Showing papers on "Management of heart failure published in 1993"
TL;DR: Controversy persists regarding direct vascular effects, objective end points of assessment and the magnitude of adverse effects such as activation of neurohormonal pathways and these issues may be addressed by the establishment of reasonable Objective end points, better stratification of patients in clinical trials and prospective trials in large clinical series.
45 citations
TL;DR: Evidence from the laboratory and from other institutions indicates that two new calcium antagonists, amlodipine and felodIPine, exert favorable neurohormonal effects in patients with heart failure, and these two agents are also the only calcium antagonists that have been shown to enhance exercise tolerance in patientsWith heart failure in controlled clinical trials.
Abstract: Since my educational warning in 1987, several controlled and uncontrolled trials have shown that shortand long-term therapy with calcium antagonists is deleterious to patients with chronic heart failure [1-3]. The reasons underlying the adverse effect of these drugs are unclear, however. Although it is generally assumed that the unfavorable clinical effects of calcium antagonists are related to their negative inotropie actions, this hypothesis cannot explain the available data with these drugs. Following long-term therapy with calcium antagonists, cardiac function improves, but the clinical status of patients deteriorates [4,5]. This finding suggests that another mechanism must explain the adverse effects of these drugs in patients with advanced left ventricular dysfunction. In 1989 I hypothesized that the deleterious effects of calcium antagonists might be related to their predilection to activate endogenous neurohormonal systems rather than to their cardiodepressant actions [6]. If this were the ease, what could be done to remedy this situation? Perhaps calcium antagonists could be developed that did not exert detrimental neurohormonal effects. Is this possible? The answer may be "yes." Recent evidence from our laboratory and from other institutions indicates that two new calcium antagonists, amlodipine and felodipine, exert favorable neurohormonal effects in patients with heart failure [7,8]. Interestingly, these two agents are also the only calcium antagonists that have been shown to enhance exercise tolerance in patients with heart failure in controlled clinical trials [8,9]. These intriguing observations require confirmation, but they suggest the possibility that some calcium antagonists might be useful in the treatment of advanced left ventrieular dysfunction. Additional studies are in progress to evaluate the potential efficacy of amlodipine and felodipine in the management of heart failure. Two studies deserve special mention, because they are investigating the effects of amlodipine and felodipine on morbidity and mortality. The Prospective Randomized Amlodipine Survival Evaluation (PRAISE) is examining the effect of amlodipine on survival in 1000 patients with class III and IV heart failure. The third Veterans Affairs Heart Failure Trial (V-HeFT III) is evaluating the effect of felodipine on cardiovascular morbidity in 900 patients with class II and III heart failure. The results on both studies should be available by the end of 1994. Until these studies are completed, what should physicians do? I believe that physicians should wait for the results of the PRAISE and V-HeFT III studies before reaching a decision to prescribe amlodipine or felodipine for the treatment of heart failure. Is there anything they can do in the meantime? The available data suggest that, unlike many calcium antagonists, amlodipine and felodipine are well tolerated in patients with heart failure. Hence, they might be preferred calcium antagonists for the treatment of angina peetoris or hypertension in patients with advanced left ventrieular dysfunction.
11 citations
TL;DR: Although ACE inhibitors exert beneficial pharmacodynamic effects on the renal bed in patients with heart failure, clinical consideration of volume and neurohormonal status prior to institution of therapy is prudent.
Abstract: ObjectiveTo review the effects of angiotensin-converting enzyme (ACE) inhibitors on renal pathophysiology and the compensatory mechanisms involved in heart failure A clinical application of the use of these agents in the setting of concomitant heart failure and renal insufficiency also is presentedData SourcesA MEDLINE search was conducted using the terms heart failure, congestive; renal insufficiency; and angiotensin-converting enzyme inhibitorsStudy SelectionAll applicable animal and human trials were reviewedData SynthesisAdvances in the management of heart failure have led to new insights into the complex pathophysiology of this condition, particularly the favorable clinical effects noted with the ACE inhibitors The net effect of ACE inhibitors on the renin-angiotensin system in patients with heart failure is to augment renal blood flow to a greater extent than cardiac output Glomerular filtration rate is either unchanged or decreased by ACE inhibition Sodium excretion is augmented primarily by
5 citations
TL;DR: The response of individual patients to several forms of drug treatment, including digoxin, ACE inhibitors, and beta-blockade, is unpredictable and Prospective identification of patients liable to respond well to these drugs is not yet possible, but would greatly assist the choice of treatment.
