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

Patients who cannot be reperfused after thrombolytic therapy have a high mortality rate. Noninvasive clinical markers of reperfusion have been widely studied, yet their prognostic significance remains unclear. To assess the prognostic value of commonly used noninvasive clinical markers of early reperfusion we studied 327 patients who received intravenous thrombolytic treatment (1.5 MU streptokinase in 1 hour or 100 mg alteplase in 3 hours) within 6 hours of acute infarction. Successful clinical reperfusion (SCR) was defined as the presence of at least two of the following criteria at 2 hours after thrombolytic treatment: (1) significant relief of pain (a 5-point reduction on a 1 to 10 subjective scale), (2) > or =50% reduction of sum of ST segment elevation, and (3) abrupt initial increase of creatine kinase levels (more than twofold over the upper-normal or baseline elevated values). Clinical variables that were significantly associated by univariate analysis were tested by multivariate analysis to obtain independent predictors of 30-day mortality rate. SCR was present in 210 (64%) patients (group 1), and absent in 117 (36%) patients (group 2). The groups were similar for most baseline characteristics, although group 2 patients were slightly older (mean 60 vs 57 years, p < 0.02). Thirty-day outcomes for group 2 patients compared with group 1 patients were heart failure in 23.1% and 10.5% (p < 0.005), progression to cardiogenic shock in 12.8% and 0.5%, (p < 0.00001), and death in 16.2% and 3.8% (p < 0.0001), respectively. By multivariate analysis the Killip class at admission (p < 0.00001), the absence of SCR (p = 0.017), anterior infarct location (p = 0.021), and age (p = 0.03) were independent predictors of mortality rate, and sex (p = 0.051) had borderline significance. The absence of SCR defined a group of patients with significantly higher mortality rate (odds ratio 4.89, 95% confidence interval 2.07 to 11.57). Three simple noninvasive clinical criteria of successful reperfusion may be used to identify a group of patients with poor prognosis after thrombolytic therapy in whom alternative strategies could be applied.
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PMID:Prognostic value of clinical markers of reperfusion in patients with acute myocardial infarction treated by thrombolytic therapy. 935 29

Very large clinical trials have become the norm in the evaluation of thrombolytic agents, and these 'megatrials' are administratively complex and expensive. It remains to be seen whether new thrombolytics will lead to further large reductions in fatality from an acute myocardial infarction, but new agents may well have advantages in areas such as safety and ease of administration, in addition to other clinical benefits (i.e. fewer cases of cardiac shock, heart failure and atrial fibrillation). The problem is how to introduce such new agents without a megatrial for each one. Endpoints other than fatality have some advantages and, in thrombolysis, angiographic studies are a necessary step in the development of new agents. However, such studies may not always correlate precisely with the results of mortality endpoint studies. Measurements of the resolution of ST segment elevation in myocardial infarction seem to provide a very useful method of assessing thrombolysis, but although such a technique can be applied to large numbers of patients, it cannot totally replace mortality endpoint trials. The 'equivalence' of two treatments is a clinical, not a statistical, concept, although statistical principles that allow equivalence to be investigated with medium-sized trials should be applied. Demonstrating equivalence in outcome between the new thrombolytic reteplase and streptokinase was the aim of the INJECT study.
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PMID:The concept of equivalence and its application to the assessment of thrombolytic effects. 944 37

A study made to gain insight into the bodily immune and fibrinolytic systems in 72 patients with cardiac insufficiency developed against the background of cardial atherosclerosis showed imbalance in the ratio of cellular to humoral links of immunity and enhancement of the autoimmune processed activity, inhibition of activity of the monocytomacrophagal link. Disturbances in the fibrinolytic system were manifested by blood and urine lowering of activity of the plasminogen activator, with the antiplasmin activity being on the decrease as well, which fact is regarded as formation of a new stationary state in the system of haemocoagulation maintaining hemostasis.
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PMID:[The immune and fibrinolytic systems in heart failure developing against a background of cardiac atherosclerosis]. 947 78

