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

Our understanding of the clinical course of heart failure and the mechanism by which ACE inhibitors reduce mortality and morbidity is being enhanced by recent results from large trials. The belief that heart failure constitutes a gradual progression of symptoms and signs leading eventually to death has been challenged by the finding that many patients die suddenly, before the onset of symptoms at rest. Indeed, many studies have shown that sudden death, with or without the progression of heart failure, is the most common mode of death. Studies suggest that ACE inhibitors reduce mortality in heart failure both by preventing or delaying the progression of heart failure or sudden death, and by reducing the incidence of myocardial infarction. ACE inhibitors may improve ventricular function by a variety of mechanisms, including effects on neuro-endocrine systems, haemodynamic effects, and direct actions on the myocardium. ACE inhibitors may also have a long-term effect on plaque growth or rupture, which may account for the observed reduction in the incidence of myocardial infarction. Although ACE inhibitors would be expected to lower the risk of arrhythmias, through their ability to reduce pressure and volume overload, this effect has not been observed consistently in large- scale trials. One of the most important clinical benefits of ACE inhibition may prove to be the reduction in myocardial infarction. The use of an ACE inhibitor should be considered in all patients with significantly impaired systolic left ventricular function (in the absence of contra- indications), even those who are asymptomatic, although the precise level of ventricular dysfunction at which treatment should be initiated remains to be clarified. The ability of long-term ACE inhibitor treatment to reduce ischaemic events in patients with normal left ventricular function is currently being studied. The optimum dose remains to be determined, although beneficial results have been obtained with enalapril, 20 mg daily, captopril, 150 mg daily and ramipril 5 mg b.i.d.
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PMID:The clinical course of heart failure and its modification by ACE inhibitors: insights from recent clinical trials. 817 72

Patients surviving acute myocardial infarction are susceptible to heart failure, recurrence of angina, reinfarction, arrhythmias, and sudden cardiac death. Most deaths occur in the first six months after infarction. Advancing age is the most important nonmodifiable prognostic factor for long-term prognosis, whereas left ventricular function assessed clinically or measured as either ejection fraction or end-systolic volume is the most important modifiable factor. Other significant long-term prognostic factors include: postinfarction angina at rest, inducible ischemia during exercise testing with or without radioisotope imaging, severity and extent of coronary artery disease, patency of the infarct-related artery, late ventricular arrhythmias, decreased heart rate variability, cigarette smoking, hypercholesterolemia, and diabetes mellitus. Identification of these adverse prognostic factors permits risk stratification and enables physicians to determine the most appropriate and cost-effective treatment. Most patients should have a stress test for inducible ischemia and a non-invasive (echo or radionuclide) assessment of left ventricular function. For high-risk patients such as those with prior infarction, heart failure, early postinfarction angina, or frequent late ventricular arrhythmias, coronary angiography and ventriculography prior to discharge are recommended. Assessment of late potentials and heart rate variability will help identify a subgroup of patients at risk for ventricular arrhythmias and cardiac death. However, a more accurate prediction of reinfarction is not possible at present, and no reliable test for atherosclerotic plaque instability has been developed.
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PMID:Factors affecting outcome after recovery from myocardial infarction. 819 87

