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

Results of 16 international published studies (with a total of 397 patients in NYHA-classes II-III) concerning chronic therapy with beta-adrenoceptor blockade in idiopathic dilated cardiomyopathy were analyzed. 8 studies were placebo controlled. Under beta-blockade cardiac output increased significantly by about 15% and ejection fraction by approximately 30%, apparently due to an improvement in contractility and relaxation of LV myocardium. Therapy was tolerated without complications in 93% of patients when the loading dose was 5 to 15 mg metoprolol/d (or equivalent) and a long-term dose of 100-200 mg/d metropolol (or equivalent) was reached within 4 weeks. Patients with severe heart failure (NYHA IV) had a higher risk of complications. A positive effect of beta-blockade in IDC was achieved in most cases but not earlier than after 2-3 months after initiating therapy. Despite these positive results beta-blockade in patients with IDC may not yet be recommended generally. Sufficient results of controlled trials are still lacking. Important questions with regard to the prognosis under beta-blockade, to the effects of cardioselectivity and intrinsic activity, and to the efficacy of this kind of therapy in the presence of ACE inhibitors have not been answered. Thus, major trials with controlled design are needed.
 ...
PMID:[Beta receptor blockers in dilated cardiomyopathy (clinical aspects)]. 136 61

In human end-stage heart failure an increased amount of inhibitory G-protein alpha-subunits (Gi alpha) is assumed to play a role in desensitization of the adenylyl cyclase signaling pathway. In the present study, northern blot experiments with 32P-labeled cDNA probes in ventricular tissue samples from explanted human hearts revealed that Gi alpha-2- and Gi alpha-3- mRNA are the predominant Gi alpha-mRNA subtypes in human ventricles, whereas Gi alpha-1-mRNA was not detectable. The mRNA for the stimulatory G-protein alpha-subunit (GS alpha) consisted of two mRNA sizes. Quantification of mRNA levels revealed a 103 +/- 38% increase in Gi alpha-2-mRNA levels in hearts with idiopathic dilative cardiomyopathy (IDC; n = 8), and a 77 +/- 25% increase in hearts with ischemic cardiomyopathy (ICM; n = 6) as compared to nonfailing controls (NF, n = 8). In contrast, Gi alpha-3- and GS alpha-mRNA levels were similar in failing and nonfailing hearts. To investigate whether or not the increased expression of Gi alpha-2-mRNA might be due to chronically elevated catecholamine levels, we determined the influence of a 4-day infusion of isoprenaline (Iso; 2.4 mg/kg.d), propranolol (Prop; 9.9 mg/kg.d), Iso + Prop or 0.9% NaCl as control (Ctr) on myocardial Gi alpha-mRNA and Gi alpha-protein levels in rats. In Iso-treated rats, hybridization experiments revealed a 49 +/- 18% (n = 7) and 27 +/- 7% (n = 8) increase in Gi alpha-2 and Gi alpha-3-mRNA, respectively. Pertussis toxin-catalyzed ADP-ribosylation revealed a 22 +/- 7% (n = 8) increase in Gi-protein as compared to Ctr (n = 8). These alterations were accompanied by an increased potency for the negative inotropic effect (NIE) of carbachol (mean EC50: 0.04 microM vs. 0.28 microM) in the presence of Iso in isolated electrically driven (1 Hz) papillary muscles. Prop itself had no effect, but it antagonized all Iso-induced effects. We conclude that, in human heart failure due to IDC or ICM, increased Gi alpha-2-, but not Gi alpha-3- mRNA levels accompany the increased amount of Gi alpha-protein, suggesting that this increase is at least in part due to increased de novo synthesis. The experiments in rats demonstrated that chronic beta-adrenergic stimulation leads to an increased expression of Gi alpha-mRNA and -protein, and to an enhanced potency of the negative inotropic effect of muscarinic agonists.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Regulation and possible functional implications of G-protein mRNA expression in nonfailing and failing ventricular myocardium. 149 78

