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Biomedical subjects

L Erhardt

Publications and source records attributed to L Erhardt.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cost effectiveness in the treatment of heart failure with ramipril. A Swedish substudy of the AIRE study. Acute Infarction Ramipril Efficacy.

We estimated the cost effectiveness of adding the ACE inhibitor ramipril to conventional treatment in patients with heart failure after acute myocardial infarction. These estimates were based on the Acute Infarction Ramipril Efficacy (AIRE) study and on complementary Swedish healthcare resource use data for a subset of patients. The average follow-up period was 15 months (minimum 6 months, maximum 3.8 years). The perspective of the analysis was that of the county councils (third-party payers), and we focused on the cost of drugs and hospitalisation. The marginal cost effectiveness of the treatment was estimated over 3 treatment periods: 1, 2 and 3.8 years. The cost-effectiveness ratios varied between SEK14,148 and SEK33,033 per life-year gained ($US1 = SEK7.70. Pounds 1 = SEK12.40) for the 3 treatment periods. Adding ramipril to conventional treatment for heart failure after acute myocardial infarction is therefore cost effective, and compares favourably with the cost effectiveness of other common medical therapies in the cardiovascular field.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effect of ramipril on morbidity and mode of death among survivors of acute myocardial infarction with clinical evidence of heart failure. A report from the AIRE Study Investigators.

BACKGROUND: The importance of the effects of ACE inhibitors on sudden death, progressive heart failure and recurrent infarction to the reduction in overall mortality in heart failure and after myocardial infarction is disputed. METHODS: The AIRE study randomized 2006 patients with clinical or radiological evidence of heart failure within 2-9 days of a myocardial infarction to receive ramipiril 5 mg b.d. or matching placebo. Outcomes were assessed independently by members of an end-points committee blinded to treatment allocation. RESULTS: Fewer patients developed severe resistant heart failure as their first validated end-point on rampril, despite the greater number of at-risk survivors, compared to placebo (n = 143 vs 178; risk reduction 23%; CI 5 to 39%; P = 0.017). Ramipril did not alter the rate of reinfarction or stroke. Irrespective of treatment allocation 182 (46%) patients developed resistant heart failure prior to death. A validated acute or remote myocardial reinfarction occurred in 76 (19%) patients prior to death and chest pain occurred in 90 (23%) patients around the time of death suggesting an ischaemic element to these deaths Eighty deaths occurred on the index admission, 167 during re-admission and 145 out-of-hospital. Sudden death accounted for 54% of all deaths and 93% of out-of-hospital deaths. Ramipril reduced the risk of sudden death by 30% (95% CI: 8-47%; P = 0.011). However, overall, 45% of those patients who died suddenly had severe or worsening heart failure prior to their death. Only 39% of sudden deaths were considered to be due to arrhythmias. Ramipril reduced the risk of death from circulatory failure by 18%, but this did not reach statistical significance (95% CI; 41 to -14%; P = 0.237). The magnitude of the effects on sudden death and death due to circulatory failure were not significantly different. However, 38% of the reduction in overall mortality was from the subgroup with sudden death who had developed prior severe resistant heart failure (placebo n = 35, ramipril n = 15), again emphasizing the marked benefit in preventing failure. Ramipril did not selectively alter the proportion of in- to out-of-hospital deaths. CONCLUSION: Ramipril reduces mortality and progression to resistant heart failure among patients with evidence of heart failure early after myocardial infarction. Retarding the progression of heart failure appears to be a major factor contributing to the reduction in mortality both by reducing circulatory failure and by reducing sudden death.

Adult↗
PubMed1996

Continuous vectorcardiographic changes in relation to scintigraphic signs of reperfusion in patients with acute myocardial infarction receiving thrombolytic therapy.

