Absorption kinetics and pharmacodynamics of two oral dosage forms of flecainide in patients with an episode of paroxysmal atrial fibrillation.

OBJECTIVES: The objectives were to study the absorption kinetics and pharmacodynamics of two oral formulations of flecainide in patients with atrial fibrillation (AF) and to assess the relationship between pharmacokinetic parameters and the efficacy in restoring sinus rhythm. METHODS: The data of 54 patients included in a randomised, open, parallel-group study were used. Patients received an oral solution containing 300 mg flecainide and 20 mg cisapride or three tablets each containing 100 mg flecainide. The pharmacokinetic profile of flecainide was fitted using a one-compartment model with lag-time and first-order absorption. RESULTS: The tablets gave a maximum concentration (C (max\ fit)) of 0.43+/-0.14 mg/l at 2.37+/-1.20 h. The oral solution resulted in a much faster peak concentration at 1.05+/-0.71 h (P<0.0001). The C (max\ fit) of the oral solution of 0.60+/-0.17 mg/l was higher (P=0.0002) than that of the tablets, and interindividual variabilities of C (max\ fit) were 28% and 33%, respectively. The absorption rate constant (ka) of the oral solution was twofold larger (P<0.0001). A higher ka (P=0.04) and a duration of AF less than 24 h (P=0.006) increased the probability of cardioversion. If atrial fibrillation lasted less than 24 h, only ka (P=0.016) was obtained as a significant variable in multivariate analysis. The linear models of QRS interval changes versus flecainide concentrations of both formulations had similar slopes with similar interindividual variabilities. CONCLUSIONS: The probability of cardioversion after an oral loading dose of flecainide in patients with AF is dependent on ka. Rapid loading of the effect compartment, i.e. the atria, appears to be critical to reach cardioversion. Higher flecainide serum concentrations and a more rapid absorption does not increase interindividual variability of pharmacokinetics and pharmacodynamics, which is important when safety is considered.

A randomized study of combining maze surgery for atrial fibrillation with mitral valve surgery.

AIM: Mitral valve surgery seldom suppresses atrial fibrillation (AF), present prior to surgery. Maze III surgery eliminates AF in >80% of cases, the reason why combining this procedure with mitral valve surgery in patients with AF seems worthwhile. We prospectively studied the outcome of combining the Maze III procedure with mitral valve surgery. METHODS: Thirty-five patients with AF and a mean age of 64 years undergoing mitral valve surgery were prospectively randomized according to a 2.5:1 ratio to surgery with (n=25), or without (n=10) maze III and followed for at least 1 year. RESULTS: At discharge and after 12 months freedom from AF was 56% and 92%, respectively, in the maze group, and 0% and 20%, respectively, in patients without maze (group differences at discharge p=0.002, after 12 months p=0.0007). Sinus node incompetence was seen in 1 of 25 maze patients requiring pacing. No in-hospital or late death occurred; stroke was observed in 1 patient (without maze). Quality of life markedly improved after surgery, but did not differ between patients with or without maze surgery. CONCLUSIONS: This first prospective randomized study shows that combining maze III with mitral valve surgery resulted in a significantly better elimination of preoperative AF than mitral valve surgery alone. As the quality of life did not differ between patients with, or without maze surgery, additional maze surgery is primarily recommended in patients in whom anticoagulation therapy can be avoided after surgery, specifically in patients with scheduled mitral valve plasty.

Buccal transport of flecainide and sotalol: effect of a bile salt and ionization state.

