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Biomedical subjects

C Torp-Pedersen

Publications and source records attributed to C Torp-Pedersen.

At least 37 records · Page 2Linked to original sources

In-hospital heart failure, first-year ventricular dilatation and 10-year survival after acute myocardial infarction.

BACKGROUND: Little is known about the factors that determine long-term prognosis in patients who have survived the first year after acute myocardial infarction (AMI). AIMS: To study the influence of left and right ventricular (LV and RV) dilatation during the first year after AMI on subsequent 10-year survival in comparison with in-hospital heart failure and other established prognostic indices. METHODS: Radionuclide ventriculography was performed before the era of thrombolysis and post-infarction ACE-inhibition in 57 patients with AMI at hospital discharge and again 1 year later, and compared with survival the ensuing 10 years. RESULTS: After 1 year significant LV-dilatation (>20%) had occurred in 32 (56%) patients. One year after the re-investigation the mortality in these was 19% vs. 0% in patients without dilatation (P=0.02); after 5 years the difference was 38 vs. 12% (P=0.02), whereafter it declined and became insignificant at 10 years. Neither RV-dilatation, nor LVEF determined at discharge or at the 1-year reinvestigation influenced long-term survival. In contrast, clinical heart failure recorded during the hospital stay had a sustained negative influence on long-term survival. CONCLUSION: Progressive LV dilatation after discharge and clinical heart failure during the hospital stay are both determinants of late survival after AMI, whereas LV ejection fraction at hospital discharge or 1 year later has little, if any, effect on survival beyond 1-year post-AMI.

Adult↗

Prognostic value of exercise testing in a cohort of patients followed for 15 years after acute myocardial infarction.

AIMS: To study the long-term prognostic information obtained from an exercise test following an acute myocardial infarction. METHODS: Between 1979 and 1983, 1773 consecutive patients were admitted to Glostrup County Hospital with an acute myocardial infarction. Of 1430 patients who were alive after 3 weeks, 718 performed an exercise test. Survival data were available after 15 years for all patients. RESULTS: Participation in an exercise test was associated with a risk reduction of death of 56% (95% confidence interval, 49--65%) when adjusting for known differences between the groups. Among patients who performed the test, most indicators of ischaemia were without prognostic information. Exercise tolerance, expressed in metabolic equivalents, was the best predictor of future mortality (relative risk 0.86 for an increase of one metabolic equivalent (0.80--0.92)). Only ST-segment depression of 2 mm or more could identify a population with an increased risk of death (relative risk 1.45 (1.08--1.95)). CONCLUSION: Patients who perform an exercise test after acute myocardial infarction are a low risk population compared to those who do not perform it. The detection of ischaemia during the test is of marginal prognostic value. Exercise capacity is the most powerful predictor of death that can be obtained from the test.

Adult↗

Does the electrocardiographic presence of Q waves influence the survival of patients with acute myocardial infarction?

AIMS: To compare the outcome of short- and long-term survival of patients with Q wave vs non-Q wave myocardial infarction. METHODS: A total of 6676 patients with acute myocardial infarction were enrolled on the TRAndolapril Cardiac Evaluation (TRACE) register between 1990 and 1992. Medical history, electrocardiographic diagnosis of Q wave and non-Q wave myocardial infarction, echocardiographic estimation of left ventricular systolic function determined as wall motion index, infarct complications, and survival were documented. The factors influencing the postmyocardial infarction outcome of these patients were studied after 30 days and after 8 years of follow-up, respectively. RESULTS: Cox proportional-hazard models demonstrated that the electrocardiographic Q waves had significant influence on survival during the first 30 days [risk ratio 1.4 (95% confidence limits 1.2-1.7)] but no influence thereafter [1.0 (0.9-1.1)]. The result was the same in univariate and multivariate analyses. Subgroup analysis defined by age, sex, wall motion index, presence of congestive heart failure, diabetes mellitus, arterial hypertension, subsequent myocardial infarctions and use of thrombolytic therapy did not disclose importance of Q waves on mortality. CONCLUSION: The electrocardiographic presence of Q waves is associated with increased mortality during the initial 30 days after a myocardial infarction, but has no influence thereafter.

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Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease.

