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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of heart failure comprises the use of diuretics, vasodilators and inotropic substances. Unloading of the heart and the circulation in hydropic states is classically achieved with diuretics. The retention of salt and water in chronic heart failure requires chronic treatment with diuretics. This mode of treatment is basic to all forms of hydropic heart failure. Inotropic substances such as digitalis glycosides, sympathomimetic amines or phosphodiesterase inhibitors have certain disadvantages: Inotropic stimulation increases energy demand of the working heart muscle. Most of the substances used today increase energy consumption inordinately, thereby decreasing economy of myocardial contraction. This aspect calls for caution in the application of these substances in chronic heart failure, although they seem indispensable (sympathomimetic amines) in acute hypotensive failure and shock. Digitalis glycosides, basically suited for longterm treatment, exert only mild inotropic effects. In addition inotropic stimulation brings with it arrhythmogenic effects. All inotropic substances can induce ventricular arrhythmias already at therapeutic levels. Vasodilating substances have found increasing acceptance as a particularly useful and safe group of drugs for the treatment of heart failure. Nitrates: With the different nitrate compounds and nitrate preparations an effective venodilation with preload reduction can safely be achieved. At higher doses, arteriolar also dilatation can be induced. Although tolerance may be a problem with chronic application, this can be avoided with prudent dosing. The strong venodilating property makes these drugs together with their rapid onset of action ideally suited for the treatment of acute heart failure with pulmonary congestion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of heart failure: status of therapy with vasodilator agents]. 343 15

Changes in circulating catecholamines and transmyocardial catecholamine balance associated with improved left ventricular function were studied in patients with chronic heart failure after treatment with captopril (10 patients) and hydralazine in combination with isosorbide dinitrate (eight patients). Cardiac performance improved in response to both captopril and hydralazine-nitrate treatment. The systemic haemodynamic effects were also qualitatively similar, but the hydralazine-nitrate combination caused a greater increase in cardiac index and heart rate. Captopril did not change arterial adrenaline concentrations (0.63 to 0.60 nmol/l), arterial noradrenaline (4.2 to 3.9 nmol/l), or net transmyocardial noradrenaline release (390 to 317 pmol/min), while hydralazine-nitrate increased arterial adrenaline (0.91 to 1.47 nmol/l) and transmyocardial noradrenaline release (225 to 554 pmol/min). Although both captopril and hydralazine-nitrate treatment improve left ventricular performance in patients with chronic heart failure, hydralazine-nitrate enhances cardiac sympathetic tone and captopril does not. The clinical relevance of these findings, however, is not known.
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PMID:Effects of captopril and a combination of hydralazine and isosorbide dinitrate on myocardial sympathetic tone in patients with severe congestive heart failure. 352 37

In several studies the nitrate effects on central hemodynamics during less than 24 hours have been evaluated in heart failure. Higher doses than in angina have been used. A pronounced response is seen acutely. An attenuation has been reported after 12-24 hours. A relation to continuous (intravenous, transdermal) administration of nitroglycerin has been proposed, but it is not clear. During chronic treatment with ISDN a tolerance is not obvious within 12 weeks. The heart failure patient has a different neurohumoral situation compared to angina patients. This could be one reason for differences in tolerance development during nitrate therapy.
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PMID:Development of tolerance to nitrate therapy in chronic congestive heart failure. 353 80

The Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure was designed to determine whether vasodilator drugs could alter the survival of patients with chronic congestive heart failure treated with digoxin and diuretics. Among the 642 patients entered into the study, 273 were randomly assigned to placebo, 186 were randomly assigned to the combination of hydralazine and isosorbide dinitrate, and 183 patients were randomly assigned to prazosin; all patients were followed for periods ranging from 6 months to 5.7 years. Treatment with hydralazine-nitrate produced a 28% reduction in mortality compared with that in patients receiving placebo (95% confidence interval, 3% to 46%), whereas prazosin exerted no apparent beneficial effect. Data were further examined to determine if any baseline variables had an impact on the response to treatment. Mortality in the placebo group was higher in those with coronary artery disease, with a history of antiarrhythmic drug use, and with values lower than the median for ejection fraction and exercise tolerance. A reduction in mortality with hydralazine-isosorbide dinitrate was observed in all of the above pairs of subgroups as well as in those above and below 60 years of age and those with and without a history of hypertension or excess alcohol ingestion. The benefit of hydralazine and isosorbide dinitrate was particularly prominent in younger patients with a lower ejection fraction and those with a history of hypertension and without an alcoholic history.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure: influence of prerandomization variables on the reduction of mortality by treatment with hydralazine and isosorbide dinitrate. 355 2

