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Both myocardial m-[ 123 I]iodobenzylguanidine ( 123 I-MIBG) uptake and plasma norepinephrine are markers of sympathetic activation in heart failure and have been shown to portend a poorer prognosis. However, these observations were noted before treatment with beta blockers became part of standard clinical practice. Fifty-eight patients with chronic heart failure (New York Heart Association functional class II and III, ejection fraction

OBJECTIVES Evaluation of collateral vascular circulation according to hemodynamic variables and its relation to myocardial ischemia. BACKGROUND There is limited information regarding the hemodynamic quantification of recruitable collateral vessels. METHODS Angiography of the donor coronary artery was performed before and during balloon coronary occlusion in 63 patients with one vessel disease. Patients were divided into groups of those with an absence of collateral vessels (group 1, n = 10), those with recruitable collateral vessels (group 2, n = 23) and those with spontaneously visible collateral vessels (group 3, n = 30). During balloon inflation the coronary wedge/aortic pressure ratio (Pw/Pao) was determined as were collateral blood flow velocity variables, using a 0.014″ Doppler guide wire. Myocardial ischemia was defined as ≥0.1 mV ST-shift on a 12 lead electrocardiogram at 1 min coronary occlusion. RESULTS Myocardial ischemia was present in all patients of group 1, in 14 patients of group 2 and in 3 patients of group 3. Recruitable collateral flow without ischemia showed similar hemodynamic values as in group 3 while these values were similar to group 1 in regard to the presence of recruitable collateral vessels showing ischemia. Logistic regression analysis revealed both Pw/Pao and Vicolas independent predictors for the function of collateral vessels. CONCLUSIONS Hemodynamic variables of collateral vascular circulation are better markers of the functional significance of collateral vessels than is coronary angiography. The total collateral blood flow velocity integral and coronary wedge/aortic pressure ratio are good and independent predictors of the function of collateral vessels producing complementary information.

Background Spinal cord stimulation is known to be a successful treatment for chronic intractable angina pectoris. Its effect may be anti-ischemic. It is uncertain if the clinical effect is partly caused by a placebo effect of surgery for implantation of a stimulator. In this study, clinical efficacy is investigated, together with a possible placebo effect. Methods and Results Efficacy of spinal cord stimulation as a treatment for chronic intractable angina pectoris was studied for 6 weeks in 13 treated patients and 12 control patients with chronic angina. Assessments were exercise capacity and ischemia, daily frequency of anginal attacks and nitrate tablet consumption, and quality of life (perceived quality of life and pain). Compared with control, exercise duration ( P =.03) and time to angina ( P = .01) increased; anginal attacks and sublingual nitrate consumption ( P = .01) and ischemic episodes on 48-hour electrocardiogram ( P = .04) decreased. ST-segment depression on the exercise electrocardiogram decreased at comparable workload ( P = .01). Anginal attacks and consumption of sublingual nitrates decreased ( P = .01), perceived quality of life increased ( P = .03), and pain decreased ( P = .01). Conclusions Spinal cord stimulation is effective in chronic intractable angina pectoris, and its effect is exerted through anti-ischemic action. Efficacy is unlikely to be explained as a placebo effect from surgery. (Am Heart J 1998;136:1114-20.)

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

This study was done to determine whether the difference in duration of action of the long-acting angiotensin-converting enzyme (ACE) inhibitor spirapril compared with the short-acting ACE inhibitor captopril affects clinical efficacy in patients with congestive heart failure.The effects on exercise capacity, neurohumoral status, and quality of life were studied in 20 patients with mild to moderate congestive heart failure in a double-blind, randomized, comparative study in parallel groups with a duration of 12 weeks. All assessments during the study were performed in the morning, before intake of the study medication, to avoid the expected peak effect of the ACE inhibitors used. Mean peak oxygen consumption (peak Vo2) was 17.4 mL/min/kg (range, 14.2-19.9 mL/min/kg) and mean left ventricular ejection fraction was 28% (range, 13-40%). Exercise duration in the captopril group showed a significant increase after 12 weeks (P.05) of treatment compared with the spirapril group. Peak oxygen consumption tended only to increase in the captopril-treated patients compared with the spirapril-treated patients. Serum ACE activity was significantly different between the two treatment groups during treatment (P.0001) and showed only a significant decrease in the spirapril group. There was no difference in improvement of quality of life between the two treatment groups.This study showed that the effects of the ACE inhibitors spirapril and captopril on exercise capacity are not related to the degree of inhibition of serum ACE activity.

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.

