Marie Seibæk

Long-term survival in patients hospitalized with congestive heart failure: relation to preserved and reduced left ventricular systolic function

AIMS The purpose of this study was to evaluate the influence of left ventricular systolic function on the survival in a large consecutive cohort of patients hospitalized with congestive heart failure and to determine how left ventricular systolic function interacts with co-morbid conditions in terms of prognosis. METHODS AND RESULTS Analysis of survival data from 5491 patients admitted for new or worsening heart failure to 34 departments of cardiology or internal medicine in Denmark from 1993-1996 was carried out. A standardized echocardiogram was available for 95% of the patients, and left ventricular systolic function was estimated using wall motion index score. Follow-up time was 5-8 years. Patients with preserved systolic function were older, more frequently female, and had less evidence of ischemia than patients with systolic dysfunction. After 1 year, 24% of the patients had died. Low wall motion index was a potent independent predictor of death (risk ratio for one unit increase, 0.60 (0.56-0.64)), and was of greater prognostic significance in younger patients and patients with a history of myocardial ischemia. However, even in patients with preserved systolic function, mortality was high (1 year mortality, 19%). CONCLUSION In hospitalized heart failure patients, particularly in younger patients with ischemic heart disease, mortality risk is inversely related to left ventricular systolic function.

Long-term prognostic importance of resting heart rate in patients with left ventricular dysfunction in connection with either heart failure or myocardial infarction: The DIAMOND study ☆

BACKGROUND Elevated resting heart rate is associated with increased mortality in a variety of cardiac diseases, but comparisons between different clinical settings are lacking. We investigated the long-term prognostic importance of resting heart rate in patients hospitalized with left ventricular dysfunction in connection with either heart failure (HF) or myocardial infarction (MI). METHODS In the Danish Investigations and Arrhythmia ON Dofetilide (DIAMOND) study; patients with left ventricular dysfunction were randomized to Dofetilide (class III antiarrhythmic drug) or placebo. One part of the study enrolled 1518 patients with HF and another 1510 patients with MI. Mortality analyses were performed using multivariable adjusted Cox proportional hazard models. RESULTS During 10 years of follow-up, 1076 (72%) patients with MI and 1336 (89%) patients with HF died. In multivariable adjusted models, every increment in baseline heart rate of 10 bpm was associated with an increase in mortality in both MI-patients (hazard ratio, 1.14; 95%-confidence interval (CI): 1.09-1.19; P<.0001) and HF-patients (hazard ratio, 1.10; CI: 1.06-1.15; P<.0001). The importance of resting heart rate on short-term prognosis was stronger in the MI patients compared to the HF patients (P<.0001 for interaction). There was no interaction between heart rate and beta-blockade, and inclusion of beta-blockade in the model did not change the results. CONCLUSIONS Resting heart rate was independently associated with increased risk of overall mortality. The prognostic importance of resting heart rate is stronger in patients with MI compared to patients with HF, especially in the short term.

Glucose tolerance status and severity of coronary artery disease in men referred to coronary arteriography.

Increasing attention is being paid to disturbances in glucose metabolism as key explanatory factors for the development of coronary artery disease. We studied the prevalence of impaired glucose tolerance and non-insulin-dependent diabetes and the levels of plasma insulin after an oral glucose tolerance test in 99 men with heart disease but without a history of diabetes referred to coronary arteriography; we also compared the outcome with a matched control group (n = 116). The severity of atherosclerosis in coronary angiograms was evaluated according to glucose tolerance status. Among the 99 patients with coronary artery disease, 37.4% had an abnormal oral glucose tolerance test result, whereas only 18.1% of the control group had an abnormal result (p < 0.01). Moreover, patients with heart disease and normal glucose tolerance were hyperinsulinemic compared with the control group (p < 0.01). By analysis of variance no statistically significant difference in severity of coronary atherosclerosis on coronary angiograms was found. In conclusion, we demonstrated frequent disturbances in glucose metabolism indicating insulin resistance in patients with ischemic heart disease without a history of diabetes, but we could not demonstrate a relation between these disturbances and degree of coronary atherosclerosis.

Differential prognostic importance of QRS duration in heart failure and acute myocardial infarction associated with left ventricular dysfunction

Studies of the prognostic importance of QRS duration in patients with heart failure (HF) have shown conflicting results and few studies have estimated the importance after myocardial infarction (MI).

Different prognostic impact of systolic function in patients with heart failure and/or acute myocardial infarction

To study the prognostic importance of left ventricular systolic function in patients with heart failure (HF) and acute myocardial infarction (AMI) with respect to the presence of prior heart failure and known ischemic heart disease.

Incidence of Atrial Fibrillation in Patients with either Heart Failure or Acute Myocardial Infarction and Left Ventricular Dysfunction: A Cohort Study