Important novel developments in the pharmacotherapy of cardiovascular diseases are briefly summarized. New results with lipid lowering statins in secondary prevention of atherosclerosis are mentionned. Atorvastatin, introduced recently, is compared to the other statins. The extended possibilities for inhibition of platelet-aggregation in coronary disease and after interventional coronary therapy with ticlopidine, clopidogrel and specific antagonists of platelet integrin IIb/IIIa receptors (abciximab, tirofibrane) as well as fibrinolysis with reteplase are covered. Among modern trends in pharmacotherapy of heart failure studies with angiotensin-II-receptor inhibition (losartane and related compounds) or betablockers (carvedilol) are worth mentioning.
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PMID:[New cardiovascular drugs: expanded therapeutic possibilities in coronary heart disease and in heart failure]. 1040 78

A patient with Cowden disease and multiple arteriovenous malformations (AVMs) that resulted in high output heart failure is described. Cowden disease is a familial syndrome characterized by endodermal, mesodermal and ectodermal dysplasia causing benign and malignant tumors of the skin, breast, gastrointestinal tract, and thyroid gland. Our patient had gastrointestinal polyposis, a right renal tumor, a left lung tumor, an adenomatous goiter, and typical dermatologic findings such as facial papules, acral keratosis, gingival papillomatosis and hemangiomas. AVMs were observed in the pelvis, cervical vertebra, liver, and right supraclavicular area. Transcatheter embolization was performed 7 times for the pelvic AVMs, but the effect decreased with repetition and the patient died of heart failure 2 years after the first embolization. The serum levels of tissue plasminogen activator (t-PA), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta1 were high, suggesting that these angiogenic molecules may play a role in the pathogenesis of AVMs in Cowden disease.
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PMID:Transcatheter embolization of arteriovenous malformations in Cowden disease. 1047 85

Cardiac rupture is a fatal complication of acute myocardial infarction lacking treatment. Here, acute myocardial infarction resulted in rupture in wild-type mice and in mice lacking tissue-type plasminogen activator, urokinase receptor, matrix metalloproteinase stromelysin-1 or metalloelastase. Instead, deficiency of urokinase-type plasminogen activator (u-PA-/-) completely protected against rupture, whereas lack of gelatinase-B partially protected against rupture. However, u-PA-/- mice showed impaired scar formation and infarct revascularization, even after treatment with vascular endothelial growth factor, and died of cardiac failure due to depressed contractility, arrhythmias and ischemia. Temporary administration of PA inhibitor-1 or the matrix metalloproteinase-inhibitor TIMP-1 completely protected wild-type mice against rupture but did not abort infarct healing, thus constituting a new approach to prevent cardiac rupture after acute myocardial infarction.
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PMID:Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. 1050 7

Thrombolytic therapy has become a standard treatment for selected patients with acute myocardial infarction (MI). Various thrombolytic agents have been shown to decrease mortality. However, current thrombolytic agents still suffer significant shortcomings, such as a low optimal reperfusion rate delayed reperfusion. and incomplete myocardial perfusion. Furthermore, cyclic flow variations and reocclu.sions remain a significant cause of late morbidity and mortality. In thrombolysis with tissue plasminogen activator (t-PA), heparin seems to play an important role. However, it has several features that suggest that it may not be the optimal adjunct to thrombolytics, including weak and indirect action on thrombin, little access to clot-bound thrombin, inhibition by acute-phase plasma proteins, and its direct stimulation of platelet aggregation. Argatroban (NOVASTAN(R)), a small-molecule, synthetic, direct thrombin inhibitor, has several potential advantages over heparin, and prior studies suggest superior thrombin inhibition with favorable pharmacokinetic and pharmacodynamic properties warranting further investigation The Myocardial Infarction using NOVASTAN (R) and t-PA (MINT) study is a phase II, single-blind, angiographic trial directly comparing heparin versus two doses of argatroban in 120 patients with ST-elevation MI who present within 6 hours of symptom onset. The primary objective of the MINT trial is to assess the TIMI grade 3 flow and TIMI Frame Count at 90 minutes after the initiation of t-PA. This trial will also evaluate the safety of the combination of t-PA, argatroban, and aspirin. The incidence of clinical or silent ischemia, will be monitored. All patients will be followed up to 30 days for the composite endpoint of death, nonfatal recurrent myocardial infarction, coronary artery bypass surgery, PTCA, recurrent ischemia, and shock/new-onset heart failure.
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PMID:A Randomized, Blinded Study of Two Doses of Novastan(R) (Brand of Argatroban) Versus Heparin as Adjunctive Therapy to Recombinant Tissue Plasminogen Activator (Accelerated Administration) in Acute Myocardial Infarction: Rationale and Design of the Myocardial Infarction using Novastan(R) and T-PA (MINT) Study. 1060 50