Patients with infrequent attacks of supraventricular arrhythmia may benefit from self administration of antiarrhythmic drugs on an 'as required' basis. The oral cavity is easily accessible and the potential for rapid absorption exists. The effects of ionization state and sodium glycocholate on the ex vivo transport of sotalol and flecainide across porcine buccal mucosa were studied. The permeated amounts at 3 h (Q) and fluxes (J) of sotalol in an aqueous solution at pH 7.4 and 9.0 were similar. At pH 7.4, in contrast to pH 9.0, the addition of 1.0% (w/v) sodium glycocholate decreased Q and J four and five fold. Flecainide base in propylene glycol resulted in a nine and 12 fold higher Q and J as compared with an aqueous solution of flecainide acetate at pH 5.8. The presence of sodium glycocholate reduced the transport rate of the flecainide base. However, Q and J were increased 110 and 75 fold by adding 1.0% (w/v) sodium glycocholate to a solution of flecainide acetate at pH 5.8. Sodium glycocholate seems to be an effective penetration enhancer for the buccal absorption of the more polar ionized form of flecainide in an aqueous solution. Sodium glycocholate does not seem to improve the transport of sotalol.

Rate control versus electrical cardioversion for atrial fibrillation: A randomised comparison of two treatment strategies concerning morbidity, mortality, quality of life and cost-benefit - the RACE study design.

BACKGROUND: Persistent atrial fibrillation (AF) does not terminate spontaneously and may cause left ventricular dysfunction and thromboembolic complications. For restoration of sinus rhythm electrical cardioversion (ECV) is most effective. However, AF frequently relapses, necessitating re-ECV and institution of potentially harmful antiarrhythmic drugs. If AF is accepted, rate control and prevention of thromboembolic complications using negative chronotropic drugs and warfarin is pursued. It is our hypothesis that rate control therapy is not inferior to ECV therapy in preventing morbidity and mortality. METHODS: RACE (RAte Control versus Electrical cardioversion for atrial fibrillation) is a randomised comparison of serial ECV therapy (repeat ECV as soon as possible after a relapse and institution of an antiarrhythmic drug: sotalol, class IC drug and amiodarone) and rate control therapy (resting heart rate <100 bpm using digitalis, calcium channel blockers and/or ß-blockers) in patients with persistent AF. Morbidity (heart failure, side effects of drugs, thromboembolic complications, bleeding and pacemaker implantation), mortality, quality of life and cost-effectiveness are primary and secondary endpoints. Included are patients with a recurrence of persistent AF, present episode <1 year and a maximum of two previous successful ECVs during the last two years. This study is a multicentre study in 31 centres throughout the Netherlands. All 520 patients have now been included. Follow-up is two years. The results are expected this year.

Morbidity and mortality in patients waiting for coronary artery bypass surgery.

OBJECTIVES: To describe morbidity and mortality in patients waiting for coronary artery bypass graft (CABG) surgery and to assess determinants for the occurrence of these complications. METHODS: A prospective cohort study was carried out in a tertiary referral general teaching hospital. Three hundred and sixty consecutive patients with a priority of routine or urgent who were accepted for CABG or CABG with additional valve surgery were evaluated. Follow-up began from the moment of acceptance until the procedure took place for cardiac death, myocardial infarction and unstable angina requiring hospital admission. RESULTS: The median (25-75th percentile) waiting time in the two priority groups was 100 (79-119) days for the routine group and 69 (38-91) days for the urgent group. Overall, eight patients died, seven suffered a myocardial infarction, and 33 episodes of unstable angina requiring immediate hospitalization occurred. The majority of events took place during the first 30 days on the waiting list. Unstable angina less than 3 months before acceptance was identified as an independent predictor (hazard ratio 2.5, 95% confidence interval 1.2-5.1) for complications during the wait. The prognostic value of smoking and familial cardiovascular disease was found to vary depending on the priority assigned to the patient. CONCLUSIONS: Complications occur relatively early during the time on the waiting list. If complications in coronary heart disease cannot be predicted more accurately, the only way to diminish the complication rate is drastic reduction of waiting times.

Effects of quinapril on clinical outcome after coronary artery bypass grafting (The QUO VADIS Study). QUinapril on Vascular Ace and Determinants of Ischemia.

