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Aims Most studies in chronic heart failure have only included patients with marked left ventricular systolic dysfunction (i.e. ejection fraction ≤0·35), and patients with mild left ventricular dysfunction are usually excluded. Further, exercise capacity strongly depends on age, but age-adjustment is usually not applied in these studies. Therefore, this study sought to establish whether (age-adjusted) peak Vo2was impaired in patients with mild left ventricular dysfunction. Methods Peak Vo2and ventilatory anaerobic threshold were measured in 56 male patients with mild left ventricular dysfunction (ejection fraction 0·35–0·55; study population) and in 17 male patients with a normal left ventricular function (ejection fraction >0·55; control population). All patients had an old (>4 weeks) myocardial infarction. By using age-adjusted peak Vo2values, a ‘decreased’ exercise capacity was defined as ≤ predicted peak Vo2−1×SD (0·81 of predicted peak Vo2), and a severely decreased exercise capacity as ≤ predicted peak Vo2−2×SD (0·62 of predicted peak Vo2). Results Patients in the study population (age 52±9 years; ejection fraction 0·46±0·06) were mostly asymptomatic (NYHA class I; n=40, 76%), while 16 patients (24%) had mild symptoms, i.e. NYHA class II. All 17 controls (age 57±8 years) were asymptomatic. Mean peak Vo2was lower in patients with mild left ventricular dysfunction (23·6±5·7 vs 27·1±4·6ml.min−1.kg−1in controls, P

Aims In a double-blind randomized trial in unstable angina it was shown that intravenous diltiazem reduced ischaemic events in the first 48h after inclusion better than intra-venous nitroglycerin. The present study was performed to establish the long-term prognosis of the randomized patients, with respect to their initial treatment assignment. Methods and results One year follow-up data on ischaemic end-points and anti-ischaemic medication were recorded. Results were available for all of the 121 randomized patients. One hundred and sixty-seven primary end-point events were recorded, of which 54 occurred in the first 48h and 113 during the follow-up. Survival analysis showed that event-free survival was significantly better in the diltiazem group (45·0%) than in the nitroglycerin group (34·4%), P =0·04. The incidence rate after 48h and one year for cardiac death are, respectively, 0% and 4·1%. The trend in anti-ischaemic medication was higher in the nitroglycerin group. For beta-blockers, this trend became significant after 12 months ( P =0·03). Conclusion These results show that the initial benefit obtained by early treatment with intravenous diltiazem was preserved during the first year after the initial hospitalization, and that, despite the high risk of cardiac events in our population, the overall mortality 12 months after inclusion was low.

Background The high-density lipoprotein (HDL) cholesterol concentration is inversely related to the risk of coronary artery disease. The cholesteryl ester transfer protein (CETP) has a central role in the metabolism of this lipoprotein and may therefore alter the susceptibility to atherosclerosis. Methods The DNA of 807 men with angiographically documented coronary atherosclerosis was analyzed for the presence of a polymorphism in the gene coding for CETP. The presence of this DNA variation was referred to as B1, and its absence as B2. All patients participated in a cholesterol-lowering trial designed to induce the regression of coronary atherosclerosis and were randomly assigned to treatment with either pravastatin or placebo for two years. Results The B1 variant of the CETP gene was associated with both higher plasma CETP concentrations (mean [±SD], 2.29±0.62 μg per milliliter for the B1B1 genotype vs. 1.76±0.51 μg per milliliter for the B2B2 genotype) and lower HDL cholesterol concentrations (34±8 vs. ...

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [13N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127+/-31 ml.min-1.100 g-1; group B, 124+/-30 ml.min-1.100 g-1 normal subjects, 105+/-21 ml.min-1.100 g-1 (groups A and B vs normals, P0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20+/-0.23; group B, 1.24+/-0.22; normal subjects, 1.23+/-0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71+/-0.67; group B, 2.77+/-1.29; normal subjects, 2. 91+/-1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1+/-4.5 vs 17.0+/-3.0, P0.05). In group B (coefficient of variation 19.4+/-3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.

Amiodarone is effective for long-term maintenance of sinus rhythm after electrical cardioversion of refractory atrial fibrillation or flutter. To examine its efficacy and safety for pharmacologic conversion of these arrhythmias, we studied 129 patients with refractory atrial fibrillation or flutter who had failed previous intensive conventional antiarrhythmic treatment. In anticipation of electrical cardioversion, patients were loaded with amiodarone, 600 mg/day during a 4-week period. The main outcome measure was pharmacologic conversion during this period. During the loading period, 23 patients (18%) converted to sinus rhythm. When analyzed in a multivariate model, conversion was related to desethylamiodarone plasma level (p = 0.0006), arrhythmia duration (p = 0.04), left atrial area (p = 0.02), and concomitant treatment with verapamil (p = 0.01). During ongoing atrial fibrillation after loading, the ventricular rate decreased from 100 +/- 25 to 87 +/- 27 beats/ min (p0.001). Amiodarone appeared to be safe and did not have to be discontinued because of intolerable side effects. Thus, amiodarone loading is safe and is still able to convert refractory atrial fibrillation or flutter. Conversion is related to increased desethylamiodarone plasma levels and concomitant treatment with verapamil. Because prolonged loading may increase desethylamiodarone plasma concentrations, this may enhance efficacy and obviate the need for electrical cardioversion.

Background Drugs that improve symptoms in patients with heart failure must also be assessed for their effects on survival. Ibopamine stimulates DA-1 and DA-2 receptors and causes peripheral and renal vasodilatation; the drug improves symptoms of heart failure. We assessed the effect of ibopamine on survival in patients with advanced heart failure in a multicentre, randomised placebo-controlled study.Methods Patients with advanced severe heart failure (New York Heart Association classes III and IV) and evidence of severe left-ventricular disease, who were already receiving optimum treatment for heart failure, were randomly allocated oral ibopamine 100 mg three times daily or placebo. The primary endpoint was all-cause mortality. The study was designed to recruit 2200 patients, and the minimum duration of treatment would be 6 months. We did intention-to-treat and on-treatment analyses; a post-hoc subgroup analysis was also done.Findings After we had recruited 1906 patients the trial was stopped early, because of an excess of deaths among patients in the ibopamine group. 232 (25%) of 953 patients in the ibopamine group died, compared with 193 (20%) of 953 patients in the placebo group (relative risk 1.26 [95% CI 1.04-1.53], p=0.017). The average length of follow-up was 347 days in the ibopamine group and 363 days in the placebo group. In multivariate analysis, only the use of antiarrhythmic drugs at baseline was a significant independent predictor of increased fatality in ibopamine-treated patients.Interpretation Ibopamine seems to increase the risk of death among patients with advanced heart failure who are already receiving optimum therapy, but the reasons for this increase are not clear. Our finding that antiarrhythmic treatment was a significant predictor of increased mortality in ibopamine-treated patients may be important, but exploratory analyses must be interpreted with caution.

