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Kenneth Dickstein

Publications and source records attributed to Kenneth Dickstein.

53 records · Page 3Linked to original sources
PubMed2004

Effect of combined statin and beta-blocker treatment on one-year morbidity and mortality after acute myocardial infarction associated with heart failure.

This retrospective, nonrandomized analysis evaluated the effect of initiating statin or beta-blocker treatment early in the course of heart failure developed during acute myocardial infarction compared with the effect of neither or both treatments. Early initiation of statins or beta blockers alone was associated with improved event-free survival, and the benefits of the combined treatment were additive.

Adrenergic beta-Antagonists↗
PubMed2004

The data monitoring experience in the MOXCON trial.

AIMS: This article describes a challenging data monitoring experience that occurred in a major international randomized placebo-controlled trial in patients with heart failure, in which the accumulating interim data showed an excess of deaths on the active treatment. METHODS AND RESULTS: The MOXonidine CONgestive Heart Failure trial was a randomized comparison of moxonidine, a central sympathetic inhibitor, with placebo. It was planned to recruit 4500 patients with heart failure. The primary endpoint was all-cause mortality, and average follow-up was anticipated to be around 2.5 years until 724 deaths occurred. The trial Data Monitoring Board (DMB) was to conduct safety monitoring reviews of interim data at least every six months, and make their recommendations to the Executive Committee. Within a few months of the study starting, the Data Monitoring Board (DMB) observed an emerging trend of an excess of deaths on moxonidine compared with placebo. This article describes the sequence of events that unfolded: several DMB meetings to evaluate the accumulating evidence, a DMB recommendation to stop the trial, consequent dialogue with the Executive Committee and sponsor leading to a final decision to stop the trial. Ten months after the first patient was randomized, the study was stopped based on 46 versus 25 deaths in 990 moxonidine and 943 placebo patients, respectively, P=0.01. The final published evidence had 54 versus 32 deaths, P=0.012. CONCLUSIONS: This study illustrates the problems faced by a DMB, and subsequently the trial Executive Committee and sponsor, in deciding how to act in the face of an emerging (and agonizing) negative trend for mortality in a major international trial.

Clinical Trials Data Monitoring Committees↗
PubMed2004

Effect of exercise training in patients with heart failure: a pilot study on autonomic balance assessed by heart rate variability.

BACKGROUND: Heart rate variability (HRV) is decreased in patients with congestive heart failure (CHF) and is a prognostic marker in this disease. Exercise training is now regarded as an important part of the treatment of patients with CHF, but the effect on HRV and the association between this effect and the effect on neurohormones are not well assessed. METHODS: Heart rate recording was performed in 12 patients with CHF (mean age 67+/-8 years) with CHF NYHA functional class III, before and after 12 weeks of exercise training. The association with exercise capacity and serum levels of atrial natriuretic peptide was assessed. We also evaluated the correlation between HRV and survival at follow-up 87 months later. RESULTS: At baseline there was a significant correlation between mean heart rate and work performed during max cycle test (r=0.650, P=0.022) and the HRV parameter standard deviation normal to normal (SDNN) (r=0.678, P=0.015). After exercise training there was a significant increase in work performed (30.3+/-14.2 versus 38.1+/-14.1 kJ), 6-min walk test (502+/-88 versus 552+/-59 m, P=0.006) and SDNN (117.3+/-40.7 versus 128.6+/-42.3 ms, P=0.028). At 87 months of follow-up, there was a borderline significant difference between survivors and non-survivors. Only the survivors had a significant increase in SDNN after exercise training. CONCLUSION: This pilot study demonstrates an improvement with regard to parameters for HRV after exercise training in patients with CHF. The study suggests that the positive effect of exercise training in patients with CHF involves an attenuation of the reduced HRV response, and that this improvement might have prognostic significance.

Aged↗
PubMed2003

Association between plasma chromogranin A concentration and long-term mortality after myocardial infarction.

PURPOSE: Chromogranin A, a polypeptide that is distributed throughout the neuroendocrine system, may be a marker of neuroendocrine activation. We sought to assess the long-term prognostic value of circulating levels of chromogranin A after myocardial infarction. METHODS: We studied 119 patients (88 [74%] male; median age, 70 years [interquartile range, 62 to 75 years]) with documented myocardial infarction. Chromogranin A levels in plasma were determined by radioimmunoassay from samples obtained 3 days after the onset of symptoms. RESULTS: During a median follow-up of 10.8 years, 56 patients (47%) died. The median concentration of chromogranin A in plasma was 24 ng/mL (interquartile range, 18 to 36 ng/mL). Plasma chromogranin A levels were associated with increased long-term mortality (hazard ratio [HR] = 1.17 per 10-ng/mL increase; 95% confidence interval [CI]: 1.06 to 1.28) in models that adjusted for age, clinical heart failure during the initial hospitalization, and use of thrombolytic therapy. As a dichotomous variable (cutoff, 24 ng/mL), an elevated chromogranin A level was also associated with mortality in univariate analysis (HR = 2.6; 95% CI: 1.4 to 4.8), but this relation was no longer significant after adjustment for age (HR = 1.4; 95% CI: 0.8 to 2.7). CONCLUSION: Plasma levels of chromogranin A are related to long-term mortality after myocardial infarction, perhaps because they reflect neuroendocrine activation.