OBJECTIVE: To determine the long-term outcome of serial electrical cardioversion therapy in patients with chronic atrial flutter. DESIGN: Prospective study, case series. SETTING: University hospital. PATIENTS: 50 consecutive patients with chronic (> 24 hours) atrial flutter without a previous relapse on antiarrhythmic drugs. INTERVENTIONS: Elective electrical cardioversion therapy, if necessary repeated, to obtain and keep patients in sinus rhythm. If the first cardioversion resulted in sinus rhythm, patients were not given antiarrhythmic drugs. Relapses were managed by repeated cardioversions then anti-arrhythmic drugs were used serially in a set sequence. MAIN OUTCOME MEASURE: Maintenance of sinus rhythm. RESULTS: Mean (SD) follow up was 3.5 (1.7) years. The first cardioversion was successful in 48 patients (96%). After a single shock and without antiarrhythmic drugs being used, 42% of the patients maintained sinus rhythm in the long-term. Only left atrial size was inversely related to the efficacy of one shock (P = 0.025). With serial cardioversion 90% of the patients were kept in sinus rhythm for 5 years. Univariate analysis showed that a long duration of arrhythmia and impaired cardiac function were both related to poor outcome. During follow up 3 patients died of progression of heart failure and another 5 died suddenly. None of these 5 patients was on antiarrhythmic drugs. CONCLUSIONS: Electrical cardioversion was an effective and safe method of converting chronic atrial flutter to sinus rhythm. To maintain sinus rhythm, more than half of the patients required multiple shocks and prophylactic antiarrhythmic drugs. Sudden death was relatively frequent in the study population; the limited data available from this study suggest that such deaths were caused by the underlying disease and not drug related proarrhythmia.

Objectives. We sought to establish the diagnostic accuracy of transesophageal echocardiography (TEE) during cardiopulmonary resuscitation. Background. Because of its bedside diagnostic capabilities, excellent cardiac images and lack of interference with resuscitation efforts, TEE is ideally suited to determine the cause of a circulatory arrest that is not due to severe arrhythmia. However, the diagnostic accuracy of TEE during resuscitation is unknown. Methods. TEE was performed in patients with prolonged circulatory arrest. The TEE diagnoses were compared with diagnoses from autopsy, surgery and clinical follow-up. Results. Of the 48 study patients (29 male, 19 female, mean age ± SD 61 ± 20 years), 28 had an in-hospital cardiac arrest and 20 an out-of-hospital onset of arrest. Forty-four patients eventually died; four survived to discharge. The diagnoses made with TEE were cardiac tamponade (n = 6), myocardial infarction (n = 21), pulmonary embolism (n = 6), ruptured aorta (n = 1), aortic dissection (n = 4), papillary muscle rupture (n = 1), other diagnosis (n = 2) and absence of structural cardiac abnormalities (n = 7). A definite diagnosis from a reference standard was available in 31 patients. The TEE diagnosis was confirmed in 27 of the 31—by postmortem examination (n = 19), operation (n = 2), angiography (n = 2) or clinical course (n = 4). In the other four patients the TEE diagnosis proved incorrect by postmortem examination. The sensitivity, specificity and positive predictive value of TEE were 93%, 50% and 87%, respectively. In 15 patients (31%), major therapeutic decisions were based on TEE findings. Conclusions. TEE can reliably establish the cause of a circulatory arrest during cardiopulmonary resuscitation.

This study was designed to examine the accuracy of multiplane transesophageal echocardiography (TEE) color Doppler measurements in comparison to monoplane or biplane measurements in estimating the severity of mitral regurgitation (MR). Multiplane TEE potentially increases diagnostic accuracy of transesophageal examinations; it is unknown if multiplane is more accurate in assessing the severity of MR than monoplane or biplane TEE. Left ventricular cineangiograms of 91 patients with MR (40 no or mild, 30 moderate, and 21 severe) were compared with systolic pulmonary venous flow reversal and transesophageal color Doppler measurements: jet area and length in the transverse and longitudinal plane, maximal and average of those 2 planes (biplane), and maximal and average of 11 different planes (multiplane). Flow reversal (16 patients) identified severe MR with a specificity of 96% and a sensitivity of 62%; these were 96% and only 10% to 43%, respectively, for color Doppler measurements. in the absence of flow reversal, multiplane maximal jet area predicted severe MR with a sensitivity of 88% and a specificity of 75%, which were 85% and 76%, respectively, for no or mild MR; this did not differ significantly from results obtained by monoplane or biplane measurements. Color Doppler measurements of eccentric jets were not reliable for identification of severe MR. Systolic pulmonary venous flow reversal identifies 2 of 3 patients with severe MR with a high accuracy. In patients without flow reversal, multiplane color Doppler TEE is very capable of assessing MR severity, but biplane and monoplane TEE are equally accurate. (C) 1996 by Excerpta Medica, Inc.

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.

