Aims Atrial fibrillation (AF) is a common complication in patients with acute myocardial infarction and is associated with an increase in the risk of death. The excess mortality associated with AF complicating acute myocardial infarction has not been studied in detail. Observations indicate that AF facilitates induction of ventricular arrhythmias, which may increase the risk of sudden cardiovascular death (SCD). A close examination of the mode of death could potentially provide useful knowledge to guide further investigations and treatments.Methods and results We analysed the relation between AF/atrial flutter (AFL) and modes of death in 5983 consecutive patients discharged alive after an acute myocardial infarction screened in the TRAndolapril Cardiac Evaluation registry. This cohort of patients with an enzyme-verified acute myocardial infarction was admitted to 27 centres in 1990-92. Survival status was obtained 2 years after screening of the last patient. An independent endpoint committee assessed the modes of death. Left ventricular ejection fraction was determined in all the screened patients and information about presence or absence of AF/AFL was prospectively collected. Sustained or paroxysmal AF/AFL was observed in 1149 patients (19%) during hospitalization. During follow-up, 1659 patients (34%) died: 482 (50%) patients with AF/AFL and 1177 (30%) patients without AF/AFL, P < 0.001. SCD occurred in 536, non-SCD occurred in 725, and 398 died of non-cardiovascular causes (includes 142 unclassifiable cases). The adjusted risk ratio of AF/AFL for total mortality was 1.33 (95% CI: 1.19-1.49; P < 0.0001) and the risk ratio for SCD was 1.31 (95% CI: 1.07-1.60; P < 0.009).The adjusted risk ratio of AF/AFL for non-SCD was 1.43 (95% CI: 1.21-1.70; P < 0.0001).Conclusion The excess mortality observed in patients with AF/AFL following acute myocardial infarction is due to a significant increase in both SCD and non-SCD.

Background Reports on the prognostic importance of atrial fibrillation following myocardial infarction have provided considerable variation in results. Thus, this study examined the impact of left ventricular systolic function and congestive heart failure on the prognostic importance of atrial fibrillation in acute myocardial infarction patients that might explain previous discrepancies. Methods The study population was 6676 patients consecutively admitted to hospital with acute myocardial infarction. Information on the presence of atrial fibrillation/flutter, left ventricular systolic function and congestive heart failure were prospectively collected. Mortality was followed for 5 years. Results In patients with left ventricular ejection fraction <0.25, atrial fibrillation/atrial flutter was associated with an increased in-hospital mortality (OR=1.8 (1.1–3.2); p<0.05) but not an increased 30-day mortality. In patients with 0.25≤left ventricular ejection fraction≤0.35, atrial fibrillation/atrial flutter was associated with an increased in-hospital mortality (OR=1.7 (1.3–2.3); p<0.001) and an increased 30-day mortality (OR=1.7 (1.3–2.2); p<0.001). In-hospital and 30-day mortality was not increased in patients with left ventricular ejection fraction >0.35. In patients with congestive heart failure, atrial fibrillation/atrial flutter was associated with an increased in-hospital mortality (OR=1.5 (1.2–1.9); p<0.001) and increased 30-day mortality (OR=1.4 (1.1–1.7); p<0.001) but not in patients without congestive heart failure. In hospital survivors, atrial fibrillation/atrial flutter was associated with an increased long-term mortality in all subgroups except those with left ventricular ejection fraction <0.25. Conclusions Atrial fibrillation/atrial flutter is primarily associated with increased in-hospital mortality in heart failure patients. Long-term mortality is increased in all subgroups except those with left ventricular ejection fraction <25%.

Background - In patients with left ventricular dysfunction, atrial fibrillation and flutter (AF and AFl, respectively) are common arrhythmias associated with increased morbidity and mortality. The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm, which might reduce mortality and hospitalizations.Methods and Results - In the Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies, 506 patients were in AF-AFl at baseline. Over the course of study, cardioversion occurred in 148 (59%) dofetilide- and 86 (34%) placebo-treated patients. In these patients, the probability of maintaining sinus rhythm for 1 year was 79% with dofetilide versus 42% with placebo (P <0.001). Dofetilide had no effect on all-cause mortality, but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality (risk ratio ERR], 0.44; 95% CI, 0.30 to 0.631 P <0.0001). In addition, dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause (RR, 0.70; 95% CI, 0.56 to 0.89; P less than or equal to0.005) or congestive heart failure (RR, 0.69; 95% CI, 0.51 to 0.93; P less than or equal to0.02) rehospitalization.Conclusions - Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease. The present study suggests that restoration of sinus rhythm is associated with improved survival.