OBJECTIVE: Angina and the presence of myocardial ischaemia are common in hypertrophic cardiomyopathy. Dual chamber pacing results in clinical improvement in these patients. This study evaluates the effects of permanent dual chamber pacing on absolute regional myocardial perfusion and perfusion reserve. SETTING: University hospital. PATIENTS AND DESIGN: Six patients with hypertrophic cardiomyopathy and severe symptoms of angina received a dual chamber pacemaker. Absolute myocardial regional perfusion and perfusion reserve (dipyridamole 0.56 mg/kg) were measured by dynamic positron emission tomography with 13N-ammonia both during sinus rhythm and 3 months after pacemaker insertion. Results were compared with those from 28 healthy volunteers. RESULTS: Pacing resulted in a reduction of anginal complaints and a reduction in intraventricular pressure gradient from 65 (SD 30) mm Hg to 19 (10) mm Hg. During sinus rhythm, baseline perfusion was higher in patients with hypertrophic cardiomyopathy than controls (184 (31) v 106 (26) ml/min/100 g, P < 0.01), and perfusion reserve was lower (1.6 (0.4) v 2.8 (1.0), P < 0.05). During pacing myocardial perfusion decreased to 130 (27) ml/min/100 g (P < 0.05), with variable responses in terms of perfusion reserve. Pacing caused a redistribution of myocardial stress perfusion and perfusion reserve. The coefficient of regional variation of myocardial stress perfusion decreased from 19.7 (7.0)% to 14.6 (3.9)% during pacing (12.9 (3.8)% in controls, P < 0.01). The coefficient of regional variation of perfusion reserve decreased from 16.7 (6.6)% to 11.4 (2.6)% during pacing (9.8 (4.1)% in controls, P < 0.01). CONCLUSIONS: Pacing caused a decrease of resting left ventricular myocardial blood flow and blood flow during pharmacologically induced coronary vasodilatation. Although global perfusion reserve remained unchanged, myocardial perfusion reserve became more homogeneously distributed.

The value of beta-blockers as antiarrhythmic drugs in patients with sustained VT or VF has received only little attention. This article summarizes the current state of knowledge regarding the identification of patients with sustained VT or VF with the highest benefit of beta-blockade. The antiarrhythmic mechanisms of beta-blockade and its efficacy as single or adjuvant therapy in patients with sustained VT or VF are reviewed. Current insights into the effects of beta-blockade in patients suffering from VT, in particular in the setting of heart failure, are discussed and future directions are considered.

In atrial fibrillation, exercise capacity is often reduced. This is usually ascribed to a decreased cardiac output as coin compared with sinus rhythm. Very few studies, however, have focused oil changes in the peripheral blood flow during atrial fibrillation as a potential mechanism for exercise limitation. The aim of the present study was to determine the effect of conversion of atrial fibrillation to sinus rhythm on peripheral blood flow. Calf blood flow, using an electrocardiogram-triggered venous occlusion plethysmograph, and peak oxygen consumption (peak VO2), using treadmill exercise testing, were studied in 28 patients with chronic atrial fibrillation eligible for electrical cardioversion. Measurements were performed before cardioversion, and repeated 1 day and 1 month thereafter. Calf blood flow at rest, maximal calf blood flow, and minimal calf vascular resistance during the hyperaemic response immediately following 700 J of calf exercise were determined plethysmographically. One day and 1 month after cardioversion, 23 and 14 patients were still in sinus rhythm, respectively. In patients who still had sinus rhythm after 1 month, maximal calf blood Bow increased from 37.7 +/- 12 to 40.0 +/- 13 ml. 100 ml(-1 min-1) (P

Ventricular arrhythmias remain a major problem, in particular in patients with left ventricular dysfunction or heart failure. In this group of patients, Class I drugs were shown to be ineffective, and they even increased mortality during chronic treatment. New antiarrhythmic agents should preferably not only have pure antiarrhythmic effects, but should also be free from adverse autonomic properties. In the present study, the electrophysiological, rate dependent and autonomic effects of intravenously administered almokalant, a new Class III antiarrhythmic drug, were investigated in nine pigs surviving a myocardial infarction. The ventricular effective refractory period (VERP) increased after almokalant (loading dose: 0.05 mu mol . kg(-1). min(-2), continuous infusion: 0.0025 mu mol . kg(-1). min(-1)) from 292 +/- 25 to 308 +/- 13 ms (pacing cycle length [PCL] 500 ms + 1 extrasystole [ES], from 249 +/- 19 to 261 +/- 16 ms (PCL 400 ms +1ES), and from 209 +/- 1 8 to 219 +/- 18 ms (PCL 300 ms +1ES). The VERPs increased most after three ES at PCL 400 ms: from 167 +/- 27 to 186 +/- 29 ms IP

The electrophysiologic effects of intravenously administered almokalant, a new class III antiarrhythmic drug, in 7 isoflurane-anesthetized pigs after low and high dose were investigated. Low-dose almokalant included bolus infusion of 0.05 mumol/kg/min for 5 min followed by a continuous infusion of 0.0025 mumol/kg/min for 40 min. Thereafter, a high dose of 0.2 mumol/kg/min for 5 min and 0.01 mumol/kg/min for 40 min was given. PR, QRS, AH, and HV intervals did not change during almokalant administration. The QT interval increased dose dependently from 337 +/- 17 to 442 +/- 20 ms at high dose (p < 0.05). Atrial refractory periods (AERP) were prolonged dose dependently at a 500-ms pacing cycle length from 178 +/- 15 at baseline to 227 +/- 27 and 253 +/- 23 ms during low- and high-dose almokalant infusion, respectively. For pacing cycle lengths of 400 and 300 ms, these values were 180 +/- 11, 207 +/- 25, and 259 +/- 34 and 157 +/- 12, 193 +/- 21, and 234 +/- 28 ms, respectively. At a pacing cycle length of 500 ms, mean ventricular effective refractory period (VERP) was 270 +/- 25 ms as compared with 306 +/- 24 and 337 +/- 17 during low and high dose, respectively. A similar pattern of VERP changes during both low- and high-dose infusion was noted at the shorter pacing cycle lengths, with an increase from 240 +/- 23 to 274 +/- 22 and 279 +/- 24 ms during a 400-ms cycle length and from 210 +/- 17 to 235 +/- 19 and 234 +/- 21 ms during a 300-ms cycle length. The ratio of the VERP and ventricular monophasic action potential duration (VAPD) did not change significantly. The Wenckebach cycle length increased by 36 +/- 36 and 83 +/- 37 ms with low- and high-dose almokalant infusion, respectively. The percent increase of AERP at pacing cycle lengths of 500, 400, and 300 ms during high-dose almokalant was 42, 44, and 49%, respectively; these increases for VERP were 25, 16, and 11%, respectively. In conclusion, prolongation of refractoriness by almokalant was more pronounced at the atrial than the ventricular level. Prolongation of refractoriness was maintained at short pacing cycle lengths especially in the atrium, indicating absence of reverse-use dependence of almokalant in the porcine heart. The marked atrial effects, paralleled by atrioventricular conduction slowing, and the absence of reverse use-dependence all contribute to the feasibility of use of almokalant, in particular in the treatment of supraventricular tachyarrhythmias.

