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Biomedical subjects

K Dickstein

Publications and source records attributed to K Dickstein.

At least 19 recordsLinked to original sources

The effect of altering haemodynamics on the plasma concentrations of natriuretic peptides in heart failure.

BACKGROUND: Natriuretic peptide levels reflect haemodynamics in patients with heart failure and may serve as biochemical markers of cardiac filling pressures. The purpose of this study was to detect differences in the kinetic profile between atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and their N-terminal fragments N-ANP and N-BNP, in response to rapid and persistent vasodilatation. METHODS: Sixteen men and four women aged 63.0+/-10.4 (mean+/-S.D.) with symptomatic congestive heart failure (NYHA III) and pulmonary capillary wedge pressure (PCWP)>18 mm Hg, received a 24-h infusion of nitroglycerin (N=8) or nicorandil (N=12). A reduction of PCWP was achieved for the duration of the study. Natriuretic peptides were measured by radioimmunoassay at baseline, 1, 3, 6, 12 and 24 h. RESULTS: PCWP and right atrial pressure fell rapidly and then increased modestly. ANP and N-ANP demonstrated a similar pattern. In contrast, BNP and N-BNP levels fell steadily throughout the observation period. This was accompanied by a continuous reduction of systemic vascular resistance (SVR). PCWP was highly correlated to the levels of all the natriuretic peptides. Using a longitudinal regression model evaluating responses over time, we found separate, significant relationships between all peptides and haemodynamic variables CONCLUSION: The atrial natriuretic peptides reflect rapid changes in filling pressures while the B-type peptides respond much slower. B-type peptides are less sensitive to short-term changes in filling pressures, but should reflect changes in SVR better during vasodilator therapy.

Cardiac Output, Low↗

Rapid implementation of therapeutic hypothermia in comatose out-of-hospital cardiac arrest survivors.

BACKGROUND: The implementation of therapeutic hypothermia (TH) into daily clinical practice appears to be slow. We present our experiences with rapid implementation of a simple protocol for TH in comatose out-of-hospital cardiac arrest (OHCA) survivors. METHODS: From June 2002, we started cooling pre-hospitally with sport ice packs in the groin and over the neck. In the intensive care unit (ICU), we used ice-water soaked towels over the torso. All patients were endotracheally intubated, on mechanical ventilation and sedated and paralysed. The target temperature was 33 +/- 1 degrees C to be maintained for 12-24 h. We used simple inclusion criteria: (i) no response to verbal command during the ambulance transport independent of initial rhythm and cause of CA; (ii) age 18-80 years; and (iii) absence of cardiogenic shock (SBP < 90 mmHg despite vasopressors). We compared the first 27 comatose survivors with a presumed cardiac origin of their OHCA with 34 historic controls treated just before implementation. RESULTS: TH was initiated in all 27 eligible patients. The target temperature was reached in 24 patients (89% success rate). ICU- and hospital- length of stay did not differ significantly before and after implementation of TH. Hypokalemia (P= 0.001) and insulin resistance (P= 0.025) were more common and seizures (P= 0.01) less frequently reported with the use of TH. The implementation of TH was associated with a higher hospital survival rate (16/27; 59% vs. 11/34; 32%, respectively; P< or = 0.05). Our results indicate a population-based need of approximately seven cooling patients per 100,000 person-years served. CONCLUSION: Our simple, external cooling protocol can be implemented overnight in any system already treating post-resuscitation patients. It was well accepted, feasible and safe, but not optimal in terms of cooling rate. Neither safety concerns nor costs should be a barrier for implementation of TH.

Adult↗

Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity.