Isosorbide-5-mononitrate is a longer acting active metabolite than the parent drug, isosorbide dinitrate (ISDN), with a half-life of around 4 hours. In coronary heart disease, myocardial infarction and in heart failure it causes a typical nitrate action on the central hemodynamics, but due to a complete systemic availability with high and predictable systemic drug levels, a drug action with a lower interindividual variability than with ISDN is to be expected. There is a close correlation between serum level and effect. The antianginal exercise tolerance increasing and unwanted effects as well as the development of tolerance to the drug action are comparable with those of ISDN. This naturally long-acting metabolite in ISDN works usually with a standard dosage of 20 mg twice daily.
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PMID:Oral isosorbide-5-mononitrate: pharmacokinetics and clinical efficacy. 355 38

In the management of the patient with chronic cardiac failure, the combination of an arteriolar vasodilator and venodilator should be beneficial. 8 patients with NYHA grade III-IV chronic cardiac failure were studied following placebo, after 4 weeks' therapy with the arteriolar vasodilator felodipine, and with the combination of felodipine and oral isosorbide 5-mononitrate. Haemodynamic measurements were made at rest and during dynamic exercise at an individual, fixed, near maximal workload. Ejection fraction (EF) was obtained by gated radionuclide ventriculography. At rest, heart rate was unchanged 73 +/- 6 at control, 72 +/- 4 with felodipine and 74 +/- 4 beats/min with the addition of isosorbide 5-mononitrate. Mean arterial pressure fell from 98 +/- 5 to 84 +/- 4 (p less than 0.02) and 84 +/- 3 mm Hg (p less than 0.02) with nitrate. Cardiac index increased from 2.2 +/- 0.1 to 2.5 +/- 0.2 litres/min/m2 with felodipine and further to 2.6 +/- 0.2 litres/min/m2 (p less than 0.02) with nitrate. Exercise tachycardia and mean arterial pressure were not significantly affected by therapy. Cardiac index increased on exercise from 4.4 +/- 0.3 to 4.8 +/- 0.3 litres/min/m2 with felodipine and 4.9 +/- 0.3 litres/min/m2 (p less than 0.05) with the addition of nitrate. Stroke volume index increased from 35.4 +/- 4 to 40.8 +/- 4 beats/min/m2 and further to 41.0 +/- 4 beats/min/m2 (p less than 0.05) and EF from 14 +/- 3 to 18 +/- 3% with nitrate. In conclusion, in patients with chronic cardiac failure, treatment with a calcium channel blocker produced sustained haemodynamic improvement, particularly on exercise, and combination with nitrate produced further benefit.
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PMID:Calcium channel blocker and isosorbide 5-mononitrate in the management of chronic cardiac failure. 360 8

We compared the short-term hemodynamic effects of isosorbide dinitrate (40 mg orally) and captopril (25 mg orally) in 18 patients with severe chronic heart failure in a randomized, crossover study conducted on consecutive days. Captopril and isosorbide dinitrate produced similar decreases in systemic vascular resistance, but whereas nitrate therapy decreased pulmonary arteriolar resistance significantly, captopril did not; the difference between the two drugs was highly significant (-25% vs -5%, p less than 0.001). Left ventricular filling pressures declined similarly with both captopril (-10.5 mm Hg) and with isosorbide dinitrate (-9.3 mm Hg), but because pulmonary arteriolar resistance fell significantly with nitrate therapy, mean right atrial pressure decreased more with isosorbide dinitrate than with captopril (-5.4 vs -2.8 mm Hg, respectively; p less than 0.001). Although systemic resistance declined similarly with both drugs, cardiac index increased more with nitrate therapy than during converting-enzyme inhibition (+0.47 vs +0.23 L/min/m2) (p less than 0.01), and therefore mean arterial pressure fell less with isosorbide dinitrate than with captopril (-10.5 mm Hg vs -16.7 mm Hg); p less than 0.05); two patients developed symptomatic hypotension with captopril, whereas none did so with the nitrate. The difference in the effects of the two drugs on cardiac index was not due to differences in their effects on heart rate, since heart rate fell similarly with both drugs, and thus both drugs produced similar increases in stroke volume index. These data indicate that, in patients with severe chronic heart failure, nitrates exert favorable dilating effects on the pulmonary circulation not shared by captopril.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of captopril and isosorbide dinitrate on pulmonary arteriolar resistance and right ventricular function in patients with severe left ventricular failure: results of a randomized crossover study. 389 May 6

