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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 the long-term functional outcome assessed by exercise myocardial perfusion imaging following excimer laser angioplasty compared to balloon angioplasty in coronary lesions >10 mm in length. Background: Previous randomized studies evaluating the effect of coronary interventions mainly focused on the long-term clinical and angiographic outcome. The functional outcome, assessed by myocardial perfusion scintigraphy, has not been evaluated in a randomized setting. Methods: A total of 308 patients with stable angina and a longer coronary lesion (>10 mm) were randomized to excimer laser angioplasty or balloon angioplasty. A 99mTechnetium-2-methoxy isobutyl isonitrile (MIBI) single-photon emission computed tomography (SPECT) study was performed in 139 patients before the initial angioplasty procedure and at 6 months follow-up (73 patients in the laser group versus 66 patients in the balloon group, respectively). Exercise tolerance at follow-up was compared to baseline values by means of exercise duration and double product at peak exercise. Myocardial perfusion of the randomized vascular bed was assessed semi-quantitatively on the MIBI SPECT images. The reversible defects were graded as mild, moderate or severe. Myocardial perfusion at follow-up was expressed as a percentage reduction in incidence and grading of the reversible defects compared to baseline values. Results: Forty-four (61%) patients assigned to laser angioplasty were asymptomatic at 6 months follow-up compared to 34 (52%) patients assigned to balloon angioplasty (p = NS). Improvement in exercise duration and double product were 0.7 ± 2.1 min and 4.3 ± 6.2 min/mmHg/1000, respectively, in the laser group, versus 0.3 ± 2.5 min and 3.1 ± 5.5 min/mmHg/1000, respectively, in the balloon group (both p = NS). The percentage reduction of reversible defects was 23% in patients assigned to laser angioplasty vs. 29% in patients assigned to balloon angioplasty (Relative risk [RR]: 0.79, 95% confidence interval [CI]: 0.40–1.57; p = 0.50). The mild, moderate and severe reversible defects improved in 44.4, 63.6 and 66.6%, respectively, in the laser angioplasty group vs. 66.6, 53.8 and 90%, respectively, in the balloon angioplasty group. None of the comparisons were significantly different. Conclusion: Excimer laser angioplasty compared to balloon angioplasty in coronary lesions >10 mm in length yields a similar long-term functional outcome assessed by anginal status, exercise tolerance and myocardial perfusion.

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

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.

B-mode ultrasound intima-media thickness (IMT) measurements of carotid and femoral arterial walls are used in atherosclerosis studies. In this study, the components contributing to IMT measurement variability in males with coronary artery disease were investigated by means of repeated B-mode ultrasound scans and repeated off-line video image analyses. For statistical analysis, a mixed-model analysis of variance was used. From sonographer data, it was shown that human subjects and their arterial wall segments contributed 75% of the total IMT measurement variability in this population. Inter-sonographer variance contributed 25%. The intra-sonographer variance was negligible (

Background: Little is known about the value of heart rate variability in patients with symptomatic coronary artery disease with a preserved left ventricular function. We hypothesized that in these patients heart rate variability might be a helpful adjunct to conventional parameters to predict clinical events. Methods: In a prospective 2-year follow-up study ambulatory electrocardiographic recordings were performed in 263 consecutive male patients (mean age 56 ± 8 years) with stable angina pectoris and a mean left ventricular ejection fraction of 71% ± 12%. Clinical events consisted mainly of coronary events such as percutaneous transluminal angioplasty or coronary artery bypass graft operation. Results: Low measures of standard deviation of normal R-R intervals, standard deviation of the mean R-R intervals of 5 minutes, and two spectral components of heart rate variability were found in patients who had had an event compared with patients with no event. Adjusted for severity of angina, the presence of a previous myocardial infarction, and the use of β-blockers in a logistic regression model this relation remained statistically significant for SDNN. Healthy volunteers appeared to have the highest measures of heart rate variability. Conclusion: In patients with ischemic heart disease and normal or near normal ventricular function decreased heart rate variability is associated with adverse clinical events. (Am Heart J 1998;135:571-6.)

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. ...

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.

