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Biomedical subjects

K Dickstein

Publications and source records attributed to K Dickstein.

At least 37 records · Page 2Linked to original sources
PubMed2000

The effects of moxonidine, a novel imidazoline, on plasma norepinephrine in patients with congestive heart failure. Moxonidine Investigators.

OBJECTIVE: To evaluate the dose response relationship of moxonidine on plasma concentration of norepinephrine during acute and chronic administration in patients with congestive heart failure (CHF). BACKGROUND: Sympathetic activation is increased in heart failure. Moxonidine is an imidazoline ligand acting on the central nervous system (CNS) receptors to decrease sympathetic activation. METHODS: Ninety-seven patients with heart failure and New York Heart Association class II-III symptoms and ejection fraction <40% were randomized to placebo or one of three target doses of moxonidine, 0.1, 0.2 or 0.3 mg administered twice daily. An initial dose of moxonidine 0.1 mg twice a day (b.i.d.) was followed by weekly increments of 0.1 mg b.i.d. until target dose. The second and third study days occurred after four weeks (at target dose) and after 12 weeks, respectively. At each study day, repeated blood samples were drawn. RESULTS: There was a significant dose-related decrease of systolic blood pressure across all three study days. Heart rate decreased significantly on study day 3 in a dose-related manner. The acute 2 h decrease in plasma norepinephrine in response to all three doses of moxonidine was significantly different compared with placebo after four and 12 weeks. There was a significant linear relation between dose and plasma norepinephrine after four and 12 weeks in both 2 h peak and the time averaged effect (>8 h). The number of adverse events was similar in the moxonidine and placebo groups. CONCLUSIONS: The increased sympathetic activation in CHF can be reduced by moxonidine through CNS inhibition.

Administration, Oral↗
PubMed2000

Pharmacotherapy following myocardial infarction--a review of current treatment practices.

Modern treatment of acute myocardial infarction (AMI), including thrombolysis and early interventional strategies, has reduced mortality rates but increased the number of patients requiring medical treatment. Post infarction treatment with aspirin, statins, beta-blockers and angiotensin-converting enzyme (ACE) inhibitors has improved morbidity and mortality and is cost-effective. The major successes of secondary prevention have been seen in the prevention of reinfarction, recurrent ischaemia and the development of heart failure. However, in spite of recent advances and increasing knowledge, the mortality rates remain high, partly due to the under use of the established and documented medical strategies. Implementation of the current treatment strategies into general practice remains a challenge. The field is undergoing rapid change due to the increasing use of early invasive strategies. The primary objective should remain the prevention of underlying aetiology: coronary artery disease (CAD). Secondary prevention following myocardial infarction (MI) will remain a major challenge in clinical practice within the foreseeable future.

Adrenergic beta-Antagonists↗
PubMed1999

[Chronic heart failure--suggestion to a management program].

In 1994, a Norwegian programme for diagnosis and treatment of chronic heart failure was published. Recently the American College of Cardiology, the American Heart Association and the Task Force on Heart Failure of the European Society of Cardiology have published similar guidelines. In this article, the Working Group on Heart Failure of the Norwegian Society of Cardiology presents an updated programme for evaluation and management of patients with chronic heart failure.

