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Biomedical subjects

Kenneth Dickstein

Publications and source records attributed to Kenneth Dickstein.

At least 37 records · Page 2Linked to original sources
PubMed2005

Plasma levels of soluble tumor necrosis factor receptor type I during the acute phase following complicated myocardial infarction predicts survival in high-risk patients.

OBJECTIVES: We sought to determine the relationship between circulating cytokine levels and clinical outcomes in patients with heart failure (HF) following acute myocardial infarction (AMI). BACKGROUND: Persistent inflammation plays a role in the development of HF, and various inflammatory cytokines predict cardiovascular events in acute coronary syndromes. METHODS: We measured plasma levels of interleukin (IL)-6, monocyte chemotractant protein 1, IL-10, and soluble tumor necrosis factor receptor type 1 (sTNFR1) during longitudinal testing over a period of two years in 234 patients with HF following AMI recruited for participation in the OPTIMAAL trial, focusing on the possible prognostic value of circulating cytokine levels in these patients. RESULTS: Measurement of sTNFR1 at baseline predicted all-cause mortality and cardiovascular death in patients with post-MI HF after adjustment for other biomarkers that have been shown to give prognostic information in HF patients, such as N-terminal B-type natriuretic peptide. CONCLUSIONS: Assessment of sTNFR1 levels might provide important prognostic information in patients who develop HF during the acute phase following AMI.

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PubMed2005

The impact of morbid events on survival following hospitalization for complicated myocardial infarction.

BACKGROUND: Little is known about the importance of morbid events with respect to longer term survival following MI hospital discharge. AIMS: Establish the risk of death associated with morbid events following initial discharge from MI hospitalization. METHODS: We examined the rates of morbid events (reinfarction, stroke/TIA, revascularization, heart failure (HF) hospitalization, cardiovascular hospitalization and all-cause hospitalization) and the relationships of these events to subsequent death in patients who survived the initial hospitalization for MI (n = 5301) in the OPTIMAAL trial. Events were classified as Early (< or = 30 days post discharge) and Late (> 30 days post discharge) for an average of 2.7 years follow-up. RESULTS: Death rates were higher in the Early period (0.20 deaths/patient year) than in the Late period (0.05 deaths/patient year). Once a morbid event, excluding revascularization, occurred, the acute hazard ratios (HR, determined by Cox regression) for death on the day of event were higher than at time periods following the event and were highest for reinfarction and stroke/TIA. The acute HRs for death for all 6 morbid events were especially high for events occurring during the Late period. The highest chronic HR for death was associated with HF and all-cause hospitalizations. By contrast, the chronic HR for death from revascularization in both the Early (HR = 0.3) and Late (HR = 0.4) period indicated reduced risk. CONCLUSIONS: The results document event rates following hospitalization for MI, provide quantification of the associated risk for death, and may be useful in designing clinical trials. The serious morbid events examined may serve as potential surrogate endpoints in long-term studies and identify patients that should be targeted for aggressive management.

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PubMed2005

Diagnosis and assessment of the heart failure patient: the cornerstone of effective management.

Heart Failure is a syndrome describing a pathophysiological state with diverse etiologies. Providing an adequate mechanistic definition is difficult. The current guidelines from the European Society of Cardiology define the diagnosis of heart failure based on three criteria. Patients should have symptoms compatible with heart failure at rest or on exercise. There should be objective evidence of cardiac dysfunction at rest. In doubtful cases, there should be a favourable response following therapy for heart failure. The term diagnosis derives from the Greek words "dia" and "nosi" meaning "through knowledge". It implies that a conclusion is drawn describing the patient's current status based on the available information. This information is commonly based on the symptoms, history, findings at physical examination, results from laboratory tests, and the results from various non-invasive and invasive special examinations. Diagnostic precision is crucial in deciding treatment strategy and this task presents a continuous academic and clinical challenge. Ultimately, the clinical diagnosis of heart failure is based on all the information available to the physicians. No single investigation is specific for this clinical syndrome and management strategies attempt to modify the underlying mechanisms in order to alleviate symptoms and improve survival.