AIMS: Patients with diabetes have an unfavourable prognosis after an acute myocardial infarction. In the first DIGAMI study, an insulin-based glucose management improved survival. In DIGAMI 2, three treatment strategies were compared: group 1, acute insulin-glucose infusion followed by insulin-based long-term glucose control; group 2, insulin-glucose infusion followed by standard glucose control; and group 3, routine metabolic management according to local practice. METHODS AND RESULTS: DIGAMI 2 recruited 1253 patients (mean age 68 years; 67% males) with type 2 diabetes and suspected acute myocardial infarction randomly assigned to groups 1 (n=474), 2 (n=473), and 3 (n=306). The primary endpoint was all-cause mortality between groups 1 and 2, and a difference was hypothesized as the primary objective. The secondary objective was to compare total mortality between groups 2 and 3, whereas morbidity differences served as tertiary objectives. The median study duration was 2.1 (interquartile range 1.03-3.00) years. At randomization, HbA1c was 7.2, 7.3, and 7.3% in groups 1, 2, and 3, respectively, whereas blood glucose was 12.8, 12.5, and 12.9 mmol/L, respectively. Blood glucose was significantly reduced after 24 h in all groups, more in groups 1 and 2 (9.1 and 9.1 mmol/L) receiving insulin-glucose infusion than in group 3 (10.0 mmol/L). Long-term glucose-lowering treatment differed between groups with multidose insulin (> or =3 doses/day) given to 15 and 13% of patients in groups 2 and 3, respectively compared with 42% in group 1 at hospital discharge. By the end of follow-up, HbA1c did not differ significantly among groups 1-3 ( approximately 6.8%). The corresponding values for fasting blood glucose were 8.0, 8.3, and 8.6 mmol/L. Hence, the target fasting blood glucose for patients in group 1 of 5-7 mmol/L was never reached. The study mortality (groups 1-3 combined) was 18.4%. Mortality between groups 1 (23.4%) and 2 (22.6%; primary endpoint) did not differ significantly (HR 1.03; 95% CI 0.79-1.34; P=0.831), nor did mortality between groups 2 (22.6%) and 3 (19.3%; secondary endpoint) (HR 1.23; CI 0.89-1.69; P=0.203). There were no significant differences in morbidity expressed as non-fatal reinfarctions and strokes among the three groups. CONCLUSION: DIGAMI 2 did not support the fact that an acutely introduced, long-term insulin treatment improves survival in type 2 diabetic patients following myocardial infarction when compared with a conventional management at similar levels of glucose control or that insulin-based treatment lowers the number of non-fatal myocardial reinfarctions and strokes. However, an epidemiological analysis confirms that the glucose level is a strong, independent predictor of long-term mortality in this patient category, underlining that glucose control seems to be an important part of their management.

Aged↗

Exercise training in congestive heart failure. A review of the current status.

Traditionally exercise training was considered contraindicated in heart failure patients. However, during the last 15 years numerous small studies have demonstrated that training is safe in stable heart failure patients and that this intervention improves quality of life in this population. The beneficial effects include improved autonomic balance, reduced neurohumoral activation and reduced inflammatory response in addition to the direct effect on exercise capacity. Pooling of the available data from small randomized studies confirms the positive effect of training on morbidity, and also suggests that this type of intervention improves survival. Large scale studies are on-going to confirm the beneficial effects of training on mortality. This paper reviews the effects of exercise training in patients with the syndrome of heart failure and discusses the different types of training protocols and the tools for assessing the training effect in this population.

Clinical Protocols↗

The added value of spiral computed tomographic angiography after lung scintigraphy for the diagnosis of pulmonary embolism.

OBJECTIVES: The objectives of this study were to evaluate the added clinical value of spiral computed tomographic angiography (CTA) after ventilation-perfusion lung scintigraphy (V/Q) for the management of patients with suspected pulmonary embolism (PE). METHODS: Of 987 patients who had V/Q during 2001, 64 patients (6%) had CTA performed for further evaluation. V/Q and CTA findings were retrospectively analyzed by 2 clinicians who were blinded to the patients' outcome. Patient management was determined based on clinical and V/Q data and was reassessed after the addition of CTA data. RESULTS: CTA was performed in 2 patients with normal V/Q, 16 patients with low probability, 28 patients with intermediate, 4 patients with high probability, and 14 patients with nonconclusive V/Q. Three patients (19%) with low probability, 9 (32%) with intermediate probability, 4 (29%) with nonconclusive, and 4 (100%) with high probability V/Q had PE diagnosed by CTA. CTA findings changed the management in 2 patients (13%) with low probability, 15 (54%) with intermediate probability, and 4 (29%) with nonconclusive V/Q. CONCLUSION: In our institution, V/Q remains the main imaging modality for evaluation of patients with clinically suspected PE. CTA was performed after V/Q in 6% of patients. Patients with intermediate probability and those with nonconclusive V/Q, and to a much lesser extent, patients with low probability V/Q could benefit from the addition of CTA after V/Q. In patients with normal V/Q and those with high-probability V/Q, the addition of CTA does not seem to influence patient management.

