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)

Alterations in the expression of myocardial regulatory proteins (e.g. beta-adrenoceptor, inhibitory G-proteins) in human heart failure are associated with excessive stimulation of the cAMP signalling pathway by endogenous catecholamines. The transcription factor cAMP response element binding protein (CREB) mediates cAMP-dependent transcriptional activation and is expressed in the human heart. Here, CREB protein was immunologically quantified in ventricular nuclear protein preparations from nonfailing donor hearts (n = 8) and from failing hearts transplanted due to dilative (n = 10) or ischemic cardiomyopathy (n = 6). CREB expression was unchanged in ventricular nuclei from failing hearts compared to the nonfailing controls suggesting that expressional alterations in human heart failure cannot be explained by altered expression of CREB.
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PMID:Quantification of the cAMP response element binding protein in ventricular nuclear protein from failing and nonfailing human hearts. 924 Apr 39

In addition to left ventricular pump failure and low cardiac output, structural and metabolic alterations of skeletal muscle are thought to contribute to exercise intolerance seen in patients with CHF. Studies using cardiac myocytes have implicated nitric oxide elaborated by inducible nitric oxide synthase (iNOS) as a potential agent associated with the genesis of dilated cardiomyopathy. The present study was designed to locate iNOS in the working skeletal muscle of patients with congestive heart failure. Specific antibodies were used to detect iNOS by immunohistochemistry in skeletal muscle biopsies (m. vastus lateralis) of 37 patients with left ventricular pump failure and 8 normal controls. The expression was restricted to skeletal muscle myocytes and was increased five- to ninefold in patients with chronic heart failure. There was no statistically significant difference in iNOS expression between patients with dilated cardiomyopathy and those with ischemic cardiomyopathy. The finding of a locally increased expression of iNOS and the experimental evidence that NO attenuates the contractile performance of the skeletal muscle suggest that the expression of iNOS may be responsible for the exercise intolerance seen in patients with chronic heart failure.
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PMID:Increased inducible nitric oxide synthase in skeletal muscle biopsies from patients with chronic heart failure. 925 80

Advanced coronary artery disease (CAD) and ischemic cardiomyopathy with elevated pulmonary artery pressures are criteria of a severe illness. In selected cases surgical revascularization has proved beneficial in terms of survival, reduction of morbidity and lowering the frequency of angina pectoris [6] in numerous studies over the past 25 years. But most of the earlier publications concentrated on patients with angina pectoris (AP) as a dominant symptom. Patients without AP but with predominant signs of congestive heart failure were largely excluded. This has changed recently [1-3,7,8,10,12,16,18] with the advent of the concept of hibernating myocardium. This term is defined as the presence of persistent myocardial and left ventricular dysfunction at rest due to reduced regional coronary blood flow that can be partially or completely restored to normal by myocardial revascularization [5,19]. Salvage of viable myocardium by successful revascularization improves left ventricular dysfunction. Diagnosis of hibernating myocardium is crucial because it does not leave the patient with chronic heart failure a candidate only for cardiac transplantation. Instead, these patients' left ventricular dysfunction is potentially reversible following revascularization by coronary bypass surgery. Furthermore we face a critical shortage of donor organs and extending waiting lists for possible transplant candidates. Following the start of the heart transplantation (HTX) program at our institution more than 690 operations were performed until September 1995. We screened more than 1600 patients for their eligibility as cardiac transplant recipients or for other forms of treatment. In this group of patients it has always been our policy to revascularize rather than transplant whenever possible.
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PMID:Ischemic cardiomyopathy--revascularization vs. transplantation. 927 Nov 73

The noninvasive assessment of myocardial viability has proved clinically useful for distinguishing hibernating myocardium from irreversibly injured myocardium in patients with chronic ischemic heart disease or recent myocardial infarction who exhibit marked regional and global left ventricular dysfunction. Noninvasive techniques utilized for detection of viability in asynergic myocardial regions include single-photon-emission CT perfusion imaging with 201Tl or one of the new 99mTc-labeled perfusion agents, positron emission tomographic imaging of perfusion and glucose uptake, low-dose dobutamine echocardiography for assessment of inotropic reserve, and contrast echocardiography for evaluation of microvascular integrity. The greater the number of viable myocardial segments by any of these techniques, the greater is the probability of improvement in regional and global left ventricular function, improvement in heart failure symptoms and functional capacity, and enhanced survival after revascularization. Patients with a decreased left ventricular ejection fraction and extensive myocardial viability treated medically have a high cardiac event rate. Similarly, patients with poor viability preoperatively who still undergo coronary bypass surgery have a high rate of early and late cardiac death or need for transplantation compared with patients with greater viability. Finally, some patients with severe ischemic cardiomyopathy referred for cardiac transplantation may have substantial zones of hibernation and may still be candidates for coronary bypass surgery, even in the absence of angina.
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PMID:Assessment of myocardial viability. 935 73