The QUO VADIS study was designed to explore whether 1 year of angiotensin-converting enzyme inhibition with quinapril (40 mg/day) would decrease ischemia in patients who underwent coronary artery bypass grafting (CABG). Patients (n = 149) scheduled for CABG were randomized 4 weeks before surgery. Study medication was used from randomization up to 1 year after CABG. Exercise testing was performed at randomization; the exercise test was repeated 1 year after CABG and patients underwent 48-hour Holter monitoring. Clinical ischemic events were recorded and defined as death, revascularization, myocardial infarction, recurrence of angina pectoris, ischemic stroke, or transient ischemic attack. Baseline characteristics were similar between groups. Total exercise time increased overall by 75 +/- 76 seconds 1 year after CABG (placebo +79 +/- 75 seconds, quinapril +72 +/- 79 seconds, p = 0.6). All patients had ischemic ST-segment changes at randomization; 33% of patients had ischemic ST-segment changes 1 year after CABG (placebo 29%, quinapril 37%, p = 0.4). On Holter monitoring, the number of patients experiencing > or = 1 episodes of ischemia was equal in both groups. Treatment with quinapril significantly reduced clinical ischemic events after CABG: 15% in patients on placebo versus 4% of patients on quinapril (hazard ratio 0.23, 95% confidence interval 0.06 to 0.87, p = 0.02). Long-term quinapril treatment significantly reduced clinical ischemic events within 1 year after CABG, although ischemia at exercise testing and Holter monitoring was unchanged.

[Drug treatment of erection disorders in patients with cardiovascular disease]. / Medicamenteuze behandeling van erectiestoornissen bij cardiovasculair belaste patiënten.

Erectile dysfunction is a frequent condition in cardiovascular patients. Since the arrival of oral erection-supporting medication, patients want to know how safe sexual activity is in cardiovascular disease in general and during use of erection-supporting medication in particular. Sexual intercourse with a steady partner causes no more cardiovascular risk than normal daily activities such as ironing, 2 kilometers of walking without climbing, paperhanging, playing golf or gardening. The relative risk of myocardial infarction during sexual activity is not significantly higher than for healthy persons. The incidence of cardiovascular morbidity and mortality is not higher among users of sildenafil. Sildenafil is contraindicated in patients using long-acting nitrates or who may need to use short-acting nitrates, because the combination may cause a sharp fall of the blood pressure. No interactions have been observed with beta-receptor blockers, calcium antagonists, thiazide and loop diuretics and ACE inhibitors. Before prescribing a symptomatic (pharmaceutical) treatment for patients with an erection disorder, attention should be given tot the sexological, psychological and medical backgrounds of the disorder. Secondary prevention of atherosclerotic risk factors is also important: regulation of blood pressure and blood sugar level, hyperlipidaemia and obesity, as well as a change of lifestyle (giving up smoking, adapting of diet and more physical exertion). Patients with a very low cardiac capacity should be advised to refrain from treatment of the erection disorder.

[Infectious diseases as a weapon: vigilance is needed]. / Infectieziekten als wapen; waakzaamheid geboden.

The deliberate inclusion of Bacillus anthracis spores in mail has led to several cases of anthrax in the USA of which to date four have been fatal. Shortly before these incidents, the Health Council of the Netherlands had issued an advisory document which stressed the need for a well-established infrastructure and rigorous protocols so that an immediate and adequate response to cases of bioterrorism could be ensured. Physicians are expected to know the characteristics of the relevant diseases and to immediately notify the Health Inspectorate in the event of an infectious cluster which is unusual with respect to time, place or age, a cluster of a highly serious disease in healthy persons, or a cluster characterised by flaccid paralysis with bulbar signs.

Effect of very early angiotensin-converting enzyme inhibition on left ventricular dilation after myocardial infarction in patients receiving thrombolysis: results of a meta-analysis of 845 patients. FAMIS, CAPTIN and CATS Investigators.

