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)

Dobutamine is a synthetic ionotropic catecholamine commonly used to treat heart failure and shock. The catabolic fate of dobutamine in humans has yet to be reported, although formation of 3-O-methyldobutamine represents the principal pathway of dobutamine disposition in the dog. Herein, we describe the isolation and identification of 3-O-methyldobutamine in the urine of children receiving infusions of racemic dobutamine. In a 9-year-old child with heart failure approximately 80% of dobutamine administered intravenously at steady state was detected in the urine. Forty-seven percent of infused dobutamine was identified as 3-O-methyldobutamine and its acid-hydrolyzed derivatives, the latter mostly conjugated with sulfate (33%). Thirty-two percent consisted of acid-hydrolyzed dobutamine metabolites, primarily conjugated with sulfate (16%). Sonicates of human blood mononuclear cells catalyzed the formation of 3-O-methyldobutamine from dobutamine and S-adenosylmethionine in vitro. These findings indicate that formation of 3-O-methyldobutamine constitutes a major pathway of dobutamine metabolism in humans.
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PMID:3-O-methyldobutamine, a major metabolite of dobutamine in humans. 1195 Jul 81

Levosimendan is one of the first agents of a new class of drugs known as calcium sensitizers. These drugs are believed to increase cardiac contractility by sensitizing cardiac myofibrils to calcium, and may therefore be of clinical benefit in the treatment of low-cardiac output states, particularly congestive heart failure. In addition to sensitizing troponin to intracellular calcium, levosimendan has been shown to inhibit phosphodiesterase III, which may contribute to its positive inotropic effect, and open adenosine triphosphate (ATP)-sensitive potassium channels (K(ATP)), which may produce vasodilation. Unlike currently available intravenous inotropes, levosimendan does not increase myocardial oxygen utilization, has not been shown to be proarrhythmic, and has been used effectively in the presence of beta-blocking medications. Levosimendan also has not been shown to impair ventricular relaxation, which was an initial concern with this class of drugs. Clinical studies of levosimendan have demonstrated short-term hemodynamic benefits of levosimendan over both placebo and dobutamine. While large-scale, long-term morbidity and mortality data are scarce, the Levosimendan Infusion versus Dobutamine in severe low-output heart failure (LIDO) study suggested a mortality benefit of levosimendan over dobutamine up to 180 days after treatment. Clinical studies comparing levosimendan with other positive inotropes, namely milrinone, are lacking. Levosimendan treatment appears to be well-tolerated, with the primary adverse events being headache and hypotension. No clinically significant drug-drug interactions have been reported with levosimendan to date. The clinical future of levosimendan will depend on the results of larger, ongoing clinical trials.
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PMID:Levosimendan: a unique approach to the treatment of heart failure. 1214 86

Dobutamine echocardiography (DE), magnetic resonance imaging (MRI), and thallium redistribution (TS) are used to assess cardiac viability. However, these modalities sometimes yield contradictory results. Our aim was to establish the degrees of agreement among DE, MRI, and TS in identifying myocardial viability and to analyze the minimum critical mass of live (viable) cells required for each test to identify viability. A prospective study was done in which DE, MRI, and TS were consecutively performed in 10 ischemic patients scheduled for heart transplantation. The explanted heart was analyzed to quantify the amount of live cells per segment. The pathologic data were compared with the test results to analyze the minimum mass of viable cells required by each technique to identify viability. Mean age was 58 +/- 8 years (8 men). The mean ejection fraction was 0.27 +/- 0.04. Seven patients had severe cardiac failure (New York Heart Association functional class IV) and 6 patients had refractory angina. A total of 150 cardiac segments were analyzed. Among the 150 segments, 107 (71.3%) showed some degree of myocardial necrosis. Mean total area, mean fatty area, and mean necrotic area per segment were 2.53 +/- 0.7, 0.13 +/- 0.2, and 0.55+/-0.5 cm(2), respectively. As expected, a higher amount of necrotic tissue was found in nonviable segments. From the 150 segments, DE identified 90 as viable and 60 as nonviable. These data were similar to that of MRI (98 viable and 52 nonviable). A higher proportion of viable segments was found by TS (117 viable vs 33 nonviable). The concordance between DE and TS was only moderate (kappa 0.49). The agreement between MRI and TS also showed moderate concordance (kappa 0.56). The highest agreement was found between DE and MRI (kappa 0.73). Thus, discrepancies in assessing viability by DE, MRI, and TS may be due to differences in the minimum critical mass of live myocytes required by each technique to diagnose viability. Thallium requires a lesser amount of live tissue than DE or MRI to detect viability; also, its maximum diagnostic efficiency is obtained with lesser amounts of live tissue on each segment. These considerations should be taken into account when these diagnostic tests are used for the detection of viability before revascularization procedures.
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PMID:Reason for discrepancies in identifying myocardial viability by thallium-201 redistribution, magnetic resonance imaging, and dobutamine echocardiography. 1220 1