Adrenergic beta-Antagonists↗
PubMed1999

Acute hemodynamic and neurohumoral effects of moxonidine in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Elevated plasma norepinephrine (PNE) has been shown to be an important predictor of morbidity and mortality in patients with congestive heart failure (CHF). Moxonidine selectively stimulates imidazoline receptors located in the medulla, which centrally inhibit sympathetic outflow. PNE is suppressed and peripheral vasodilation reduces systemic blood pressure. This study evaluated the acute neurohumoral and hemodynamic effects of a single dose of oral moxonidine in 32 patients (22 men, mean +/- SD age 66 +/- 10 years) with CHF. All patients were in New York Heart Association functional class III and stabilized on chronic therapy with diuretics, digitalis, and angiotensin-converting enzyme inhibitors. The mean PNE concentration was 509 +/- 304 pg/ml at baseline. Patients underwent invasive hemodynamic monitoring after double-blind randomization to either placebo (n = 12), moxonidine 0.4 mg (n = 9), or moxonidine 0.6 mg (n = 11). Moxonidine produced a dose-dependent, vasodilator response compared with placebo. Analysis of the time-averaged change from baseline over 6 hours demonstrated that moxonidine 0.6 mg caused significant reductions in mean systemic arterial pressure (p <0.0001), mean pulmonary arterial pressure (p <0.005), systemic vascular resistance (p <0.05), pulmonary vascular resistance (p <0.01), and heart rate (p <0.05). Stroke volume was unchanged. PNE was reduced substantially (-180 pg/ml at 4 hours, p <0.005) and the reduction was highly correlated with the baseline level (r = -0.968). Moxonidine was well tolerated in this single-dose study and resulted in a modest, dose-dependent, vasodilator response, with substantial reductions in systemic and pulmonary arterial blood pressure. Trials designed to evaluate the clinical efficacy of chronic moxonidine therapy in CHF added to conventional therapy would be appropriate.

Administration, Oral↗
PubMed1999

Comparison of the effects of losartan and captopril on mortality in patients after acute myocardial infarction: the OPTIMAAL trial design. Optimal Therapy in Myocardial Infarction with the Angiotensin II Antagonist Losartan.

Patients with acute myocardial infarction and evidence of heart failure or left ventricular dysfunction during the acute phase have an excessive mortality risk. Therapy with angiotensin-converting enzyme inhibitors attenuates the detrimental effects of angiotensin II and has been shown to substantially reduce morbidity and mortality in this population. Selective, angiotensin type 1 receptor antagonism with losartan, which inhibits the effects of angiotensin II regardless of its source at the receptor level, may provide more complete blockade of the renin-angiotensin system. The Optimal Therapy in Myocardial Infarction with the Angiotensin II Antagonist Losartan (OPTIMAAL) study is a multicenter, double-blind, randomized, parallel, captopril-controlled trial. The primary hypothesis is that, compared with captopril, losartan will decrease the risk for all-cause mortality by 20% in high-risk patients after acute myocardial infarction. The study population will consist of 5,000 patients, > or = 50 years of age, with heart failure during the acute phase or with a new Q-wave anterior infarction or reinfarction. Patients will be randomized to treatment with either losartan or captopril. All patients will be followed until 937 deaths occur (event-driven). The primary end point is total mortality (all-cause mortality). The secondary and tertiary end points are sudden death (and/or resuscitated cardiac death) and fatal/nonfatal reinfarction. Based on the assumed event rate, treatment effect and a 95% power to detect a 20% reduction in all-cause mortality at the 4.3% significance level (2-sided, adjusted for 2 interim analyses), the trial will enroll at least 5,004 patients and continue until a total number of 937 events has been reached (intention-to-treat analysis).

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Effects of losartan versus captopril on mortality in patients with symptomatic heart failure: rationale, design, and baseline characteristics of patients in the Losartan Heart Failure Survival Study--ELITE II.

BACKGROUND: In the Evaluation of Losartan in the Elderly (ELITE) heart failure study, a survival benefit (primarily because of a reduction in sudden deaths) was observed in symptomatic patients treated with losartan compared with captopril. METHODS AND RESULTS: The Losartan Heart Failure Survival Study--ELITE II (currently ongoing) is a double-blind, randomized clinical trial being conducted in 45 countries at 288 sites. ELITE II formally tests the hypotheses that losartan, compared with captopril, will reduce all-cause mortality (primary end point) and sudden cardiac death and/or resuscitated cardiac arrest (secondary end point). In addition, all-cause mortality and/or hospitalizations and cardiovascular mortality and/or hospitalizations will be evaluated. The trial has 90% power to detect a 25% treatment difference in all-cause mortality (event driven, 510 deaths). Substudies are examining quality of life, health care resource utilization, and mechanisms related to the reduction in sudden death. During recruitment (June 1997 to May 1998), 3,152 patients aged 60 years or older (mean age, 71.6 years), with New York Heart Association classes II (51%), III (44%), and IV (5%), and left ventricular ejection fraction of 40% or less (mean, 31%) were randomized to receive either 12.5 mg of losartan, titrated as tolerated to 50 mg once daily, or 12.5 mg of captopril, titrated as tolerated to 50 mg thrice daily. Randomization was stratified by clinical site and for baseline beta-blocker use. CONCLUSION: The ELITE II study will further define the role of losartan in the treatment of patients with symptomatic heart failure relative to the angiotensin-converting enzyme inhibitor captopril, an agent from a class currently considered standard treatment for this disease.

