[The significance of trandelapril for mortality after AMI in patients with reduced left ventricular function. TRACE Study Group]. / Trandolaprils betydning for overlevelse efter AMI hos patienter med nedsat funktion af venstre ventrikel. TRACE Study Group.

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.

Influence of age on the prognostic importance of left ventricular dysfunction and congestive heart failure on long-term survival after acute myocardial infarction. TRACE Study Group.

The aim of this study was to assess the importance of congestive heart failure and left ventricular (LV) systolic dysfunction after an acute myocardial infarction (AIM) on long-term mortality in different age groups. A total of 7,001 consecutive enzyme-confirmed AMIs (6,676 patients) were screened for entry into the TRAndolapril Cardiac Evaluation (TRACE) study. Medical history, echocardiographic estimation of LV systolic function determined as wall motion index, infarct complications, and survival were documented for all patients. To study the importance of congestive heart failure and wall motion index independent of age, we performed Cox proportional-hazard models in 4 different age strata (< or = 55 years, 56 to 65 years, 66 to 75 years, and > 75 years). Patients in these strata had 1-year mortality rates of 5%, 11%, 21%, and 32%, respectively. Three-year mortality rates were 11%, 20%, 34%, and 55%, respectively. The risk ratios (and 95% confidence limits) associated with congestive heart failure in the same 4 age strata were 1.9 (1.3 to 2.9), 2.8 (2.1 to 3.7), 1.8 (1.5 to 2.2) and 1.8 (1.5 to 2.2), respectively. The risk ratios associated with decreasing wall motion index were 6.5 (3.6 to 11.4), 3.3 (2.3 to 4.6), 2.7 (2.2 to 3.4), and 2.1 (1.7 to 2.6), respectively. In absolute percentages, there was an excess 3-year mortality associated with congestive heart failure in the 4 age strata of 14%, 24%, 25%, and 28% respectively. The absolute excess in 3-year mortality associated with LV systolic dysfunction in the 4 age strata was 15%, 19%, 25%, and 21%, respectively. Thus, the relative importance of LV systolic dysfunction and congestive heart failure diminished with increasing age. However, the absolute excess mortality associated with congestive heart failure and LV systolic dysfunction was more pronounced in the elderly than in the young.

A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group.

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.

[Semiautomatic defibrillation in out-of-hospital cardiac arrest]. / Semiautomatisk defibrillering ved hjertestop uden for hospital.

In a Danish suburban community the following attempts were made aimed at increasing survival of out-of-hospital cardiac arrest (CA): the citizens were offered training in diagnosis and treatment of CA and the ambulances serving the community were provided with a semiautomatic defibrillator. The results of these effects were evaluated over a two-year period. One hundred and seventy persons out of a population of 85,824 received training in CPR. The study included 113 cases of CA due to ischaemic heart disease. CA was witnessed in 84 cases (74%). Bystander CPR was attempted in 21 cases out of whom three survived (14%), compared to seven survivors among the remaining 92 patients (8%). If CPR was initiated within five minutes of CA, eight of 57 patients survived (15%), compared to one in 31 cases if resuscitation was attempted later. If ventricular fibrillation was present seven of 51 patients survived (14%); none of the 24 patients who initially had asystole, survived. In 336 situations tape recordings of the ECG at CA were available for analysis. Ventricular fibrillation was present in all of the 129 cases where DC-conversion was advised by the apparatus. There were two additional cases, one of ventricular fibrillation of low frequency and one of ventricular tachycardia where DC-conversion was not advised, but might have been beneficial.

[Influence of various therapeutic models on survival after prehospital cardiac arrest]. / Forskellige behandlingsmodellers indflydelse på overlevelse efter praehospitalt hjertestop.

We analyzed the outcome after prehospital cardiac arrest in a part of greater Copenhagen. Four different emergency medical systems were acting: a system providing basic life support only (group 1), a system providing basic life support and early defibrillation (group 2), a system providing basic life support followed by advanced cardiac life support (group 3), and a system providing basic life support and early defibrillation followed by advanced cardiac life support (group 4). Over a 2-year period 624 cases of cardiac arrest were reported, 34 were discharged from hospital. The survival to discharge from hospital and the one-year survival were significantly better in group 4. Our data reconfirm that early advanced cardiac life support improves survival rates for prehospital cardiac arrest.

Xamoterol in severe congestive heart failure: long-term oral treatment, a double-blind randomised study.

Twelve patients in severe congestive heart failure were given placebo, 100 mg xamoterol (Corwin) twice daily and 200 mg xamoterol twice daily, respectively, in 3 two-week periods in a double-blind randomised study. At the end of each treatment period the patients were evaluated. No differences were found between placebo and xamoterol in the following parameters: New York Heart Association function group index, heart volume, body weight, exercise duration on bicycle and treadmill, heart rate and systolic and diastolic blood pressure at rest. However, during exercise we found significantly lower heart rate and rate-pressure product during xamoterol treatment. This reduction is probably indicating occupation of beta-adrenoreceptors with concomitant reduced oxygen consumption during exercise.

Prenalterol in severe congestive heart failure. II. Long-term oral treatment. Results with comments on the methods for evaluation of drugs in congestive heart failure.