OBJECTIVES: We sought to investigate the effect of angiotensin-converting enzyme (ACE) inhibition <9 h after myocardial infarction (MI) on left ventricular (LV) dilation in patients receiving thrombolysis. BACKGROUND: The ACE inhibitors reduce mortality after MI. Attenuation of LV dilation has been suggested as an important mechanism. METHODS: The data of 845 patients with three-month echocardiographic follow-up after MI were combined from three randomized, double-blind, placebo-controlled studies. The criteria for these studies included: 1) thrombolytic therapy; 2) ACE inhibition within 6 to 9 h; and 3) evaluation of LV dilation as the primary objective. RESULTS: The ACE inhibitor was started 3.2+/-1.7 h after the patients' first (mainly, 85%) anterior MI. After three months, LV dilation was not significantly attenuated by very early treatment with an ACE inhibitor. The diastolic volume index was attenuated by 0.5 ml/m2 (95% confidence interval [CI] -1.5 to 2.5, p = 0.61), and the systolic volume index by 0.5 ml/m2 (95% CI -1.0 to 1.9, p = 0.50). Subgroup analysis demonstrated that LV dilation was significantly attenuated by ACE inhibitor treatment for patients in whom reperfusion failed. In contrast, LV dilation was almost unaffected by ACE inhibitor treatment in successfully reperfused patients. CONCLUSIONS: We could not demonstrate attenuation of LV dilation in patients receiving thrombolysis by ACE inhibitor treatment within 6 to 9 h after MI. We speculate that very early treatment with an ACE inhibitor has a beneficial effect on LV remodeling only in patients in whom reperfusion failed. Other mechanisms may be responsible for the beneficial effects of ACE inhibitors in successfully reperfused patients after MI.

Angiotensin II formation in human vasculature after chronic ACE inhibition: a prospective, randomized, placebo-controlled study. QUO VADIS Investigators.

The QUO VADIS (the effects of QUinapril On Vascular Ace and Determinants of ISchemia) study was a randomized, double-blind, placebo-controlled trial designed to evaluate the effects of long-term angiotensin-converting enzyme (ACE) inhibition on angiotensin II formation in human vasculature. Patients (n = 187) scheduled for coronary artery bypass surgery used study medication 27 +/- 1 days before surgery. Segments of internal mammary arteries were exposed to increasing doses (0.1 nM-1 microM) of angiotensin I and II in organ baths. The rate of local angiotensin II formation is a function of the reciprocal of the difference between the pEC50's of the dose response curves to angiotensin I and II (-log/mol) and of the area between the curves (units). Quinapril (40 mg) and captopril (3 x 50 mg) similarly and significantly reduced mean blood pressure compared with placebo (p = 0.04). Difference between pEC50's was 0.90 +/- 0.08 in quinapril patients compared with 0.60 +/- 0.08 for placebo (p = 0.01); the area between curves was 91 +/- 8 for quinapril patients compared with 67 +/- 8 for placebo (p = 0.03). Angiotensin II formation was decreased to a lesser extent with captopril and was not statistically different from placebo (p = 0.3); the difference between pEC50's was 0.83 +/- 0.15; the area between curves was 84 +/- 12. This is the first randomized study to demonstrate that long-term oral treatment with an ACE inhibitor reduces vascular angiotensin II formation in humans.

Death on the waiting list for cardiac surgery in The Netherlands in 1994 and 1995.

OBJECTIVE: To describe the causes and circumstances of death regarding patients who died in 1994 and 1995 while on a waiting list for cardiac surgery in the Netherlands. DESIGN: Retrospective multicentre case study. SETTING: 11 Dutch cardiac surgery centres. PATIENTS: All patients reported as dying while on the waiting list for cardiac surgery in 1994 and 1995. MAIN OUTCOME MEASURES: Classification of death by an independent adjudication committee into "erroneously reported", "waiting list related" or "not waiting list related". Death was judged as "waiting list related" if the clinical course would have been substantially different if there had been unrestricted surgical capacity. RESULTS: 138 and 129 deaths were reported in 1994 and 1995, respectively. 43 deaths (16%) were considered as erroneously reported. 181 of the remaining 224 cases were adjudicated as waiting list related. Median time from acceptance for surgery to death was 35 days (interquartile range 14-75 days). 97 of 181 deaths occurred within six weeks following addition to the waiting list. The estimated incidence of death ranged from 1.33 per 1000 patient-weeks during weeks 2-4 to 0.68 per 1000 patient-weeks after 12 weeks. CONCLUSIONS: The causes and circumstances of death are waiting list related for approximately 100 patients per year in the Netherlands. At least half of the deaths may occur within the first six weeks. Waiting lists for cardiac surgery engender high risks for the patients involved.