Aged↗
PubMed2003

N-terminal proatrial natriuretic peptide in primary care: relation to echocardiographic indices of cardiac function in mild to moderate cardiac disease.

AIMS: In patients with chronic heart failure plasma levels of N-terminal proatrial natriuretic peptide (Nt-proANP) correlate to cardiac filling pressures. The aim of the present study was to examine the relation between Nt-proANP plasma levels and echocardiographic indices of cardiac dysfunction in patients recruited from primary care. METHODS AND RESULTS: After clinical examination by the primary care physician, the patients were referred to one of two centres for echocardiography and blood sampling. In patients with mild to moderate symptoms of heart failure (n=52) and in asymptomatic patients with long-standing hypertension (n=46) or previous myocardial infarction (n=97), peptide levels were most closely related to parameters of left atrial wall stress. Patients who according to echocardiographic predefined criteria had diastolic or systolic dysfunction had two- and three-fold higher Nt-proANP than controls. According to receiver operating curve (ROC) analysis, Nt-proANP measurements were helpful in ruling out left ventricular systolic dysfunction, but not diastolic dysfunction. CONCLUSION: In patients with mild to moderate cardiac disease, Nt-proANP plasma concentration was related to increased atrial wall stress. Peptide measurement could assist in ruling out the presence of LV systolic dysfunction, but was otherwise of limited value when used for diagnostic subgrouping into echocardiographically determined function categories.

Adult↗
PubMed2002

[Prioritization of hospital autopsies].

BACKGROUND: Routines for requesting autopsies in hospitals in Norway differ. At the Central Hospital in Rogaland, physicians usually fill out a form requesting an autopsy when a patient dies. The physician can choose between "high", "ordinary" or "low priority". In this study we investigated which patients were given highest priority and which factors influenced the priority made by the referring physician. MATERIAL AND METHODS: This was a retrospective study. All requests for an autopsy during the year 2000 were reviewed, except forensic medicine cases and perinatal deaths. We included 785 requests in the study. 237 autopsies were performed: an autopsy rate of 30.2%. RESULTS AND INTERPRETATION: The requesting physicians considered 17% "high priority", 44% "ordinary priority" and 39% "low priority". Significantly higher priorities were set for those who died young, those who died after a short stay in hospital, and for those who died in intensive care units. Sex and time of death did not influence priorities. The recommendation required on the autopsy request form leads to more appropriate decisions by pathologists and strengthens the relationship between clinicians and pathologists.

Aged↗
PubMed2002

Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan.

BACKGROUND: ACE inhibitors attenuate the detrimental effects of angiotensin II, and improve survival and reduce morbidity in patients with acute myocardial infarction and evidence of heart failure or left-ventricular dysfunction. Selective antagonism of the angiotensin type 1 receptor represents an alternative approach to inhibition of the renin-angiotensin system. We did a multicentre, randomised trial to test the hypothesis that the angiotensin II antagonist losartan would be superior or non-inferior to the ACE inhibitor captopril in decreasing all-cause mortality in high-risk patients after acute myocardial infarction. METHODS: 5477 patients 50 years of age or older (mean age 67.4 years [SD 9.8]), with confirmed acute myocardial infarction and heart failure during the acute phase or a new Q-wave anterior infarction or reinfarction, were recruited from 329 centres in seven European countries. Patients were randomly assigned and titrated to a target dose of losartan (50 mg once daily) or captopril (50 mg three times daily) as tolerated. The primary endpoint was all-cause mortality. Analysis was by intention to treat. FINDINGS: There were 946 deaths during a mean follow-up of 2.7 (0.9) years: 499 (18%) in the losartan group and 447 (16%) in the captopril group (relative risk 1.13 [95% CI 0.99-1.28], p=0.07). The results for the secondary and tertiary endpoints were as follows: sudden cardiac death or resuscitated cardiac arrest 239 (9%) versus 203 (7%), 1.19 (0.98-1.43), p=0.07, and fatal or non-fatal reinfarction 384 (14%) versus 379 (14%), 1.03 (0.89-1.18), p=0.72. The all-cause hospital admission rates were 1806 (66%) versus 1774 (65%), 1.03 (0.97-1.10), p=0.37. Losartan was significantly better tolerated than captopril, with fewer patients discontinuing study medication (458 [17%] vs 624 [23%], 0.70 [0.62-0.79], p<0.0001). INTERPRETATION: Since we saw a non-significant difference in total mortality in favour of captopril, ACE inhibitors should remain first-choice treatment in patients after complicated acute myocardial infarction. Losartan cannot be generally recommended in this population. However, it was better tolerated than captopril, and was associated with significantly fewer discontinuations. Although the role of losartan in patients intolerant of ACE inhibition is not clearly defined, it can be considered in such patients.