The ideal therapy for patients with chronic heart failure should reduce symptoms related to pulmonary congestion or low perfusion, prevent the progression of left ventricular dysfunction and, ultimately, should reduce mortality. Extensive studies in humans have investigated the effects of angiotensin-converting enzyme (ACE) inhibitors on these goals of therapy. As an example, the ACE inhibitor cilazapril significantly improved exercise tolerance, as borne out by a meta-analysis of six placebo-controlled, randomized 3-month trials. Comparison of the effects of cilazapril and captopril vs. placebo in one of the trials documented similar improvement in exercise tolerance (14 vs. 17%). Results from other randomized comparative trials suggest that the improvement in symptoms represents a class effect of ACE inhibitors. A beneficial effect of ACE inhibition on the progression of left ventricular dysfunction has also been demonstrated in the SOLVD trial, and a reduction of mortality has been amply documented in several mortality trials (CONSENSUS I, SOLVD, V-HeFT-II, SAVE, AIRE, SMILE) in patients with or without preceding myocardial infarction. Reports that ACE inhibitors also reduce the incidence of reinfarction after myocardial infarction have not been confirmed in all studies but raise the interesting concept that ACE inhibition may interact, in a beneficial but thus far not well-understood way, with key processes in the development of atherosclerosis, thereby preventing plaque rupture, thrombus formation, and myocardial infarction. Taken together, a large database convincingly demonstrates that ACE inhibitors are effective not only in improving symptoms but also in the prevention of progression of left ventricular dysfunction, in the reduction of mortality, and possibly in stabilizing the atherosclerotic disease process.
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PMID:Clinical benefit of angiotensin-converting enzyme inhibitors in chronic heart failure. 872 95

Experimental studies and molecular biological techniques have demonstrated the importance of angiotensin II in ventricular and vascular remodelling and in atherogenesis. Large scale clinical trials analysing the effects of converting enzyme inhibitors on the mortality and morbidity in post-infarction left ventricular dysfunction, have shown beneficial effects of these agents on major events of coronary artery disease. Experimental studies have shown reduction of intimal thickening and of the multiplication and migration of smooth muscle cells and of vascular fibrosis. Converting enzyme inhibitors seem to restore endothelial function by acting as donors of NO and could play a role in the stabilisation of atheromatous plaque, the prevention of platelet aggregation and on the activation of intravascular fibrinolytic systems. Large scale clinical trials (SOLVD and the prevention and treatment arms of SAVE) have also shown a 23% reduction in the risk of reinfarction and a 15% reduction in the risk of unstable angina. The results of ongoing trials in patients with coronary artery disease without cardiac failure are awaited with great impatience.
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PMID:[Angiotensin converting enzyme inhibitors and ischemic heart diseases]. 894 14

Ischaemic heart disease will kill over 150,000 people in the next year in Britain, more than any other single disease process, and cost more than 1.4bn pounds in health care alone. Faced with the continuing problems arising from ischaemic heart disease cardiological clinician scientists are moving from technology based solutions to basic sciences. This article explains how basic science may contribute to new understanding and treatments for patients with ischaemic heart disease. Highlighted are three problems which face any clinical cardiologist on a daily basis and for which basic science may provide solutions: the uncertainty of plaque stability in coronary disease; restenosis after percutaneous transluminal angioplasty; and the shortage of organs for cardiac transplant programmes for patients with heart failure.
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PMID:The future of the management of ischaemic heart disease. 904 Mar 35

Long-term intermittent urokinase therapy has been developed for patients with severe coronary artery disease and refractory angina pectoris. This therapeutic approach is predominantly effective at the microcirculatory level based on a combination of rheologic and fibrinolytic effects; furthermore, plaque regression seems to be a possible mechanism. Patients with refractory angina pectoris are characterized by severe coronary artery disease without a therapeutic option for conventional revascularization procedures, only slight impairment of left ventricular systolic function and hyperfibrinogenemia, which results in further enhancement of myocardial ischemia due to microcirculatory impairment of blood flow. In this article data on the anti-ischemic effectiveness as well as first results on the impact of this therapeutic approach on hemodynamics are described. A dose-response study, which compared 3 x 50,000 IU with 3 x 500,000 IU urokinase three times a week over a treatment period of 12 weeks demonstrated subjective as well as objective antiischemic effectiveness. Only patients who were treated with 500,000 IU per injection achieved marked increases in exercise capacity, while some patients in the low-dose group presented even with a deterioration of exercise performance. First hemodynamic studies could not show marked changes of systolic parameters, either at rest or during exercise. But a decrease of pulmonary capillary wedge pressure at rest after treatment with 500,000 IU per injection indicates an improvement of diastolic function as a result of enhanced myocardial perfusion. Echocardiographic measurements of transmitral Doppler flow in 21 patients with end-stage coronary artery disease demonstrated normalization of early and late diastolic filling rates in most cases. These changes were accompanied by a reduction of clinical signs of heart failure. Long-term intermittent urokinase therapy is a valuable approach as it not only improves quality of life during the actual treatment period but by the persistence of therapeutic effects following the cessation of therapy.
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PMID:[Chronic intermittent urokinase therapy: anti-ischemic and hemodynamic effects]. 917 24