With use of invasive methods, coronary endothelial function is generally studied by examining the response of epicardial coronary arteries to intracoronary administered acetylcholine or to cold pressor testing. Because invasive methods have substantial inherent limitations, studies should attempt to evaluate coronary endothelial function noninvasively. This study examines a noninvasive technique for endothelium-related coronary stress testing. In myocardial regions supplied by nonstenotic coronary arteries, we compared positron emission tomography (PET) myocardial perfusion imaging with intracoronary Doppler flow velocity measurements during endothelium-related stress testing. PET perfusion was examined at rest and during cold pressor testing in 10 patients with 1-vessel coronary artery disease. In nonstenotic coronary arteries, flow velocity measurements were obtained at rest, during cold pressor testing, and during intracoronary administered acetylcholine. Perfusion and flow velocity responses and stress/rest ratios were compared between the techniques during the various circumstances. Positive correlations were found between: (1) cold pressor Doppler flow velocity responses and acetylcholine Doppler flow velocity responses (r = 0.84, SEE = 0.19, p = 0.003); (2) cold pressor PET perfusion responses and cold pressor Doppler flow velocity responses (r = 0.70, SEE = 0.17, p = 0.02); and (3) cold pressor PET perfusion responses and acetylcholine Doppler flow velocity responses (r = 0.62, SEE = 0.19, p = 0.05). These results suggest that in angiographically normal coronary arteries, both the flow velocity and the perfusion responses during cold pressor testing may be related to the response to acetylcholine.

We evaluated the value of color and pulsed Doppler transesophageal echocardiographic parameters and of V waves in estimating the severity of mitral regurgitation (MR) in 62 consecutive patients (38 men and 24 women, aged 39 to 80 years) with angiographically proven chronic pure MR (15 grade I/II, 47 grade III/IV). Twenty patients were examined before cardiac surgery under general anesthesia. Sensitivity, specificity, and positive and negative predictive values of systolic pulmonary venous flow reversal for the presence of grade III/IV MR were 87%, 93%, 98%, and 64%, respectively; these were for jet areas greater than or equal to 8.0 cm(2)-66%, 100%, 100%, and 48%, for jet lengths greater than or equal to 50 mm-70%, 87%, 94%, and 48%, for enlarged V waves-86%, 38%, 83%, and 43%, and for either flow reversal or a let urea greater than or equal to 8.0 cm(2)-96%, 93%, 98%, and 88%. We conclude that a combination of measurements improved the negative predictive value considerably, which is of importance in a population with a high pretest probability of severe MR. Enlarged V waves are not reliable in predicting severe MR. The optimal cutoff value for let area and let length was lower in anesthesized patients than in conscious patients; in anesthesized patients, sensitivity, specificity, and positive and negative predictive values of let area greater than or equal to 5.0 cm(2) for grade III/IV MR were 67%, 100%, 100%, and 50%, respectively; these were 87%, 100%, 100%, and 71% for flow reversal. Because the results of mitral repair are often evaluated with transesophageal echocardiography during surgery, our findings have clinical implications for evaluation of severe MR in anesthesized patients: pulmonary venous flow direction is the first-choice measure; jet area can be used when a low cutoff point is chosen.

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

To assess the acute hemodynamic and long-term clinical effects of isradipine, a calcium antagonist of the dihydropyridine class, we performed a double-blind, placebo-controlled parallel study in 19 patients with coronary artery disease (CAD) and stable chronic heart failure (CHF). Their mean age was 56 +/- 5 years, and left ventricular ejection fraction (LVEF) was 0.18 +/- 0.05. Patients were treated with diuretics and digoxin only. All were clinically stable and in sinus rhythm. The acute hemodynamic study showed that (intravenous) isradipine increased cardiac index (+36%) and stroke volume index (+30%) (both P < 0.001), while systemic vascular resistance (-33%) and mean arterial pressure (-10%) decreased (both P < 0.005). Filling pressures and heart rate were not affected. Of the 19 patients, 17 completed the 12 week study; 2 patients on placebo (1 death, 1 side-effects) but no patient on isradipine (5 mg 3 times daily) dropped out. After 12 weeks, peak oxygen consumption (VO2), LVEF, echocardiographic indices, and other clinical parameters were unaffected by treatment. Repeat invasive hemodynamic measurements showed that the initial improvement by isradipine was not present anymore. In conclusion, despite a beneficial acute hemodynamic effect, isradipine has no favorable clinical influence during prolonged treatment in patients with mild to moderate CHF.