The purpose of the present study was to determine the prevalence of thromboembolic events in patients with primary and secondary (ischemic) dilated cardiomyopathy (DC), with regard to basic rhythm, sinus or atrial fibrillation. Retrospectively, over three years, from January 1, 1989 to December 31, 1991, the case histories of 75 inpatients with DC, mean age 56.2 +/- 14.1 years, 41 in sinus rhythm and 34 in atrial fibrillation from Clinic Hospital Split were analyzed and compared to those of 75 controls (heart failure with no DC). The incidence of thrombi, embolisms and mortality in both subgroups was similar, while the prevalence of thromboembolic events was significantly higher in the analyzed than in the control group (decompensated patients with ischemic cardiomyopathy and without cardiomegaly) (9/75:1/75, p < 0.05). Prospectively, between 9 and 22 months, from December 1, 1991 to September 30, 1993 51 consecutive decompensated outpatients with DC, in NYHA class II and III, mean age 54.2 +/- 15 years, were followed-up. Bilirubin, lactic dehydrogenase, prothrombin time and activated partial thromboplastin time were determined. 1-D and 2-D transthoracic echocardiographic exam was performed and clinical status was assessed. There were 24 patients in sinus rhythm and 27 patients in atrial fibrillation. The prevalence of thromboembolic events, thrombi and mortality in both subgroups was similar. The laboratory findings, indicators of possible thrombogenesis or thrombolysis, did not show any significant difference in both subgroups. The incidence of thrombi in both parts of this study was low, amounted to only 9.5% (12/126) with no clear signs of thromboembolism (these patients were anticoagulated!). Altogether 12.6% (16/126) patients suffered thromboembolic events, 9 in retrospective and 7 in prospective part of the trial (more patients were anticoagulated in prospective then in retrospective study, 5 versus 19; p < 0.05). We conclude that thromboembolism in patients with decompensated DC are rare, but appear at significantly higher rate than in decompensated patients with ischemic cardiomyopathy and no cardiomegaly. The beneficial effects of anticoagulant therapy are to be expected in these patients regardless of the basal rhythm. This hypothesis must, however, be assessed in a prospective, multicentric trial.
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PMID:[Occurrence of thromboembolic complications in patients with dilated cardiomyopathy. Retrospective-prospective study]. 937 20

Continuing high morbidity and mortality have spurred an ongoing search for new therapeutic agents for patients with congestive heart failure. Calcium antagonists (CAs) have been under active investigation in patients with heart failure since their introduction into clinical medicine, because their anti-ischemic and vasodilator properties were thought to be of potential benefit in this patient population. However, review of published clinical trials of CAs in patients with heart failure reveals that some of these drugs are associated with detrimental effects, including acute hemodynamic deterioration, increased symptoms of heart failure, and increased mortality. The adverse effects of short-acting CAs in patients with heart failure include negative inotropic effects and neurohormonal activation. Long-acting CAs, such as amlodipine and felodipine, had fewer negative inotropic effects, showed less evidence of neurohormonal activation, and were better tolerated in clinical trials. Amlodipine, in combination with an angiotensin-converting enzyme inhibitor, had a neutral effect in patients with ischemic heart failure and an unexplained benefit in a subgroup of patients with non-ischemic cardiomyopathy. Although the preliminary experience with long-acting dihydropyridine CAs in heart failure has been encouraging, safety concerns raised by past trials dictate that no CA can be recommended for the treatment of heart failure at this time.
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PMID:Safety of calcium antagonists in patients with congestive heart failure. 938 7

The role of calcium antagonists in patients with ischemic heart failure is currently unclear. We examined the effects of amlodipine on exercise capacity and central and regional hemodynamics in 32 patients with mild to moderate chronic heart failure in a single-center, double-blind, randomized placebo-controlled trial. All were taking at least 40 mg of furosemide daily with an angiotensin-converting enzyme inhibitor. Ischemic heart disease was the most common cause of heart failure, but no patient had symptom-limiting angina. Mean treadmill exercise capacity in patients taking amlodipine increased by 96 seconds (95% confidence interval -23 to 215) and 50 seconds (-34 to 135) in the placebo group; mean difference in change between treatments was 70 seconds (-90 to 233), p = 0.38. Active treatment with amlodipine did not affect self-paced corridor walking times. Similarly, there were no significant effects on cardiac output, oxygen uptake, heart rate, and mean arterial pressure at rest or during exercise. Calf and renal blood flow were also unchanged by treatment. The lack of significant effect demonstrated by these data suggests a limited role for amlodipine in patients with ischemic cardiomyopathy, although it may prove beneficial in those with nonischemic disease. More data are required before amlodipine can be recommended for all patients with chronic heart failure.
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PMID:Effects of amlodipine in patients with chronic heart failure. 939 99