Clinical Laboratory Techniques↗
PubMed2005

Soluble CD40 ligand in acute and chronic heart failure.

AIMS: Inflammatory cytokines may play a pathogenic role in heart failure (HF). CD40-CD40 ligand (CD40L) interactions are important in atherogenesis and based on its role in inflammation we sought to evaluate the role of CD40L in human HF. METHODS AND RESULTS: Serum levels of soluble (s) CD40L were measured in 236 patients with acute HF following myocardial infarction, treated with either angiotensin-converting enzyme (ACE)-inhibition or angiotensin II blockade and followed for 2 years, and in 116 patients with chronic HF. Our main findings were: (i) patients with acute HF had increased sCD40L levels, particularly those with severe HF, diabetes, or hypertension; (ii) when these patients were followed longitudinally, persistently raised sCD40L levels were found throughout the observation period with no effect of captopril or losartan; (iii) the increase in sCD40L during follow-up was not seen in patients receiving warfarin therapy; (iv) patients with chronic HF also had raised sCD40L, significantly correlated with clinical severity, neurohormonal dysregulation, and left ventricular dysfunction; (v) studies from different blood compartments suggest that the vasculature of lower extremities and the failing myocardium itself may produce and secrete sCD40L in chronic HF. CONCLUSION: Our findings may suggest a pathogenic role for enhanced CD40-CD40L interactions in human HF.

Acute Disease↗
PubMed2005

Comparison of losartan and captopril on heart failure-related outcomes and symptoms from the losartan heart failure survival study (ELITE II).

BACKGROUND: Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors improves outcomes and symptoms in patients with heart failure (HF). We compared effects of losartan to captopril on mortality, morbidity, and functional status for patients in the ELITE II study. METHODS AND RESULTS: A total of 3152 patients, aged 60 years or older, with New York Heart Association (NYHA) classes II to IV HF and ejection fraction < or = 40% were assigned to receive losartan 50 mg once daily or captopril 50 mg 3 times daily. Outcome measures included all-cause and HF-related mortality, hospitalizations, and discontinuations; change in NYHA class; and quality of life (QoL). HF-related outcomes were not significantly different between therapies. Similar improvements from baseline (P < .01) in NYHA class were observed within both treatment groups. Among 1856 QoL participants, 1343 patients survived at least 1 year; the QoL for 1-year survivors improved in both treatment groups (P < .001 vs baseline) and did not differ between groups. CONCLUSIONS: In ELITE II, the effects of losartan on HF-related outcomes, NYHA class, and QoL were not superior to those of captopril. Although angiotensin-converting enzyme inhibitors remain the treatment of choice for patients with HF, the similarity of the findings in the present analysis supports a role for angiotensin-receptor antagonists in this patient population.

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PubMed2005

Recurrent infarction causes the most deaths following myocardial infarction with left ventricular dysfunction.

PURPOSE: The development of left ventricular systolic dysfunction or heart failure following an acute myocardial infarction (MI) is a powerful marker of an adverse prognosis. Recurrent MI could be an important cause of death, either directly or by provoking arrhythmias. METHODS: The OPTIMAAL trial randomized 5477 patients with heart failure or evidence of left ventricular dysfunction following acute MI to losartan or captopril. Over a follow-up of 2.7 years, there were 946 deaths. Of the 180 (19%) of these deaths for which autopsy reports were available, acute MI was found in 57% (102 of 180) of the autopsies. By comparison, an endpoints adjudication committee using clinical data attributed death to acute MI in only 29 cases. An acute MI was found at autopsy in 55% (37 of 67) of the deaths that had been classified as due to an arrhythmia and in 81% (21 of 26) of the deaths classified as due to progressive heart failure. Including autopsy diagnoses, the rate of acute MI in patients who died suddenly was independent of the time elapsed since the index MI, but in patients not classified as dying suddenly, there was a time-related decrease in recurrent MI from 78% in the first 30 days to 30% by the end of follow-up. However, only 19% of patients who died underwent autopsy, so recurrent MI may have been substantially more common and perhaps had a different relation to time since the index MI if more patients had undergone autopsy. CONCLUSIONS: In patients with evidence of major cardiac dysfunction after MI, recurrent MI found at autopsy is common and has often not been clinically detected.