Adolescent↗

Characteristics and prognostic impact of plasma fibrin monomer (soluble fibrin) in patients with coronary artery disease.

We measured fibrin monomer (FM), soluble fibrin, as a marker of thrombin activity in plasma samples obtained in parallel with the first two routine samples for cardiac markers in 165 patients with acute chest pain admitted consecutively to our hospital. A reference limit of FM in a healthy population was set at 3.0 mg/l. Elevated plasma FM was observed in 48.8% of patients with acute coronary syndromes, in 42.3% of patients with specific non-coronary disease, in 31.5% of those with stable angina pectoris and in 18.2% of patients with non-specific chest pain. No significant difference was observed between sample 1 and sample 2 in patients not receiving thrombolytic treatment during the sampling period (P = 0.46). In patients with coronary artery disease, FM was significantly related to the level of cardiac troponin T (P = 0.001), but no correlation was observed between the individual plasma FM and cardiac troponin T values. Outcome analysis during the following 30 months after the index event in patients with acute coronary syndromes revealed higher FM levels in those with coronary re-events or death than in patients without new events (P = 0.001). This observation indicates a prognostic potential of FM in risk evaluation of patients with coronary artery disease.

Adult↗

Comparison of baseline data, initial course, and management: losartan versus captopril following acute myocardial infarction (The OPTIMAAL Trial). OPTIMAAL Trial Steering Committee and Investigators. Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan.

The OPTIMAAL study was a multicenter, double-blind, randomized, parallel, trial in high-risk patients who were treated early after acute myocardial infarction that compared treatment with an angiotensin-converting enzyme inhibitor (captopril) and a selective angiotensin II antagonist (losartan) on survival and morbidity. A total of 5,477 patients with heart failure during the acute phase or with a new Q-wave anterior infarction or reinfarction were recruited. This study describes the baseline data and initial course of the cohort and compares these data and patient management across countries.

Aged↗

Effect of simvastatin in preventing progression of carotid artery stenosis.

This study examines the effect of simvastatin on progression of carotid artery stenosis and shows that the drug substantially reversed the anticipated disease development. This finding indicates that treatment with simvastatin may reduce the risk for stroke in patients with known carotid artery disease.

Aged↗

Comparison of aqueous and gellan ophthalmic timolol with placebo on the 24-hour heart rate response in patients on treatment for glaucoma.

PURPOSE: Topical beta-blocker treatment is routine therapy in the management of patients with glaucoma. Therapy results in systemic absorption, however, the degree of reduction of resting and peak heart rate has not been quantified. DESIGN: This trial evaluated the effect of placebo, 0.5% aqueous timolol (timolol solution) and a 0.5% timolol suspension that forms a gel on application to the conjunctiva (timolol gellan) on the 24-hour heart rate in patients currently being treated for glaucoma to quantify the reduction in mean heart rate. METHODS: Forty-three Caucasian patients with primary open-angle glaucoma or ocular hypertension with a mean (+/-SD) age of 63 (+/-8) years were randomized and crossed over in a double-masked manner to 14 days of treatment with placebo (morning and evening in both eyes), timolol solution (morning and evening in both eyes), or timolol gellan (morning in both eyes with placebo in the evening). On the 13th day of each period, heart rate was recorded continuously during a typical, ambulant 24-hour period. RESULTS: Both timolol solution and timolol gellan reduced the mean 24-hour heart rate compared with placebo (P < or = .001), and this reduction was most pronounced during the daytime (-7.5% change in mean heart rate, -5.7 beats/min). Timolol gellan showed a numerically but not significantly smaller reduction in 24-hour heart rate, compared with timolol solution. During the night, the mean 12-hour heart rate on placebo and timolol gellan were both significantly less than on timolol solution; the difference between solution and gellan treatments was statistically significant (P = .01). CONCLUSIONS: Both timolol solution and timolol gellan decrease the mean 24-hour heart rate compared with placebo. This response was most pronounced during the active daytime period. These data quantify the modest bradycardia associated with ophthalmic beta-blocker therapy in a typical patient population on therapy for glaucoma. Although exercise performance was not assessed in this trial, reductions of this magnitude should not have substantial clinical consequences.

