Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ventricular tachycardia (VT), ventricular fibrillation (VF), and atrial flutter (AFL) are potentially fatal or serious complications arising after cardiac surgery. Generally, we treat these complications with class I antiarrhythmic agents and/or direct counter shock (DC). However, sometimes these complications do not respond to antiarrhythmic agents and require frequent DC. Moreover, these class I agents induce heart failure due to their negative inotropic effect. Nifekalant hydrochloride (NIF) is a class III antiarrhythmic agent that prolongs the refractory period of the atrial and ventricular myocardium without any negative inotropic action. From July 2003 to September 2004, we treated 11 patients with NIF for perioperative arrhythmias (VT 5, VF 2, and AFL 4). NIF was administered by continuous intravenous infusion (0.3 to 0.4 mg/ kg/h) to prevent the recurrence of VT/VF and AFL. NIF prevented the recurrence of VT in 3 of the 5 cases. No recurrence was observed in 2 cases with VF. Furthermore, NIF prevented the recurrence of AFL in all the 4 patients. None of the patients exhibited changes in heart rate, cardiac output, and QTc interval. Additionally, no occurrence of Torsades de pointes was observed in any of the cases. In conclusion, NIF is an effective and safe antiarrhythmic agent for the treatment of perioperative arrhythmias under continuous monitoring of the QTc interval.
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PMID:[Treatment for perioperative arrhythmias with nifekalant hydrochloride]. 1652 93

Ranolazine (Ranexa), a piperazine derivative, is a new antianginal agent approved for the treatment of chronic stable angina pectoris for use as combination therapy when angina is not adequately controlled with other antianginal agents. While the exact mechanism of action of ranolazine is not known, its antianginal and anti-ischaemic effects do not appear to depend upon changes in blood pressure or heart rate. An extended-release (ER) oral formulation of ranolazine has been developed to facilitate twice-daily administration whilst maintaining therapeutically effective plasma concentrations. In patients with chronic stable angina, ranolazine ER monotherapy was shown to improve exercise duration at trough plasma drug concentration in a dose-dependent manner compared with placebo. The drug was effective as adjunctive therapy in patients with chronic stable angina whose condition was not controlled adequately with conventional antianginal therapy. In randomised clinical trials, ranolazine ER was well tolerated, with no overt effects on cardiovascular haemodynamics or conduction, apart from a modest increase in corrected QT (QTc) interval (but no torsades de pointes). Importantly, the efficacy and tolerability of ranolazine ER were not affected by comorbid conditions, including old age, heart failure (HF) or diabetes mellitus. Comparative trials of ranolazine ER with other antianginal agents and trials examining its effects on long-term morbidity and mortality in patients with ischaemic heart disease are required to determine with greater certainty the place of the drug in current antianginal therapy. Nevertheless, ranolazine ER may well prove to be a useful alternative and adjunct to conventional haemodynamic antianginal therapy in the treatment of chronic stable angina.
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PMID:Ranolazine: a review of its use in chronic stable angina pectoris. 1662 Jan 47

Ranolazine (Ranexa), a piperazine derivative, is a new antianginal agent approved for the treatment of chronic stable angina pectoris for use as combination therapy when angina is not adequately controlled with other antianginal agents. While the exact mechanism of action of ranolazine is not known, its antianginal and anti-ischemic effects do not appear to depend upon changes in BP or heart rate. An extended-release (ER) oral formulation of ranolazine has been developed to facilitate twice-daily administration whilst maintaining therapeutically effective plasma concentrations. In patients with chronic stable angina, ranolazine ER monotherapy was shown to improve exercise duration at trough plasma drug concentration in a dose-dependent manner compared with placebo. The drug was effective as adjunctive therapy in patients with chronic stable angina whose condition was not controlled adequately with conventional antianginal therapy. In randomized clinical trials, ranolazine ER was well tolerated, with no overt effects on cardiovascular hemodynamics or conduction, apart from a modest increase in corrected QT interval (but no torsades de pointes). Importantly, the efficacy and tolerability of ranolazine ER were not affected by old age and co-morbid conditions (heart failure or diabetes mellitus). Comparative trials of ranolazine ER with other antianginal agents and trials examining its effects on long-term morbidity and mortality in patients with ischemic heart disease are required to determine with greater certainty the place of the drug in current antianginal therapy. Nevertheless, ranolazine ER may well prove to be a useful alternative and adjunct to conventional hemodynamic antianginal therapy in the treatment of chronic stable angina.
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PMID:Spotlight on ranolazine in chronic stable angina pectoris. 1708 71

