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)

The case is reported of a 69-year-old man with refractory heart failure due to ischemic cardiomyopathy. All other available treatments having failed and 250 mg doses of furosemide having been administered without success, dobutamine infusion was tried, at first with 72 hours of continuous infusion of 5 mcg/kg/min, followed by intermittent infusion at the same dosage, first with 12-h intervals, subsequently at the rate of 2-3 infusions weekly, and finally, after about 50 days, with a single weekly infusion. Clinical and hemodynamic results were brilliant with the patient passing from grade IV NYHA to grade II and from ejection fraction 21% (Teichholz M-mode measurement) to 55%, 14 months after the start of dobutamine treatment. Discussing the possible mechanisms of this favourable result, the authors stress the possible improvement of the contractility of the "stunned" or "hibernating" myocardial segments. On the basis of their experience and of data in the literature the authors underline the validity of a therapeutic protocol of intermittent dobutamine infusion for severe heart failure.
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PMID:[Recovery of pump function in ischemic hypokinetic cardiopathy subjects treated with weekly intermittent infusion of dobutamine. A clinical case]. 818 Dec 5

Recent technological advances in cardiopulmonary bypass circuits achieving surface bonding with heparin have permitted prolonged extracorporeal life support (ECLS) in experimental studies without the use of systemic anticoagulation. Excessive bleeding and the need for massive transfusions after extended ECLS with systemic heparinization have often led to the development of sepsis and multisystem organ failure. The Carmeda bioactive surface circuit, along with a Bio-Medicus centrifugal pump (Bio-Pump) and the femoral veno-arterial route, were used successfully in 3 patients requiring ECLS between April 1992 and December 1992. In 2 patients the need for ECLS was acute allograft dysfunction after orthotopic cardiac transplantation with no evidence of cellular rejection. Both patients were receiving multiple inotropes and intraaortic balloon counter-pulsation; their condition continued to deteriorate rapidly before the initiation of ECLS. The third patient failed to be weaned from cardiopulmonary bypass after myocardial revascularization for ischemic cardiomyopathy. Time on ECLS ranged from 57 to 128 hours. No systemic anticoagulation was used. One patient received no heparin, and the other 2 patients received intermittent heparin infusion to maintain an average activated clotting time of 195 and 214 seconds. Multisystem organ dysfunction present before initiation of ECLS was rapidly reversed, and all patients were weaned successfully without any immediate major complications. The ability to conduct prolonged ECLS without systemic anticoagulation and without repeat sternotomy opens new avenues for the use of this procedure in profound heart failure.
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PMID:Femoral veno-arterial extracorporeal life support with minimal or no heparin. 832 46

The complex pathology that leads to heart failure has hampered the search for optimal therapy. Even so, ACE inhibitors have become a cornerstone of treatment. After an acute MI, the goal of ACE inhibition is to limit LV remodeling and progression to ischemic cardiomyopathy and congestive failure. In advanced failure, the goal is to reverse peripheral vascular changes and ameliorate symptoms.
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PMID:Heart failure: its progression and its therapy. 836 50

In chronic heart failure cardiac beta-adrenoceptors are decreased. In this study we investigated whether a) in severely failing human ventricles beta-adrenoceptors are uniformly decreased or regional variations exist, and b) the beta-adrenoceptor decrease is caused by increased internalization or is a real loss in beta-adrenoceptors. For this purpose we assessed beta-adrenoceptor number and subtype distribution in a particulate fraction (mainly sarcolemmal plasma membranes) and a light vesicle fraction of right and left ventricular segments (obtained by cutting transversal rings of 2 cm from the midventricular regions) of explanted hearts from 2 patients with end-stage congestive dilated cardiomyopathy (DCM) and one patient with end-stage ischemic cardiomyopathy (ICM). In all three hearts ventricular beta-adrenoceptor number was very low (7.5-10 and 21-26 fmol/mg protein in DCM, 15-22 fmol/mg protein in ICM compared to 68-74 fmol/mg protein in non-failing ventricles). beta-Adrenoceptors were uniformly decreased over the whole ventricular region and no considerable regional variations existed. The same held true for beta 1- and beta 2-adrenoceptors. In ICM decrease in beta-adrenoceptors was due to a concomitant reduction in beta 1- and beta 2-adrenoceptors, in DCM it was mainly caused by beta 1-adrenoceptor down-regulation. In all ventricular segments investigated light vesicle beta-adrenoceptors amounted to about 5-7% of total ventricular beta-adrenoceptors, and this was not significantly different from non-failing left ventricles. We conclude that a) in severely failing human ventricles beta-adrenoceptors are evenly down-regulated and no regional variations exist, and b) the decrease in beta-adrenoceptors is not due to enhanced internalization but is a real loss of beta-adrenoceptors.
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PMID:Down-regulated beta-adrenoceptors in severely failing human ventricles: uniform regional distribution, but no increased internalization. 838 22