VDDR pacing after His-bundle ablation for paroxysmal atrial fibrillation: a pilot study.

His-bundle ablation followed by pacemaker implantation is today a widely accepted therapeutic choice when drug refractoriness of symptomatic AF is evident. The selection of pacing mode in patients suffering from paroxysmal AF is still controversial. Preservation of AV synchrony is an attractive option in patients with paroxysmal AF who undergo His-bundle ablation. The purpose of this study was to examine prospectively the contribution of VDDR pacing for preservation of AV synchrony. After His-bundle ablation a VDDR pacing system was implanted in 17 patients with paroxysmal AF, and all antiarrhythmic drugs were withdrawn. The endpoint of the study was defined as the onset of chronic AF. To document the onset of chronic AF 48-hour Holter recordings were made every 6-8 weeks. After a mean followup of 18.2 (range 14-21) months, VDDR pacing is still operative in 13 patients (77%). Four patients developed chronic AF after a mean follow-up of 6 months. Of several baseline characteristics, only the intraatrial P wave at implantation was significantly smaller in patients developing chronic AF than in patients in whom the VDDR mode is still operative. This pilot study suggests that VDDR pacing is an attractive pacing method for patients with paroxysmal AF after His-bundle ablation. A low intraatrial P wave electrogram at implant was associated with a higher risk for the development of chronic AF.

Absorption kinetics of oral sotalol combined with cisapride and sublingual sotalol in healthy subjects.

AIMS: To study the absorption kinetics of sotalol following administration of different formulations. A formulation which results in fast absorption might be useful in the episodic treatment of paroxysmal supraventricular tachycardia (SVT), atrial fibrillation (Afib) or atrial flutter (Afl). METHODS: In an open randomized crossover study seven healthy male volunteers were given an intravenous infusion of 20 mg sotalol, for assessing the absolute bioavailability, an oral solution containing 80 mg sotalol, an oral solution containing both 80 mg sotalol and 20 mg cisapride and an 80 mg sotalol tablet, which was taken sublingually. RESULTS: The addition of cisapride decreased the time at which maximum serum concentrations were reached (tmax) from 2.79 (1.85-4.34) h to 1.16 (0.68-2.30) h (P=0.009) [95% CI: -2.59, -0.55] and increased the absorption rate constant (ka) from 0.49 (0.31-0.69) h(-1) to 1.26 (0.52-5.61) h(-1) (P=0.017). The absolute bioavailability of sotalol was reduced by cisapride from 1.00+/-0.15 to 0.70+/-0.26 (P=0.006), while maximum serum concentrations of both oral solutions were not significantly different. Compared with the sublingually administered tablet with a median tmax of 2.12 (0.89-3.28) h, the sotalol/cisapride oral solution gave a smaller tmax (p=0.009) [95% CI: -1.64, -0.36]. The ka of the sotalol/cisapride solution was significantly (P=0.010) larger than the ka of 0.56 (0.33-0.75) h(-1) found after sublingual administration of the tablet. CONCLUSIONS: The sotalol/cisapride oral solution might be suitable for the episodic treatment of SVT, Afib or Afl.

Effects of aspirin on angiotensin-converting enzyme inhibition and left ventricular dilation one year after acute myocardial infarction.