Atherosclerosis and its consequences account for most of the morbidity and mortality in Western countries. It is a disease of the intima and primarily involves four cell types, i.e., endothelial and vascular smooth muscle cells, monocytes and platelets. In recent years, knowledge on the cellular and molecular mechanisms of these cells and their alterations by cardiovascular risk factors and in atherosclerosis has greatly expanded. In particular, it has become clear that endothelial cells play a crucial role in the regulation of platelet function, coagulation, and vascular tone and structure. Interestingly, endothelial dysfunction occurs early, particularly if cardiovascular risk factors such as hyperlipidemia, hypertension and diabetes are present. This could lead to adhesion of circulating platelets and monocytes and increased accumulation of lipids in the intima, as well as increased contraction, migration and proliferation of vascular smooth muscle cells. One of the enzymes with a key role in vascular homeostasis is angiotensin I converting enzyme (ACE). ACE is located on the endothelial cell membrane and is responsible for the conversion of angiotensin I into angiotensin II, as well as for the breakdown of bradykinin. While the antihypertensive effect of ACE inhibitors probably contributes to their antiatherogenic effects, other mechanisms are likely to be of greater importance. These direct antiatherogenic effects attributable to ACE inhibition are related to their vasculoprotective properties, including antiproliferative and antimitogenic activity, effects on endothelial function, protection against plaque rupture, antithrombotic effects, and possible antioxidant properties. There is overwhelming evidence to demonstrate the beneficial effects of long-term ACE inhibitor treatment in heart failure, acutely for suspected myocardial infarction (MI), and following MI in patients with left ventricular dysfunction. Hypercholesterolemia is a health risk, and epidemiological studies have shown a line between total cholesterol levels and the risk of cardiac events. Studies have shown that lowering the levels of total and low-density lipoprotein cholesterol using HMG-CoA reductase inhibitors can result in a decrease in cardiac morbidity and mortality. Angiographic studies of coronary arteries have demonstrated a disparity between the decrease in cardiac events and the extent of regression of coronary artery lesions. Mechanisms other than the regression of coronary stenosis may therefore be important in the beneficial effect of cholesterol lowering. It may be of major importance that lipid-lowering therapy is associated with improved endothelial function and decreased platelet activity. Thus, both ACE inhibitors and HMG-CoA reductase inhibitors have vasculoprotective properties which may explain their beneficial effects on cardiovascular morbidity and mortality.
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PMID:[Pharmacotherapy of arteriosclerosis and its complications. Effect of ACE inhibitors and HMG-CoA-reductase inhibitors]. 919 90

Calcium deposits account for most of the dry weight of atherosclerotic lesions. Previously considered uncommon, vascular calcification is now known to be present in 80% of significant lesions and in at least 90% of patients with coronary artery disease. Previously considered a passive process, it is increasingly recognized as an active, regulated process. Previously considered benign, it is now becoming recognized as a major risk factor for cardiovascular events, and a major contributor to systolic hypertension, heart failure, plaque rupture and stenosis. To confirm the similarity of vascular calcification with embryonic osteogenesis, we demonstrated the expression of bone morphogenetic protein in calcified human lesions, and we developed an in vitro model of vascular calcification that provides a useful experimental system for elucidating the molecular regulation of this process, which we have shown to include alkaline phosphatase induction and expression of bone matrix proteins and differentiation factors. Understanding the regulatory mechanisms of vascular calcification will allow future therapeutic approaches to prevent and possibly reverse this disease and its clinical consequences.
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PMID:Role of molecular regulation in vascular calcification. 922 60