Nine patients with severe congestive heart failure were treated with a partial beta-1-agonist prenalterol for 9.6 months on average. Five of the nine patients improved with an increase in NYHA-functional capacity of one class. In four of these patients, the improvement was maintained for 12 months. Upon discontinuation, deterioration occurred only in one case; in the latter, improvement reoccurred on reinstitution of prenalterol treatment. Significant improvement on exercise testing, however, occurred only in two patients. Prediction as to which patients would benefit from oral prenalterol was not possible from the pretreatment haemodynamic variables; similarly, the effect of oral prenalterol treatment could not be predicted from the response to prenalterol given intravenously. A critical review of the methods for evaluation of therapeutic intervention in congestive heart failure concludes the article.

Prenalterol in severe congestive heart failure. I. The immediate haemodynamic effects as compared to nitroglycerine.

The immediate haemodynamic effects of prenalterol and nitroglycerine were examined in 15 patients, with severe chronic heart failure. Prenalterol was given intravenously in increasing doses of 2, 4, and 8 mg. Cardiac index increased significantly by 16%, 24%, and 32%, respectively. Heart rate increased by 16%, 19%, and 24%. Stroke volume index, systemic artery pressure, pulmonary artery pressure, and right atrial pressure did not change. Prenalterol reduced systemic vascular resistance by 15%, 17%, and 24%, respectively. Forearm blood flow and forearm vascular resistance was unchanged. Cardiac index and heart rate were not changed by 0.5 mg nitroglycerine, administered sublingually. Systolic and diastolic blood pressure were on average reduced by 14% and 12%, respectively. Systolic and diastolic pulmonary artery pressure and right atrial pressure were similarly reduced by 17%, 31%, and 39%, respectively. Nitroglycerine lowered calculated systemic vascular resistance by 11%, whereas forearm blood flow and forearm vascular resistance was unchanged. The conclusion is that prenalterol acutely increased cardiac index and improved haemodynamics in 14 out of 15 patients, mainly due to an increased heart rate. Nitroglycerine did not change cardiac index in the same group of patients.

Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease.

ICI 141,292 is a new beta 1-adrenoceptor blocking drug. The beta 1-adrenoceptor antagonistic effect of ICI 141,292 was examined in a double-blind, randomised crossover study in eight healthy young volunteers and compared with atenolol. Three doses of ICI 141,292 (1, 2 and 4 mg) and atenolol 5 mg were administered intravenously. The attenuation in exercise induced tachycardia varied between 16.0 and 21.2% (P less than 0.01). A significant reduction in blood pressure could be demonstrated following all three doses of ICI 141,292 and atenolol during exercise. At rest in the sitting position HR decreased approximately 8% following all three doses of ICI 141,292 and 14.9% after atenolol 5 mg. No changes in blood pressure were observed under resting conditions after any of the drugs. In six patients with ischaemic heart disease the intrinsic sympathomimetic activity following intravenous administration of four sequential doses (0.5, 0.5, 1.0 and 2.0 mg) of ICI 141,292 was examined. HR decreased 7% (P less than 0.05) following ICI 141,292 1 mg with no further decrease following the succeeding doses. Cardiac output decreased 5.2% (P less than 0.05) following a cumulative dose of 4 mg. No significant changes were observed in mean arterial blood pressure, stroke volume or total peripheral resistance whereas an increase in supine resting mean pulmonary arterial pressure of 3.4 mm Hg (P less than 0.05) could be demonstrated. ICI 141,292 seems to be a potent (at least five times as potent as atenolol) beta 1-adrenoceptor blocking agent possessing moderate intrinsic sympathomimetic activity.

Myocardial infarction and cerebral infarction in a Danish suburban community.

A comparison was made of 485 cases of cerebral infarction (CI), registered prospectively in Frederiksberg, Copenhagen, with 495 cases of myocardial infarction (AMI), recorded retrospectively in the same population. The overall annual incidence of AMI was 6.5 per 1,000 population for males, 3.8 for females; the rates for CI were 2.4 and 2.5, respectively. The age-incidence curves, particularly those for AMI, were significantly steeper in the females than in the males. Correspondingly, the male predominance in the AMI-group subsided with age. Age-specific incidence-rates rose exponentially with advancing age; for each sex and diagnosis the relationship can thus be expressed as a simple mathematical formula, which may facilitate comparisons of incidence patterns in different communities. Theories explaining the similarities and differences of the age-incidence curves for AMI and CI are discussed.

A pressure independent orifice equation for the estimation of diastolic mitral valve area in mitral insufficiency: correlation with cardiac catheterisation data using a radioactive Krypton indicator method for the determination of regurgitant filling volume.

We have investigated the application of an hydraulic orifice equation for the computation of diastolic mitral valve area in conditions of regurgitation. The new equation is given by Af = 21 Vf/T2, where Af is the total forward flow mitral valve area in cm2, Vf is the diastolic filling volume in ml, T is the diastolic filling period and 21 is a discharge coefficient derived from clinical haemodynamic data. Areas computed by the new formula correlate with valve areas as computed by the Gorlin formula at a level given by r = 0.93, n = 27. The results suggest that the new formula may be utilised in the context of mitral insufficiency and further, considerating the nature of the haemodynamic variables involved, an echographic quantification of this condition by M-mode or bidimensional echocardiography may be possible.

DC-conversion of atrial fibrillation after mitral valve operation. An analysis of the long-term results.

In a prospective study comprising 43 patients with atrial fibrillation after mitral valve surgery, an evaluation was made of the prognostic significance of clinical, radiological, haemodynamic and operative factors for the maintenance of sinus rhythm after DC-conversion. Atrial fibrillation with a duration of less than 12 months proved to be the only single factor of significance for sustained sinus rhythm after 12 months and it is suggested as a simple clinical criterion for selection of patients for DC-conversion after mitral valve operation.