There are conflicting reports on the interaction of aspirin with angiotensin-converting enzyme inhibitors in heart failure and systemic hypertension. A post hoc analysis of the Captopril and Thrombolysis Study (CATS) study was conducted. At randomization, 94 patients (31.5%) took aspirin. In patients who took aspirin, the cumulative alpha-hydroxy butyrate dehydrogenase release was 1,151 +/- 132 IU/L in patients randomized to captopril compared with 1,401 +/- 136 IU/L in patients randomized to placebo (difference -250 +/- 189 [95% confidence interval (CI) -620 to 120]). This difference was comparable to the difference in patients who did not use aspirin (-199 +/- 147 [95% CI -488 to 897]). One year after acute myocardial infarction, an increase in left ventricular end-diastolic volume index of 2.2 +/- 3.0 ml/m2 in captopril-treated and 1.9 +/- 2.9 ml/m2 in placebo-treated patients was observed in patients who took aspirin (difference 0.4 +/- 4.2 [95% CI -8.2 to 8.9]). This difference was also comparable to the difference in patients who did not take aspirin (2.2 +/- 3.8 [95% CI -5.2 to 9.7]). One year after acute myocardial infarction, patients who did take aspirin had a mean change in LV end-diastolic volume index of 2.1 +/- 2.1 ml/m2 compared with 8.4 +/- 1.9 ml/m2 in patients who did not use aspirin (p = 0.02). Thus, aspirin does not attenuate the acute and long-term effects of angiotensin-converting enzyme inhibition after acute myocardial infarction, but independently reduces LV dilation after myocardial infarction.

Long-term anti-ischemic effects of angiotensin-converting enzyme inhibition in patients after myocardial infarction. The Captopril and Thrombolysis Study (CATS) Investigators.

OBJECTIVES: This study was conducted to test the hypothesis that angiotensin-converting enzyme (ACE) inhibition reduces myocardial ischemia and related events after myocardial infarction (MI). BACKGROUND: The oxygen demand/supply ratio of the myocardium is influenced by angiotensin II as a result of its arterial vasoconstrictive and inotropic effects and through its interaction with the sympathetic nervous system. METHODS: We studied 244 patients who had been included in a double-blind, randomized, placebo-controlled, post-MI, ACE inhibition intervention study (Captopril and Thrombolysis Study [CATS]). All patients underwent exercise testing before and 3 and 12 months after hospital discharge. After 1-year double-blind treatment, all patients continued receiving single-blind placebo for 1 month. RESULTS: Total exercise time increased in both groups after 3 months (placebo: +86 +/- 13 s; captopril: +69 +/- 12 s, p = 0.8 between groups) and increased further after 1 year (placebo: +13 +/- 11 s; captopril: +33 +/- 13 s, p = 0.7 between groups). There were also no differences in mean ST segment depression. During the 12 months, significantly fewer ischemia-related events occurred in the captopril group (82 vs. 52, p = 0.015). This difference was found between 3 and 12 months but not during the first 3 months. After withdrawal from double-blind medication, nine ischemic events were reported in teh captopril group compared with one in the placebo group (p = 0.006 between groups). CONCLUSIONS: The present data show that captopril may reduce the incidence of ischemia-related events after MI, which becomes apparent after 3 months. However, no anti-ischemic effect was observed during exercise testing. After withdrawal from ACE inhibition, a high incidence of clinical events occurred, suggesting a rebound phenomenon.

Evolution of coronary atherosclerosis in patients with mild coronary artery disease studied by serial quantitative coronary angiography at 2 and 4 years follow-up. The Multicenter Anti-Atheroma Study (MAAS) Investigators.