Treatment of chronic heart failure (CHF) remains a major medical problem. Although in the last decades the benefits of several therapies in different patient populations with left ventricular dysfunction have been established, morbidity and mortality of CHF patients are high. Consequently, in the last decade improvement of survival has become the primary therapeutic endpoint in CHF studies, and the evaluation of the influence of (new) drugs on mortality has become crucial. In the present article an overview of the large mortality trials is given, and the shifts and alterations in the drug treatment strategy of CHF are discussed.

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.

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.

Objectives. We addressed the question whether in patients with cardiac chest pain referred for stress myocardial perfusion scintigraphy, Tc-99m MIBI SPECT stress imaging should always be followed by a rest imaging procedure. Background. Using Tc-99m MIBI imaging a stress-rest sequence is usually performed implying that the resting study always follows the stress study irrespective of the results of the stress study. As a normal stress study would eliminate a subsequent resting study, it appears desirable to potentially define certain subsets of patients in whom a normal stress study can be expected in order to determine a more selective referral approach to the nuclear medicine department. The consequences of such a more streamlined approach would less impose on the logistics of the department of nuclear medicine, with decrease of investigation time, radiation dose, and costs in a time of retrenchment in the medical sector. Methods. A consecutive series of 460 patients (mean age 58.2 years) was studied who were stratified to 269 patients without prior myocardial infarction, and to 191 patients with documented evidence of a previously sustained mycoardial infarction. All patients underwent Tc-99m MIBI SPECT imaging according to a two-day stress-rest protocol. Results. Patients with and without a previous myocardial infarction showed suboptimal overall predictive accuracies for the exercise electrocardiograms (58% and 60%, respectively). In the total group of 460 patients, 94 (20%) patients showed a normal stress-rest Tc-99m MIBI SPECT; this occurred in 86/269 (32%) patients without a previous myocardial infarction and in only 8/191 (4%) patients with a previous myocardial infarction. Conclusions. Patients with a stress defect at Tc-99m MIBI SPECT imaging should always undergo a resting SPECT study irrespective of the clinical and stress electrocardiographic findings. As patients without a previous myocardial infarction had a normal stress SPECT study in almost one-third (32%) of patients compared to only 4% in patients with a previous myocardial infarction, it may be useful to employ different referral and imaging strategies i.e. a stress-only versus a stress-rest procedure. To schedule referring patients differently according to the presence or absence of a previously sustained myocardial infarction may be cost-saving, less demanding for the nuclear medicine personnel, and patient-convenient. In addition, a stress-only imaging procedure reduces radiation exposure to the individual patient.

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.

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

The delivery of new Palmaz-Schatz stents in native coronary arteries can be facilitated by using the technique of deep seating of a 6 French guiding catheter. Two patient histories are described to illustrate this new technique. (C) 1996 Wiley-Liss, Inc.

Safety and efficacy of propafenone and disopyramide for long-term maintenance of sinus rhythm after electrical cardioversion was studied in 56 patients with chronic atrial fibrillation (median arrhythmia duration, 5 months). After cardioversion, patients were randomly assigned to receive double-blind propafenone 300 mg tid (25 patients) or disopyramide 250 mg tid (31 patients). Downward dose adjustment was allowed in case of intolerable side effects. The endpoints were arrhythmia recurrence; and side effects not amenable to dose reduction. For patients randomized to propafenone (mean dose, 878 +/- 65 mg/day), 66% [95% confidence interval [(CI) 46-85%] and 55% (95% CI, 34-76%) remained in sinus rhythm at 3 and 6 months, respectively (Kaplan-Meier method). Similar figures were found with disopyramide (mean dose, 704 +/- 81 mg/day): 71% (95% CI, 54-87%) and 67% (95% CI, 50-84%) at 3 and 6 months, respectively (p = NS). In the patients with a relapse of atrial fibrillation, the ventricular rate while still using the prophylactic agents did not increase significantly compared with precardioversion. However, one patient on disopyramide had an excessively high relapse heart rate (170 vs. 100 beats/min). Side effects were more frequent on disopyramide. Side effects necessitating drug discontinuation occurred in 12 patients: 4 patients (16%) on propafenone and 8 (26%) on disopyramide. Severe adverse effects occurred in two patients, who developed heart failure while on disopyramide. There were no proarrhythmic events or deaths. Thus, propafenone and disopyramide are equally effective for maintaining sinus rhythm after cardioversion of atrial fibrillation. Propafenone is, however, better tolerated than disopyramide, which may cause heart failure.