Background Physical exercise and mental work cause alterations in cardiac autonomic control. β-Blockers protect the heart against stress, and this effect may be in part centrally mediated. In this context, the lipophilicity of the drug would be clinically relevant. Methods and Results Thirty postinfarct patients were randomized to receive 100 mg atenolol or 200 mg metoprolol CR in a double-blind, crossover manner, each for a 6-week period. Heart rate (HR) variability was used to study autonomic effects during mental and physical stress and to study circadian variations. Mean 24-hour HR decreased from 77±7 to 60±6 beats per minute after atenolol and to 62±6 beats per minute after metoprolol ( P =.046). At baseline, mental performance tasks did not affect HR, but decreased HR variability (SDNN index from 51±26 to 30±13 milliseconds [ms], P 2 , P =.046; and low-frequency power from 538±447 to 290±275 ms 2 , P P P =.004). β-Blockade could not prevent this decrease. No differences between atenolol and metoprolol were observed for absolute high- and low-frequency power or after adjustment for HR. Vagal blockade with methylatropine during chronic β-blocker treatment nearly abolished all components of spectral power. HR was found to be the parameter most strongly affected by β-blockade but not by an influence on vagal tone. No differences were found between atenolol and metoprolol. Conclusions In stable postinfarct patients, chronic treatment with metoprolol and atenolol attenuates the reduction in HR variability induced by mental performance tasks, but the effects during exercise are limited. β-Blockers do not appear to increase vagal tone in this stable patient group. The point of action in these patients is mainly a reduction in HR, probably due to a reduction in stress-induced sympathetic activation. Clinically significant differences between atenolol and metoprolol were absent, indicating that the degree of lipophilicity does not distinguish among the β-blockers what their salutary effects are on HR variability during the specific challenges used.

Although atrial fibrillation is common in patients with heart failure, patients with atrial fibrillation are often excluded from congestive heart failure trials or are not analyzed separately. Consequently, while the effect of angiotensin-converting enzyme inhibitors in patients with sinus rhythm is well established, the effect on patients with atrial fibrillation is unknown. The authors hypothesized that these agents might be particularly effective in this patient category, given their antiadrenergic properties and the importance of adequate rate control. Therefore, the effects of lisinopril 10 mg once daily were evaluated in 30 patients with congestive heart failure and chronic atrial fibrillation (mean age, 68 +/- 6 years) in a double-blind, randomized, placebo-controlled trial. All patients were in New York Heart Association class II or III and were stable on conventional therapy (digoxin, diuretics, nitrates). After 6 weeks, mean peak oxygen consumption increased from 14.7 +/- 3.4 to 15.9 +/- 2.9 mL/min/kg in the lisinopril group (P = .034). Plasma norepinephrine levels during exercise and at peak exercise tended to be lower when the patients were taking lisinopril (10.8 +/- 4.2 to 8.9 +/- 4.4 nmol/L and 16.3 +/- 9.2 to 14.3 +/- 7.7 nmol/L, P < .1). Heart rate during exercise and ambulatory monitoring was not significantly affected. Left ventricular fractional shortening tended to increase after lisinopril (23 +/- 7 to 27 +/- 9%, P = .073). Left atrial volume was unchanged, as were plasma atrial natriuretic peptide levels. After subsequent electrical cardioversion, treatment was continued for 6 more weeks, allowing assessment of the effect of lisinopril on maintenance of sinus rhythm; maintenance of sinus rhythm was 71% in the lisinopril group and 36% in the placebo group (P = NS). This study shows that treatment with an angiotensin- converting enzyme inhibitor improves peak oxygen consumption in patients with congestive heart failure and chronic atrial fibrillation. Attenuation of adrenergic drive during exercise may play a role in mediating this effect.

The effect of dihydropyridines in patients with unstable angina is discouraging. To find out the effect of the non-dihydropyridine-like calcium-channel blocker diltiazem, a randomised, double-blind trial was conducted comparing diltiazem with glyceryl trinitrate, both given intravenously, in 129 patients with unstable angina. The endpoints were refractory angina or myocardial infarction, individually and as a composite endpoint. Refractory angina alone or together with myocardial infarction occurred significantly less commonly in the diltiazem group. While patients were on the trial drugs the numbers with refractory angina were 6 (10%) in the diltiazem group versus 17 (28%) in the glyceryl trinitrate group (relative risk 0.36, p = 0.02), and the numbers with refractory angina and myocardial infarction were 9 (15%) versus 23 (38%) (relative risk 0.40, p = 0.007). Over 48 h the number were: refractory angina 8 (13%) versus 18 (30%), relative risk 0.45, p = 0.03, and refractory angina and myocardial infarction 12 (20.0%) versus 25 (41%), relative risk 0.49, p = 0.02. Patients in the diltiazem group had better (p < 0.05) event-free survival while taking the drugs. Heart-rate pressure product was reduced significantly only by diltiazem (p < 0.05). The incidence of bradyarrhythmias did not differ significantly. Atrioventricular conduction disturbances occurred in 5 (8%) patients in the diltiazem group but were not seen in the glyceryl trinitrate group (p = 0.03). These disturbances could be reversed by decreasing the dose of the drug or withdrawing it. No temporary pacemakers were required. Headache requiring an analgesic or dose adjustment occurred significantly less in the diltiazem group: 3 (5%) versus 15 (25%), relative risk 0.20 (p < 0.004). These results indicate that intravenous diltiazem, compared with intravenous glyceryl trinitrate, significantly reduces ischaemic events and can be used safely in patients with unstable angina.