Abstract: The termheart failure has become a label for more than one clinical entity. For many years heart failure has been used to denote patients with various heart diseases who have begun to suffer from fluid retention, pulmonary venous hypertension, or systemic venous hypertension, either alone or in combination. More recently, the termheart failure has been applied to the combination of effort intolerance and reduced left ventricular contractility due to ischemic heart disease or other myocardial disease. Comparison of the results of epidemiological studies and therapeutic trials is complicated by variation in the composition of the patient populations selected for study. Drug treatment of heart failure remains fairly empirical. Distinction should be made between immediate or prognostic benefits related to the etiological diagnosis, and benefits related specifically to prevention and relief of, for example, fluid retention, rhythm disturbances, or ventricular hypertrophy. The response of individual patients to several forms of drug treatment, including digoxin, ACE inhibitors, and beta-blockade, is unpredictable. Prospective identification of patients liable to respond well to these drugs is not yet possible, but would greatly assist the choice of treatment. At present, trial of therapy is required in each patient to establish benefit and to avoid long-term treatment of nonresponders.
2 citations
1 citations
Journal Article•
TL;DR: On the other hand, the in-hospital mortality rate of cardiogenic shock, resulting from acute myocardial infarction, remains high, although primary PTCA has apparently resulted in substantial improvement in mortality of myocardials infarct shock.
Abstract: Development of heart failure complicating acute myocardial infarction is directly related to the extent of myocardial infarction and complex architectural changes defined as infarct expansion and remodeling. ACE inhibitors are an exciting class of agents that have the potentiality to prevent left ventricular dilatation, evolution of heart failure and death in the acute myocardial infarction setting. Besides, reperfusion is a important intervention that prevents infarct expansion in the early period after myocardial infarction. Early reperfusion limits expansion by infarct size reduction while late reperfusion reduces expansion independent of myocardial salvage by limiting transmural damage and improving the infarct healing. Therefore, reperfusion therapy decreases the incidence of congestive heart failure and significantly improves the prognosis of heart failure. On the other hand, the in-hospital mortality rate of cardiogenic shock, resulting from acute myocardial infarction, remains high, although primary PTCA has apparently resulted in substantial improvement in mortality of myocardial infarction shock. Thus, reperfusion treatment may be more effective in preventing rather than treating cardiogenic shock.
1 citations
01 Dec 1993
TL;DR: Concern relates to presence and predominance of cAMP-dependent mechanisms to induce these effects, which means sympathomimetic agents and phosphodiesterase inhibitors, such as milrinone or enoximone, are without beneficial effects, but instead shorten survival during long-term therapy.
Abstract: Although prevention of heart failure recently has become a realistic issue, management of heart failure once the syndrome has developed, is mainly supportive, based on the various cardiac and peripheral changes which occur in the course of heart failure. Of these, abnormal neurohormonal activation is of major pathophysiologic and prognostic significance. Consequently, modulation of neuroendocrine activation is now recognized a prime target in the treatment of heart failure, besides diuretic therapy. In this respect, the value of converting enzyme inhibition is well established. Future developments in this area include dopaminergic agents, vasopressin antagonists, angiotensin II receptor antagonists, renin inhibitors, spironolactone and, possibly, ANF peptidase inhibitors. Besides diuretics, necessary when signs of fluid retention are present, the approach to heart failure management involves other pharmacologic issues. In view of abnormal vascular control with vasoconstriction prevailing during progressive heart failure, it clearly makes sense to vasodilate. However, of available vasodilators, only the combination of relatively high dose nitrates and hydralazine has proven to be of clinical significance, in terms of hemodynamics, exercise capacity and survival. It is possible, though, that novel generation dihydropyridine derivatives may prove beneficial as well. Thus far, there has been much debate concerning the usefulness and particularly the safety of positive inotrope therapy and inodilator treatment. Taken together, this concern relates to presence and predominance of cAMP-dependent mechanisms to induce these effects. Thus, sympathomimetic agents and phosphodiesterase inhibitors, such as milrinone or enoximone, are without beneficial effects, but instead shorten survival during long-term therapy. This may be different where compounds which act through cAMP-independent mechanisms, i.e., calcium sensitization or sodium channel stimulation, are concerned, but needs to be confirmed yet.(ABSTRACT TRUNCATED AT 250 WORDS)
1 citations