Objective : To investigate effects of stent flexibility on 6 months' clinical and angiographic outcome in long stented lesions. Design : A total of 44 genuine coronary artery lesions (lesion length >20 mm and h 30 mm) were randomized to implantation with a 30 mm long flexible coiled stainless steel stent (Freedom Force ® , Global Therapeutics) ( n = 23) or a 30 mm long stiff tubular stainless steel stent (Crown ® , Johnson & Johnson) ( n = 21). Results : Target vessel revascularization was performed in 10 patients (45%) in the Freedom Force ® stent group, and in 7 patients (33%) in the Crown ® stent group (ns). No significant differences concerning minimum lumen diameter (MLD), early gain, late loss or binary restenosis rate were seen. In the Freedom Force ® stent group all restenoses were located within the stent. In the Crown ® stent group three (27%) of the restenoses were located at the edge of the stent (ns). Conclusion : In a limited number of patients no significant differences could be detected in clinical or angiographic parameters between patients treated with long tubular or long coiled stents.

Background Nonrandomized studies suggest that atrial fibrillation is independently associated with increased mortality in patients with heart failure. Whether restoring and maintaining sinus rhythm will have a beneficial impact on cardiovascular mortality in patients with heart failure has never been tested in an adequately powered randomized trial.Objective The primary objective of the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial is to determine whether, restoring and maintaining sinus rhythm significantly reduces cardiovascular mortality compared with a rate-control strategy in patients with atrial fibrillation and CHF.Methods AF-CHF is a prospective multicenter trial (109 centers in Canada, United States, South America, Europe, and Israel), that will randomize 1450 patients with CHIF with left ventricular ejection fraction less than or equal to 35% and atrial fibrillation to 1 of 2 treatment strategies: (1) rhythm control with the use of electrical cardioversion combined with antiarrhythmic drugs (amiodarone or other class III agents), (2) rate control with the use of beta-blockers, digoxin, or pacemaker and AV nodal ablation. Cardiovascular mortality is the primary end point and the intention-to-treat approach the primary method of analysis. We anticipate an 18.75% 2-year. cardiovascular mortality in the rate control arm with a 25% mortality reduction in the rhythm control group.Results As of August 13, 2002, 334 patients have been enrolled from 68 participating centers. Enrollment is expected to be concluded in May 2003 with a minimum follow-up of 2 years.Conclusion The results of this trial should provide definitive information concerning 2 widely applicable treatment strategies of atrial fibrillation in a large cohort of patients with CHF.

Background In patients with left ventricular dysfunction, atrial fibrillation and flutter (AF and AFl, respectively) are common arrhythmias associated with increased morbidity and mortality. The present study investigated the potential of dofetilide in AF-AFl patients with left ventricular dysfunction to restore and maintain sinus rhythm, which might reduce mortality and hospitalizations. Methods and Results In the Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies, 506 patients were in AF-AFl at baseline. Over the course of study, cardioversion occurred in 148 (59%) dofetilide- and 86 (34%) placebo-treated patients. In these patients, the probability of maintaining sinus rhythm for 1 year was 79% with dofetilide versus 42% with placebo ( P <0.001). Dofetilide had no effect on all-cause mortality, but restoration and maintenance of sinus rhythm was associated with significant reduction in mortality (risk ratio [RR], 0.44; 95% CI, 0.30 to 0.64; P <0.0001). In addition, dofetilide therapy was associated with a significantly lower risk ratio versus placebo for either all-cause (RR, 0.70; 95% CI, 0.56 to 0.89; P ≤0.005) or congestive heart failure (RR, 0.69; 95% CI, 0.51 to 0.93; P ≤0.02) rehospitalization. Conclusions Dofetilide is safe and increases the probability of obtaining and maintaining sinus rhythm in patients with structural heart disease. The present study suggests that restoration of sinus rhythm is associated with improved survival.

Aims To investigate the occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction Methods and Results The occurrence and prognostic significance of atrial fibrillation/-flutter were studied in 6676 consecutive patients with acute myocardial infarction screened in 27 centres in Denmark for inclusion into the TRAndolapril Cardiac Evaluation (TRACE) study. Information about occurrence of atrial fibrillation/-flutter juring hospitalization was prospectively collected for the following three periods: day 1-2, day 3-4 and from day 5 until discharge. A total of 1395 patients (21%) suffered from atrial fibriliation/-flutter in one or more of the specified periods during hospitalization. Patients with atrial fibrillation/-flutter were significantly older, a significantly greater proportion were women, left ventricular systolic dysfunction was more extensive, thrombolytic therapy was received less frequently, and anterior Q wave myocardial infarction was experienced more frequently than patients without atrial fibrillation/-flutter. History of acute myocardial infarction and/or angina pectoris was similar in patients with and without atrial fibrillation/-flutter, whereas significantly more patients with atrial fibrillation/-flutter had a history of hypertension, congestive heart failure, diabetes mellitus, pulmonary disease and stroke. The unadjusted in-hospital mortality rate was significantly higher in patients with atrial fibrillation/-flutter in one or more of the specified periods during hospitalization (18%) than in patients without atrial fibrillation/-flutter (9%), P<0.001. After adjustment for baseline characteristics, the presence of atrial fibrillation/-flutter was still associated with increased in-hospital mortality; odds ratio=1.5 (95% Cl: 1.2-1.8), P<0.001. In patients surviving hospitalization, the unadjusted 5-year mortality rate was also significantly higher in patients suffering from atrial fibrillation/-flutter (56%) than in patients without atrial fibrillation/-flutter (34%), P<0.001. After adjustment for important prognostic baseline characteristics, the presence of atrial fibrillation/flutter was still associated with an increased mortality, relative risk=1.3 (95% Cl: 1.2-1.4). Subgroup analysis revealed that sustained atrial fibrillation/-flutter during hospitalization was associated with the highest risk of dying, relative risk=1.4 (95% Cl: 1.2-1.7). Conclusion Atrial fibrillation/-flutter often occurs after acute myocardial infarction and our analysis demonstrated that it was an independent predictor of an increased short and long-term mortality.