Objective-In the absence of an obvious cause for cardiac arrest, patients with idiopathic ventricular fibrillation are difficult to manage. A subset of patients has inducible arrhythmias. In others sympathetic excitation plays a role in the onset of the cardiac arrest. This study evaluates a prospective stepped care approach in the management of idiopathic ventricular fibrillation, with therapy first directed at induced arrhythmias and secondly at adrenergic trigger events.Setting-University Hospital.Patients-10 consecutive patients successfully resuscitated from idiopathic ventricular fibrillation.Interventions-Programmed electrical stimulation to determine inducibility, followed by serial drug treatment. Assessment of pre-arrest physical activity and mental stress status by interview, followed by beta blockade. Cardioverter-defibrillator implantation in noninducible patients not showing significant arrest related sympathetic excitation.Main outcome measure-Recurrent cardiac arrest or ventricular tachycardia.Results-Five patients were managed with serial drug treatment and four with beta blockade. In one patient a defibrillator was implanted. During a median follow up of 2.8 years (range 6 to 112 months) no patient died or experienced defibrillator shocks. One patient had a recurrence of a well tolerated ventricular tachycardia on disopyramide.Conclusions-Idiopathic ventricular fibrillation may be related to enhanced sympathetic activation. Prognosis may be favourable irrespective of the method of treatment. Whether the present approach enhances prognosis of idiopathic ventricular fibrillation remains to be determined. However, it may help to avoid potentially hazardous antiarrhythmic drugs or obviate the need for implantation of cardioverter-defibrillators.

The role of ischaemia in post-infarct patients with ventricular tachyarrhythmias is not firmly established Using coronary angiography, 82 post-infarct patients with sustained ventricular tachycardia or fibrillation were subclassified into three groups. Fourteen patients (17%) had significant coronary artery disease, suggesting that ischaemia was the primary cause (group A). In 13 patients (16%) ischaemia was considered a coexistent factor (group B). In 55 patients (67%) ischaemia did not play a role (group C). The 1-year cumulative arrhythmia-free rate was 100%, 75%, 68% and the 2-year arrhythmia-free rate 100%, 56%, 52% for groups A, B and C, respectively. Using life-fable analysis, group A had the most favourable long-term outcome in relation to arrhythmia recurrence Outcomes of groups B and C were comparable. In a univariate analysis, arrhythmia recurrence was determined by the arrhythmogenic role of ischaemia, the left ventricular ejection fraction and the time from the old infarct to the index arrhythmia. In the absence of arrhythmic events in group A, multivariate analysis of groups B and C identified depressed ejection fractions (RR 0.69, CI 0.49-0.98) and a prolonged time interval from the last infarct (>5 years, RR 2.53, CI 1.12-5.75) as independent predictors for arrhythmia recurrence.The present approach helps in the identification of post-infarct patients with ventricular tachycardia and fibrillation, who benefit from stand-alone anti-ischaemic therapy. If ischaemia does not play a major arrhythmogenic role, prognosis depends on the left ventricular ejection fraction and on the age of the previous infarct. Despite adequate anti-ischaemic therapy, prognosis remains poor if the ejection fraction is below 40% or the infarct occurred more than 5 years before.

Spirapril is a new angiotensin-converting enzyme (ACE) inhibitor with a long duration of action. To determine whether duration of inhibition of serum ACE activity may affect regional blood flow (RBF), we compared spirapril with captopril, an ACE inhibitor with a short duration of action. Both the short- and long-term effects were studied in patients with mild to moderate congestive heart failure (CHF). Calf, renal, and hepatic BF measurements were performed in the morning before intake of the study medication; 24 h after the previous dose of spirapril (n = 9 patients) and 12 h after the previous dose of captopril (n = 9 patients). Serum ACE activity after 1, 6, and 12 weeks was significantly reduced in patients receiving spirapril, but not in those receiving captopril. The decrease in mean arterial pressure (MAP) was more pronounced in the spirapril group. Calf BF showed a slight but not significant increase in both spirapril- and captopril-treated patients. Effective renal BF increased significantly only in patients treated with spirapril. Although filtration fraction (FF) tended to decrease in the spirapril group, the decrease was significant only in the captopril group. No changes were observed in hepatic BF. Cerebral BF (CBF) measurements were performed after intake of the first dose of study medication and after 12 weeks, immediately after drug intake. Significant reduction in MAP in the two treatment groups both after the first dose and after 12 weeks did not affect CBF. Despite a significantly prolonged decrease in MAP and serum ACE activity in spirapril-treated patients, no marked differences in RBF were noted between the two ACE inhibitors.

In a prospective open study we evaluated whether intravenous dopamine infusions can be safely switched to enterally administered ibopamine in dopamine-dependent patients. Six patients defined as being clinically stable, normovolaemic, but dopamine dependent, i.e. with repeated inability to stop intravenous dopamine, were included. Ibopamine was administered via a nasogastric or nasoduodenal tube. During the initial 48-hour period of ibopamine administration the dopamine infusion was gradually decreased and then discontinued. Arterial blood pressure was continuously recorded via a 20-gauge cannula in the radial artery. Urine output was measured each hour. In all 6 patients it was possible to decrease and then discontinue the dopamine infusion whilst maintaining haemodynamic stability and an appropriate diuresis. It was then possible to discharge the patients from the intensive care unit. Normovolaemic, clinically stable but dopamine-dependent patients may be weaned off intravenous dopamine by substitution of enterally administered ibopamine, allowing discharge from the intensive care unit.