OBJECTIVES: Changes in the electrical activity of the heart reflecting the infarct process can be recorded by continuous vector-ECG, a method which is now clinically available for cardiac supervision. Shifts of the ST-segment and QRS-vector reflect ischaemia and necrosis of the myocardium. Continuous vector-ECG changes were evaluated against myocardial scintigraphy in 18 patients with acute myocardial infarction treated with streptokinase in order to study the impact of improved myocardial perfusion. DESIGN: Myocardial perfusion was analysed with 99Tcm-Sestamibi (Cardiolite, DuPont Scandinavia AB, Kista, Sweden) single photon emission computerized tomography (SPECT). Registrations were performed before and after thrombolysis in order to estimate the amount of myocardium with impaired perfusion initially (threatened myocardium) and the degree of perfusion improvement in this myocardial area. X, Y, Z vectors were registered continuously by Frank leads (Ortivus Medical, Täby, Sweden). QRS-vector difference, and the time to plateau phase and the ST-vector magnitude were used as a measurement of ischaemia and size of the myocardial infarction. RESULTS: In seven out of 11 patients treated within 3 h of onset of symptoms, an improvement in myocardial perfusion in the initially hypoperfused areas was achieved in contrast to none of the seven patients treated > 3 h after onset of pain (P < 0.05). In the whole patient material, there was a negative correlation between the time to plateau level for the QRS-vector and the improvement in myocardial perfusion (r = -0.53, P < 0.05). Among patients treated within 3 h, there was a negative correlation between the plateau level for the QRS-vector magnitude compared to the improvement in myocardial perfusion (r = -0.61, P < 0.05) and a negative correlation between the plateau level and the myocardial perfusion level after therapy (r = -0.69, P < 0.05). In these patients, there were also negative correlations between the maximal ST-vector magnitude and the myocardial perfusion both before and after thrombolysis (r = -0.81, P < 0.05 and r = -61, P < 0.05, respectively). CONCLUSION: Patients with marked improvement in myocardial perfusion indicating successful thrombolysis reach their plateau levels of the QRS-change faster and have lower total QRS-vector differences than patients without successful thrombolysis as reflected by myocardial scintigraphy. Patients with a high ST-vector magnitude have low perfusion levels both before and after therapy indicating a pronounced ischaemic damage of the myocardium. Thus, VCG-changes reflect impairment in myocardial perfusion during acute myocardial infarction.

Aged↗
PubMed1996

Prevalence of factor V gene mutation amongst myocardial infarction patients and healthy controls is higher in Sweden than in other countries.

OBJECTIVE: Haemostatic imbalance may be an aetiological factor in the development of acute coronary syndromes. Inherited resistance to activated protein C (APC) is a common disorder associated with hypercoagulability and lifelong risk of venous thrombosis. APC resistance is due to a single mutation in the gene coding for coagulation factor V (FV:Q506). To test the importance of the FV:Q506 mutation in premature myocardial infarction (MI), its prevalence was investigated in Swedish patients with MI before the age of 50 years. DESIGN, SETTING AND SUBJECTS: In a retrospective case-control study, the FV:Q506 mutation was investigated in 101 survivors of MI (79 men, 22 women) and in 101 healthy sex- and age-matched controls. MAIN OUTCOME MEASURE: The prevalence of FV:Q506 mutation. RESULTS: The FV:Q506 mutation was found in 18% of patients versus 11% of controls (P = 0.16). The mutation was significantly more frequent amongst male patients than amongst controls (23 vs. 10%; P = 0.03), the calculated odds ratio being 2.6 (95% CI, 1.1-6.4). CONCLUSION: The high prevalence of the FV:Q506 mutation found amongst Swedish MI patients, especially amongst men, is noteworthy, and calls for further studies on the outcome of MI in APC-resistant patients. The prevalence of the FV:Q506 mutation in controls is higher than figures reported from other countries, suggesting that at least 10% of the Swedish population are carriers of a congenital prothrombotic disorder.

Adult↗
PubMed1996

Effects of beta receptor antagonists on left ventricular function in patients with clinical evidence of heart failure after myocardial infarction. A double-blind comparison of metoprolol and xamoterol. Echocardiographic results from the Metoprolol and Xamoterol Infarction Study (MEXIS).