Phospholamban forms an integral part of the cardiac sarcoplasmic reticulum (SR) and regulates the activity of SR Ca(2+)-ATPase (SERCA2a). A number of studies have suggested a decrease in SERCA2a relative to phospholamban in heart failure. To test the hypothesis that changes in the relative abundance of phospholamban to SERCA2a could account for the pathophysiological abnormalities in Ca2+ handling observed in failing myocardium, we created a recombinant adenovirus designed to overexpress phospholamban (Ad.RSV.PL). In neonatal rat cardiomyocytes, Ad.RSV.PL increased the expression of phospholamban in a concentration-dependent fashion, reaching 280 +/- 43% at a multiplicity of infection (MOI) of 10.0 plaque forming units (pfu)/cell at 48 hours. The relationship between Ca(2+)-ATPase activity and [Ca2+] was shifted rightward in membrane preparations from cardiomyocytes infected with Ad.RSV.PL. Intracellular Ca2+ transients measured in the neonatal cells infected with Ad.RSV.PL (MOI, 10 pfu/cell) were characterized by (1) a significant prolongation of the relaxation phase (344 +/- 26 versus 710 +/- 56 milliseconds, P < .01), (2) a decrease in peak [Ca2+]i (967 +/- 43 versus 630 +/- 33 nmol/L, P < .01), and (3) an elevation in resting [Ca2+]i (143 +/- 14 versus 213 +/- 17 nmol/L, P < .05). Similarly, the time course of shortening was prolonged in myocytes infected with Ad.RSV.PL. These effects were partially restored by simultaneous transduction with an adenovirus carrying SERCA2a. Cardiomyocytes infected with Ad.RSV.PL had an abnormal frequency response: a decrease in peak [Ca2+]i and an increase in resting [Ca2+]i with increasing frequency. These findings indicate that adenovirus-mediated gene transfer of phospholamban modifies intracellular Ca2+ handling and the frequency response in cardiomyocytes. Our results suggest that alterations in the ratio of phospholamban to SERCA2a could account for the abnormalities in Ca2+ handling observed in heart failure and that overexpression of SERCA2a can largely correct these abnormalities.
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PMID:Adenoviral gene transfer of phospholamban in isolated rat cardiomyocytes. Rescue effects by concomitant gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase. 1123 Jan 2

Despite progress in the invasive revascularization procedures and even though conventional antianginal treatment has improved the quality of life in patients with symptomatic coronary artery disease considerably, an increasing number of patients suffers from end-stage coronary artery disease and refractory angina pectoris. For these refractory patients long-term intermittent urokinase therapy was developed as an antithrombotic intervention, which is based on its capacity to enhance thrombolysis and blood rheology, and may possibly lead to plaque regression. The coronary syndrome of refractory angina pectoris is characterized by a mismatch of severe coronary insufficiency and a relatively large amount of viable myocardium as indicated by an only moderately impaired left ventricular function. Prior to initiation of long-term intermittent urokinase therapy all potential measures to improve myocardial perfusion have to be considered in each patient. These supportive measures include rigorous reduction of LDL-cholesterol, which has proven antiischemic properties due to an improved endothelial function of epicardial conductance vessels possibly resulting in an antianginal effect. Apart from the proven antiischemic properties of long-term intermittent urokinase therapy in patients with refractory angina pectoris, objective signs of ischemic myocardial heart failure improve. Follow-up studies demonstrated a significant increase of left ventricular ejection fraction as evaluated with multi-gated blood pool analysis. Furthermore, left ventricular diastolic function normalized after a treatment period of 12 weeks. As the clinical effects last well beyond the actual treatment period and as they are accompanied by a remarkable increase in the quality of life, a complex approach as this one is justified in this highly symptomatic patient group.
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PMID:[Conservative therapeutic approaches in terminal coronary heart disease. Chronic intermittent urokinase therapy]. 944 Nov 57


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