Angiotensin converting-enzyme (ACE) inhibition reduces mortality among patients surviving an acute myocardial infarction, but whether to give ACE-inhibitors to all patients or target their use to selected patients is unclear. Seven thousand and one consecutive enzyme-confirmed myocardial infarctions were screened. One thousand seven hundred and forty-nine patients with echocardiographic signs of left ventricular dysfunction were randomized to oral trandolapril (876 patients) or placebo (873 patients) starting from days three to seven following the infarction. Average follow-up was 27 months. There were 304 deaths (34.7 percent) among patients on trandolapril vs. 369 deaths (42.3 percent) among patients on placebo (p = 0.0013). Relative risk (RR) of death in the trandolapril group was 0.78 (95% confidence interval (CD 0.67-0.91). Trandolapril reduced cardiovascular death (RR 0.75, CI 0.63-0.89) and sudden death (RR 0.76, CI 0.59-0.98). Progression to severe/resistant heart failure was reduced (RR 0.71, CI 0.56-0.90). Recurrent myocardial infarction (fatal or non-fatal) was not significantly reduced (RR 0.86, CI 0.66-1.13). It is concluded that long-term treatment with trandolapril in patients with reduced left ventricular function shortly after myocardial infarction significantly reduced total mortality. The substantial mortality risk reduction was obtained in 25% of consecutive patients screened for entry encouraging a selective use of ACE inhibition following myocardial infarction.

INTRODUCTION:Dofetilide, a new class III antiarrhythmic drug, was tested for its ability to reduce mortality and morbidity in patients with congestive heart failure and left ventricular dysfunction.METHODS:In 34 Danish centers, 1518 patients with NYHA class III or IV heart failure and wall motion index of the left ventricle < or = 1.2 (ejection fraction < or = 35%) were randomized to receive dofetilide or placebo in a double blind study. The dose of dofetilide was adjusted to renal function and the QT interval. Patients were monitored continuously with ekg during the first three days in the study. Minimum follow up was one year.RESULTS:Dofetilide did not affect mortality. Hospitalizations for worsening of heart failure were reduced significantly, hazard ratio 0.75 (0.63-0.89) Dofetilide effectively converted atrial fibrillation to sinus rhythm. After one year, 61% of patients with atrial fibrillation had converted on dofetilide and 33% on placebo (p < 0.001).DISCUSSION:Dofetilide can be used to convert atrial fibrillation to sinus rhythm and to maintain sinus rhythm in patients with congestive heart failure and left ventricular dysfunction. Dofetilide does not affect mortality.

BACKGROUND Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces mortality among survivors of acute myocardial infarction, but whether to use ACE inhibitors in all patients or only in selected patients is uncertain. METHODS We screened 6676 consecutive patients with 7001 myocardial infarctions confirmed by enzyme studies. A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction (ejection fraction, < or = 35 percent). On days 3 to 7 after infarction, 1749 patients were randomly assigned to receive oral trandolapril (876 patients) or placebo (873 patients). The duration of follow-up was 24 to 50 months. RESULTS During the study period, 304 patients (34.7 percent) in the trandolapril group died, as compared with 369 (42.3 percent) in the placebo group (P = 0.001). The relative risk of death in the trandolapril group, as compared with the placebo group, was 0.78 (95 percent confidence interval, 0.67 to 0.91). Trandolapril also reduced the risk of death from cardiovascular causes (relative risk, 0.75; 95 percent confidence interval, 0.63 to 0.89; P = 0.001) and sudden death (relative risk, 0.76; 95 percent confidence interval, 0.59 to 0.98; P = 0.03). Progression to severe heart failure was less frequent in the trandolapril group (relative risk, 0.71; 95 percent confidence interval, 0.56 to 0.89; P = 0.003). In contrast, the risk of recurrent myocardial infarction (fatal or nonfatal) was not significantly reduced (relative risk, 0.86; 95 percent confidence interval, 0.66 to 1.13; P = 0.29). CONCLUSIONS Long-term treatment with trandolapril in patients with reduced left ventricular function soon after myocardial infarction significantly reduced the risk of overall mortality, mortality from cardiovascular causes, sudden death, and the development of severe heart failure. That mortality was reduced in a randomized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infarction.

