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)

Left ventricular systolic dysfunction is mainly a result of coronary artery disease (CAD). Decrease in myocardial contractility results as a response to a chronic hypoperfusion state that produces a change in cardiac myocyte metabolism, resulting in a perfusion-contraction mismatch in which function is sacrificed for survival. If revascularization is performed in a timely fashion, metabolism can be restored leading to recovery of function. Through the use of noninvasive imaging modalities, assessing myocardial viability can be easily performed and will aid in selecting those patients who will benefit from revascularization. Viable myocardium can be identified by nuclear modalities that have a high sensitivity but a lower specificity, such as thallium-201 single photon emission computed tomography and positron emission tomography (PET); or by the use of dobutamine stress echocardiogram (DSE), which has a decreased sensitivity but a better specificity. A modality that is increasingly being used with an overall good sensitivity and specificity is contrast-enhanced magnetic resonance imaging. The purpose of this review is to explore the amount of myocardial viability that is relevant to pursue revascularization, since as myocardial function improves there is a decrease in morbidity and mortality from heart failure and arrhythmias.
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PMID:Viable myocardium: how much is enough? 1566 Jun 92

Assessment of myocardial viability is clinically important in the work-up of patients with ischemic cardiomyopathy. Numerous studies in the past 2 decades demonstrated that revascularization improves left ventricular ejection fraction (LVEF), heart failure symptoms and prognosis in patients with viable myocardium. Conversely patients without viable tissue do not benefit from revascularization. Also, a substantial amount of viable myocardium (at least 25% of the left ventricle) is needed to result in improvement of LVEF. Hence, both identification and quantification of the extent of viable myocardium are required for a careful selection of candidates for revascularization. Indeed, the presence of a substantial amount of viable myocardium decreases the risk of surgery in patients with reduced LVEF. Several diagnostic techniques are available to identify myocardial viability. Positron emission tomography (PET), myocardial perfusion imaging, and stress echocardiography are considered the traditional techniques to evaluate myocardial viability. Recently, newer techniques including cardiac magnetic resonance (CMR), myocardial contrast echocardiography (MCE) and electromechanical mapping have been introduced. In this manuscript the status of the currently available techniques to assess viability was reviewed. Also the relative merits of each technique for prediction of functional recovery and prognosis was addressed. The available retrospective data support the clinical use of viability assessment. Patients with ischemic cardiomyopathy should undergo viability testing to determine therapeutic strategy. In the presence of substantial amount of viable myocardium, patients should undergo revascularization since benefits in terms of left ventricular function, remodeling, symptoms and prognosis may be anticipated. However, prospective randomized trial are needed to confirm these data.
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PMID:Assessment of myocardial viability in chronic ischemic heart disease: current status. 1572 38

The left ventricular assist device (LVAD) is usually used in patients with end-stage heart failure as a bridge to transplantation. Recently, some studies have reported functional recovery with the use of an LVAD, although the mechanisms responsible for recovery are not fully understood. We investigated the functional recovery of the infarcted, failing rat heart in response to mechanical unloading after heterotopic transplantation. Heart failure was induced in Lewis rats by ligating the left anterior descending artery. After 4 weeks, the infarcted hearts were harvested and heterotopically transplanted. The transplanted infarcted heart was removed after 2 weeks of unloading and examined for hypertrophy and fibrosis, as well as for mRNA levels encoding for brain natriuretic peptide, sarco(endo)plasmic reticulum Ca(2+)-ATPase2a (SERCA2a), and beta1- and beta2-adrenergic receptors. Normal and infarcted rats without transplantation served as control animals. The infarcted heart was hypertrophied as evidenced by an increase in heart weight and myocyte diameter. After unloading the infarcted heart for 2 weeks, there was a decrease in heart weight and myocyte diameter. However, the percentage of myocardial fibrosis increased after unloading. The mRNA expression of brain natriuretic peptide and the beta2-adrenergic receptor significantly improved after mechanical unloading. The levels of SERCA2a mRNA tended to increase after unloading. In conclusion, unloading the failing, infarcted heart can help normalize left ventricular hypertrophy and cardiac gene expression. This unloading model appears to partially mimic the conditions of hemodynamic support with an LVAD in heart failure patients and potentially offers insights into the mechanisms of functional recovery.
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PMID:Heterotopic transplantation of the failing rat heart as a model of left ventricular mechanical unloading toward recovery. 1574 45