AIMS: Angiographic studies on the natural course of both focal and diffuse coronary atherosclerosis have not been performed before, but can both be assessed by quantitative coronary angiography. The objective of this study was to describe the natural course of focal and diffuse coronary atherosclerosis over time. METHODS AND RESULTS: In 129 patients with mild coronary artery disease, but not on lipid-lowering medication, three coronary angiograms were made each 2 years apart. Nine hundred and sixty five angiographically diseased and non-diseased segments were analysed by quantitative coronary angiography. Mean lumen diameter and minimal lumen diameter were used as measures of diffuse and focal coronary atherosclerosis. Mean lumen diameter and minimum lumen diameter decreased by 0.02 and 0.03 mm per year. The rate of progression was similar in the angiographically non-diseased, as in the mildly and moderately diseased segments. Progression of diffuse coronary atherosclerosis was largest in severely stenosed lesions (percentage diameter stenosis > or = 50%) and in the right coronary artery with a loss of 0.19 mm and 0.16 mm in mean lumen diameter. Progression of focal disease was most prominent in new and mild lesions and the right coronary artery, with a decrease in minimum lumen diameter of 0.34 mm and 0.22 mm. In most subgroups, progression occurred gradually over time. On a per segment level, progression and the occurrence of new lesions occurred in 4.4% and 4.2%. Regression and disappearance of a lesions was found in 2.3% and 1.9%. On a per patient level, 36% were progressors, 12% had a mixed response, 36% were stable, and 16% were regressors. CONCLUSION: Diffuse and focal coronary atherosclerosis progressed at the same rate in the first and second 2 years in stenosed and non-stenosed segments. The rate of coronary atherosclerosis progression was small, but was higher for focal than for diffuse disease. A minority of lesions progressed and spontaneous regression was rare.

Plasma angiotensin-converting enzyme activity and left ventricular dilation after myocardial infarction.

BACKGROUND: Left ventricular dilation after acute myocardial infarction (MI) is mainly determined by infarct size. In addition, this detrimental structural adaptation seems to be augmented in patients with the ACE DD genotype. The ACE DD genotype is associated with increased ACE activity. The aim of the present study was to evaluate whether ACE activity per se may carry prognostic significance for subsequent left ventricular dilation as assessed by echocardiography during 1-year follow-up after acute MI. METHODS AND RESULTS: Left ventricular end-systolic and end-diastolic volume indexes were assessed by two-dimensional echocardiography. In 102 consecutive patients, plasma ACE activity was determined 3.7 +/- 0.1 hours after the onset of MI. In 64 of these patients, left ventricular volume indexes obtained at baseline and 1 year after MI were used for the present analysis. Patients were divided ino a group having low ACE activity (< or = IU/L, n = 15) and a group having high ACE activity (> 12 IU/L, n = 49). Infarct size was a significant predictor of the increase in left ventricular volume indexes (P = .0001) in these patients. Multivariate regression analysis, after correction for infarct size, demonstrated that elevated plasma ACE activity is a significant predictor of the increase in left ventricular end-diastolic and end-systolic volume indexes (P = .0006 and P = .02, respectively) 1 year after MI. CONCLUSIONS: Elevated plasma ACE activity determined soon after the onset of MI may be a significant predictor of the development of left ventricular dilation and may identify patients at risk.

Exercise capacity after His bundle ablation and rate response ventricular pacing for drug refractory chronic atrial fibrillation.

OBJECTIVE: To evaluate exercise capacity of patients with chronic atrial fibrillation in whom His bundle ablation followed by ventricular rate response pacing (VVIR) was carried out because of drug refractoriness. DESIGN: Prospective study. PATIENTS: 25 consecutive patients, all with chronic symptomatic drug refractory atrial fibrillation, underwent His bundle ablation. Before this intervention all patients were on antiarrhythmic drugs to attain acceptable heart rate control and to relief symptoms. MAIN OUTCOME MEASURES: Exercise capacity, including measurements of VO2, was examined before and after a mean interval of seven months following His bundle ablation. RESULTS: Exercise capacity after His bundle ablation increased from a mean of 109 (SD 49) W to 118 (46) W (P < 0.002), but VO2 at peak exercise did not change significantly. Maximum exercise capacity was achieved with a significantly lower maximum driven heart rate than the spontaneous heart rate before ablation. CONCLUSIONS: Exercise capacity of patients who underwent His bundle ablation followed by VVIR pacing remained unchanged or improved during a mean follow up of seven months. Larger patient populations with longer follow up are necessary to examine determinants of improved exercise capacity.