Aged↗
PubMed1998

Plasma N-terminal atrial natriuretic peptide predicts hospitalization in patients with heart failure.

The plasma concentration of N-terminal atrial natriuretic peptide (N-ANP) has been shown to be predictive of both clinical status and survival in patients with heart failure. In this analysis the relationship between N-ANP, morbidity and hospitalization time was evaluated in 417 patients with stable, congestive heart failure recruited from an active, outpatient heart failure registry. Hospital admissions along with the duration of stay occurring after the initial N-ANP sampling during the period of data collection were recorded. A total of 755 admissions occurred, accounting for 7917 days' hospitalization. Relative hospitalization times (in-hospital days/observation period) per N-ANP quartiles I-IV were: 1.2 (+/- 2.7)%, 5.5 (+/- 12.2)%, 10.0 (+/- 21.5)% and 20.8 (+/- 34.3)%, respectively. Although N-ANP levels were correlated with age (r = 0.234, p < 0.0001), division by age quartiles did not significantly predict relative hospitalization times. These data indicate that the degree of cardiac endocrine activation and subsequent N-ANP release is related to morbidity in patients with heart failure and that moderate elevation in N-ANP levels is associated with a substantially increased hospitalization time. N-ANP sampling should be of value as a supplement to clinical evaluation in the assessment of the individual patient with this common syndrome.

Aged↗
PubMed1998

Cardiac troponins I and T in patients with suspected acute coronary syndrome: a comparative study in a routine setting.

We compared cardiac troponin I (cTnI), using Access, Sanofi Pasteur, and cardiac troponin T (cTnT), using Elecsys, Boehringer Mannheim, in the first two routine blood samplings in a routine panel of cardiac markers for the biochemical diagnostic evaluation of patients with symptoms of acute myocardial infarction (AMI). No significant differences in the overall clinical performances of cTnI and cTnT were observed for the diagnosis of AMI (n = 68), but cTnI demonstrated lower initial sensitivity and higher specificity compared with cTnT. cTnT was increased to higher relative values than cTnI (P = 0.023). Discordances were found between cTnI and cTnT in sample I but not in sample II; positive cTnT/negative cTnI was more common than the opposite discordance (P = 0.027). cTnT was more frequently increased in patients with unstable angina pectoris (UAP) than cTnI (P = 0.038), with no significant differences between sample I and sample II; discordant results with respect to cTnI and cTnT appeared in 6 (33%) of these patients, all of which were positive for cTnT and negative for cTnI. Four patients with UAP (22%) developed AMI within 4 months; three were associated with increased cTnI and cTnT at the time of initial testing, and one was discordant (positive cTnT). In patients classified with no acute coronary syndrome (n = 84), five concordant positives for cTnI and cTnT were observed, indicating the existence of a myocardial injury of recent origin in these patients. AMI evolved in one of these patients 5 months later. We conclude that cTnT and cTnI detect acute myocardial injury with equal clinical performance in AMI patients classified by WHO criteria. cTnT was more frequently increased in patients with UAP than cTnI, but the clinical significance of this discordance could not be determined from this study.

Acute Disease↗
PubMed1997

[Calcium channel blockers in heart failure].

Patients with heart failure are particularly susceptible to the negative effects of calcium channel blockers because the failing heart demonstrates a defect in the delivery of calcium to the contractile proteins, and an attenuation of the normal sympathetic reflexes. Currently these drugs have no place in the treatment of heart failure caused by systolic dysfunction of the left ventricle. Calcium channel blockers should probably not be described for patients with coronary artery disease and left ventricular dysfunction. When the patient needs additional treatment for angina and beta-blockers or nitrates have not given satisfactory results, it may be appropriate to prescribe amlodipine or felodipine.