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.

Correlations between New York Heart Association functional class, left ventricular ejection fraction, and peak oxygen consumption were compared to heart rate variability and analyzed in 79 heart failure patients with left ventricular ejection fraction

Two patients are described with reproducible cardiac asystole post-exercise. No structural heart disease was demonstrable. At autonomic function testing no abnormal responses were noted. Also, head-up tilt tests were normal. However, electrophysiologic testing and heart rate variability during 24-h Holter monitoring were indicative of a high vagal tone in both patients. The findings suggest that post-exertional asystole may not be due solely to a vasovagal mechanism; excessive rebound vagotonia per se may also play a role.

Few data are available about the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels. REGRESS is a double-blind, placebo-controlled, multicenter study to assess the effect of a 2-year treatment with the 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis using quantitative coronary arteriography in 885 male patients with a total serum cholesterol value of 155-310 mg/dl (4-8 mmol/liter). Among symptomatic men with significant coronary atherosclerosis and normal to moderately raised levels of serum cholesterol, patients treated with pravastatin had less progression of coronary atherosclerosis and fewer new cardiovascular events than patients in the placebo group. Ultrasound examinations of carotid and femoral arteries were performed in 255 patients. Changes in intimal-medial thickness also showed a treatment effect from pravastatin; however, on a per patient basis, there was no correlation with the treatment effect in the coronary arteries.

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.

To determine the additional diagnostic value of biplane transesophageal echocardiography (TEE) in patients undergoing mitral valve surgery, we studied 48 patients with severe mitral regurgitation. Transesophageal echocardiographic video recordings were reorganized in separate transverse and longitudinal sections to allow independent evaluation. Mechanism of mitral regurgitation and anatomic abnormalities of the mitral valve were assessed by all 3 transesophageal echocardiographic modalities and were related to surgical findings. Biplane TEE detected increased leaflet mobility with a sensitivity of 91% and a specificity of 84%, and restricted leaflet mobility with a sensitivity of 100% and a specificity of 97%. Biplane TEE was accurate in the diagnosis of most of the anatomic abnormalities associated with these mechanisms. However, the sensitivity for detecting subvalvular abnormalities (including papillary muscle abnormalities) was poor, and measurement of the annular diameter had a poor correlation with annular dilatation. Although the yield of biplane TEE was better than either transverse or longitudinal TEE alone, the differences did not reach statistical significance, because of the size of the patient group. The surgical procedure (either valve repair or replacement) was correctly predicted with transverse TEE in 71%, with longitudinal TEE in 69%, and with biplane TEE in 79% of the patients. All 3 transesophageal echocardiographic modalities are very capable of assessing the anatomic abnormalities and mechanism of mitral regurgitation, as well as predicting the feasibility of valve repair.

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.

Coronary artery disease is an increasingly common medical problem in the elderly, and relatively few studies investigating drug therapy focus on this population. To assess the efficacy and safety of the calcium channel blocker, felodipine, and isosorbide mononitrate (ISMN), as adjunct to optimal beta-blocker therapy in elderly patients, a placebo-controlled, double-blind study was conducted in 46 patients, aged between 65 and 80 years, with documented stress-induced angina pectoris and myocardial ischemia. With use of a latin-square design, with 3 periods of 4 weeks each, exercise testing was performed after each period. Felodipine, 5 mg once daily, significantly improved both time to ischemic threshold and pain threshold (p = 0.02 and p = 0.003, respectively, vs placebo), and tended to increase total exercise time (p = 0.06 vs placebo). In contrast, ISMN, 20 mg twice daily, did not significantly affect these parameters. Comparison of the 2 active treatment arms showed that, overall, felodipine was more effective than ISMN, with a statistically significant difference for time to ischemic threshold (p = 0.02). With regard to safety, felodipine was also better tolerated than ISMN, which led to more patients discontinuing study medication with ISMN (p0.05 between ISMN and felodipine). It is concluded that in elderly patients who are treated with optimal beta blockade, felodipine, but not ISMN, leads to an additional significant reduction in ischemic parameters during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and major clinical end points were compared in 61 patients treated with a Stack autoperfusion balloon versus 36 patients who received a Palmaz-Schatz stent for acute or threatened closure during coronary angioplasty. The groups were comparable regarding baseline clinical characteristics. Procedural success was achieved in 43 patients (70%) treated with an autoperfusion balloon versus 34 patients (94%) who received a stent (p0.02). Emergency bypass surgery was performed in 13 patients (21%) with the autoperfusion balloon versus none of the patients with a stent (p0.001). In the stent group, 3 patients (8%) died (p0.05); 2 deaths were caused by thrombotic reclosure, and 1 patient died after unsuccessful stent delivery. Subacute reclosure during hospitalization occurred in none of the patients with autoperfusion versus 8 patients with the stent (22%) (p0.0002). Therefore, the number of patients with successful stent implantation at discharge decreased to 26 (72%). At 3-month follow-up in all patients with a successful intervention, reclosure or angiographic restenosis (50%) occurred in 13 patients with autoperfusion (30%) versus 3 patients with stents (12%) (p = NS). There was no difference in event-free survival during follow-up. Thus, both interventions were equally successful in the treatment of acute and threatened closure. More emergency surgery was performed in the autoperfusion balloon group, whereas a higher subacute reclosure rate was seen in the stent group. At 3-month follow-up, there were no significant differences regarding reclosure, restenosis, and event-free survival.