To study the hemodynamic and renal effects of the orally (p. o.) active dopamine (DA) agonist ibopamine, we examined 10 patients with mild to moderate congestive heart failure (CHF). who were stable while treated with digoxin and diuretics. All patients were in New York Heart Association (NYHA) functional class II-III; their mean age was 63 years (range 51-79 years), and mean left ventricular ejection fraction (LVEF) was 28% (range 18-360%). The protocol consisted of a control study-day with measurements of renal characteristics including glomerular filtration rate (GFR). effective renal plasma How (ERPF), and filtration fraction (FF). One-week later, systemic and renal hemodynamics were measured simultaneously before and after patients received one 100-mg tablet of ibopamine. Ibopamine caused a slight but significant increase in both FRPF (from 288 ± 32 ml/min/1.73 m 2 at baseline to 316 ± 32 ml/min/1.73 m 2 after ibopamine) and GFR (from 77 ± 8 to 85 ± 8 ml/min/1.73 m 2 ; both p < 0.05); FF was not affected (mean value 0.26 ± 0.02). Sodium excretion was not influenced by ibopamine. but diuresis increased significantly. Cardiac output (CO) increased significantly (from 4.0 ± 0.4 L/min at baseline to a maximum of 5.0 L/min after ibopamine, p < 0.05). mainly due to decreased systemic vascular resistance (SVR). Heart rate (HR) and blood pressure (BP) were unchanged throughout the studies. The percentage of contribution of CO to renal blood flow (RBF) was not significantly affected by ibopamine. In conclusion, ibopamine causes a slight but significant increase in both ERPF and GFR and a significant increase in diuresis, but no increase in sodium excretion in patients with mild to moderate CHF. In addition, the drug increases CO and decreases SVR to a similar extent. Therefore, the renal effects of ibopamine with equal pre- and postglomerular vasodilation, appear to be primarily due to its systemic hemodynamic effects.

In atrial flutter, chemical conversion with class I drugs is often unsuccessful, whereas class III drugs seem more promising. The different electrophysiological effects of these drugs may explain this discrepancy. To date, only experimental data show the differential effects of these drugs on conversion rate and atrial flutter cycle length. This study evaluates the effects of the class IC antiarrhythmic drug flecainide, and of dofetilide, a new class III drug, on conversion rate and flutter cycle length in patients with atrial flutter. Flecainide (11 patients) was given as an intravenous bolus of 2 mg.kg-1 in 10 min and dofetilide (10 patients) as a maximum intravenous bolus of 8 micrograms.kg-1 in 15 min. Baseline characteristics were comparable between both groups. Only one patient treated with flecainide converted to sinus rhythm. This patient showed the largest flutter cycle length increase (280 to 420 ms). By contrast, seven of the 10 patients treated with dofetilide converted to sinus rhythm. Patients treated with flecainide showed a significantly larger increase in atrial flutter cycle length at the end of the infusion compared to the dofetilide-treated patients (from 226 +/- 28 to 317 +/- 52 ms vs from 221 +/- 26 to 239 +/- 39 ms, respectively). In conclusion, dofetilide is more effective than flecainide in the conversion of atrial flutter to sinus rhythm, despite the fact that flecainide produced a more prolonged flutter cycle length. Thus, action potential prolongation in the absence of conduction slowing seems more effective in terminating human atrial flutter than depression of the excitability.

Restoration of sinus rhythm may improve functional capacity in atrial fibrillation in the short-term. Little is known, however, about its long-term effect on functional status. The aim of the present study was to evaluate the long-term effect of cardioversion on peak oxygen consumption (VO2) in patients with chronic atrial fibrillation. Patients with such a condition and due to undergo electrical cardioversion were eligible for the study. Patients underwent treadmill exercise testing with measurement of peak VO2 before cardioversion, and at 1 month and 2 years thereafter. Based on the rhythm present at those times after cardioversion, patients were categorized into three groups: those in sinus rhythm after 1 month and 2 years (Group I); those in sinus rhythm after 1 month, but with atrial fibrillation after 2 years (Group II); and those who were in atrial fibrillation both at 1 month and 2 years following cardioversion (Group III). Thirty-nine patients were included, and underlying heart disease was present in 24 of them (62%). In the comparison of the baseline characteristics of Group I (n = 17), Group II (n = 11), and Group III (n = 11), underlying heart disease was more frequent in Group I (88%, 45%, and 36%, respectively); otherwise they were similar. In Group I, peak VO2 showed an insignificant increase from 21.1 +/- 5.0 to 22.3 +/- 5.0 ml.min-1.kg-1 month after. cardioversion. After 2 years of sinus rhythm, peak VO2 showed a further increase to 23.8 +/- 5.0 ml.min-1.kg-1 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective-To evaluate the effect of cardioversion on peak oxygen consumption (peak Vo(2)) in patients with long-standing atrial fibrillation, to assess the importance of underlying heart disease with respect to the response to exercise, and to relate functional capacity to long-term arrhythmia outcome.Design-Prospective controlled clinical trial.Setting-Tertiary referral centre.Patients-63 consecutive patients with chronic atrial fibrillation accepted for treatment with electrical cardioversion. Before cardioversion all patients were treated with digoxin, verapamil, or combination of both to attain a resting heart rate less than or equal to 100 beats per minute.Interventions-Electrical cardioversion.Main outcome measures-Peak Vo(2) measured before and 1 month after electrical cardioversion to compare patients who were in sinus rhythm and those in atrial fibrillation at these times. Maintenance of sinus rhythm for a mean follow up of 19 (7) months.Results-Mean (1SD) peak Vo(2) in patients in sinus rhythm after 1 month (n = 37) increased from 21.4 (5.8) to 23.7 (6.4) ml/min/kg (+11%, P Conclusion-Restoration of sinus rhythm improved peak Vo, in patients with atrial fibrillation, irrespective of the presence of underlying heart disease. Peak Vo(2) was not a predictive factor for long-term arrhythmia outcome after cardioversion of atrial fibrillation. These findings suggest that cardioversion is the best method of improving functional capacity in patients with atrial fibrillation, whether or not they have underlying heart disease and whatever their functional state.

To examine the predictive value of ventricular arrhythmias on ambulatory electrocardiographic (ECG) monitoring, 211 patients with left ventricular dysfunction and congestive heart failure (76% men, age 63 +/- 4 years, left ventricular ejection fraction 0.26 +/- 0.10) were studied. During a follow-up of 21 +/- 11 months, there were 45 cardiac deaths: 22 were due to progressive pump failure and 23 were sudden. Patients with a low left ventricular ejection fraction (or = 0.27) and ventricular tachycardia on 24 h ECG were at higher risk of dying suddenly and from progressive pump failure (both P0.0001). Patients who died suddenly were found to have significantly longer (P = 0.003) and faster (P = 0.029) ventricular tachycardias on their baseline ambulatory ECG, than survivors. This association was not observed in patients who died of progressive pump failure. Therefore, low left ventricular ejection fraction and ventricular tachycardia on 24 h ECG recording predict an increased risk of cardiac mortality. Our results also suggest that longer and faster ventricular tachycardia recorded by 24 h ECG may identify patients at risk of sudden death, a finding which has not been described before.

