p less than 0.05) but had no significant effect on cardiac index. Epinephrine alone at 10 and 30 ng/kg/min significantly raised cardiac index from 2.7 +/- 0.2 to 3.0 +/- 0.2 (p less than 0.05) and 3.6 +/- 0.3 (p less than 0.05) l/min/m2. After calcium, epinephrine failed to significantly increase cardiac index. Epinephrine at 30 ng/kg/min significantly increased mean arterial pressure from 87 +/- 1 to 95 +/- 2 mm Hg (p less than 0.05). After calcium, epinephrine had no significant effect on blood pressure. In addition, epinephrine's hyperglycemic effect was blunted by calcium. Plasma epinephrine levels were similar during control and calcium infusions. We conclude that calcium blunts epinephrine's beta-adrenergic actions in postoperative cardiac surgery patients.

The interactions between diltiazem and three parameters of left ventricular function using cardiac death as the end point were investigated in 2,466 patients, aged 25-75 years, who were involved in the long-term diltiazem postinfarction trial. Indexes of left ventricular function included pulmonary congestion on chest x-ray, acute anterolateral Q wave myocardial infarction on electrocardiogram, and radionuclide ejection fraction. Pulmonary congestion and acute anterolateral infarction had significant (p less than 0.01) interactions with treatment allocation, and the third variable, ejection fraction, showed a similar trend (p less than 0.1). There was a diltiazem-related reduction in cardiac death (Cox hazard ratio, 0.76-0.86) for each of the parameters reflecting good ventricular function, and a significant diltiazem-related increase in cardiac death (Cox hazard ratio, 1.52-1.85) for each of the parameters associated with impaired function. Three-factor interactions highlighted the extremes of the favorable and adverse effects of diltiazem in subsets with unimpaired and impaired left ventricular function. These findings permit more appropriate selection of patients for the safe and effective administration of diltiazem to postinfarction patients.

A double-blind, parallel group, multicenter clinical trial of pentoxifylline compared with placebo enrolled 150 patients with moderately severe chronic occlusive arterial disease (COAD) at three centers in Scandinavia. The study consisted of a 4-6 week single-blind, placebo-controlled run-in phase, during which the stabilization of the initial claudication distance of all patients was assessed before randomization to a 6-month double-blind observation period. The diagnosis of COAD was established by clinical findings, conventional angiography, and noninvasive peripheral Doppler pressure assessment at rest and after exercise. The results of the overall intention-to-treat analysis of the study population show statistically significant superiority of pentoxifylline over placebo for all absolute claudication distance summary and end point measures. By using two clinically relevant parameters, which are a resting ankle/arm pressure ratio 0.8 or less and a duration of COAD for greater than 1 year, a target population could be defined in whom trial results became highly significant. For nontarget patients with mild COAD, we conclude that basic therapeutic measures should include the treatment of risk factors and the initiation of physical training. For target patients, however, a multifactorial therapeutic approach, including the use of pentoxifylline, is justified.

The effect of ketanserin on intermittent claudication (measured by treadmill walking distance and ankle systolic pressure) was assessed in 594 patients, a subset of the 3,899 patients who composed a double-blind study of the effect of ketanserin on cardiovascular events. Complete data sets at the beginning and end of 1 year's treatment with ketanserin or placebo were available in 436 patients. There was no difference between the groups in the improvement in pain-free treadmill walking distance. The placebo effect on treadmill walking distance increased continuously for at least 1 year at the rate of about 15% every 6 months. There was no significant change in either group in the ankle systolic pressure at the end of the treatment period but in the group given ketanserin, brachial systolic pressure was decreased and the ankle to arm systolic pressure ratio therefore increased. There was only a very weak association between treadmill walking distance and ankle to arm systolic pressure ratio both at the beginning and in terms of change over 1 year. Therefore, this pressure ratio is probably not a useful way of assessing the effects of medical treatment of claudication.

Paroxysmal atrial fibrillation (PAF) is a problematic clinical arrhythmia that is usually symptomatic. Unfortunately, few adequate trials and trial methods are available for assessment of the value of therapy, and traditional treatment has often been ineffective or associated with unacceptable side effects. Transtelephonic monitoring is a new method that allows evaluation of paroxysmal arrhythmias and arrhythmia-related symptoms in outpatients. We used a patient-initiated transtelephonic monitor system to evaluate the potential of flecainide, a class 1C antiarrhythmic, in prevention of symptomatic recurrences of PAF. Sixty-four patients qualified for the study (two or more PAF attacks documented within a 4-week baseline period) and entered a dose-finding phase to determine drug tolerance. Dose was incremented at weekly intervals from 200-300 and finally to 400 mg/day. The largest dose that was well tolerated was selected for the 4-month, double-blind, randomized, crossover comparison with placebo. Fifty-five patients entered and 53 received both treatments in the double-blind phase; 48 of these patients without protocol violations were evaluable for efficacy comparisons. Evaluable patients had undergone an average of 3.8 previous drug trials (range, 1-8); 30 were men, 18 had hypertension, and 14 had ischemic heart disease. The study demonstrated a highly significant correlation (p less than 0.0001) between perceived symptoms and documented PAF by transtelephonic monitoring. The rate of symptoms and PAF attacks was also significantly reduced by therapy (median dose, 300 mg/day). The first PAF attack occurred after a median of 3 days on placebo versus 14.5 days on flecainide (p less than 0.001) therapy. Similarly, the time interval between attacks was lengthened, from a median of 6.2 days on placebo to 27.0 days on flecainide (p less than 0.001) therapy. PAF was prevented in 15 patients (31%) during flecainide and four (9%) during placebo therapy (p = 0.013). However, during the study, 13 patients dropped out, seven because of adverse effects (five cardiac), five for other reasons, and one because of cardiac arrest/death. Adverse cardiac events occurred in a total of seven patients (11%) during flecainide therapy. Thus, transtelephonic monitoring is a useful method for documentation of the occurrence of paroxysmal arrhythmias such as PAF and its related symptoms during daily living and for assessment of new therapies in an outpatient setting.

For treatment of biopsy-proven rejections after cardiac transplantation, pulsed steroids of 1,000 mg methylprednisolone/day for 3 days have been conventionally used. This regimen results in severe side effects, both metabolically and with respect to the risk of infection. In a prospective and a more comprehensive retrospective clinical study, we investigated the effect of a 50% reduction in that dosage. A total of 512 positive biopsies were analyzed in 128 patients. Of these, 64 patients (120 biopsies) in group 1 received 500 mg/day for 3 days while the remaining 107 patients (392 biopsies) in group 2 were treated with 1,000 mg/day for 3 days (43 patients belonged to both groups 1 and 2). Response to treatment was assessed by control biopsies in a standardized time period until the next biopsy-proven rejection (maximum of 10 biopsies). The results in short and longer follow-up periods, considering the incidence and a newer empirical numerical grading scale, have demonstrated clearly comparable effects of myocardial histology. Reduced dosage of steroids is feasible and safe, and a decrease in steroid-related side effects can be achieved without jeopardizing the graft.