Patients with transmural (with ST segment elevation) myocardial infarction should immediately be considered for reperfusion therapy. Fibrinolytic therapy with streptokinase, alteplase, or reteplase should be started within 30 minutes of presentation for patients without bleeding risk. Alternatively, patients at tertiary care hospitals can undergo emergency coronary angioplasty. Other lifesaving pharmacologic interventions include administering aspirin, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors. Oxygen, morphine sulfate, heparin, and nitroglycerin are also useful. No benefit has been demonstrated for calcium channel blockers, magnesium, or prophylactic lidocaine. Patients need to be closely monitored for conduction abnormalities, arrhythmias, and heart failure.
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PMID:Acute Transmural Myocardial Infarction. 1109 6

Brain natriuretic peptide (BNP) gene expression accompanies cardiac hypertrophy and heart failure. The vasoconstrictor endothelin-1 (ET) may be involved in the development of these diseases. ET has also been shown to activate phospholipase A(2) (PLA(2)), and the resulting metabolites are important second messengers. We studied how ET and PLA(2) metabolites regulate BNP gene expression. The human BNP (hBNP) promoter (from -1818 to +100) coupled to a luciferase reporter gene was transferred into neonatal ventricular myocytes (NVMs), and luciferase activity was measured as an index of promoter activity. ET induced BNP mRNA in NVMs as assessed by Northern blot. It also stimulated the hBNP promoter, an effect completely inhibited by actinomycin D. To test the involvement of different PLA(2) isoforms, transfected cells were treated with various PLA(2) inhibitors before stimulation with ET. Only Ca(2+)-independent PLA(2) blockade prevented ET-stimulated hBNP promoter activity. The PLA(2) metabolite lysophosphatidic acid (LPA) also activated the hBNP promoter, but arachidonic acid itself did not. ET regulation of the hBNP promoter is pertussis toxin-sensitive. The nonreceptor tyrosine kinase Src and the small GTPase Rac mediate the effects of both ET and LPA in stimulation of the hBNP promoter. We studied the involvement of cis elements in ET-stimulated hBNP promoter activity. Deletion of BNP promoter sequences from -1818 to -408 and from -408 to -40 reduced the effect of ET by 60% and 80%, respectively. Moreover, ET-stimulated luciferase activity was reduced by 50% when the proximal GATA element was mutated. These data suggest that (1) ET activates the hBNP promoter through a transcriptional mechanism; (2) LPA, perhaps generated by iPLA(2), is involved in the effect of ET; (3) Src and Rac mediate ET and LPA stimulation of the hBNP promoter; and (4) ET regulation of the hBNP promoter targets both distal and proximal cis elements.
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PMID:Src and Rac mediate endothelin-1 and lysophosphatidic acid stimulation of the human brain natriuretic peptide promoter. 1123 Mar 22

Three patients presenting with massive venous pulmonary thrombo-embolism are described, who have been selected from a series of 22 patients treated with thrombolysis during a 6-year period. A 23-year-old female presented with tachycardia and dyspnoea. She had pulmonary angiography following scintigraphy with a perfusion deficit of more than 60%. Thrombolysis resulted in open blood vessels and a disappearance of the complaints. A 51-year-old woman presented with profound hypoxemia, probably due to a patent foramen ovale, with shunting and tachycardia. Perfusion defects on scintigraphy combined with a normal chest radiograph in the absence of pre-existent pulmonary disease established the diagnosis. She responded favourably to intravenous streptokinase. The third patient was an 80-year-old woman with hypertension. She developed dyspnoea, tachycardia and shock following immobilisation due to a fractured hip. Despite an initial improvement on streptokinase, she deteriorated and died from right-sided heart failure. The diagnostic tests should be limited and aimed at ruling out left-sided heart failure and pericardial tamponade. Echocardiography is often diagnostic in these patients. Thrombolysis may be life saving but there are no randomised trials to prove that survival rate is indeed better compared to heparin therapy. Streptokinase is less expensive than alteplase and there is no evidence from trials to suggest that it is inferior to more expensive thrombolytics such as alteplase or urokinase.
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PMID:[Three patients with massive pulmonary embolism]. 1199 57


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