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PubMed2005

Plasma natriuretic peptides up to 2 years after acute myocardial infarction and relation to prognosis: an OPTIMAAL substudy.

BACKGROUND: Few studies have compared the relative prognostic value of different natriuretic peptides after acute myocardial infarction (AMI). None has described peptide levels beyond the early post-AMI period. This study describes temporal profiles of 4 natriuretic peptides to 2 years after AMI and relationship with outcome. METHODS AND RESULTS: We assessed profiles of N-terminal proANP (N-ANP), B-type natriuretic peptide (BNP), N-terminal proBNP (N-BNP), and C-type natriuretic peptide (CNP) (study entry, 1 month, 1 year, and 2 years) in 236 patients with AMI complicated by clinical or radiologic evidence of heart failure. We assessed the prognostic value for baseline levels of each peptide for death or reinfarction. We observed distinct natriuretic peptide profiles. BNP and N-BNP levels were highest at baseline and fell thereafter. N-ANP levels increased from baseline to 30 days and fell thereafter. During follow-up (mean 938 days), 34 patients died and a further 25 suffered nonfatal AMI. Baseline natriuretic peptide levels did not have independent predictive power for outcome. N-BNP levels fell from baseline to 30 days in patients surviving to the end of follow-up (P = .005) but were similar at both times (P = .76) for those dying after 30 days. Age (P < .0005) and change in N-BNP from baseline to 30 days (P = .026) had independent predictive value for death after 30 days. CONCLUSION: N-ANP, BNP, N-BNP, and CNP show distinct plasma profiles after AMI. Failure of plasma N-BNP to fall in the 30 days after AMI indicates adverse prognosis.

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PubMed2004

Prognostic risk of atrial fibrillation in acute myocardial infarction complicated by left ventricular dysfunction: the OPTIMAAL experience.

AIMS: The present study aimed to determine the frequency and the impact on clinical outcome of atrial fibrillation (AF) in patients with acute myocardial infarction (AMI) and left ventricular dysfunction. METHODS AND RESULTS: In the OPTIMAAL trial, 5477 patients with AMI and signs of left ventricular dysfunction were included. At baseline, 655 patients (12%) had AF, and 345 (7.2%) developed new-onset AF during follow-up (2.7 +/- 0.9 years). Older patients, patients with history of angina and worse Killip class had and developed AF more frequently (P < 0.001). Patients with AF at baseline were at increased risk relative to those without AF for mortality [adjusted hazard ratio (HR) of 1.32, P = 0.001] and for stroke (HR 1.77, P < 0.001). New-onset AF was associated with increased subsequent mortality for the first 30 days following randomization (HR 3.83, P < 0.001) and the entire trial period (HR 1.82, P < 0.001). Risk of stroke was increased for the first 30 days (HR 14.6, P < 0.001) and for the whole trial period (HR 2.29, P < 0.001). CONCLUSION: AF is frequently observed in patients with AMI complicated by heart failure. Current AF, and the development of new AF soon after AMI, is associated with increased risk of death and stroke.

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PubMed2004

Prognostic value of osteoprotegerin in heart failure after acute myocardial infarction.