Two hundred and ten patients with clinical evidence of heart failure, developing after an acute myocardial infarction, were randomized to treatment with the beta 1-receptor antagonist metoprolol 50-100 mg b.i.d. (n = 106) or the beta 1-receptor partial agonist xamoterol 100-200 mg b.i.d. (n = 104). Left ventricular systolic and diastolic function were assessed with echocardiography and transmitral Doppler cardiography before and after 3 and 12 months of double-blind treatment. E-point septal separation and percent left ventricular fractional shortening were used as indices of systolic function. The ratio between peak early and late mitral diastolic flow (E/A ratio) and isovolumic relaxation time were used as indices of diastolic function. In the xamoterol group, there was a deterioration in E-point septal separation (P < 0.05). A difference between the treatment groups was present both at 3 months (E-point septal separation 11.4 vs 13.0 mm, P < 0.01, fractional shortening 27.1 vs 25.2%, P < 0.05) and 12 months (E-point septal separation 11.1 vs 13.2 mm. P < 0.005, fractional shortening 26.9 vs 25.0%, P < 0.05). E/A ratio increased in the metoprolol group (P < 0.05) but not in the xamoterol group. At 3 months there was a significant difference (0.85 vs 0.67, P < 0.005) between the groups but not at 12 months. In comparison with the beta 1-receptor antagonist metoprolol, the beta 1-receptor partial agonist xamoterol impaired left ventricular systolic function in patients with clinical evidence of heart failure after an acute myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed1996

Mode of death in chronic heart failure. A request and proposition for more accurate classification.

The proportion of patients reported to die suddenly or from progressive circulatory failure is not consistent among studies of heart failure. Lack of an adequate or consistent classification of how patients die contributes to the current confusion over the mode of death in heart failure. Defining how patients with heart failure die could be important in developing strategies to reduce the continuing high mortality associated with this condition. We identified 27 studies that reported 50 or more deaths among patients with heart failure to ascertain how death was classified. Definitions of sudden death appeared heterogeneous and the majority of studies failed to publish or make reference to how circulatory failure was defined. A framework for the classification of the mode of death has been developed in which clear separation of the activity and place at the time of death, cause of death, mode of death, and events prior to death is made (ACME: Activity, Cause, Mode and Event). This mode of classifying death has been successfully piloted in two mortality studies; AIRE and NETWORK. Classifying mortality in this way will help identify pathways leading to death and hence suggest therapies and strategies to reduce mortality in patients with heart failure, a group of patients whose prognosis remains poor.

Adult↗
PubMed1996

ACE inhibitors before or after heart failure?

Heart failure is a progressive disease and once the process has started it continues with further deterioration of cardiac function or ends in sudden death. In many patients changes within the heart start to develop long before clinical symptoms occur. The left ventricle goes through a number of adaptions-remodelling-to compensate for increased pressure or volume load or subsequent myocardial infarction. Several of these compensatory changes have prognostic implications and indicate increased risk of clinical heart failure or cardiac events. Thus, increased left ventricular dimensions, volume and mass together with reduced systolic function are all markers of poor prognosis. Treatment with angiotensin-converting enzyme (ACE) inhibitors before the onset of clinical heart failure has been shown to improve prognosis. Identification of individuals at high risk is difficult since signs and symptoms of heart failure are often lacking. A strategy to find these patients must use objective methods to characterise the state of the left ventricle. It is likely that not only patients with significant reduction of systolic function but also other signs of impaired left ventricular dysfunction will benefit from treatment with ACE inhibitors. Only by preventive treatment may we be able to decrease the number of patients with new onset of clinical heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Fosinopril attenuates clinical deterioration and improves exercise tolerance in patients with heart failure. Fosinopril Efficacy/Safety Trial (FEST) Study Group.