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.

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.

Although a number of studies have shown that the incidence of late potentials is lower after thrombolytic therapy, it is not known whether this is paralleled by fewer arrhythmic events during long-term follow-up. In patients with first acute myocardial infarction, filtered QRS duration was significantly shorter when treated with streptokinase (95 +/- 11 ms, n = 53) than when treated with conventional therapy (99 +/- 12 ms, n = 77, p0.05). The low-amplitude signal (D40) was shorter after thrombolysis (28 +/- 11 vs 33 +/- 12 ms, p0.02). Terminal root-mean-square voltage did not differ significantly (41 +/- 24 vs 35 +/- 23 microV). Irrespective of treatment, late potentials were predictive in the complete group (n = 171) for arrhythmic events during follow-up (13 +/- 6 months, range 6 to 24) (hazard ratio 7.7, p0.02, Cox proportional-hazards survival analysis), but treatment (streptokinase vs conventional) did not significantly affect outcome when added to the model. It is concluded that thrombolysis prevents the development of late potentials. However, this study does not confirm the hypothesis that prevention of late potentials leads to a decrease in arrhythmic events.

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.

The initiating mechanisms of exercise-induced ventricular tachycardia were studied in a population of 5842 patients who performed 9064 bicycle exercise tests. Sixty (1%) patients had 194 episodes of ventricular tachycardia during the test. Forty-two percent of these occurred during exercise and 58% during recovery. Two different initiating electrocardiographic patterns were observed. In 17 (28%) patients ventricular tachycardia was initiated by a short-long-short sequence of R-R intervals (group 1). Thirty-eight (63%) patients did not have this pattern of interval changes preceding ventricular tachycardia (group 2). Five (8%) other patients showed both patterns. The clinical characteristics of the groups were different for angina and cardiomyopathy but not for previous myocardial infarction. In group 1 ventricular tachycardia was related to recovery (76%; p

Early occlusion of intracoronary stents has been exclusively attributed to thrombosis. Using intracoronary angioscopy, we have found 2 patients in whom this common and serious complication of coronary stenting was caused by obstructive intima dissection rather than thrombosis.

BACKGROUND Successful coronary thrombolysis involves a risk for reocclusion that cannot be prevented by invasive strategies. Therefore, we studied the effects of three antithrombotic regimens on the angiographic and clinical courses after successful thrombolysis. METHODS AND RESULTS Patients treated with intravenous thrombolytic therapy followed by intravenous heparin were eligible when a patent infarct-related artery was demonstrated at angiography < 48 hours. Three hundred patients were randomized to either 325 mg aspirin daily or placebo with discontinuation of heparin or to Coumadin with continuation of heparin until oral anticoagulation was established (international normalized ratio, 2.8-4.0). After 3 months, in which conservative treatment was intended, vessel patency and ventricular function were reassessed in 248 patients. Reocclusion rates were not significantly different: 25% (23 of 93) with aspirin, 30% (24 of 81) with Coumadin, and 32% (24 of 74) with placebo. Reinfarction was seen in 3% of patients on aspirin, in 8% on Coumadin, and in 11% on placebo (aspirin versus placebo, p < 0.025; other comparison, p = NS). Revascularization rate was 6% with aspirin, 13% with Coumadin, and 16% with placebo (aspirin versus placebo, p < 0.05; other comparisons, p = NS). Mortality was 2% and did not differ between groups. An event-free clinical course was seen in 93% with aspirin, in 82% with Coumadin, and in 76% with placebo (aspirin versus placebo, p < 0.001; aspirin versus Coumadin, p < 0.05). An event-free course without reocclusion was observed in 73% with aspirin, in 63% with Coumadin, and in 59% with placebo (p = NS). An increase of left ventricular ejection fraction was only found in the aspirin group (4.6%, p < 0.001). CONCLUSIONS At 3 months after successful thrombolysis, reocclusion occurred in about 30% of patients, regardless of the use of antithrombotics. Compared with placebo, aspirin significantly reduces reinfarction rate and revascularization rate, improves event-free survival, and better preserves left ventricular function. The efficacy of Coumadin on these end points appears less than that of aspirin. The still-high reocclusion rate emphasizes the need for better antithrombotic therapy in these patients.