Aged↗
PubMed2002

Effect of exercise training on skeletal muscle fibre characteristics in men with chronic heart failure. Correlation between skeletal muscle alterations, cytokines and exercise capacity.

BACKGROUND: In patients with congestive heart failure (CHF) there is a shift from aerobic type I muscle fibres to less aerobic type II fibres. Exercise training has been shown to have beneficial effects on exercise performance, peripheral pathology and the neurohumoral profile in stable patients with CHF. This study evaluated the effect of a 3 month exercise training program on skeletal muscle characteristics and the correlation of these to cytokines and exercise capacity in CHF patients. METHODS: Skeletal muscle biopsies for enzyme-histochemical analysis were performed in 15 CHF patients in New York Heart Association classes II-III, with a mean ejection fraction of 33+/-5% before and after a 12 week training period. The patients were trained for 30 min, five times a week at 80% of the peak heart rate achieved at baseline ergometer cycle test. Fifteen healthy men were used as controls. Plasma samples were examined by enzyme immunoassays for levels of pro-inflammatory cytokines. RESULTS: (a) At baseline we found muscle atrophy in five of the patients. The percent area of type I fibres (40.7+/-12.0 vs. 56.4+/-11.0%, P<0.05) and the thickness of type IIA (56.10+/-7.8 vs. 71.6+/-11.9 microm, P<0.001) and B-fibres (49.0+/-8.9 vs. 63.9+/-10.6 microm, P<0.001) were reduced, whereas the percent area of type IIA fibres (52.1+/-13.3 vs. 36.4+/-9.9%, P<0.05) was increased in heart failure patients compared to healthy controls. There was a modest correlation between fibre thickness and the level of interleukin 6 (r=-0.657, P=0.008). (b) After exercise training there was a reduction in muscle area examined by light-microscopy, measured as a percentage of field (-2.7, P=0.003) with an concomitant increase in interstitium. This reduction correlated to the increase in the 6-min walk test (r=-0.558, P=0.031). The thickness of type IIB fibres increased (+5.6 microm, P=0.068) and the area of type I fibres decreased (-6.1%, P=0.062). CONCLUSIONS: Patients with CHF have a relatively increased area of type IIA fibres and a relatively decreased area of type I fibres compared to healthy individuals. The thickness of type IIA and type IIB fibres is decreased compared to normal individuals. A modest negative correlation between the level of interleukin 6 and fibre thickness at baseline, suggests that inflammatory cytokines may be involved in the pathogenesis of the CHF related myopathy. A significant correlation between the reduction of muscle area, with increased interstitum, and the increase in the 6-min walk test may indicate that the improvement is due to increased capillary density permitting better flow reserve to exercising muscles.

Aged↗
PubMed2001

How long should angiotensin-converting enzyme inhibitors be given to patients following myocardial infarction: implications of the HOPE trial.

Long-term treatment with angiotensin-converting enzyme inhibitors reduces post-infarction morbidity and mortality in patients with left ventricular (LV) systolic dysfunction or symptomatic heart failure. Until recently, the effect of such treatment in patients with preserved LV function has not been known. The results from the Heart Outcome Prevention Evaluation trial have indicated that long-term treatment with ramipril leads to a significant reduction in cardiovascular events in patients with atherosclerotic disease, including those with prior myocardial infarction and preserved LV function. These results suggest that long-term angiotensin-converting enzyme inhibition should also be considered in post-infarction patients with normal cardiac function.

Journal Article↗
PubMed2001

ELITE II and Val-HeFT are different trials: together what do they tell us?

The Losartan Heart Failure Survival Study (ELITE II) and the Valsartan Heart Failure Trial (Val-HeFT) both evaluated the efficacy and tolerability of a selective angiotensin II receptor antagonist on morbidity and mortality in patients with symptomatic heart failure. The trials differed, however, in terms of their primary hypothesis, study design, and treatment regimens, and this must be taken into consideration when comparing and interpreting the data from these studies. The data are in many ways complementary, and add to our understanding of the optimal treatment of symptomatic heart failure. Additional studies are needed, however, to fully define the role of angiotensin II receptor antagonists in the management of this very heterogeneous group of patients.

Journal Article↗