Long-term LVADs are primarily used as a bridge to transplantation because cardiac transplantation currently offers a better long-term outlook for most patients. Some patients will not get the opportunity for transplantation due to organ shortages and long waiting lists, however, and alternate care strategies must be considered. LVAD weaning and explantation may be an appropriate course of action for patients who have IDC and in whom transplantation is not the optimal therapy. The data demonstrate that LVAD weaning may be performed successfully in selected patients with IDC, and that transplantation may be delayed or avoided altogether; however, VAD weaning is not without its risks. Many of the patients have demonstrated recurrence of heart failure at various times after undergoing device removal. Through proper monitoring, most of these patients can be identified early enough to be relisted for transplantation, although some will require reinsertion of an LVAD while waiting. The critical steps in establishing a successful VAD weaning program are proper patient selection, ventricular unloading in the early stages, the institution of heart failure medications, frequent monitoring for ventricular recovery, and a period of ventricular retraining before explantation. In addition, the surgeons must be able to perform the explantation procedure with a low operative mortality. As experience with LVAD weaning and explantation grows, we may be able to better predict which patients may be successfully treated without resorting to transplantation. Explantation may eliminate, or safely delay, the need for cardiac transplantation. Although it is unlikely that these patients will be studied in a randomized fashion, the collection of accurate and complete data may allow us to establish a database that can answer many of today's questions.
 ...
PMID:Short- and long-term mechanical ventricular assistance towards myocardial recovery. 1505 90

In experimental animals, bradykinin type-1 receptors (BK-1Rs) are induced during inflammation and ischemia, and, by exerting either cardioprotective or cardiotoxic effects, they may contribute to the pathogenesis of heart failure. Nothing is known about the expression of BK-1Rs in human heart failure. Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13), due to idiopathic dilated cardiomyopathy (IDC; n = 7) or to coronary heart disease (CHD; n = 6), and from normal hearts (n = 6). The expression of BK-1Rs was analyzed by means of competitive RT-PCR, Western blot analysis, and immunohistochemistry. Expression of BK-1R mRNA was increased in both IDC (2.8-fold) and CHD (2.1-fold) hearts compared with normal hearts. The observed changes were verified at the protein level. Expression of BK-1Rs in failing hearts localized to the endothelium of intramyocardial coronary vessels and correlated with an increased expression of TNF-alpha in the vessel wall. Treatment of human coronary artery endothelial cells with TNF-alpha increases their BK-1R expression. These novel results show that BK-1Rs are induced in the endothelium of intramyocardial coronary vessels in failing human hearts and so may participate in the pathogenesis of heart failure.
 ...
PMID:Increased expression of bradykinin type-1 receptors in endothelium of intramyocardial coronary vessels in human failing hearts. 1584 Sep 6

Patients with Chagas' cardiomyopathy have the worst prognosis when compared to other aetiologies. It has been suggested that a more intense inflammatory activation could be responsible for this excessive mortality. We studied 35 patients with idiopathic dilated cardiomyopathy (IDC group) and 28 patients with Chagas' heart disease (Chagas' group) and 12 control subjects. We compared plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptor type 1 (sTNF-R1), soluble Fas (sFas), interleukin 6 (IL-6), and brain natriuretic peptide type B (BNP) concentrations between the groups. TNF-alpha and IL-6 concentrations were higher in the IDC and Chagas groups as compared to controls (p<0.001 and p=0.001, respectively). sTNF-R1 concentration was higher in IDC after stratification for functional class (p=0.039), and there was a trend toward higher plasma TNF-alpha concentration in the Chagas' group (p=0.092). IL-6 concentration was higher in Chagas than in IDC (p=0.005). Higher IL-6 levels were associated with worse outcome (p=0.03 for Chagas; p=0.003 for IDC). sFas concentration was similar among groups. BNP concentrations were higher in IDC (350 pg/ml) and in Chagas (444.6 pg/ml) as compared to the controls (20.3 pg/ml; p<0.01). Higher BNP levels were associated with death and heart transplantation in both aetiologies. Inflammatory activation in Chagas heart disease differs from IDC and is associated with heart failure severity.
 ...
PMID:The influence of aetiology on inflammatory and neurohumoral activation in patients with severe heart failure: a prospective study comparing Chagas' heart disease and idiopathic dilated cardiomyopathy. 1604 6