A European coronary angioscopy working group has been established to create and evaluate a classification system for angioscopic observation. The 'Ermenonville' classification features items, graded in 3-5 categories, such as lumen diameter, shape of narrowing, colours of surface, atheroma, dissection, thrombus, etc. Inter- and intra-observer agreement on the interpretation of angioscopic images, using this classification system, was studied within the working group. Kappa values for chance-corrected intra-observer agreement of the diagnostic items were 0.51-0.67. The mean kappa values for inter-observer agreement were very low at 0.13-0.29. The important items, such as red thrombus and dissection were studied after recoding as either present or absent. These items proved to have a good intra-observer agreement, and an acceptable inter-observer agreement after recoding. Other angioscopic diagnoses should be made with caution. Multicentre angioscopy studies should make use of an angioscopy core laboratory. A set of definitions for coronary angioscopy is proposed, and this working group will re-evaluate observer agreements using these definitions.

BACKGROUND--Spinal cord stimulation (SCS) may be a useful additional therapy for pain in patients with therapeutically refractory angina pectoris. But doubts remain about whether it also relieves ischaemia. METHODS--Indices of ischaemia were studied with and without SCS in 10 patients with otherwise intractable angina and evidence of myocardial ischaemia on 48 h ambulatory electrocardiographic (ECG) recording. Primary end points assessed by 48 h ECG recordings were total ischaemic burden, number of ischaemic episodes, and duration of ischaemic episodes. In addition, symptoms were assessed by a diary of glyceryl trinitrate intake and angina attacks. RESULTS--During SCS the total ischaemic burden of the entire group was significantly reduced from a median of 27.9 (1.9-278.2) before SCS to 0 (0-70.2) mm x min with SCS (p < 0.03). In six out of the 10 patients there was no myocardial ischaemia during 48 h ambulatory ECG monitoring with SCS. The number of ischaemic episodes was reduced from a median of 3 (1-15) before SCS to 0 (0-9) with SCS (p < 0.04). The duration of ischaemic episodes decreased from a median of 20.6 (1.7-155.4) min before SCS to 0 (0-48.3) min with SCS (p < 0.03). This was accompanied by a significant improvement in symptoms with a reduction in daily glyceryl trinitrate intake from a median of 3.0 (0-10) before SCS to 0.3 (0-10) tablets per 48 h (p < 0.02) and a decrease in the frequency of anginal attacks from a median of 5.5 (2-14) before SCS to 1.0 (0-10) per 48 h with SCS (p < 0.03). CONCLUSIONS--SCS not only reduced symptoms but also myocardial ischaemia. Therefore, SCS appears to be both a safe and an effective therapy for patients with refractory angina.

Cyclooxygenase inhibitors may affect the hemodynamic status of patients with heart failure adversely and may also block the vasodilatory effects of angiotensin-converting enzyme (ACE) inhibitors in such patients. Relatively low doses of the cyclooxygenase inhibitor acetylsalicylic acid (ASA) are now used routinely in ischemic heart disease, the most important cause of heart failure. Therefore, we investigated the hemodynamic interaction between ASA and captopril in heart failure. In a randomized, cross-over study, 13 patients with congestive heart failure (CHF) who were already receiving maintenance treatment with an ACE inhibitor received a single dose of 25 mg captopril combined with 236 mg ASA or placebo. Peripheral blood flow was studied noninvasively by venous occlusion plethysmography of the calves. Liver blood flow was estimated from indocyanine green (ICG) clearance. Administration of captopril alone significantly decreased blood pressure (BP), and ICG clearance. Calf blood flow remained unchanged. However, after arterial occlusion, hyperemic calf blood flow persisted for longer. Captopril alone did not significantly change the plasma levels of the vasodilating prostaglandins PGI2 and PGE2 or the vasoconstricting thromboxane A2 (TXA2). In contrast, captopril combined with ASA reduced the plasma levels of these vasoactive substances, with significant decreases in PGE2 and TXA2 as compared with captopril alone, yet the hemodynamic alterations after captopril plus ASA were similar to those observed after captopril alone. A single antithrombotic dose of ASA (236 mg) in 13 patients with CHF [New York Heart Association (NYHA) class II-IV] undergoing chronic treatment with ACE inhibitors had no discernible effect on hemodynamic status.(ABSTRACT TRUNCATED AT 250 WORDS)

OBJECTIVE--To determine the relation between functional capacity and heart rate response to exercise in patients with atrial fibrillation. SUBJECTS--73 consecutive patients with chronic atrial fibrillation. MAIN OUTCOME MEASURES--Relation between functional capacity, measured as peak oxygen consumption (peak VO2; ml/min/kg), and heart rate at all stages of exercise in univariate and multivariate analyses. RESULTS--Peak VO2 showed no correlation with resting heart rate, but it showed a negative correlation with heart rate during the first stage of exercise (r = -0.94, p < 0.01). Indeed, heart rate during the early stages of exercise (stages 1-5) was higher in patients with a peak VO2 less than or equal to 20 ml/mm/kg than in those with a peak VO2 greater than 20 ml/min/kg (heart rate 140 v 125 beats/min, p < 0.05). At maximal exercise, however, peak VO2 was positively correlated with heart rate (r = 2.15, p < 0.0001). CONCLUSION--In patients with atrial fibrillation and impaired functional capacity heart rate at low levels of exercise is augmented but maximal heart rate attenuated compared with patients with preserved functional capacity. Excessive heart rate responses to minor exercise may have deleterious effects on left ventricular function and thereby further limit functional capacity.

Aspirin, alone or in combination with dipyridamole, is known to prevent occlusion of aortocoronary vein grafts. The benefit of dipyridamole in addition to aspirin remains controversial, and the efficacy and safety of oral anticoagulants for prevention of vein-graft occlusion have not been established. We assessed one-year angiographic vein-graft patency after aortocoronary-bypass surgery in 948 patients assigned to receive aspirin, aspirin plus dipyridamole, or oral anticoagulants in a prospective, randomised trial. The design was double-blind and placebo-controlled for the aspirin groups, but open for oral anticoagulant treatment. Dipyridamole (5 mg/kg per 24 h intravenously for 28 h, followed by 200 mg twice daily) and oral anticoagulants (desired prothrombin time range 2.8-4.8 international normalised ratio) were started before surgery, and aspirin (50 mg per day) was started after surgery. Clinical outcome was assessed by the incidence of myocardial infarction, thrombosis, major bleeding, or death. Occlusion rate of distal anastomoses was 11% in the aspirin plus dipyridamole group versus 15% in the aspirin group (relative risk 0.76, 95% CI 0.54-1.05) and 13% in the oral anticoagulants group. Clinical events occurred in 20.3% of patients receiving aspirin plus dipyridamole compared with 13.9% of the aspirin group (relative risk 1.46, 95% CI 1.02-2.08) and 16.9% of the oral anticoagulants group. Our data provide no convincing evidence that addition of dipyridamole to 50 mg aspirin per day improves aortocoronary vein-graft patency. Moreover, there is evidence that the combination increases the overall clinical-event rate. Compared with aspirin, oral anticoagulants provided no benefit.