We describe 2 patients who developed prolonged QTc interval on electrocardiogram while being treated with voriconazole. The first patient had undergone induction chemotherapy for acute myelogenous leukemia, and her course had been complicated by invasive aspergillosis and an acute cardiomyopathy. She developed torsades de pointes 3 weeks after starting voriconazole therapy. She was re-challenged with voriconazole without recurrent QTc prolongation or cardiac dysfunction. The second patient had a significantly prolonged QTc interval while on voriconazole therapy. We recommend careful monitoring for QTc prolongation and arrhythmia in patients who are receiving voriconazole, particularly those who have significant electrolyte disturbances, are on concomitant QT prolonging medications, have heart failure such as from a dilated cardiomyopathy, or have recently received anthracycline-based chemotherapy. The potential for synergistic cardiotoxicity must be carefully considered.
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PMID:Torsades de pointes associated with voriconazole use. 1731 69

Chronic atrioventricular block dogs have been established as an in vivo model of drug-induced torsades de pointes arrhythmias. We compared the cardiovascular profile of the canine model with that of sham-operated animals using echocardiographic and haemodynamic methods. In the echocardiographic study, the larger diameters of the left atria, inferior vena cava and left ventricle in end-diastole in addition to greater fractional shortening, end-diastolic volume, stroke volume and ejection fraction were more often detected in the chronic atrioventricular block dogs than in the sham-operated animals. During haemodynamic examination, lower cardiac output and higher pulmonary capillary wedge pressure were detected in chronic atrioventricular block dogs more than in sham-operated animals; however, these changes were within the physiological limits, and the results suggest that the chronic atrioventricular block dogs have a pathophysiological profile of chronic compensated heart failure.
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PMID:Cardiovascular profile of the canine torsades de pointes arrhythmia model assessed by echocardiographic and haemodynamic methods. 1757 14

The purpose of this study was to identify risk factors of Torsade de pointes (TdP) ventricular tachycardia in patients medicated with a class III antiarrhythmic drug (dofetilide) and left ventricular systolic dysfunction with heart failure (HF) or recent myocardial infarction (MI). The 2 Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) studies enrolled patients with HF (DIAMOND-HF) or MI (DIAMOND-MI) and left ventricular systolic dysfunction. The present analysis includes only patients treated solely with dofetilide. The incidence of TdP was 2.1% (32 of 1,511). Twenty-five of the incidences occurred in the DIAMOND-HF study and 7 cases in the DIAMOND-MI study (p = 0.0015). TdP was more frequent in women than in men (47% vs 28%, p = 0.02). Risk factors for developing TdP were female gender (odds ratio 2.2, 95% confidence interval [CI] 1.0 to 5.0), MI within 8 weeks (odds ratio 0.3, 95% CI 0.1 to 0.7), being in New York Heart Association class III or IV (odds ratio 3.2, 95% CI 1.2 to 8.6), and baseline QTc duration (odds ratio 1.14, 95% CI 1.00 to 1.30) per 10 ms. Women with chronic HF, QTc duration >400 ms. and New York Heart Association class III or IV had a risk of TdP of 10%, whereas no TdP episodes were observed in patients with QTc duration <400 ms. In conclusion, severity of HF, female gender, and QTc duration make it possible to identify patients with a high risk of early TdP when treated with dofetilide. Patients with recent MI less often had TdP compared with patients with chronic HF.
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PMID:Risk factors and predictors of Torsade de pointes ventricular tachycardia in patients with left ventricular systolic dysfunction receiving Dofetilide. 1771 37

Pheochromocytoma is an infrequent secondary cause of arterial hypertension, often associated with paroxysmal headache, sweating, weight loss, and palpitations. Cardiovascular complications of pheochromocytoma include sudden death, heart failure due to toxic cardiomyopathy, and hypertensive encephalopathy. Here we report the case of a female with an acquired long-QT-syndrome as a rare complication of an extra-adrenal pheochromocytoma. Diagnosis was made after sotalol-induced Torsades de Pointes.
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PMID:Torsades de Pointes: a rare complication of an extra-adrenal pheochromocytoma. 1834 33