OBJECTIVES: We sought to determine the relationship between osteoprotegerin (OPG) and clinical outcomes in patients with heart failure (HF) after acute myocardial infarction (AMI). BACKGROUND: Arterial calcification is a prominent feature of arterial atherosclerosis and is associated with the occurrence of AMI. Osteoprotegerin is a recently discovered member of the tumor necrosis superfamily that may link the skeletal with the vascular system. METHODS: We assayed plasma OPG levels in 234 patients with AMI complicated with HF and their relation to adverse outcomes during follow-up in patients randomly assigned to angiotensin-converting enzyme inhibition or angiotensin II antagonism. Blood was sampled at baseline (median three days after AMI), one month, and at one and two years. RESULTS: Elevated plasma levels of OPG at baseline were associated with adverse outcomes during a median of 27 months follow-up; OPG remained an independent prognostic indicator also after adjustment for other known predictors of mortality and cardiovascular events after AMI (e.g., creatinine clearance, N-terminal B-type natriuretic peptide, high-sensitivity C-reactive protein). In non-survivors, plasma OPG levels were persistently elevated during longitudinal testing, suggesting that OPG may be of value for monitoring patients at risk. CONCLUSIONS: Osteoprotegerin is a novel marker for cardiovascular mortality and clinical events in patients with AMI complicated with HF. These findings are compatible with the hypothesis suggesting a possible association between mediators of bone homeostasis and cardiovascular disease.

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PubMed2004

Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction.

BACKGROUND: The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction. Renal failure is associated with one of the highest risks, but the influence of milder degrees of renal impairment is less well defined. METHODS: As part of the Valsartan in Acute Myocardial Infarction Trial (VALIANT), we identified 14,527 patients with acute myocardial infarction complicated by clinical or radiologic signs of heart failure, left ventricular dysfunction, or both, and a documented serum creatinine measurement. Patients were randomly assigned to receive captopril, valsartan, or both. The glomerular filtration rate (GFR) was estimated by means of the four-component Modification of Diet in Renal Disease equation, and the patients were grouped according to their estimated GFR. We used a 70-candidate variable model to adjust and compare overall mortality and composite cardiovascular events among four GFR groups. RESULTS: The distribution of estimated GFR was wide and normally shaped, with a mean (+/-SD) value of 70+/-21 ml per minute per 1.73 m2 of body-surface area. The prevalence of coexisting risk factors, prior cardiovascular disease, and a Killip class of more than I was greatest among patients with a reduced estimated GFR (less than 45.0 ml per minute per 1.73 m2), and the use of aspirin, beta-blockers, statins, or coronary-revascularization procedures was lowest in this group. The risk of death or the composite end point of death from cardiovascular causes, reinfarction, congestive heart failure, stroke, or resuscitation after cardiac arrest increased with declining estimated GFRs. Although the rate of renal events increased with declining estimated GFRs, the adverse outcomes were predominantly cardiovascular. Below 81.0 ml per minute per 1.73 m2, each reduction of the estimated GFR by 10 units was associated with a hazard ratio for death and nonfatal cardiovascular outcomes of 1.10 (95 percent confidence interval, 1.08 to 1.12), which was independent of the treatment assignment. CONCLUSIONS: Even mild renal disease, as assessed by the estimated GFR, should be considered a major risk factor for cardiovascular complications after a myocardial infarction.

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PubMed2004

Effect of single doses of SLV306, an inhibitor of both neutral endopeptidase and endothelin-converting enzyme, on pulmonary pressures in congestive heart failure.

SLV306, a potent neutral endopeptidase (NEP) inhibitor with additional endothelin-converting enzyme (ECE)-inhibitory activity, in doses of 200, 400, and 800 mg reduced pulmonary and right atrial pressures, although there was not a clear dose response. Systemic blood pressure, heart rate, and cardiac output were unaffected. SLV306 increased plasma natriuretic peptides and big endothelin-1 levels in a dose-dependent manner, confirming NEP and ECE inhibition. The combined inhibition of NEP and ECE may be useful in heart failure by reducing right and left cardiac filling pressures.

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