Blunted insulin-stimulated endothelial function may be a mechanism for the development of atherothrombotic disease in type 2 diabetes, but it is unknown whether hypoglycemic drug therapy can modulate this abnormality. We studied patients with type 2 diabetes and stable ischemic heart disease (n = 28) and lean, healthy control subjects (n = 31). Forearm blood flow was measured by venous occlusion plethysmography during dose-response studies of acetylcholine (ACh) and sodium nitroprusside (SNP) infused into the brachial artery. In the patients and 10 healthy control subjects, ACh was repeated after intrabrachial infusion of insulin. Patients were restudied after 2 months of insulin therapy with four daily subcutaneous injections (treatment group, n = 19) or without hypoglycemic drug therapy (time control group, n = 9). Insulin infusion raised venous serum insulin in the forearm to high physiological levels (133 +/- 14.6 mU/l in patients) with a minor increase in systemic venous serum insulin. This increased the ACh response by 149 +/- 47, 110 +/- 33, 100 +/- 45, and 106 +/- 44% during the four ACh doses in healthy control subjects (P < 0.0001) but had no effect in patients (P = 0.3). After 2 months, HbA(1c) in the treatment group had decreased from 10.0 +/- 0.4 to 7.5 +/- 0.2%. Although neither the ACh response (P = 0.09) nor the SNP response (P = 0.4) had changed significantly, insulin stimulation had a significant effect, as the ACh response increased by 58 +/- 25, 84 +/- 66, 120 +/- 93, and 69 +/- 36% (P = 0.0002). In the time control group, insulin stimulation remained without effect after 8 weeks (P = 0.7). In conclusion, insulin therapy partly restores insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease.

Acetylcholine↗

Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial.

BACKGROUND: Arrhythmias cause much morbidity and mortality after myocardial infarction, but in previous trials, antiarrhythmic drug therapy has not been convincingly effective. Dofetilide, a new class III agent, was investigated for effects on all-cause mortality and morbidity in patients with left-ventricular dysfunction after myocardial infarction. METHODS: In 37 Danish coronary-care units, 1510 patients with severe left-ventricular dysfunction (wall motion index < or = 1.2, corresponding to ejection fraction < or = 0.35) were enrolled in a randomised, double-blind study comparing dofetilide (n=749) with placebo (n=761). The primary endpoint was all-cause mortality. Secondary endpoints included cardiac and arrhythmic mortality and total arrhythmic deaths. Analyses were by intention to treat. FINDINGS: No significant differences were found between the dofetilide and placebo groups in all-cause mortality (230 [31%] vs 243 [32%]), cardiac mortality (191 [26%] vs 212 [28%]), or total arrhythmic deaths (129 [17%] vs 140 [18%]). Atrial fibrillation or flutter was present in 8% of the patients at study entry. In these patients, dofetilide was significantly better than placebo at restoring sinus rhythm (25 of 59 vs seven of 56; p=0.002). There were seven cases of torsade de pointes ventricular tachycardia, all in the dofetilide group. INTERPRETATION: In patients with severe left-ventricular dysfunction and recent myocardial infarction, treatment with dofetilide did not affect all-cause mortality, cardiac mortality, or total arrhythmic deaths. Dofetilide was effective in treating atrial fibrillation or flutter in this population.

Adult↗

Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group.

BACKGROUND: We undertook a prospective systematic overview based on data from individual patients from five long-term randomised trials that assessed inhibitors of angiotensin-converting enzyme (ACE) in patients with left-ventricular dysfunction or heart failure. METHODS: Three of the trials enrolled patients within a week after acute myocardial infarction. Data were combined by use of the Peto-Yusuf method. FINDINGS: Overall 12,763 patients were randomly assigned treatment or placebo and followed up for an average of 35 months. In the three post-infarction trials (n=5,966), mortality was lower with ACE inhibitors than with placebo (702/2995 [23.4%] vs 866/2971 [29.1%]; odds ratio 0.74 [95% CI 0.66-0-83]), as were the rates of readmission for heart failure (355 [11.9%] vs 460 [15.5%]; 0.73 [0.63-0.85]), reinfarction (324 [10.8%] vs 391 [13.2%]; 0.80 [0.69-0.94]), or the composite of these events (1049 [35.0%] vs 1244 [41.9%]; 0.75 [0.67-0.83]; all p<O.001). For all five trials the ACE inhibitor group had lower rates of death than the placebo group (1,467/6,391 [23.0%] vs 1,710/6,372 [26.8%]; 0.80 [0.74-0.87]) and lower rates of reinfarction (571 [8.9%] vs 703 [11.0%]; 0.79 [0.70-0.89]), readmission for heart failure (876 [13.7%] vs 1202 [18.9%]; 0.67 [0.61-0.74]), and the composite of these events (2161 [33.8%] vs 2610 [41.0%]; 0.72 [0.67-0.78]; all p<0.0001). The benefits were observed early after the start of therapy and persisted long term. The benefits of treatment on all outcomes were independent of age, sex, and baseline use of diuretics, aspirin, and beta-blockers. Although there was a trend towards greater reduction in risk of death or readmission for heart failure in patients with lower ejection fractions, benefit was apparent over the range examined.