Adrenergic beta-Antagonists↗

The role of losartan in the management of patients with heart failure.

BACKGROUND: Heart failure places a burden on patients and health care systems worldwide. Although the advent of angiotensin-converting enzyme (ACE) inhibitors markedly improved management of this chronic disorder, treatment is still not optimal, and morbidity and mortality remain high. OBJECTIVE: This review summarizes existing data on losartan, an angiotensin II (AII)-receptor antagonist, and compares its potential role with that of ACE inhibitors in the management of patients with heart failure. METHODS: Relevant primary studies and review articles were identified through a MEDLINE search of the English-language literature for the past 5 years and through examination of the reference lists of the articles so identified. Search terms included, but were not limited to, angiotensin-converting enzyme inhibitors, angiotensin II-receptor antagonists, and losartan. RESULTS: Preclinical and clinical studies of losartan have demonstrated consistent hemodynamic effects (via selective antagonism of the AII type 1 receptor) and a safety profile similar to that of placebo (presumably a reflection of the selective approach to AII blockade). In addition, large-scale end-point studies have shown losartan to have comparable efficacy to ACE inhibitors on a number of morbidity and mortality measures. CONCLUSIONS: There is strong evidence for the broad applicability of AII-antagonists in heart failure and for the use of AII-antagonists in the treatment of a broader population of patients with heart failure, not only those who are unable to tolerate treatment with ACE inhibitors.

Angiotensin Receptor Antagonists↗

Assessing the effect of exercise training in men with heart failure; comparison of maximal, submaximal and endurance exercise protocols.

AIMS: No consensus exists regarding the most appropriate exercise testing protocol for patients with congestive heart failure. This study describes the effect of exercise training on performance using three different protocols (maximal, submaximal and endurance testing) in patients with heart failure. METHODS AND RESULTS: Thirty men (mean age 67+/-8 years) with congestive heart failure in NYHA class III (mean ejection fraction 32+/-5%) were evaluated prior to and following exercise training. A maximal exercise cycle test with gas exchange measurements, a submaximal 6 min walk test and an endurance treadmill test with blood lactate sampling were used to evaluate exercise capacity after 12 weeks of exercise training. There was a 44.6% (P<0.001) increase in work performed during the maximal cycle test, with no significant increase in peak VO(2). The distance covered by the submaximal 6 min walk test increased by 8.1% (P<0.001). Lactate measured as area under the curve during the matched work intensity treadmill endurance test was reduced by 19.5% (P<0.005). CONCLUSION: We demonstrated a significant improvement in maximal, submaximal and endurance exercise capacity following 12 weeks of exercise training in patients with congestive heart failure. Endurance tests may be more sensitive and appropriate when assessing the efficacy of intervention in this population. Specifically, demonstration of reduced lactate production at matched work intensities suggests more efficient work and decreased dependence on anaerobic metabolism following training. Although maximal cycle tests are commonly used in clinical work, submaximal and endurance testing might be preferable for evaluating new treatment regimens in this population as they are easy to perform, are reproducible, and reflect daily tasks better than the maximal cycle test in this population.

Aged↗