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

Prolonged angioplasty balloon inflation with an autoperfusion balloon for failed conventional coronary angioplasty, was compared with emergency surgery for this condition. Restenosis was assessed 6 weeks after successful intervention with the autoperfusion balloon.Forty consecutive patients with persistent acute occlusion and/or severe intimal dissection during conventional angioplasty, were treated with the autoperfusion balloon. They were candidates for emergency surgery if it failed. Total inflation time was significantly longer (p

The electropharmacologic effects and pharmacokinetics of almokalant, a new class III antiarrhythmic, were investigated in a randomized, placebo-controlled, double-blind study, and efficacy was evaluated. Ten post-myocardial infarction patients with complex ventricular arrhythmias were included and received, in randomized order on consecutive days, 4.5 mg (12.8 mumol) of almokalant or placebo intravenously over 10 minutes. One patient received infusion at a higher, rate and developed self-terminating torsades de pointes. In the remaining 9 patients the corrected QT interval increased significantly- At the end of placebo infusion the corrected QT was 445 +/- 18 ms and after almokalant 548 +/- 53 ms (p = 0.0015). The signal-averaged electrocardiographic parameters did not change. The number of ventricular premature complexes decreased significantly during the first 15 minutes after almokalant infusion (p = 0.04). No additional proarrhythmic or other significant adverse events were noted, The almokalant plasma concentration showed a biphasic decrease. with an elimination half-life of 2.4 +/- 0.1 hours Almokalant was rapidly cleared from the body with a clearance of 11 +/- 1 ml/min/kg. When given with certain precautions almokalant appears safe and well-tolerated and may be antiarrhythmic by prolonging refractoriness.

To compare the value of the New York Heart Association (NYHA) classification and measurement of peak oxygen consumption (VO2) in the assessment of functional status and prognosis in patients with mild to moderate chronic congestive heart failure (CHF), 94 patients with clinically stable NYHA class II and III CHF were prospectively studied. In all patients, left ventricular ejection fraction was less than or equal to 40% (mean 22 +/- 9); 49 patients were in NYHA class II, and 45 were in NYHA class III. Mean peak VO2 was 17 +/- 5 ml/min/kg. During a follow-up period of 23 +/- 11 months, 21 patients died. The 1-, 2- and 3-year cumulative survival rates for the 94 patients were 88, 79 and 69%, respectively. Functional status, as assessed both by peak VO2 and NYHA classification, and left ventricular ejection fraction were significantly worse in the group of nonsurvivors. The most powerful independent predictor of mortality was peak VO2. Although mean peak VO2 was significantly higher in NYHA class II than in NYHA class III (20 +/- 4 vs 13 +/- 3 ml/min/kg, p less than 0.0001), categorization into subgroups on the basis of the attained peak VO2 revealed a marked discrepancy with the NYHA classification. Nevertheless, the survival curves of patients subdivided at a peak VO2 of 16 ml/min/kg showed a strong resemblance with survival curves of both NYHA classes.(ABSTRACT TRUNCATED AT 250 WORDS)

Programmed electrical stimulation was performed in 12 patients with moderate to severe congestive heart failure and ventricular tachycardia (VT) to study possible arrhythmogenic properties of ibopamine, a new orally active dopamine agonist. Ibopamine induced no significant changes in spontaneous cycle length, PR, QRS, QTc, AH or HV intervals, and also right ventricular effective refractory periods were unaffected (for paced cycle lengths of 600 and 430 ms, respectively, using 1 extrastimulus: 287 ± 16 ms at baseline vs 283 ± 27 ms after ibopamine and 270 ± 23 ms during the control study vs 262 ± 19 ms after ibopamine). In 6 of the 8 patients with coronary artery disease but in none of the 4 patients with dilated cardiomyopathy, sustained VT was induced before and after ibopamine. Proarrhythmia was present in 1 patient, who became inducible after ibopamine. However, 1 patient had sustained VT only at baseline but not after ibopamine. The number of extrastimuli required for VT induction was equal (2.7 ± 0.2 vs 2.7 ± 0.2). Holter monitoring showed no changes in ventricular premature complexes, ventricular couplets and runs of VT after 1 week of ibopamine therapy. The signal-averaged electrocardiogram was abnormal in 11 and showed late potentials in 5 patients, but no changes occurred after ibopamine. During hemodynamic evaluation, increases in cardiac (32%) and stroke volume (34%) indexes were seen after administration of 100 mg of ibopamine, accompanied by a decrease in vascular resistance and filling pressures. Plasma norepinephrine decreased significantly after ibopamine (p = 0.02) but plasma epinephrine was unaffected. In conclusion, ibopamine has no significant proarrhythmic effects in patients with congestive heart failure and VT, presumably because of its favorable influence on hemodynamics and plasma norepinephrine levels.