We report the case of a 35-year-old man who was suffering from severe heart failure due to cardiomyopathy. He underwent heart transplantation years ago and developed complex ventricular arrhythmias in the following months in combination with recurrent episodes of syncope due to hypertrophic non-obstructive cardiomyopathy in the transplanted heart, so a dual chamber ICD was implanted. Months later repetitive episodes of intermittent T-wave oversensing with consecutive activation of the ICD could be observed. Surgical revision of the electrode was performed and the patient was closely followed up. One year later, further episodes of T-wave oversensing led to multiple inappropriate IDC-shocks. A very short AV-conduction time was programmed to allow ventricular capture whenever possible, because T-wave oversense after ventricular capture would be annotated as single ventricular ectopy not resulting in antitachycardia pacing. As a consequence, the patient was free from inappropriate ICD-shocks, but showed several shorter episodes of T-wave oversensing. They were all initiated by atrial activity that was seen in the refractory period, thus leading to a loss of AV synchrony. Programming a very short post ventricular atrial refractory period (PVARP) in addition to a short AV-delay led to the complete disappearance of T-wave oversensing in this patient. During a 9-month follow-up, no further tachycardia episodes were detected by the device.
 ...
PMID:[Avoidance of intermittent T-wave oversensing with device programming]. 1678 69

To determine whether statin therapy improves survival in patients with heart failure (HF) secondary to nonischemic dilated cardiomyopathy (non-IDC), data from 1,024 patients with non-IDC (New York Heart Association functional class III and IV HF) and left ventricular ejection fraction < or =0.35 who were enrolled in the BEST were analyzed. The association of statin therapy at the initial screening visit with all-cause and cardiovascular mortality was evaluated using multivariate Cox proportional hazards models. After adjusting for age, gender, race, systolic blood pressure, total cholesterol, New York Heart Association functional class IV, estimated glomerular filtration rate, current cigarette smoking, left ventricular ejection fraction, angiotensin-converting enzyme inhibitor use, antiplatelet therapy, diabetes mellitus, treatment group (beta blocker or placebo), and hypertension, statin use was independently associated with decreased all-cause mortality (hazard ratio 0.38, confidence interval 0.18 to 0.82, p = 0.0134) and also with decreased cardiovascular death (hazard ratio 0.42, confidence interval 0.18 to 0.95, p = 0.037). In conclusion, in patients with moderate or severe HF due to non-IDC entered into BEST, statin therapy at entry was independently associated with a decrease in all-cause and cardiovascular mortality.
 ...
PMID:Effect of statin therapy on survival in patients with nonischemic dilated cardiomyopathy (from the Beta-blocker Evaluation of Survival Trial [BEST]). 1749 77

We report two pediatric patients with IDC who underwent autologous PSCT. Both cases were referred to our clinic for cardiac transplantation because of end-stage heart failure resistant to conventional therapy with digoxin, diuretics, ACE inhibitors, and sympathomimetics. They had ejection fractions below 35%. In each case, autologous stem cell transplantation was performed via the coronary arteries, and five wk after the procedure transthoracic echocardiography showed a striking gain in their ejection fractions and an improvement in the left ventricular dimensions compared with the initial measurements. Although heart transplantation is the only option for children with IDC, stem cell transplantation can lessen the waiting list mortality and prolong the time for a patient to wait for a suitable donor.
 ...
PMID:Peripheric stem cell transplantation in children with dilated cardiomyopathy: preliminary report of first two cases. 2047 Mar 56

Accumulating work in experimental animals suggests that bradykinin (BK) exerts cardioprotective effects via bradykinin type-2 receptors (BK-2Rs). In human end-stage heart failure, BK-2Rs are significantly downregulated by mechanisms that have remained elusive. Heart tissues from idiopathic dilated cardiomyopathy (IDC; n = 7), coronary heart disease (CHD; n = 6), and normal patients (n = 6) were analyzed by RT-PCR, SSCP, and Western blotting. In normal and IDC hearts, BK-2R expression increased with age, with a lower relative increase in IDC hearts. BK-2R mRNA and protein levels showed a positive linear correlation, suggesting transcriptional regulation. Two known BK-2R promoter polymorphisms, -58T/C and -9/+9, were found to be present in the study population. The allelic frequencies for the C-allele in -58T/C were 0.58 in normal and CHD hearts and 0.81 in IDC hearts. Furthermore, the allelic frequencies for the -9 and +9 alleles were 0.42 and 0.58 in normal hearts and 0.64 and 0.36 in IDC hearts, respectively. All analyzed CHD hearts were homozygous for the -9 allele. Thus, the expression of cardioprotective BK-2Rs in human hearts is increased with age in normal and IDC hearts and may be regulated on the transcriptional level. Moreover, comparison of normal subjects and patients with failing hearts revealed different allelic frequencies in each of two known BK-2R gene polymorphisms.
 ...
PMID:Bradykinin type-2 receptor expression correlates with age and is subjected to transcriptional regulation. 2197 24