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Long-term prognosis of diabetic patients with myocardial infarction: relation to antidiabetic treatment regimen. The TRACE Study Group.

AIMS: The present study was performed to evaluate pre-admission history, presentation, initial treatment and long-term mortality in patients with myocardial infarction and diabetes. METHODS AND RESULTS: Between 1990 and 1992, 6676 patients with acute myocardial infarction were screened for entry into the Trandolapril Cardiac Evaluation (TRACE) study. In this cohort 719 (11%) of the patients had a history of diabetes. Among the diabetic patients 19% were treated with insulin, 52% with oral hypoglycaemic agents and 29% with diet only. The diabetic patients were slightly older, more likely to be female and had a higher prevalence of known cardiovascular disease. Even though the diabetic patients had the same frequency of ST-segment elevation on the electrocardiogram and the same admission delay, treatment with thrombolysis and aspirin was less frequently prescribed to the diabetic patients than to patients without diabetes. The mortality rate was significantly increased in the diabetic patients, 7-year mortality being 79% in insulin-treated, 73% in tablet-treated and 62% in diet-treated diabetic patients compared with 46% in patients without diabetes. In a multivariate analysis only diabetic patients treated with oral hypoglycaemic agents or with insulin had an increased mortality compared with non-diabetic patients. CONCLUSIONS: Patients with diabetes mellitus and myocardial infarction are treated with thrombolysis to a lesser extent than non-diabetic patients. Diabetic patients treated with oral hypoglycaemic agents or insulin, but not those treated with diet alone, have a significantly increased mortality following acute myocardial infarction compared with non-diabetic patients.

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Dofetilide: a class III anti-arrhythmic drug for the treatment of atrial fibrillation.

Dofetilide is a class III anti-arrhythmic drug that has been approved for the treatment of atrial fibrillation. Two clinical studies, which enrolled 996 patients, demonstrated pharmacological conversion to sinus rhythm to occur in 30% of patients. Following pharmacological or electrical conversion, median time to relapse exceeded one year. Two large clinical studies that enrolled 3028 patients have been performed in high-risk patients with severe heart failure and large myocardial infarctions. The outcomes of these studies were neutral with respect to survival and demonstrated the safety of dofetilide. After pharmacological or electrical conversion of atrial fibrillation to sinus rhythm in these studies, the probability of remaining in sinus rhythm during the following year was 75%. Dofetilide has a single significant side effect: risk of developing torsade de pointes ventricular tachycardia. Therefore, dosage must be carefully adjusted to the length of QTc interval, calculated creatinine clearance and the presence of heart failure or recent infarction. In addition, treatment must be initiated in hospital with three days of continuous telemetry. Dofetilide can be co-administered with digoxin and beta-blockers. Other anti-arrhythmic drugs, as well as drugs that interfere with the renal elimination or the metabolism of dofetilide, must be avoided. Dofetilide is an option when persistent atrial fibrillation is a clinical problem. In the setting of severe heart failure and large myocardial infarctions, only amiodarone and dofetilide have proven safety and dofetilide is a strong candidate for first choice treatment when the aim is to achieve sinus rhythm.

Animals↗

Serum-ionised magnesium in patients with acute myocardial infarction. Relation to cardiac arrhythmias, left ventricular function and mortality.

Measurement of serum-ionised magnesium has recently become available, and we report the first study of the relation of this parameter to arrhythmias, left ventricular function and mortality in patients with an acute myocardial infarction. Serum-ionised magnesium was determined in 217 consecutive patients admitted to hospital with an enzyme confirmed AMI. 70 healthy subjects acted as a control group. The main study parameters were occurrence of arrhythmias, left ventricular function estimated by echocardiography, and mortality after 10 months for the AMI patients. AMI patients had significantly lower serum-ionised magnesium compared to healthy controls but the level of serum-ionised magnesium in the acute phase of a MI was neither related to arrhythmias, left ventricular function nor mortality.

Adult↗

Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.