We compared the cardiac inotropic, chronotropic, and myocardial O(2) consumption (MVO(2)) responses to the sodium (Na(+)) channel enhancer, LY341311 [(S)-4-[3-[[1-(diphenyl-methyl)-3-azetidinyl]oxy]-2-hydroxypropoxy]-1H-indole-2-carbonitrile monohydrate], with the beta-receptor agonist dobutamine in conscious dogs with heart failure. Heart failure was induced in chronically instrumented dogs by right ventricular pacing at 240 beats per minute for 3 to 4 weeks. LY341311 (10-100 microg/kg/min i.v.) dose dependently increased cardiac contractile function as reflected, at the highest dose, by increases in left ventricular dP/dt(max) (55 +/- 7%), and fractional shortening (62 +/- 9%), accompanied by increases in cardiac stroke work (111 +/- 18%) and minute work (34 +/- 10%) and decreases in heart rate (33 +/- 4%). Dobutamine (2-15 microg/kg/min i.v.) increased contractile responses to a similar degree but also increased heart rate (15 +/- 5%) at the highest dose. Complete ganglionic blockade with hexamethonium and atropine or with hexamethonium alone abolished the bradycardic effect but not the inotropic response to LY341311. At similar levels of inotropic response, dobutamine (10 microg/kg/min) increased MVO(2) by 23 +/- 7% (P < 0.05), whereas LY341311 (100 microg/kg/min) had no effect. In the presence of left atrial pacing at a constant heart rate and at matched contractile work, MVO(2) was increased by LY341311 to the same extent as dobutamine. These data indicate that autonomically mediated bradycardia produced by LY341311 contributes to a favorable net metabolic effect on myocardial O(2) utilization in the failing heart while providing inotropic support comparable to a beta-receptor-mediated agonist.
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PMID:Combined inotropic and bradycardic effects of a sodium channel enhancer in conscious dogs with heart failure: a mechanism for improved myocardial efficiency compared with dobutamine. 1238 50

Patients with acute congestive heart failure generally present with profound fluid retention states and dyspnea due to pulmonary edema. If the condition is not aggressively and appropriately treated, irreversible cardiac decompensation may ensue, leading to cardiogenic shock, multiorgan failure, and death. Intravenous inotropic, vasopressor, and vasodilator therapies have proved effective in initial stabilization of acute heart failure decompensation, but these agents, particularly the traditionally used ones, are generally limited by side effects that can be egregious and include substantive ventricular arrhythmias. Dobutamine has largely replaced agents with rather profound toxicity, such as isoproterenol and epinephrine. The phosphodiesterase-inhibiting agent milrinone, having both vasodilator and inotropic properties, can produce tachycardia and significant ventricular arrhythmias, but has proven quite useful for seriously ill patients. Clinical trials of levosimendan have found a positive inotropic response when the drug is given parenterally; vasodilating properties are also evident. Clinical trials are under way to evaluate the potential benefits of endothelin receptor antagonists when given intravenously. Intravenous administration of nesiritide, a recombinant human B-type natriuretic peptide, has been shown to produce favorable hemodynamic effects, including balanced vasodilation associated with a rapid improvement in clinical symptoms.
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PMID:New therapeutic choices in the management of acute congestive heart failure. 1243 58

A forty-one-year-old male, with no risk factors for coronary artery disease (CAD) and with moderate alcohol intake, was admitted in 1992 to Portalegre Hospital with heart failure due to viral cardiomyopathy. He was re-admitted in 1998 with acute pulmonary edema and was put on mechanical ventilation for 48 hours, and transferred to Pulido Valente Hospital when stable. The physical exam was without abnormalities. ECG showed first degree AV block, left ventricular hypertrophy and 2 mm ST depression in the precordial leads. The echocardiogram revealed left ventricular dilatation and depressed systolic function. Coronary angiography showed single-vessel CAD and coronary artery anomaly. Dobutamine stress echocardiography was halted due to hypertension, making it impossible to evaluate ischemic response. Holter monitoring showed five-complex ventricular tachycardia. The patient was discharged medicated with amiodarone, with indication for cardiac scintigraphy and electrophysiological study.
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PMID:Left main coronary artery originating in the right sinus of Valsalva. 1500 65

Stress echocardiography is a useful noninvasive modality for measuring dynamic outflow gradient and contractility changes in patients with hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM). In patients with HCM, stress echocardiography may determine the degree of outflow tract obstruction at rest and with activity, can detect occult systolic dysfunction in symptomatic patients with a normal resting left ventricular ejection fraction, and can also be utilized to monitor the efficacy of treatment. In individuals suffering from DCM, stress echocardiography is an important aid in the evaluation of the etiology, diagnosis, and prognosis of the disease as well as the functional status of the patient during either exercise or simulated stress conditions. Dobutamine stress echocardiography, by providing a measurement of the myocardial reserve, is a useful tool to predict the systolic recovery and clinical outcome of patients with heart failure. The stress-induced change in the wall motion score index can also be used as an accurate alternative to predict the peak oxygen consumption rate and exercise capacity of the same patient population. Finally, stress echocardiography has also been used in the identification of the predilated phase of cardiomyopathy in individuals with high clinical suspicion of the disease.
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PMID:An overview of stress echocardiography in the study of patients with dilated or hypertrophic cardiomyopathy. 1520 31