This study was a 12-week, double-blind, placebo-controlled, multinational trial of fosinopril in 308 patients with mild to moderately severe heart failure (New York Heart Association [NYHA] functional class IIS 17%, IIM 48%, and III 35%; mean ejection fraction [+/-SD] 26.5% [+/-6.9%]; bicycle exercise duration 1 to 11 min). An initial dose of 10 mg once daily was titrated as tolerated to 40 mg once daily. Patients all received diuretic therapy; digoxin was optional. The primary endpoint was maximal bicycle exercise time; a secondary endpoint was occurrence of the following prospectively defined, ordered clinical events indicative of worsening heart failure: death, study discontinuation, hospitalization, emergency room visits, and need for supplemental diuretic. At study endpoint (last value obtained for each patient), bicycle exercise time increased more with fosinopril (38.1 s) than with placebo (23.5 s) (P = 0.101 by ANCOVA and 0.010 by prospectively defined dropout-adjusted endpoint analysis). More patients remained free of clinical events indicative of worsening heart failure when treated with fosinopril (89%) than with placebo (75%), and the worst events of fosinopril-treated patients tended to be less severe than those of placebo patients (P = 0.001). Analysis of the occurrence of individual clinical events showed that the need for supplemental diuretic was markedly reduced with fosinopril (8% vs 20%, of patients, P = 0.002), as were hospitalizations (3% vs 12% of patients, P = 0.002) and study discontinuations (2% vs 12% of patients, P < 0.001) for worsening heart failure; the two groups had similar incidences of death (3% of patients in the fosinopril group vs 2% in the placebo group, P = 0.723). In addition, symptoms of dyspnoea (P = 0.017), fatigue (P = 0.019), and NYHA functional class (P = 0.008) improved with fosinopril relative to placebo. In conclusion, fosinopril, at an initial dose of 10 mg once daily, subsequently titrated as tolerated to 40 mg once daily, increased exercise tolerance and reduced the frequency of clinical events indicative of worsening heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Heart failure after myocardial infarction: the importance of diastolic dysfunction. A prospective clinical and echocardiographic study.

Clinical signs of heart failure based on predefined criteria were analysed in 217 survivors (< 75 years of age) of an acute myocardial infarction (AMI). A Doppler investigation and M-mode echocardiography were performed 3-5 days after the index infarction. All patients were stratified according to left ventricular end-diastolic diameter </> or = 28 mm.m-2 body surface area. Fractional shortening, E-point septal separation, Keren's echo-index based on left ventricular end-diastolic diameter, fractional shortening and E-point septal separation were used as indices of systolic function, and the E/A ratio and isovolumic relaxation time as indices of diastolic function. Fifty-one per cent of the patients (n = 111) had heart failure. Left ventricular end-diastolic diameter was < 28 mm.m-2 body surface area in 32 (29%) of the heart failure patients and in 44 (45%) of those without heart failure. An abnormal Keren's echo-index was found in 58 (52%) of the heart failure patients compared with 17 (18%) without heart failure. The E/A ratio was lower (0.65 vs 0.77, P = 0.01) in heart failure patients with a normal left ventricular end-diastolic diameter compared with patients without heart failure and a normal left ventricular end-diastolic diameter. Infarct size, E-point septal separation, heart rate and age were determinants of heart failure in multivariate analyses with all patients included. Infarct size and the E/A ratio were determinants of heart failure in patients with a normal left ventricular end-diastolic diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Effects of beta receptor antagonists in patients with clinical evidence of heart failure after myocardial infarction: double blind comparison of metoprolol and xamoterol.

OBJECTIVE: To evaluate whether xamoterol, a partial agonist, would improve exercise time more than metoprolol in patients with mild to moderate heart failure after a myocardial infarction. DESIGN: Single-centre double blind randomised parallel group comparison of metoprolol 50-100 mg and xamoterol 100-200 mg twice daily. PATIENTS: 210 patients aged 40-80 years (173 men) with clinical evidence of heart failure early after a myocardial infarction. 106 were given metoprolol and 104 xamoterol. MAIN OUTCOME MEASURES: Exercise test results and performance at three months; the exercise test, quality of life, and clinical assessments at baseline (5-7 days after the infarction) and after 3, 6, and 12 months. RESULTS: Exercise time increased at three months by 22% in the metoprolol group and 29% in the xamoterol group, but with no significant difference between the groups. Patients taking xamoterol showed overall non-significantly higher mean values of exercise time achieved with higher heart rates at rest and exercise. Improvements in quality of life, clinical signs of heart failure, and New York Heart Association functional class were seen in both treatment groups over one year, with minor benefits of xamoterol on breathlessness, peripheral oedema, and functional class. Eighteen patients taking metoprolol and 22 taking xamoterol withdrew from the study during one year, with a low mortality, reinfarction rate, and progress of heart failure in both treatment groups. Mean dose from baseline to 3 months was 135 mg metoprolol and 347 mg xamoterol. CONCLUSION: beta 1 Receptor antagonists with or without partial agonist activity are safe to use in mild to moderate heart failure after a myocardial infarction. Exercise tolerance, quality of life, and clinical signs and functional class of heart failure improve, and few patients show deterioration in their condition. Exercise tolerance is no better with xamoterol than metoprolol.