Acute activation of the serine-threonine kinase Akt is cardioprotective and reduces both infarction and dysfunction after ischemia/reperfusion injury (IRI). However, less is known about the chronic effects of Akt activation in the heart, and, paradoxically, Akt is activated in samples from patients with chronic heart failure. We generated Tg mice with cardiac-specific expression of either activated (myristoylated [myr]) or dominant-negative (dn) Akt and assessed their response to IRI in an ex vivo model. While dn-Akt hearts demonstrated a moderate reduction in functional recovery after IRI, no function was restored in any of the myr-Akt-Tg hearts. Moreover, infarcts were dramatically larger in myr-Akt-Tg hearts. Biochemical analyses demonstrated that chronic Akt activation induces feedback inhibition of PI3K activity through both proteasome-dependent degradation of insulin receptor substrate-1 (IRS-1) and inhibition of transcription of IRS-1 as well as that of IRS-2. To test the functional significance of these signaling changes, we performed in vivo cardiac gene transfer with constitutively active PI3K in myr-Akt-Tg mice. Restoration of PI3K rescued function and reduced injury after IRI. These data demonstrate that PI3K-dependent but Akt-independent effectors are required for full cardioprotection and suggest a mechanism by which chronic Akt activation can become maladaptive.
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PMID:PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury. 1607 47

Implantation of a left ventricular assist system (LVAS) in patients with idiopathic dilated cardiomyopathy (DCM) may improve cardiac function and allow explantation of the device. Generally, an ejection fraction of more than 40% is considered necessary for successful weaning from an LVAS, but less than 10% of DCM patients with an LVAS can achieve such a significant recovery of cardiac function. Cardiac resynchronization therapy, or atrial-synchronized biventricular pacing, has been found to treat congestive heart failure and ventricular dyssynchrony effectively. Here we report on a patient with an LVAS, in whom enough functional recovery could be obtained with resynchronization therapy for the device to be explanted successfully. A 32-year-old man was implanted with a Toyobo-NCVC paracorporeal LVAS to treat his intractable heart failure caused by idiopathic dilated cardiomyopathy. While on the LVAS for 8 months, his cardiac function recovered to some extent. The ejection fraction of his left ventricle (LVEF) improved from 9% to 41%. He chose explantation of the device rather than heart transplantation. Because he occasionally showed a wide QRS pattern on his ECG, epicardial biventricular pacing leads as well as a biventricular pacemaker were implanted on LVAS explantation surgery. An echocardiogram 2 weeks after explantation showed a marked difference in his LVEF by switching his biventricular pacing on and off (40% with biventricular pacing on and 29% with it off). Biventricular pacing may help recovery of cardiac function in selected LVAS patients and contribute to the increase in bridge to recovery cases.
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PMID:Successful bridge to resynchronization therapy with a left ventricular assist system in a patient with idiopathic dilated cardiomyopathy. 1623 39

The development of heart failure (HF) after acute myocardial infarction (MI) is recognized as a major complication that leads to a significant increase in morbidity and mortality. Given the availability of effective treatments for improving both quality of life and survival for patients at increased risk for developing HF after MI, early identification of these individuals is critical. Noninvasive cardiac imaging offers a detailed characterization of two important pathophysiological processes related to the development of HF post-MI: left ventricular (LV) remodeling and LV functional recovery. Cardiovascular MRI has recently emerged as the preferred noninvasive imaging modality because of its ability to provide the most comprehensive and informative evaluation of these processes. In addition to allowing for an accurate and reproducible longitudinal follow-up of LV volumes and mass, MRI also offers information on infarct size, the presence of microvascular obstruction, and the transmural extent of infarct scar, all of which are valuable parameters that can assist in identifying patients at risk for developing HF after MI.
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PMID:Cardiac imaging to identify patients at risk for developing heart failure after myocardial infarction. 1633 11