BackgroundWe examined the incidence of new-onset atrial fibrillation in patients with left ventricular dysfunction. Patients either had a recent myocardial infarction (with or without clinical heart failure) or symptomatic heart failure (without a recent MI). Patients were with and without treatment with the class III antiarrhythmic drug dofetilide over 36 months.MethodsThe Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies included 2627 patients without atrial fibrillation at baseline, who were randomised to treatment with either dofetilide or placebo.ResultsThe competing risk analyses estimated the cumulative incidences of atrial fibrillation during the 42 months of follow-up to be 9.6% in the placebo-treated heart failure-group, and 2.9% in the placebo-treated myocardial infarction-group.Cox proportional hazard regression found a 42% significant reduction in the incidence of new-onset AF when assigned to dofetilide compared to placebo (hazard ratio 0.58, 95% confidence interval 0.40-0.82) and there was no interaction with study (p = 0.89).In the heart failure-group, the incidence of atrial fibrillation was significantly reduced to 5.6% in the dofetilide-treated patients (hazard ratio 0.57, 95% confidence interval 0.38-0.86).In the myocardial infarction-group the incidence of atrial fibrillation was reduced to 1.7% with the administration of dofetilide. This reduction was however not significant (hazard ratio 0.61, 95% confidence interval 0.30-1.24).ConclusionIn patients with left ventricular dysfunction the incidence of AF in 42 months was 9.6% in patients with heart failure and 2.9% in patients with a recent MI. Dofetilide significantly reduced the risk of developing atrial fibrillation compared to placebo in the entire study group and in the subgroup of patients with heart failure. The reduction in the subgroup with recent MI was not statistically significant, but the hazard ratio was similar to the hazard ratio for the heart failure patients, and there was no difference between the effect in the two studies (p = 0.89 for interaction).

Anaemia and Long Term Mortality in Heart Failure Patients: A Retrospective Study

Background: Anaemia has been demonstrated as a risk factor in patients with heart failure over periods of a few years, but long term data are not available. We examined the long-term risk of anaemia in heart failure patients during 15 years of follow-up. Methods: We evaluated survival data for 1518 patients with heart failure randomized into the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) trial. The follow-up time was from 13 to 15 years. After 15 years 11.5% of the patients were still alive. Results: Anaemia was present in 34% of the patients. 264 (17%) had mild, 152 (10%) had moderate and 98 (7%) had severe anaemia. Hazard ratio of death for patients with mild anaemia compared with patients with no anaemia was 1.27 (1.11-1.45, p<0.001), for moderate anaemia 1.48 (1.24-1.77, p<0.001) and for severe anaemia 1.82 (1.47-2.24, p<0.001), respectively. In multivariable analyses anaemia was still associated with increased mortality with hazard ratios of 1.19 (1.04–1.37, p=0.014) for mild anaemia, 1.23 (1.03–1.48, p=0.024) for moderate anaemia and 1.33 (1.07–1.66, p=0.010) for severe anaemia, respectively. In landmark analysis the increased mortality for mild anaemia was only significant during the first 2 years, while moderate anaemia remained significant for at least 5 years. There were too few patients left with severe anaemia after 5 years to evaluate the importance on mortality beyond this time. Conclusion: Anaemia at the time of diagnosis of heart failure is an independent factor for mortality during the following years but loses its influence on mortality over time.

Prognostic Importance of Change in QRS Duration Over Time Associated With Left Ventricular Dysfunction in Patients With Congestive Heart Failure: The DIAMOND Study

BACKGROUND The prognostic importance reported for QRS duration in patients with heart failure (HF) and left ventricular dysfunction varies. No prior study has investigated the prognostic importance of change in QRS duration over time. METHODS AND RESULTS The Danish Investigations and Arrhythmia ON Dofetilide (DIAMOND) study randomized 1518 patients with HF to dofetilide (class III antiarrhythmic drug) or placebo. All patients had left ventricular dysfunction. QRS duration was systematically measured at randomization and every 3 months after that. During 10 years of follow-up, 1324 (89%) of the patients died. QRS duration increased from baseline by 1.36 ms (95% confidence interval [CI]: -0.26 to -2.98; P = .1) after 12 months and by 3.65 ms (CI: 0.22-7.07; P = .04) after 24 months. QRS duration measured at baseline was not of prognostic significance after multivariable adjustment (adjusted hazard ratio [HR] 1.01, CI: 0.99-1.04; P = .2 per 10-ms increment in QRS duration). The adjusted relative risk associated with a 10-ms increase in QRS duration over time was 2% (HR 1.02, CI: 1.01-1.04; P = .03). A 10-ms increment in QRS 12 months after randomization was associated with a HR of 1.05 (CI: 1.00-1.09; P = .03). CONCLUSIONS In patients with left ventricular dysfunction and HF, QRS duration increased over time and the increase was associated with increasing mortality.

The Reliability of Echocardiographic Left Ventricular Wall Motion Index to Identify High‐Risk Patients for Multicenter Studies

Objective: To study whether the use of echocardiographic left ventricular (LV) wall motion index (WMI) is a dependable parameter for identifying patients with LV dysfunction to be enrolled in multicenter trials. Methods: Videotaped echocardiographic examinations from 200 randomly selected patients that were screened for inclusion into the DIAMOND‐CHF and DIAMOND‐MI trials were reevaluated by an external expert echocardiographer. WMI was calculated using the 16‐segment LV model. Results: The external echocardiographer systematically found lower values of WMI than the core laboratory. The average difference in WMI was 0.18 (SD: 0.33) in the DIAMOND‐CHF trial and 0.09 (SD: 0.33) in the DIAMOND‐MI trial. The difference in WMI exceeded 0.33 in 34% of the patients in both trials. The cutoff value for inclusion into the DIAMOND trials was WMI ≤ 1.2. There was an agreement on WMI dichotomized to below or above 1.2 in 82% of the patients in both trials ( κ coefficient 0.66 for the DIAMOND‐CHF and 0.55 for the DIAMOND‐MI). Conclusions: Despite substantial interlaboratory variation in WMI in individual patients and a systematic lower WMI score by the external echocardiographer there was an acceptable overall agreement for identifying patients with severe impairment of LV function. This not only underscores the value of LV‐WMI as a useful tool for selecting high‐risk patients to be included in multicenter studies but also serves to warn against the use of rigid cutoff values for WMI in the treatment of individual patients.