BACKGROUND: Atrial fibrillation occurs frequently in patients with congestive heart failure and commonly results in clinical deterioration and hospitalization. Sinus rhythm may be maintained with antiarrhythmic drugs, but some of these drugs increase the risk of death. METHODS: We studied 1518 patients with symptomatic congestive heart failure and severe left ventricular dysfunction at 34 Danish hospitals. We randomly assigned 762 patients to receive dofetilide, a novel class III antiarrhythmic agent, and 756 to receive placebo in a double-blind study. Treatment was initiated in the hospital and included three days of cardiac monitoring and dose adjustment. The primary end point was death from any cause. RESULTS: During a median follow-up of 18 months, 311 patients in the dofetilide group (41 percent) and 317 patients in the placebo group (42 percent) died (hazard ratio, 0.95; 95 percent confidence interval, 0.81 to 1.11). Treatment with dofetilide significantly reduced the risk of hospitalization for worsening congestive heart failure (risk ratio, 0.75; 95 percent confidence interval, 0.63 to 0.89). Dofetilide was effective in converting atrial fibrillation to sinus rhythm. After one month, 22 of 190 patients with atrial fibrillation at base line (12 percent) had sinus rhythm restored with dofetilide, as compared with only 3 of 201 patients (1 percent) given placebo. Once sinus rhythm was restored, dofetilide was significantly more effective than placebo in maintaining sinus rhythm (hazard ratio for the recurrence of atrial fibrillation, 0.35; 95 percent confidence interval, 0.22 to 0.57; P<0.001). There were 25 cases of torsade de pointes in the dofetilide group (3.3 percent) as compared with none in the placebo group. CONCLUSIONS: In patients with congestive heart failure and reduced left ventricular function, dofetilide was effective in converting atrial fibrillation, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure. Dofetilide had no effect on mortality.

Adult↗

Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction.

BACKGROUND: Studies have suggested that ACE inhibitors have an antiarrhythmic effect on ventricular arrhythmias. Whether they have an effect on atrial fibrillation is unknown. METHODS AND RESULTS: We investigated the effect of ACE inhibition with trandolapril on the incidence of atrial fibrillation in patients with reduced left ventricular function secondary to acute myocardial infarction. The patients in this study were those who qualified for inclusion into the TRAndolapril Cardiac Evaluation (TRACE) study, a randomized double-blind placebo-controlled study and who had sinus rhythm on the ECG obtained at randomization. Patients who fulfilled the criteria for inclusion were randomized to treatment with the ACE inhibitor trandolapril or placebo and were followed up for 2 to 4 years. Development and time to occurrence of atrial fibrillation in one 12-lead ECG recorded at the outpatient visits was the primary end point of this investigation. Of the 1749 patients included in the TRACE study, 1577 had sinus rhythm on the ECG recorded at randomization. Of these patients, 790 were randomized to trandolapril treatment and 787 to placebo treatment. The groups differed only slightly with respect to baseline characteristics. A total of 64 patients developed atrial fibrillation during the 2- to 4-year follow-up period. Significantly more patients developed atrial fibrillation in the placebo group than in the trandolapril group, 5.3% (n=42) versus 2.8% (n=22), respectively, P<0.05. Cox multivariable regression analysis, adjusting for important baseline characteristics, revealed that trandolapril treatment significantly reduced the risk of developing atrial fibrillation (RR, 0.45; 95% CI, 0.26 to 0.76; P<0.01). CONCLUSIONS: The results from the present study demonstrate that trandolapril treatment reduces the incidence of atrial fibrillation in patients with left ventricular dysfunction after acute myocardial infarction.

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Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation.

BACKGROUND: The survival benefit from the use of inhibitors of angiotensin-converting enzyme (ACE) in patients with acute myocardial infarction is usually presented in terms of risk ratios and lives saved per 1000 people treated. A more relevant way to present the extent of benefit would be in terms of an increase in life expectancy, but this approach has not previously been possible because of limited data on long-term outcome. We aimed to calculate the effect of trandolapril on life expectancy with follow-up data from the Trandolapril Cardiac Evaluation (TRACE) Study. METHODS: The TRACE study previously showed a significant survival benefit with trandolapril in patients with reduced left-ventricular function after an acute myocardial infarction who were treated for at least 2 years. We ascertained the survival status of all patients in the TRACE study in June, 1998, at which time they had been followed up for a minimum of 6 years. We estimated life expectancy as median lifetime, which was the time for 50% of the patients to have died. Change in life expectancy is expressed as change in median lifetime. Analysis was by intention to treat. FINDINGS: The life expectancy of patients was 4.6 years for those given placebo versus 6.2 years for those on trandolapril. Thus, for patients on trandolapril, median lifetime was increased by 15.3 months or 27% (95% CI 7 to 51). Analysis of follow-up after the end of the study indicated no decrease of this benefit during the course of double-blind treatment; continued use of trandolapril was recommended at study closure. INTERPRETATION: In patients with severely reduced left-ventricular function, long-term treatment with an ACE inhibitor during the critical period after myocardial infarction is associated with a substantial increase in life expectancy.

Adult↗

Prognostic usefulness of repeated echocardiographic evaluation after acute myocardial infarction. TRACE Study Group. TRAndolapril Cardiac Evaluation.

The prognostic value of repeated echocardiographic measurement of left ventricular function after acute myocardial infarction was evaluated. We found that repeated measurements of wall motion index in survivors of acute myocardial infarction, with no reinfarction, provide important prognostic information about death and worsening of heart failure.

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Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation.

A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.

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