Association studies suggest beta(1)-adrenergic receptor (beta(1)-AR) polymorphisms are disease modifiers in heart failure. The Arg389 variant has increased coupling to G(s) in transfected cells and evokes enhanced ventricular function in transgenic mice. Here, we assessed the differential effects of the human Gly389 and Arg389 beta(1)-AR polymorphisms on myocardial recovery after ischemic injury. Function was studied in transgenic mice with cardiac-specific expression of either human Gly389 or Arg389 beta(1)-AR at baseline and after 20 min of ex vivo ischemia and reperfusion (I/R). In 3-mo-old mice of either genotype, there was poor recovery after I/R (approximately 38% vs. approximately 68% for nontransgenic). Paradoxically, at 6 mo of age, functional recovery remained severely depressed in Gly389 hearts (approximately 32%) but was similar to nontransgenic for Arg389 hearts (approximately 60%). In Arg389 hearts, agonist-promoted adenylyl cyclase activities were depressed by approximately 35% at 6 mo of age, and G protein-coupled receptor kinase (GRK) activity was increased by approximately twofold compared with Gly389. Furthermore, I/R evoked an approximately threefold increase in ERK2 phosphorylation in Arg389 but an approximately twofold decrease in Gly389 hearts. Individually, these changes have been shown to mitigate I/R injury; thus the Arg389-beta(1)-AR uniquely evokes specialized pathways that act to protect against I/R injury. The improved recovery of function after I/R in Arg389 hearts relative to Gly389 appears to be due to an adaptive multimechanism program with allele-specific alterations in receptor signaling, GRK activity, and ERK2. Thus genetic variation of the human beta(1)-AR may play a role in cardiac functional recovery after ischemic injury.
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PMID:Myocardial beta1-adrenergic receptor polymorphisms affect functional recovery after ischemic injury. 1653 90

Due to the poor correlation between symptoms and left ventricular (LV) ejection fraction in a chronic heart failure (HF) population, the ability to identify patients who demonstrate LV functional recovery poses a dilemma for the clinician. Serial echocardiograms are not practical in a large outpatient HF population. Plasma brain natriuretic peptide (BNP) levels have a high predictive value for excluding patients with ventricular dysfunction and therefore could serve as a marker for identifying patients who demonstrate improved LV function. To evaluate this point, the researchers obtained baseline BNP levels in 380 chronic systolic HF patients seen in an outpatient HF clinic. Each patient already had a baseline echocardiogram performed before or on entry into the clinic. Fifty patients were identified in this group as having normal BNP levels (< or = 100 pg/mL). Echocardiograms were then repeated in this group and compared with initial echocardiographic data obtained from a retrospective chart review. The results showed that the mean LV ejection fraction for the group was increased (p < 0.001), mean LV internal dimension was decreased (p < 0.001), and the number of patients with an ejection fraction > 50% increased from zero to 20 (p < 0.001). Thus, normal BNP levels can correlate with LV recovery and could potentially offer a cost-effective method of assessing changes in LV function in patients with chronic HF.
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PMID:Brain natriuretic peptide levels and left ventricular functional recovery in a chronic heart failure population. 1659 41

Kidney transplantation is now recognized as the treatment of choice for patients with chronic renal failure. Despite the extension of indications to patients suffering severe hypertension, ischemic heart disease, and chronic heart failure, the worldwide results are superb. However, perioperative cardiac complications occur in 6% to 10% of transplanted patients. Aggressive intraoperative volume expansion is still recommended to maximize graft functional recovery (up to 30 mL/kg/h, central venous pressure [CVP] > 15 mm Hg), but patients with preexistent cardiac disease or poor myocardial function are exposed to the risk of fluid overload, acute respiratory failure, and prolonged ventilation. Among the last 90 cases performed at our institution, good functional recovery of the graft was present in 94% of the patients within 2 weeks, despite a much more conservative intraoperative hydration policy (crystalloids 2400 +/- 1000 mL, 15 mL/kg/h, CVP 7-9 mm Hg). Graft failure which occurred in 5 patients was significantly correlated only with donor age, while perioperative cardiovascular complications had been present in 9 cases (10%) who were coronary artery disease patients (55%). Age above 50 years was the only significant risk factor. Supranormal volume loading is probably not always warranted in kidney transplantation.
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PMID:Perioperative fluid management in kidney transplantation: is volume overload still mandatory for graft function? 1664 77

We did a PubMed and Cochrane Database System review of different studies on the diverse effects of erythropoietin (EPO), focusing mainly on the cardiovascular system. The direct erythropoietic action of EPO is well studied and widely used. Published studies report dramatic improvement in the course of heart failure with EPO treatment. New controlled clinical trials on large and diverse groups of patients are warranted. Antiapoptotic effects of EPO are newly discovered, opening new horizons in both clinical investigation and therapy. The salvage of cardiomyocytes in acute coronary syndromes, limiting the size of myocardial infarction and improving functional recovery, is only one of multiple potential applications of this effect. Derivatives of EPO with selective antiapoptotic properties seem to hold the best prospects for future studies. Heart failure and ischemic heart disease are potential areas where adding EPO to the conventional treatment may be beneficial.
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PMID:Cardiovascular effects of erythropoietin: anemia and beyond. 1678 33


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