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.

Abstract To date, lipid-lowering therapy appears to be the most effective medical intervention to retard progression of coronary atherosclerosis. In spite of promising experimental results, clinical trials completed so far have failed to demonstrate that calcium channel blockers (CCBs) alone influence the evolution of established coronary atherosclerosis. To assess whether the two therapies may have an additive or synergistic beneficial effect on human atherosclerosis, we reviewed in this regard the data of the angiographic Regression Growth Evaluation Statin Study (REGRESS) trial. REGRESS was designed to determine the effect of lipid-lowering therapy with pravastatin in symptomatic patients with normal to moderately raised cholesterol levels. Angiographically, with respect to the minimum obstruction diameter, in the pravastatin group, patients had on average 0.05 mm (95% confidence interval [CI]: 0.01-0.09) less progression if cotreated with CCBs compared with no CCB cotreatment, whereas in the placebo (no pravastatin) group, no effect of CCB treatment was observed (interaction test for differential effect of CCB treatment in patients with pravastatin compared with patients receiving placebo: P =.0016). With respect to the mean segment diameter, similar although not significant ( P =.33) results were found. With respect to new lesion formation, in the pravastatin group, there were 50% (CI: 25-83) fewer patients with new angiographic lesions if cotreated with CCBs compared with no CCB cotreatment, whereas in the placebo (no pravastatin) group, no significant effect of CCB treatment was observed (interaction test: P =.0026). No beneficial effects of CCB treatment on clinical events were observed. Although the REGRESS trial was not designed to evaluate combination therapy, the results suggest strongly that addition of CCBs to 3-hydroxy-3-methylglutaryl–coenzyme reductase inhibitor therapy (pravastatin) acts synergistically in retarding the progression of established coronary atherosclerosis.

Distal coronary hemoperfusion during percutaneous transluminal coronary angioplasty (PTCA)-with an autoperfusion balloon or active system-facilitates prolonged balloon inflation. Prolonged inflations may tack up intimal dissections and improve the primary angioplasty result in complex lesions. Additionally, distal perfusion may reduce the likelihood of cardiogenic shock during high-risk PTCA. Autoperfusion balloons are most frequently used to treat acute or threatened closure. There currently is no prospective clinical study showing that stent implantation for this complication is more successful and more cost-effective. The blood flow rates through autoperfusion balloons may not abolish myocardial ischemia, and higher flow rates can often be achieved with pumps. Therefore, during high-risk PTCA, pumps may be preferred to prevent hemodynamic collapse. Clinical application of perfusion pumps is hampered by the risk for mechanical hemolysis during prolonged perfusion and the high velocity of the bloodstream that exits the PTCA catheter, causing distal vessel wall trauma. (C) 1996 Wiley-Liss, Inc.

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.

We studied heart rate variability in ambulatory electrocardiographic recordings from 312 patients with significant coronary artery disease and a left ventricular ejection fraction of > or = 30%. Only those patients who had both episodes of ischemia and nonsustained ventricular arrhythmias showed diminished values for parasympathetic nonspectral and spectral heart rate (HR) variability parameters. The root mean square of difference of successive R-R intervals (RMSSD) and high-frequency (HF) power in this group were 28 +/- 3 msec and 9 +/- 1 msec, respectively. The highest values of these HR variability parameters were found in patients with nonsustained ventricular tachycardia and no ischemia (81 +/- 21 msec and 14 +/- 1 msec, respectively, p < or = 0.05). A relation was seen between transient myocardial ischemia and low-frequency power and between transient ischemia and ventricular tachycardia. These data suggest that the autonomic nervous system may play a role in ischemia and in ischemia-related ventricular arrhythmias.