Dofetilide may induce aberrant intraventricular conduction due to its Class III effect. This report describes an atrial fibrillation patient in whom intraventricular conduction was studied before and after dofetilide using multiple endocardial recordings. Dofetilide provoked aberrant conduction during atrial fibrillation, and aberrancy could be mimicked with programmed atrial stimulation after restoration of sinus rhythm. However, during right ventricular stimulation, isolated bundle branch reentrant beats were recorded after induction of critical retrograde conduction delays. This occurred in the setting of relatively large differences in refractoriness between the right bundle branch and the right ventricular myocardium. This favored distal retrograde bundle branch block during ventricular extrastimulation, in turn enhancing bundle branch reentry. This potential proarrhythmic mechanism deserves close attention in the further development of dofetilide and also of other new ''pure'' Class III agents.

In an open-label study, electrophysiology and pharmacokinetics of TYB-3823, a new antiarrhythmic compound, were investigated. Sixteen patients underwent an electrophysiologic study before and after intravenous (i.v.) administration of TYB-3823. Two patients each received the following increasing doses: 0.2, 0.4, 0.8, and 1 mg/kg. Eight patients received 1.2-mg/kg. TYB-3823 concentrations followed a biexponential decrease with a terminal half-life (t1/2) of 3.88 +/- 0.87 h. Clearance was 47.2 +/- 18.5 L/h, and volume of distribution was 250 +/- 77 L. Dose-dependent pharmacokinetics were evident. Significant effects of TYB-3823 were apparent at doses greater-than-or-equal-to 0.8 mg/kg (n = 12), including increase in the AH and HV interval from 92 +/- 17 to 105 +/- 19 ms (p

Objective.-To study efficacy and safety of low-dose amiodarone for maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation or flutter.Design.-Nonrandomized trial; mean duration of follow-up, 20.7 months.Setting.-Referral center; institutional practice; both hospitalized and ambulatory care.Patients.-Eighty-nine consecutive patients having chronic atrial fibrillation or flutter and eligible for cardioversion. Patients had failed previous treatment aimed at maintaining sinus rhythm. During follow-up one patient was withdrawn because of side effects; all patients were available for follow-up.Intervention.-Before cardioversion, patients received 600 mg of amiodarone daily during a 4-week loading period. After conversion, the daily maintenance dose was 204+/-66 mg (mean+/-SD).Main Outcome Measures.-Arrhythmia recurrence and adverse effects causing drug discontinuation.Results.-During loading, 15 patients (16%) converted, and after electrical cardioconversion, 90% of all patients had sinus rhythm. Actuarially, 53% of these patients were still in sinus rhythm after 3 years. In patients with compromised left ventricular function, 93% maintained sinus rhythm after 6 months. One patient died due to congestive heart failure. Intolerable side effects occurred in one patient. No proarrhythmia was observed. Logistic regression analysis revealed that amiodarone was ineffective in patients with mitral stenosis or chronic arrhythmia.Conclusions.-Low-dose amiodarone is effective for maintaining sinus rhythm in patients with difficult to treat chronic atrial fibrillation or flutter and is associated with a low incidence of serious side effects.

The efficacy of beta-blockade after myocardial infarction (MI) has been investigated in a series of studies. When beta-blockers are used during the first hours after the onset of MI, a reduction in infarct size, mortality, and nonfatal reinfarction may occur. Bisoprolol is a highly beta-1-selective beta-blocker, without intrinsic sympathomimetic activity (ISA), and with a plasma elimination half-life of 10-12 h, permitting treatment with one daily dose. Because no experience with bisoprolol was available in MI, its safety and efficacy were studied in two open, uncontrolled pilot studies. The first study was a dose-finding study in 37 patients with a 3-day-old MI. Bisoprolol was given intravenously and carefully titrated in steps of 1 mg up to a cumulative maximum dose of 5 mg. Subsequently, the patients received 10 mg of oral bisoprolol once daily (o.d.) until the end of the study. Based on the results of this first pilot study, a second pilot study was performed in which bisoprolol was given within the first 6 h after the onset of MI. Intravenous (i.v.) bisoprolol was titrated in two steps of 2.5 mg each, directly followed by 10 mg of oral bisoprolol o.d. The aim of this study was to investigate the influence of i.v. and subsequent oral bisoprolol on central hemodynamics. The results of these studies demonstrate that i.v. and subsequent oral administration of bisoprolol is well tolerated and indicate that the selected dose regimen is hemodynamically safe.

Using available data on time-concentration and time-effect relationships in normal persons the results of infusion of digoxin in various time periods were simulated and compared with administration of digoxin by bolus injections, using a three-compartment pharmacokinetic model to which a separate small side-effect compartment was subsequently added. The validity of the simulations was tested in 11 patients with rapid atrial fibrillation. Serum digoxin concentrations, ventricular rate and side effects were monitored in a double-blind study comparing an infusion of 1.5 mg digoxin over 6 h with administration of three bolus injections of 0.5 mg digoxin 8 h apart.In agreement with the predictions of the model, the maximal fall in ventricular rate was reached after 8–9 h in the infusion group and after 19–20 h in the bolus injection group, without any detectable difference in side effects.There were certain discrepancies between the results of the clinical study and the predictions of the model, e.g. in serum digoxin concentrations, perhaps due to impaired clearance in the patients.However, it is concluded that the tested model is valid in elderly patients with rapid atrial fibrillation.