Adrenergic beta-Antagonists↗
PubMed1995

Long-term prognostic importance of exercise echocardiography after an episode of unstable angina.

The aim of this study was to determine whether exercise echocardiography gives long-term prognostic information in patients with unstable angina. Treadmill exercise echocardiography was performed before discharge in 33 consecutive patients (23 men, 10 women) with unstable angina. A wall motion score index (WMSI) was calculated from visual interpretation of 9 left-ventricular segments, registered with two-dimensional echocardiography. Within an 8-year follow-up period, there were 10 medical events (2 cardiac deaths and 8 myocardial infarctions). New or worsening wall motion abnormalities and a low WMSI immediately after the exercise test were associated with subsequent myocardial infarction or cardiac death during follow-up (p < 0.05). Only 1 of the patients with a WMSI above the median suffered a myocardial infarction, which was not fatal. In contrast, 9 (56%) of the 16 patients with a WMSI below the median suffered myocardial infarction or cardiac death during follow-up. These findings in patients with unstable angina suggest that exercise echocardiography is a sensitive method for detecting those with increased risk of myocardial infarction or cardiac death. These high-risk patients might benefit from a more aggressive therapeutic approach.

Adolescent↗
PubMed1993

Low-dose warfarin decreases coagulability without affecting prothrombin complex activity.

OBJECTIVES: To assess the efficacy of a fixed, low dose of warfarin in lowering factor VII coagulant activity (FVII:C) and to investigate the effects on the plasma coagulation cascade. DESIGN: An open pilot study with two dose levels of warfarin: 1.25 and 2.5 mg day-1 during two consecutive 4-week periods. All subjects received aspirin 75 mg day-1. Prothrombin fragment 1 + 2 (F(1 + 2)), protein C, protein S, FVII:C, factor X and P-prothrombin complex activity (P-PT) were measured at baseline, at 2-week intervals and 4 weeks after end of treatment. Coagulation activation peptide F(1 + 2) was used as a marker of thrombin formation. SUBJECTS: Twelve male patients with a history of myocardial infarction. Inclusion was made through a written questionnaire. RESULTS: Warfarin 1.25 mg day-1 lowered FVII:C from 113 U dl-1 to 107 U dl-1 (P = 0.025) and F(1 + 2) from 1.60 nmol l-1 to 1.27 nmol l-1 (P = 0.013) but had no effect on protein C or P-PT. A dose of 2.5 mg day-1 induced further lowering of FVII:C (91 U dl-1, P = 0.0042), and also of protein C from 116% to 99% (P = 0.034) and P-PT from 107% to 81% (P = 0.0096) mean values. CONCLUSION: Warfarin 1.25 mg day-1 seems to exert an anticoagulant effect without reduction in PT or the natural anticoagulant protein C and is suggested, in combination with aspirin, to be a safe and simple therapy against arterial thrombotic disease, making regular PT controls unnecessary.

Adult↗
PubMed1993

Validation of primary and secondary outcomes and classification of mode of death among patients with clinical evidence of heart failure after a myocardial infarction: a report from the Acute Infarction Ramipril Efficacy (AIRE) Study Investigators.

The AIRE study--a trial involving over 2,000 patients with clinical heart failure after myocardial infarction--assessed different outcomes. The primary outcome was total mortality. The secondary outcome was time to death, or progression to severe/resistant heart failure, reinfarction or stroke. Tertiary analyses included hospitalization and mode of death. To obtain maximum quality in the validation of outcomes and to optimize the quality of the data in the study, an end-points committee reviewed all data following preset definitions prior to code break. All definitions used are reported here. Experience of the validation process demonstrated that there are wide variations in clinical practice and terminology not only among countries but also among individual investigators. Variation in the clinical handling and treatment of patients makes it imperative to validate outcomes centrally on the basis of available facts.

Cause of Death↗