The present study was undertaken to reassess prospectively the immediate and long-term results of direct-current electrical cardioversion in chronic atrial fibrillation or atrial flutter, and to determine factors predicting clinical outcome of the arrhythmia after direct-current cardioversion. Two-hundred forty-six patients underwent direct-current electrical cardioversion and were followed during a mean of 260 days. Multivariate analysis was used to identify factors predicting short- and long-term arrhythmia outcome. Cardioversion was achieved in 70% of patients with atrial fibrillation and in 96% of patients with atrial flutter. Stepwise logistic regression analysis revealed that arrhythmia duration (p less than 0.001), type of arrhythmia (fibrillation vs flutter, p less than 0.02) and age (p less than 0.05) independently influenced conversion rate. On an actuarial basis, 42 and 36% of patients remained in sinus rhythm during 1 and 2 years, respectively. Multivariate regression analysis revealed that the type of arrhythmia (p = 0.0008), low precardioversion functional class (p = 0.002) and the presence of nonrheumatic mitral valve disease (p = 0.03) independently increased the length of the arrhythmia-free episode. Rheumatic heart disease shortened this period (p = 0.03). In conclusion, patients having a high probability of conversion together with a prolonged post-shock arrhythmia-free episode can be identified. This may improve the cost-benefit ratio of cardioversion.

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.

The purpose of this study was to analyze the determinants of atrial natriuretic peptide level in patients with congestive heart failure and atrial fibrillation. In particular, the duration of atrial fibrillation was analyzed because atrial fibrillation per se might have a specific effect on atrial natriuretic peptide level. The study group consisted of 26 patients with mild to moderate stable congestive heart failure and chronic atrial fibrillation. Plasma samples of atrial natriuretic peptide were obtained at rest and were analyzed with radioimmunoassay. Median atrial natriuretic peptide level was 213 (range 42 to 438) ng/L. Multivariate determinants of atrial natriuretic peptide level were use of calcium antagonists and the duration of atrial fibrillation; both factors showed an inverse relation with atrial natriuretic peptide level. The finding that atrial natriuretic peptide level was lower among patients with atrial fibrillation of longer duration suggests a form of insufficiency of the atria to produce atrial natriuretic peptide because of degenerative changes in the atria inherent to chronic atrial fibrillation.

Clinical decision-making in an individual elderly patient with severe aortic stenosis (AS) is difficult. The prognosis is influenced by increased age and various cardiac morbidity and comorbidity, and the benefit of surgery is uncertain because the prognosis with conservative treatment has rarely been described. The study aim was to identify those patients who would gain from surgical therapy.The long-term survival of a cohort of elderly patients after an initial diagnosis of severe aortic stenosis was analyzed. Multivariate analysis was used to develop patient profiles on the basis of four main variables of age, severity of AS, cardiac morbidity, and comorbidity, to illustrate the benefit of surgical treatment over conservative treatment.A total of 280 consecutive patients agedor = 70 years (median age 78 years) with a first-time diagnosis of isolated AS made between 1991 and 1993 was included. Of these patients, 120 underwent surgery. The seven-year predicted survival ranged from 6.9% to 83% in surgically treated patient, and from 0.6% to 48% in conservatively treated patients. The benefit of surgical treatment over conservative treatment was greatest in patients aged80 years, with a more critical AS, cardiac morbidity, and without (7-year survival 78% versus 14%) or with (7-year survival 56% versus 1%) comorbidity. Minimal benefit was seen in patients aged80 years with a less critical AS and without cardiac morbidity.This model illustrated the benefit of surgical treatment over conservative treatment in 16 different profiles of elderly patients with severe AS. These findings may provide support for clinical decision making in individuals within this patient group.

BACKGROUND: We sought to investigate whether beta-blockers exert a presynaptic effect in the myocardium as measured by 123I-metaiodobenzylguanidine. METHODS: The study comprised 59 patients with congestive heart failure, New York Heart Association class II or III, and left ventricular ejection fraction