Objective: To determine whether ambulatory blood pressure eight weeks after withdrawal of antihypertensive medication is a more sensitive measure than seated blood pressure to predict blood pressure in the long term. Design: Patients with previously untreated diastolic hypertension were treated with antihypertensive drugs for one year; these were withdrawn in patients with well controlled blood pressure, who were then followed for one year. Setting: Primary care. Subjects: 29 patients fulfilling the criteria for withdrawal of antihypertensive drugs. Main outcome measures: Sensitivity, specificity, and positive and negative predictive value of seated and ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs. Results: Eight weeks after withdrawal of medication, mean diastolic blood pressure returned to the pretreatment level on ambulatory measurements but not on seated measurements. One year after withdrawal of medication, mean diastolic blood pressure had returned to the pretreatment level both for seated and ambulatory blood pressure. For ambulatory blood pressure, the sensitivity and the positive predictive value eight weeks after withdrawal of medication were superior to those for seated blood pressure; specificity and negative predictive value were comparable for both types of measurement. Receiver operating characteristic curves showed that the results were not dependent on the cut off values that were used. Conclusion: Ambulatory blood pressure eight weeks after withdrawal of antihypertensive drugs predicts long term blood pressure better than measurements made when the patient is seated. Key messages Ambulatory measurements showed that the mean blood pressure returned to the pretreatment level within eight weeks after withdrawal of medication Eight weeks after drugs were withdrawn, ambulatory blood pressure was a good predictor of blood pressure in the long term, whereas seated blood pressure was not Restarting antihypertensive drugs at this time would be justified on the basis of early ambulatory blood pressure monitoring

Objective-To examine the effect of exercise on cycle length in atrial flutter.Patients-15 patients with chronic atrial flutter. Seven patients were taking digoxin and six verapamil; two were not taking medication.Methods-All patients underwent bicycle ergometry. Flutter cycle length was measured at rest and at peak exercise.Results-Mean flutter cycle length increased from 245 ms to 256 ms (P = 0.002). Six patients developed 1:1 atrioventricular conduction. Significant increases in fluter cycle length were observed irrespective of development of 1:1 atrioventricular conduction and use of digoxin and verapamil.Conclusion-Exercise prolongs flutter cycle length. This effect would promote development of 1:1 atrioventricular conduction during exercise, causing inordinately high ventricular rates.

In this study we compared efficacy and safety of prehospital with in-hospital thrombolytic treatment with anistreplase in patients with acute myocardial infarction (AMI). Three-hundred and fifty patients with chest pain were screened for eligibility by the municipal ambulance staff and/or the general practitioner. Patients were included in the absence of contraindications and if the telephone-transmitted ECG showed AMI. In a 6 month period 16 patients (5%) were eligible, but only seven (2%) were randomized. Age over 70 years, duration of chest pain for longer than 4 h and logistic problems were the major factors responsible for the low inclusion rate. The mean time spent at home with and without the ECG procedure was 38 +/- 14 and 14 +/- 8 min, respectively (P less than 0.001). These results demonstrate that in a medium sized town prehospital delivery of intravenous thrombolytic therapy by paramedics and/or the general practitioner is not feasible, leads to unnecessary time delay and may therefore yield no clinical benefits.

Recently, bisoprolol has been investigated regarding its effects on exercise tolerance and the duration of action in patients with coronary heart disease (CHD) following single oral administration. It appears, however, that the extent of effects of 5 mg bisoprolol is not fully established yet. Therefore, the effects of 5 and 10 mg bisoprolol and the duration of action were assessed in 12 patients (10 male, 2 female; mean age 60.2 years) with stable angina pectoris due to CHD after repeated administration. Patients were given 5 or 10 mg bisoprolol once daily for 2 weeks according to a double-blind, randomized cross-over design. At entry one exercise tolerance test (ETT) served as baseline measurement and following each treatment period ETTs were performed before (24-hour value) and 3 hours after tablet intake. Exercise capacity (in W X min) was calculated until the onset of angina, 0.1 mV ST-segment depression and at peak exercise. Compared to baseline all workload values during active therapy were significantly improved (P less than or equal to 0.05) except for the workload till onset of angina with bisoprolol 5 mg at 24 hours. The effects at 3 hours were significantly stronger than those after 24 hours for both dosages. Significantly stronger effects were observed 3 hours as well as 24 hours after intake during treatment with 10 mg compared to 5 mg: at peak exercise on heart rate (P less than or equal to 0.05) and exercise capacity (P less than or equal to 0.01), at identical workload on heart rate (P less than or equal to 0.01) and rate-pressure product (P less than or equal to 0.01). It was found that bisoprolol 5 mg once daily leads to therapeutic effects with a clearly maintained duration of action over 24 hours, but further increase of peak exercise capacity may be achieved with 10 mg.

In 1981, a large, double-blind, randomized trial was started in The Netherlands to evaluate the therapeutic effects of nifedipine and/or metoprolol in patients with unstable angina. This study has been called the Holland Interuniversity Nifedipine/metoprolol Trial (HINT) and required several hundred patients to establish potential therapeutic effects. From December 1982 to January 1984 the effects of nifedipine on left ventricular (LV) performance in a subgroup of 52 HINT patients were studied using radionuclide techniques. All patients (23 on nifedipine, 29 controls) underwent thallium-201 scintigraphy or radionuclide angiography just before and 48 h after the start of experimental medication. The radionuclide angiographic studies were also performed at 1 and 4 h after treatment. Nifedipine did not influence the incidence or disappearance of perfusion defects on the 48-h thallium images. No significant differences in overall LV ejection fraction (EF) were seen at any time between nifedipine-treated patients and controls. However, paired observations in 37 patients showed improvement of LVEF after 48 h in 8 patients on nifedipine and in only 1 control patient. Scintigraphic measurements on admission were not related to clinical outcome after 48 h. Concomitant administration of metoprolol did not influence LVEF in either group. It is concluded that nifedipine improves LVEF after 48 h in a subset of patients with unstable angina without affecting myocardial perfusion. This finding indicates that nifedipine has a predominant effect on afterload reduction in patients with unstable angina. However, early scintigraphic measurements had no significant predictive value for subsequent cardiac events.

Using multiple regression analysis, we examined perioperative hemodynamic and electrocardiographic variables as predictors of operative mortality in surgery for coronary heart disease. Data were first analyzed as univariates and, if significantly related to mortality, they were subjected to stepwise logistic multivariate regression analysis. The preoperative predictor variables were: heart rate, ventricular arrhythmia and ST-T shift. The intraoperative predictor variables were: ventricular arrhythmia and ST-T shifts; and the postoperative predictor variables were: left ventricular stroke work index, blood pressure, mixed venous oxygen content and intrapulmonary shunt. When only electrocardiographic data were analyzed, the preoperative variables were: ventricular arrhythmia, ST-T shift and anterior wall infarction. The intraoperative variables were: ventricular arrhythmia and ST-T shift. The postoperative electrocardiogram did not give additional information. The common denominator of the relevant hemodynamic and electrocardiographic variables appears to be an accumulation of pre- and perioperative myocardial damage, which leads to operative mortality.