To examine important points surrounding the indications for heart transplantation (HTX) to care after HTX, we reviewed 22 patients with refractory heart failure aged less than 60 years who had been observed for the past 6 years. Sixteen patients had dilated cardiomyopathy; 1, dilated hypertrophic cardiomyopathy; 3, restrictive cardiomyopathy; and 2, ischemic cardiomyopathy; there were 15 males and 7 females, and 6 of the 22 patients were children. The 22 patients were divided into two groups according to their response to tailored medical therapy. Group 1 (n = 6) consisted of those whose cardiac function improved to New York Heart Association (NYHA) status 2 from NYHA status 3 or 4. Group 2 (n = 16) still exhibited refractory heart failure. Seven of these 16 patients went on to have successful HTX. Survival in groups 1 and 2 combined was significantly lower than actuarial survival post-HTX cited in the registry of the International Society for Heart and Lung Transplantation, and group 2 had an even lower survival than the total groups 1 and 2 survival. Survival in children was much lower than that in adults. Seven of the 16 patients in group 2 showed a genetic link, but there was no genetic link in group 1 patients. One patient in group 2 had a panel reactive antibody (PRA) value of 46% and died while awaiting HTX. Post-HTX care in terms of immunosuppressant therapy, was modified for each patient. It is particularly necessary to consider the time a patient will wait on the list for candidates for HTX who are children, have a genetic link, or are positive for PRA. A genetic approach is helpful to determine indications for HTX. Sensitive monitoring of post-HTX immunosuppression is needed.
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PMID:Points to note from indications for heart transplantation to post-heart transplant care: from the care of patients with refractory heart failure and overseas heart transplantation. 947 40

End-stage human heart failure is associated with changes in expression of steady-state messenger RNA (mRNA) levels. These changes correspond to alterations in protein levels and myocardial function and may have clinical implications regarding etiology, clinical state, or prognosis. However, analysis of mRNA levels in endomyocardial biopsies can be accomplished only by the quantitative polymerase chain reaction, which is difficult to standardize. The aim of the study was to evaluate whether the RNase protection assay is applicable to measure mRNAs of multiple genes simultaneously in small amounts of ventricular myocardium comparable to myocardial biopsies. Total RNA was prepared from left ventricular myocardium from terminally failing hearts with idiopathic (n=9) or ischemic cardiomyopathy (n=7) and from nonfailing control hearts (n=10). mRNA was measured by an optimized RNase protection assay for the beta1-adrenoceptor, the stimulatory G protein alpha-subunit (Gsalpha), phospholamban, the calcium ATPase of the sarcoplasmic reticulum (SERCA), beta-myosin heavy chain (beta-MHC), and the atrial natriuretic peptide (ANP). We extracted 10.7+/-2.1 microg total RNA from three myocardial biopsies taken in vitro. All of the six genes were measurable in duplicate in a total of 7 microg RNA. mRNAs of beta1-adrenoceptor, phospholamban, and SERCA were lower in failing than in nonfailing myocardium by 50%, 33%, and 42% respectively, whereas beta-MHC and Gsalpha mRNAs were unchanged. mRNA of ANP was expressed at high levels only in the failing myocardium, providing a highly specific and sensitive marker for discriminating nonfailing and failing hearts. A direct comparison with ANP and Gsalpha levels obtained by Northern blot analysis with 7.5 microg total RNA showed a good correlation between the two methods. The RNase protection assay is thus a suitable method for simultaneous measurements of multiple mRNA levels in human myocardial biopsies. Changes in mRNA levels closely reflected those identified by other methods using larger amounts of RNA. Increased myocardial ANP mRNA levels determined by the RNase protection assay may serve as a molecular marker of heart failure.
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PMID:Analysis of gene expression patterns in small amounts of human ventricular myocardium by a multiplex RNase protection assay. 950 Jun 79

Left ventricular remodelling plays an important pathogenetic role in progressive circulatory insufficiency both in dilated cardiomyopathy (DCMP) and in ischemic heart disease with postinfarction cardiosclerosis. In terminal cardiac failure structural changes (changed geometry of the left ventricle, in particular) become stereotypic. The dobutamin test in DCMP reveals low functional reserve of the total and segmentary contractility compared to ischemic cardiomyopathy. This may help in echocardiographic diagnostic difficulties.
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PMID:[Comparative characteristics of left ventricular remodeling in dilatation cardiomyopathy and ischemic disease]. 950 6


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