The nitrate group of drugs is one of the most commonly used therapeutic modalities. The application of the nitrates is generally directed at ameliorating the symptoms of occlusive coronary artery disease (angina) and/or congestive heart failure. Although studies are available that attempt to refute the concept of nitrate-induced tolerance in angina pectoris, well-designed and well-controlled reports are appearing that convincingly establish the occurrence of one or more expressions of tolerance (e.g., shorter duration of action, loss of intensity of effect) with long-term dosing in this clinical setting. The type and degree of tolerance to nitrate therapy in angina pectoris depend on a number of pharmaceutic-pharmacokinetic considerations, including route of administration, dose strength, dosing frequency, and magnitude and duration of drug delivery. Reports concerning the development of tolerance to nitrates in congestive heart failure are also somewhat conflicting. However, one form and dose of nitrate therapy has been studied rather extensively: isosorbide dinitrate at 40 mg orally every 6 hours. The administration of this preparation over 3 months to a population with heart failure resulted in the development of tolerance to the systemic arterial-arteriolar effects, whereas the pulmonary vascular and venous dilative effects were maintained throughout the long-term dosing period. Exercise tolerance improved for the long-term isosorbide dinitrate group compared to the group receiving long-term placebo therapy. The mechanism(s) of tolerance to the nitrates is not known; altered disposition of reduced sulfhydryl groups at receptor and intracellular sites is the leading hypothesis.
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PMID:Nitrate tolerance. 392 42

Patients with angiographic non-surgical triple vessel coronary artery disease are usually considered to have a poor prognosis. We studied the evolution of 110 consecutive patients (mean age of 54.8 years) who underwent coronary angiography between April 1979 and March 1983 and followed up for an average of 24 months after the investigation. There were 10 deaths during the study period, all of "cardiac" causes (5 sudden deaths, 1 cardiac failure and 4 myocardial infarctions). Ninety nine of the 100 survivors at the time the study was closed had a medical treatment (nitrate derivatives, beta-blockers, calcium antagonists, usually associated). The actuarial survival was 94 +/- 2.2% at one year, 87.3 +/- 3.5% at 4 years. The quality of life expressed in terms of angina and breathlessness was good on the whole, as only 16 and 10 patients respectively had Grade III angina and dyspnea at the end of the study. Lack of resources and a follow-up period which was too short to assess the mortality rate meant that we were unable to analyse the factors which influenced the prognosis in this group of patients. These results support those of recent studies showing a mortality rate of patients with angiographic non-surgical triple vessel coronary artery disease that does not exceed 3 to 4% per year; these results seem to have improved over the last twenty years.
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PMID:[Median-term clinical development of patients with nonsurgical triple coronary vessel disease]. 393 40

Vasodilator treatment with long-activity nitrate derivatives intensifies the effects of treatment with digitalis and diuretics in left ventricular insufficiency. The object of this study was to evaluate, in an open comparative trial, the clinical effects of a prolonged adjunctive treatment with Mycoril, which is composed of a sustained-release nitrate derivative (pentaerythrityl tetranitrate: PETN) and an antianoxic agent (piridoxilate). The study was conducted in 90 patients with cardiac insufficiency who were treated and followed-up for at least one year. Study patients were divided into two groups matched for age, sex and etiology. The control group (42 patients) received digitalis and diuretics; the treatment group (48 patients) was given digitalis, diuretics and Mycoril in a daily dose of 4 to 6 capsules. The results show a significant improvement of symptoms in patients with ischemic cardiac insufficiency treated with Mycoril (83%) compared with the control group (52%) (p less than 0,03). Diuretics were needed in lower doses or withdrawn in a significantly higher number of patients in the Mycoril group (67%) than in the control group (38%) (p less than 0,01). This study provides clinical confirmation of the value of adjunctive treatment with a product such as Mycoril in patients under digitalis and diuretic therapy.
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PMID:[Effects of the PETN-piridoxylate combination in the long-term treatment of cardiac failure in the aged patient]. 631 Jul 65


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