In 198 patients with acute myocardial infarction serial measurements of plasma creatine kinase isoenzyme MB (CK MB) were performed at four hour intervals. In every patient, maximal CK MB activity (peak activity) was compared with calculated total release per litre plasma. In 28 patients (group 1) sufficient plasma samples were available for calculation of the apparent first order inactivation constant kd. Mean apparent kd in group 1 patients was 0 . 085 +/- 0 . 018 h-1 (mean +/- SD). Total release in group 1 was calculated with individual apparent kd values (Q) and with the mean kd value (Q*). In the remaining 170 patients (group 2), Q* only was calculated. A linear relation between peak activity P and total release (both Q and Q*) was found, extending over the whole range of CK MB peak activities that are routinely observed (4-216 U/l). It was immaterial whether a one or a two compartment model was used: both yielded a close linear relation. Though the mean ratio between Q* and peak activity depends on the value of kd chosen for calculation of total release (the ratio increasing with increasing kd), linearity between peak activity and Q* was found for any value of kd up to 0 . 4 h-1. In group 1, shapes of calculated CK MB release curves Q*(t), expressed relative to maximal release Q(40), were sufficiently similar so as to be superimposable; the section of the release curves extending from 12 hours before until two hours after peak time could be tentatively described by a linear time course with a slope of 4 . 2 +/- 0 . 5% per hour (mean +/- SD). We conclude that peak activity of CK MB is a reliable estimate of cumulative CK MB release and may be clinically more practicable than calculation of Q(40). Both the similarity and the large apparently linear section of the calculated enzyme release curves possibly permit early prediction of Q(40), with acceptable precision.

The efficacy of sustained-release diltiazem (diltiazem-SR) 120 mg b.i.d. was compared with metoprolol 100 mg b.i.d. in 12 patients with stable angina. Following a 1-week placebo period, patients received diltiazem-SR or metoprolol in two 3-week treatment periods, in a randomized double-blind crossover design. Total exercise time was increased more with diltiazem-SR than with metoprolol (1.2 min vs 0.4 min, P = 0.02), although the reduction in frequency of weekly anginal attacks was equal with both drugs (5 +/- 3 with placebo to 1 +/- 1 with both drugs). The difference between diltiazem-SR and metoprolol may, in part, be due to the fact that the tests were performed 12 h after drug administration. The diltiazem plasma levels were in the therapeutic range; metoprolol plasma levels, in contrast, were all below the therapeutic range. In addition, the patients might be tired out earlier during beta-blockade therapy, because a greater increase in exercise time with diltiazem-SR compared with metoprolol was found in those patients in whom the exercise endpoint changed from angina to fatigue. Thus, diltiazem-SR effectively reduces the frequency of anginal attacks when given twice daily, and improves exercise capacity to a greater extent than metoprolol 12 h after last dose.

The efficacy of diltiazem in comparison with metoprolol in chronic stable angina was assessed in 33 male patients during a 15-week blind cross-over study. After an initial two-week run-in period, baseline measurements were made. Subsequently, the patients entered a blind cross-over study consisting of two six-week treatment periods with diltiazem 240 mg (60 mg q.i.d.) or metoprolol 200 mg (100 mg b.i.d.). Dose adjustment to either 360 mg diltiazem (120 t.i.d.) or 400 mg metoprolol (200 b.i.d.) was allowed two weeks after the start of treatment. There was a one-week washout period between the two treatment periods. Compared to baseline values both drugs reduced the number of anginal attacks (diltiazem - 55%, P = 0.02; metoprolol - 73%, P = 0.01) and showed improvement of the measured exercise variables (exercise duration: diltiazem + 16%, P less than 0.001; metoprolol + 4%, P = NS; time to angina: diltiazem + 21%, P = 0.02, metoprolol + 14%, P = NS; maximal ST-depression: diltiazem + 13%, P = NS, metoprolol + 33%, P = 0.002). No significant change in LVEF was noticed. Both drugs reduced the mean heart rate on Holter tape (diltiazem - 11%, P = 0.006; metoprolol - 14%, P = 0.004). No effects on conduction were noticed. Although at the borderline of significance, diltiazem increased the total exercise duration as compared to metoprolol (16 vs. 4%, P = 0.05). It is concluded that diltiazem improves exercise tolerance in patients with stable angina pectoris and appears to be a safe and effective alternative to the beta-blocking agent metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Apex echocardiography has been chosen as an approach to detect and quantify acute myocardial infarction because the usual parasternal acoustic windows are often occluded. Fifty-three patients were studied, all within 12 hours after the onset of symptoms of their first myocardial infarction. Three apical long axis views were obtained, that is the two and four chamber views, and the right anterior oblique equivalent or three chamber view. Satisfactory echocardiograms were obtained in 48 patients (91%). The individual apical views were divided into equal segments and the area of asynergy was estimated in each view. Left ventricular asynergy was present in all 48 patients. In 46 patients a positive correlation between the electrocardiogram and the echocardiogram was obtained, as far as infarct localisation was concerned. The estimated asynergic area correlated well with the peak value of the isoenzyme of creatine kinase (CK MB). Apex echocardiography is a reliable alternative method of detecting and quantifying myocardial infarction soon after the onset of symptoms.

Haemodynamic effects of nicardipine were studied in 12 patients with documented coronary artery disease. Following nicardipine 10 mg, given intravenously to patients at rest, the heart rate increased, mean arterial pressure decreased, cardiac index increased, and systemic vascular resistance decreased significantly. Compared with the control exercise values, significant increases in heart rate and cardiac index and significant decreases in mean arterial pressure, systemic vascular resistance, and left ventricular end diastolic pressure occurred when nicardipine, 10 mg i.v., was given to the patients during exercise. All 12 patients complained of angina during the exercise phase, but following treatment with nicardipine, 10 mg i.v., only four patients reported angina when exercising to the same level. Exercise capacity on oral nicardipine treatment tended to increase whilst the ejection fraction response to exercise did not change. Thus, nicardipine was a potent vasodilator, which produced a marked reduction of systemic vascular resistance and left ventricular end diastolic pressure during exercise.

In a prospective serial study of 96 patients with acute myocardial infarction, two dimensional echocardiography identified left ventricular thrombus in 18 patients. The majority of thrombi (15) developed within the first 4 days after admission. In three patients thrombi were identified for the first time 4 months after the acute episode. All 18 patients had received therapeutic anticoagulants on admission and had large anterior wall infarctions complicated by severe pump failure and motion abnormalities echocardiographically. None of the patients had systemic embolisation during the study period. Thus, left ventricular thrombus is a not uncommon though silent complication of acute anterior wall infarction even when patients receive therapeutic anticoagulants.

Prehospital prevention of primary ventricular fibrillation using 300 mg lidocaine intramuscularly seems to be ineffective in view of the rather low plasma lidocaine levels obtained with this regimen. Preliminary results of 400 mg lidocaine administered by paramedics using an automatic injector are encouraging. In-hospital prevention of primary ventricular fibrillation can be achieved by routine administration of intravenous lidocaine in rather high dosages provided that adequate measures are taken. When, however, recurrent attacks of primary ventricular fibrillation supervene, repeated defibrillation seems to be preferable rather than continuous institution of various antiarrhythmic drugs.