The TRAndolapril Cardiac Evaluation (TRACE) study is evaluating the effect of angiotensin-converting enzyme inhibition with trandolapril on mortality (overall and cardiovascular) and cardiovascular morbidity in patients surviving myocardial infarction (MI) with reduced left ventricular (LV) function. TRACE is a randomized, double-blind, placebo controlled study conducted in 27 centers in Denmark. Eligible patients had a MI verified by elevated cardiac enzymes, electrocardiographic changes, and/or chest pain as well as reduced LV function, as shown by electrocardiographic evaluation of wall motion index less than or equal to 1.2. (A wall motion index less than or equal to 1.2 approximates to a left ventricular ejection fraction less than or equal to 35%.) Patients with residual ischemia and/or heart failure were not excluded. Trandolapril or placebo was added to conventional therapy 3-7 days after MI. Between May 1990 and June 1992, 6,674 patients (7,010 infarctions) were screened. A total of 2,614 patients had a wall motion index less than or equal to 1.2; of these, 1,749 were included. Overall 1-year mortality of the patients entered into the study was 24%. Treatment will be continued for 2-4 years (mean, 3 years), ending In mid 1994. The design and organization of the study, the outcome of screening, and demographic features of the screened population are described.

Two brothers both with hypertrophic obstructive cardiomyopathy, one of them also with neurofibromatosis are described. Only a few cases with this combination of diseases have been reported. The possibility of a coincidence or a causal relationship is mentioned. The importance of echocardiography in persons with cardiac murmurs is emphasized even in cases where the electrocardiogram and thoracic x-ray are normal.

In 26 patients with left ventricular aneurysm and ventricular tachycardia and/or ventricular fibrillation following myocardial infarction, coronary angiography, left ventriculography and electrophysiologic examination were performed preoperatively. Surgery in all cases consisted of aneurysmectomy and mapping-guided endocardial resection of the area found to be the arrhythmogenic center. Four patients died peroperatively or during the postoperative hospital stay. The 22 survivors were followed up for 3-48 (mean 22) months postoperatively. There were no late deaths. Repeated electrophysiologic studies were performed in 18 of the survivors. Freedom from ventricular tachycardia and fibrillation was achieved in 21 patients, 17 after surgery alone and four after combined surgical and medical treatment. The remaining patient still has ventricular tachycardia despite combined treatment.

Levels of radioactive cholesterol found in the arterial wall after a few hours' in vivo exposure to plasma containing labelled cholesterol are so small that the contaminating plasma in the tissue may contribute significantly to the radioactivity measured in the wall. By the simultaneous use of [3H]- and [14C]cholesterol the contamination was found to be less than 15 nl of plasma/cm2 of intimal surface of the thoracic aorta in mini-pigs, and this contamination accounted for less than 5% of the total radioactivity found in the intima—media tissue 7 h after the injection of serum with bioincorporated labelled cholesterol.

Blood flow in the circumflex branch of the left coronary artery was recorded by electromagnetic flowmeter. In a group of dogs progressive hemodilution was performed until the diastolic reactive hyperemic response to 10 s occlusion of the circumflex branch disappeared ("optimum" hemodilution). At this degree of hemodilution the distribution of blood flow in the left ventricular free wall was evaluated by measuring tissue activity concentrations of Xe-133 and radioactive microspheres after bolus injection into the aortic root. "Optimum" hemodilution was accompanied by a sixfold increase in systolic coronary flow, a 3-fold increase in diastolic flow and a relative endocardial hypoperfusion. These results indicate that the endocardial blood flow reserve is lower than the epicardial. This conclusion is supported by the influence of spontaneous oscillations of arterial blood pressure (Traube-Hering waves) on systolic and diastolic coronary blood flows before and during "optimum" hemodilution. In another group of dogs maximum coronary vasodilatation was produced by occlusion of the left coronary artery for 10 s. In this group the distribuition of Xe-133 and radioactive microspheres were measured after bolus injection into the aortic root at peak diastolic reactive hyperemia. The epi- and endocardial distribution of both Xe-133 and microspheres was uniform in the left ventricular wall, indicating a uniform flow to these regions. This might be explained by an increased endocardial perfusion during systole due to loss of myocardial contractility or by a decline towards resting level in epicardial flow at the time of injection, corresponding to a shorter duration of the hyperemic period in the epi- than endocardial region.