As an increasing number of non-cardiac drugs have been reported to cause QT interval prolongation and torsades de pointes (TdP), we extensively studied the utility of atrioventricular (AV) block animals as a model to predict their torsadogenic action in human. The present review highlights such in vivo proarrhythmia models. In the case of the canine model, test substances were administered p.o. at conscious state >4 weeks after the induction of AV block, with subsequent Holter ECG monitoring to evaluate drug effects. Control AV block dogs (no pharmacological treatment) survive for several years without TdP attack. For pharmacologically treated dogs, drugs were identified as high, low or no risk. High-risk drugs induced TdP at 1-3 times the therapeutic dose. Low-risk drugs did not induce TdP at this dose range, but induced it at higher doses. No-risk drugs never induced TdP at any dose tested. Electrophysiological, anatomical histological and biochemical adaptations against persistent bradycardia-induced chronic heart failure were observed in AV block dogs. Recently, we have developed another highly sensitive proarrhythmia model using a chronic AV block cynomolgus monkey, which possesses essentially the same pathophysiological adaptations and drug responses as those demonstrated in the canine model. As a common remodelling process leading to a diminished repolarization reserve may present in patients who experience drug-induced TdP and in the AV block animals, the in vivo proarrhythmia models described in this review may be useful for predicting the risk of pharmacologically induced TdP in humans.
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PMID:Sensitive and reliable proarrhythmia in vivo animal models for predicting drug-induced torsades de pointes in patients with remodelled hearts. 1855 73

In 2007 a meeting on drug-induced torsades de pointes (TdP) was held in London, UK, under the auspices of the British Society for Cardiovascular Research (BSCR). One of the objectives was to explore the validity of available biomarkers, risk factors and preclinical investigational methods for the detection of drug-induced TdP liability - preclinical methods and clinical 'thorough QT' testing. The first symposium was entitled "How validated are current models and biomarkers for testing drug-induced torsades de pointes liability?" Validation, as far as the symposium was concerned, meant that the endpoints measured in the method predict TdP liability specifically, selectively and quantitatively. Topics (and the publications derived from the presentations) were: human volunteer phase 1 studies [Vik, T., Pollard, C., & Sager, P. (2008-this issue), the anaesthetized rabbit TDP model [Carlsson, L. (2008-this issue), the AV blocked canine preparation [Oros, A., Beekman, J. D. M., & Vos, M. A. (2008-this issue), QT interval and its corrections in the in vivo conscious canine [Fossa, A. A. (2008-this issue), the rabbit heart failure model [Hamlin, R. L., & Kijtawornrat, A. (2008-this issue), the rabbit Langendorff preparation and the Screenit approach [Dumotier, B. M., Deurinck, M., Yang, Y., Traebert, M., & Suter, W. (2008-this issue), the wedge preparation [Yan G.-X. (2008-this issue)] and hERG screens [Hancox, J. C., McPate, M. J., El Harchi, A., & Zhang, Y. h. (2008-this issue). Unbeknownst to the speakers before the start of the sessions, the audience were invited, during the session, to rate each approach on a 0 to 10 scale in terms of the extent to which each approach appeared to be validated. The outcome of this exercise forms the basis of this article. We invite you to evaluate for yourselves the accompanying reviews in this edition of Pharmacology and Therapeutics.
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PMID:Perception of validity of clinical and preclinical methods for assessment of torsades de pointes liability. 1859 Jul 66

Abnormal excitability of myocardial cells may give rise to ectopic beats and initiate re-entry around an anatomical or functional obstacle. As K(+) currents control the repolarization process of the cardiac action potential (AP), the K(+) channel function determines membrane potential and refractoriness of the myocardium. Both gain and loss of the K(+) channel function can lead to arrhythmia. The former because abbreviation of the active potential duration (APD) shortens refractoriness and wave length, and thereby facilitates re-entry and the latter because excessive prolongation of APD may lead to torsades de pointes (TdP) arrhythmia and sudden cardiac death. The pro-arrhythmic consequences of malfunctioning K(+) channels in ventricular and atrial tissue are discussed in the light of three pathophysiologically relevant aspects: genetic background, drug action, and disease-induced remodelling. In the ventricles, loss-of-function mutations in the genes encoding for K(+) channels and many drugs (mainly hERG channel blockers) are related to hereditary and acquired long-QT syndrome, respectively, that put individuals at high risk for developing TdP arrhythmias and life-threatening ventricular fibrillation. Similarly, down-regulation of K(+) channels in heart failure also increases the risk for sudden cardiac death. Mutations and polymorphisms in genes encoding for atrial K(+) channels can be associated with gain-of-function and shortened, or with loss-of-function and prolonged APs. The block of atrial K(+) channels becomes a particular therapeutic challenge when trying to ameliorate atrial fibrillation (AF). This arrhythmia has a strong tendency to cause electrical remodelling, which affects many K(+) channels. Atrial-selective drugs for the treatment of AF without affecting the ventricles could target structures such as I(Kur) or constitutively active I(K,ACh) channels.
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PMID:Role of potassium currents in cardiac arrhythmias. 1865 69


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