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

Objectives.This study assessed the effects of digoxin and ibopamine on variables of heart rate variability in relation to neurohormonal activation.Background.Analysis of heart rate variability can be used to study the autonomic dysfunction that characterizes chronic heart failure. In the Dutch Ibopamine Multicenter Trial, patients with heart failure were found to have increased neurohormonal activation with placebo therapy but not with digoxin and ibopamine therapy.Methods.We studied 59 patients with mild to moderate heart failure (mean [±SEM]age 60 ± 1 years, mean ejection fraction 0.30 ± 0.01). Patients were randomized to double-blind treatment with digoxin (0.25 mg [n = 22]), ibopamine (100 mg three times a day [n = 19]) or placebo (n = 18); background therapy consisted of furosemide (up to 80 mg).Results.After 3 months, plasma norepinephrine levels had increased with placebo, whereas they decreased with digoxin (+31 vs. −60 pg/ml, respectively, p < 0.01). With ibopamine, a nonsig nificant decrease was observed (−27 pg/ml, p = 0.10). All variables of heart rate variability showed a deterioration in the placebo group. With digoxin, the percent differences between successive RR intervals >50 ms (pNN50) increased (+ 1.7 ± 0.9%, p < 0.01), along with absolute and normalized high frequency power (+40 ± 33 ms2, p < 0.05 and +2.4 ± 1.7%, p < 0.01, respectively). These changes were observed during daytime hours only and were most pronounced in patients with the most impaired baseline heart rate variability. With ibopamine, nonsignificant trends similar to the changes with digoxin were observed.Conclusions.In patients with early stages of heart failure, digoxin may prevent a progressive deterioration in heart rate variability, whereas ibopamine does not show statistically significant effects. The changes in heart rate variability with digoxin parallel an observed decrease in neurohormonal activation. Digoxin apparently enhances cardiac vagal tone in the setting of neuroendocrine activation.

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.

In patients with acute myocardial infarction (MI), quick initiation of thrombolytic therapy is the best strategy for improvement of survival and reduction of morbidity. Streptokinase, a purified product of haemolytic streptococci, is the most commonly administered agent. The compound anistreplase (a complex of streptokinase to plasminogen), is available but currently not often used. The nonantigenic competitor for these two compounds for the indication of MI is alteplase (recombinant tissue plasminogen activator; rt-PA). Due to former use of streptokinase or its derivative anistreplase, patients may develop specific antibodies to the foreign protein, whereas cross-reacting antibodies may be due to streptococcal infections. These antibodies may neutralise streptokinase or its derivative in case of (re)administration and may mediate adverse events, sometimes serious. Since advanced age by itself is certainly not a contraindication to thrombolytic therapy, and because reinfarction occurs frequently, the benefit-risk ratio of re-exposure to streptokinase or its derivative is decreased in the elderly who present with reinfarction. In the framework of tailored thrombolytic therapy, alteplase or urokinase appear to be the drugs of choice in these patients.

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.

There is increasing evidence that clinical deterioration in manifest chronic heart failure is related to both hemodynamic and neurohumoral factors. Only few data are available, however, on the progression of disease in its early stages, when treatment has not yet been initiated. The aim of this study was therefore to examine the changes in clinical and neurohumoral variables that occur over 6 months in patients with clinically stable and untreated heart failure, and to evaluate the influence of drugs that may affect these variables. Accordingly, we studied 64 patients with heart failure who were in New York Heart Association functional class II (88%) and III (12%). They were randomized to double-blind treatment with the oral dopamine agonist ibopamine (100 mg 3 times daily; n = 22), digoxin (0.25 mg once daily; n = 22) or placebo (n = 20). Their age (mean +/- SD) was 60 +/- 8 years, and left ventricular ejection fraction (mean +/- SD) was 0.33 +/- 0.08. Of the 64 patients, 56 (88%) completed the 6-month study period (p = NS between groups). Exercise time decreased in patients treated with placebo after 6 months (median -62 seconds; p < 0.05 vs baseline), but it increased with ibopamine (+48 seconds), and digoxin (+17 seconds; both p < 0.05 vs placebo). Plasma norepinephrine increased in the placebo group after 6 months (median + 31 pg/ml, p < 0.05 vs baseline), but decreased in patients receiving active drug treatment (ibopamine: -24 pg/ml, digoxin: -98 pg/ml, both p < 0.05 vs placebo). Plasma renin and aldosterone levels were unchanged after 6 months in the placebo group, but digoxin therapy slightly reduced plasma renin concentration (-5 microU/ml; p < 0.05 vs placebo).(ABSTRACT TRUNCATED AT 250 WORDS)

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.