Congestive heart failure is an increasingly common condition carrying a poor prognosis and a decay in the quality of life. Usually frequent and lengthy hospitalizations are required with heart failure, with obvious discomfort for the patient and increase in health costs. Heart transplantation is rarely possible due to shortage of donors. Thus, improvement of pharmacological strategies for the management of these patients is desirable. The present study evaluated the effects of intermittent dobutamine infusion in elderly patients (mean age 75.9 years), hospitalized for advanced (NYHA, 1973, class IV) congestive heart failure of ischemic etiology. Dobutamine infusions of 2, 4 and 6 microg/kg/min for 36 h every 2-4 weeks were randomly prescribed to 24 subjects, who were then followed up every three months for an average of ten months. Data on mortality, cardiovascular events and NYHA (1973) functional classifications were systematically collected. Our study shows that while in this series of patients mortality remained high (50% at 12 months), there was an improvement in the NYHA-classification during the follow-up, and a decrease in the need for hospitalization. In addition, side effects were relatively rare, with only two patients interrupting dobutamine treatment. We conclude that intermittent dobutamine infusion is a reasonable treatment option in elderly patients with congestive heart failure unresponsive to conventional treatments.
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PMID:Intermittent dobutamine therapy in patients with advanced congestive heart failure. 1537 51

The natural history of aortic stenosis is well defined. There is overwhelming evidence that patients with this disease who develop symptoms require prompt aortic valve replacement, as average survival rapidly falls. Once surgery has been performed age-corrected rates of survival approach the rate in the normal population. Conversely, asymptomatic patients with severe aortic stenosis have an excellent clinical prognosis. Nevertheless, there is a low risk of sudden death or rapid rate of progression to the symptomatic state. This low risk while patients remain asymptomatic does not outweigh the risk associated with valve replacement surgery or the complications of artificial prostheses, so surgery is not recommended for the entire group of asymptomatic patients. Therefore, therapeutic decisions in patients with aortic stenosis are based on the definition of symptomatic status and of hemodynamic severity, so accurate evaluation of these two issues is mandatory. However, establishing symptomatic status and severity of valve disease can be challenging because assessment of subjective symptoms and functional capacity is sometimes ambiguous, particularly in the elderly. Furthermore, it is well recognized that assessment of hemodynamic obstruction defined by echocardiographic indexes such as transvalvular pressure gradient and aortic valve area, is suboptimal because of technical difficulties and poor correlation with symptoms. Hence, aortic stenosis evaluation should be also performed introducing in clinical practice new simple indexes, such as function- and pressure-corrected indexes and energy loss index, that could provide a different estimate of disease severity, based on prognostic indication of adverse clinical outcome. Indeed, clinical outcome represents the real endpoint for defining severity and should be incorporated in clinical assessment and used to aid patient management in unclear situations. The development of heart failure in patients with aortic stenosis is associated with a high mortality rate and requires a careful management that includes an initial evaluation of the severity of the stenosis and the functional state of the left ventricle. Left ventricular dysfunction is usually due to afterload mismatch, but as end stage develops, decline in the intrinsic myocardial contractility becomes the most relevant mechanism. However, separating the effect of myocardial contractile dysfunction from that of afterload mismatch on pump performance is difficult. Dobutamine echocardiography can be useful both by testing myocardial contractile reserve and by separating true from relative aortic stenosis. Unfortunately the optimal management of patients with severe aortic stenosis and left ventricular dysfunction remains controversial, and we still have missing data to determine which patients are more likely to benefit from aortic valve replacement, by improving survival and functional status, with an acceptable perioperative mortality rate.
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PMID:[Echocardiography in aortic stenosis: new insights into challenging scenarios]. 1547 Nov 50

Cardiovascular magnetic resonance (CMR) has established itself as probably the single best way of phenotyping the failing heart. It is the accepted gold standard for measuring cardiac function, volumes, and mass, but within the same scan session additional techniques are available for greater definition. Tissue characterization with the contrast agent gadolinium is well validated and allows the precise visualization and quantification of myocardial infarction. This can be used for viability assessment and to determine heart failure etiology. Dobutamine stress CMR and CMR perfusion hold advantages over conventional techniques. The new frontiers of CMR in heart failure hold the promise of unique insights quantifying myocardial iron, nonischemic fibrosis, microvascular perfusion, plaque characterization, and CMR-targeted intervention. The development and validation of these techniques represent major research challenges for the future. From a clinical perspective, an equal challenge is in increasing the availability of the modality for patients and physicians.
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PMID:Cardiovascular magnetic resonance and the evaluation of heart failure. 1561 Jun 47


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