Calcium Channel Blockers↗
PubMed1997

[Treatment of heart failure with beta-blockaders].

Since 1975 several studies have indicated that treatment with beta-adrenergic blocking drugs has a positive effect on prognosis in patients with left ventricular dysfunction. After myocardial infarction, treatment with timolol and propranolol improves prognosis in patients with symptoms of cardiomegaly and heart failure. In patients with idiopathic dilated cardiomyopathy, treatment with metoprolol improves the left ventricular ejection fraction and symptoms of heart failure, and may have a positive effect on prognosis. Recent studies of patients with chronic congestive heart failure also indicate that carvedilol has a positive effect on mortality and morbidity. The authors review some relevant studies, to stimulate the use of beta-adrenergic blocking drugs to treat certain types of heart failure.

Adrenergic beta-Antagonists↗
PubMed1997

Comparison of the degree of hemodynamic tolerance during intravenous infusion of nitroglycerin versus nicorandil in patients with congestive heart failure.

BACKGROUND: Continuous exposure to organic nitrates is associated with substantial tachyphylaxis. This study compares the development of tolerance during continuous intravenous treatment with nitroglycerin versus nicorandil over a 24-hour period. METHODS AND RESULTS: Twenty patients with congestive heart failure and pulmonary capillary wedge pressure (PCWP) > or = 18 mm Hg were randomly assigned to nitroglycerin or nicorandil in a double-blind, crossover study. Doses were titrated to obtain a reduction of PCWP of at least 30% and then maintained. The mean pretreatment PCWP for nitroglycerin was 25.4 +/- 6.7 mm Hg, decreasing to 19.0 +/- 6.8 mm Hg at 24 hours. The values for nicorandil were 24.3 +/- 6.3 mm Hg and 15.6 +/- 4.5 mm Hg, respectively. Between-treatment difference was significant (p < 0.01). The difference between the minimal PCWP value and the 24-hour PCWP value for nitroglycerin was 5.1 mm Hg vs 1.4 mm Hg for nicorandil (p < 0.005). The mean systemic vascular resistance was 1418 +/- 355 dynes.sec.cm-5 before nitroglycerin infusion, decreasing to 1312 +/- 353 dynes.sec.cm-5 at 24 hours. Corresponding values for nicorandil were 1420 +/- 366 dynes.sec.cm-5 and 967 +/- 274 dynes.sec.cm-5. Between-treatment difference was significant (p = 0.005). Tachyphylaxis developed in 12 (60%) patients during nitroglycerin infusion versus three patients (15%) during nicorandil infusion. CONCLUSION: This study demonstrates that intravenous nicorandil administration results in significantly less hemodynamic tolerance over a 24-hour period compared with nitroglycerin. This finding may represent a clinical advantage for nicorandil in the short-term treatment of patients with congestive heart failure.

Aged↗
PubMed1997

Effects of angiotensin II receptor blockade on N-terminal proatrial natriuretic factor plasma levels in chronic heart failure.

BACKGROUND: Plasma N-terminal proatrial natriuretic factor (N-terminal proANF) has been shown to reflect intraatrial pressures in heart failure patients, and may be used as a biochemical parameter of atrial pressures. It is still unclear how treatment of heart failure influences the relationship between hemodynamic parameters and plasma levels of N-terminal proANF. METHODS AND RESULTS: This double-blind, placebo-controlled study investigated whether 12 weeks of treatment with the angiotensin II receptor blocker losartan influenced N-terminal proANF plasma levels in 129 chronic heart failure patients. After 12 weeks of treatment, N-terminal proANF level was increased in patients given placebo by 344 +/- 1126 pmol/L, whereas in patients given 50 mg losartan, the levels had decreased by 251 +/- 886 pmol/L (P < .01 vs placebo). The change in N-terminal proANF correlated significantly with the corresponding change in pulmonary capillary wedge pressure (r = .53, P < .001). CONCLUSION: The correlation between N-terminal proANF plasma levels and pulmonary capillary wedge pressure at baseline, as well as the correlation between the changes in these parameters during treatment, suggests that plasma N-terminal proANF may be used to monitor effects on left ventricular filling pressures in patients treated with losartan.

Aged↗