Previous studies have pointed out that congestive heart failure (CHF) with normal ejection fraction presents a uniform clinical profile that is indistinguishable from heart failure with low ejection fraction. Thirty-six patients with systemic hypertension who had recently experienced CHF with normal ejection fraction (> or = 50%) and no clinical history of ischemic cardiomyopathy were studied. The patients were divided into 2 groups according to degree of echocardiographic hypertrophy: group A (19 patients) with a ventricular mass/volume ratio > 1.8, and group B (17 patients) with a ratio < 1.8. Group A patients had a higher ejection fraction (67 +/- 6 vs 57 +/- 3%, p < 0.01), smaller ventricular diameters and a lower thallium-201 positive rate at peak stress (10 vs 70% in group B, p < 0.001), with 8 of 10 showing severe coronary stenosis. Clinically, group A had a more frequent audible fourth sound (79 vs 17%, p < 0.001), a low incidence of audible third sound (5 vs 55%, p < 0.001) and a cardiothoracic ratio < or = 0.5 (63 vs 17%, p < 0.01). The degree of radionuclide-detected resting diastolic dysfunction and exercise intolerance was similar in both groups. In conclusion, CHF with normal ejection fraction in hypertensive patients presents 2 different profiles: one characterized by severe hypertrophy and the other by a high rate of myocardial regional ischemia. Therapy should be aimed at pathophysiologic regression of the hypertrophy in the first case, and at improvement of the ischemia in the second.
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PMID:Congestive heart failure from left ventricular diastolic dysfunction in systemic hypertension. 842 73

From January 1985 through December 1990, 534 patients underwent endomyocardial biopsy at Johns Hopkins Hospital for suspected myocarditis. One hundred thirty-eight (26%) biopsy specimens were diagnosed histologically by 2 cardiac pathologists as either active (n = 85, 16%) or borderline (n = 53, 10%) myocarditis. Of the 138 patients, 60 were excluded based on either specific concurrent clinical conditions or noncongestive heart failure presentations. Immunohistochemical staining for common leukocyte antigen infiltrating cells performed on the remaining 78 specimens confirmed the presence of focal or multifocal inflammatory infiltrates in 58, of which 49 had histologic evidence of active myocarditis. All 49 patients presented with congestive heart failure and left ventricular ejection fractions of < 40%. Compared with patients with either idiopathic dilated cardiomyopathy (n = 207) or ischemic cardiomyopathy (n = 44), these patients with myocarditis had a less striking male predominance (58 vs 69 and 83%, respectively) (p = 0.02) and were younger (43 +/- 16 vs 50 +/- 17 and 55 +/- 13 years, respectively, p = 0.005). Racial distributions were similar. A recent history of a discrete flu-like illness was obtained in 52%, two-thirds of which were clustered between the months of December and March. Onset of heart failure peaked between December and April (63% and was low between May through September (22%). A peak in the proportion of patients found to have active myocarditis on biopsy occurred in 1986 (17 vs 7 to 10% in other years).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Demographic features and prevalence of idiopathic myocarditis in patients undergoing endomyocardial biopsy. 846 93

A major problem in cardiac transplantation is the death of candidates due to the increasing shortage of donors and the consequent longer waiting periods. To determine whether clinical markers for death could be identified in these patients, 168 adult candidates with heart failure (NYHA class III and IV) listed between August 1987 and December 1989 were analyzed. There were 104 patients with ischemic cardiomyopathy (ISCM) and 64 with idiopathic dilated cardiomyopathy (IDCM). Transplantation was performed in 93 patients (55%). Actuarial 1 year survival was 61% in the ISCM group and 78% in the IDCM group (P = NS). Freedom from sudden death at one year was significantly lower in the ISCM group (73%) than in the IDCM group (96%) (P < 0.01). The rate of patients who did not die from terminal myocardial failure was 83% in the ISCM group and 81% in the IDCM group (P = NS). There were no significant differences between the two groups in right atrial, pulmonary artery, and pulmonary wedge pressures, transpulmonic pressure gradient, pulmonary vascular resistance, cardiac index, and ejection fraction. We conclude that candidates for cardiac transplantation with ISCM are at higher risk for sudden death during the first year on the waiting list than patients with IDCM. These results warrant consideration of aggressive arrhythmia control measures, including an automatic implantable defibrillator, to "bridge" these high risk patients to transplantation.
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PMID:Prediction of mortality in patients awaiting cardiac transplantation: increased risk of sudden death in ischemic compared to idiopathic dilated cardiomyopathy. 864 72

Homozygosity for the deletion allele of the angiotensin-converting enzyme gene (DD) has been associated with a variety of cardiovascular diseases, including ischemic and idiopathic dilated cardiomyopathy, in Caucasians. In this study of 104 Chinese patients with end-stage heart failure due to idiopathic dilated or ischemic cardiomyopathy, the DD genotype frequency was low (12% and 11%, respectively) and was not seen more often than in a control group of 183 subjects without cardiac disease (13%). Therefore, in the Chinese, the DD genotype is less common than in Caucasians and does not appear to be associated with the development of either ischemic or idiopathic dilated cardiomyopathy.
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PMID:Lack of association between insertion/deletion polymorphism of the angiotensin-converting enzyme gene and end-stage heart failure due to ischemic or idiopathic dilate cardiomyopathy in the Chinese. 864 25

In human heart failure beta-adrenergic receptors are downregulated which contributes to the reduced responsiveness to positive inotropic beta-agonists in the diseased heart. The present study addressed the question whether the number of beta-adrenergic receptors in the failing human heart is regulated at the level of the mRNA and whether the absolute steady-state levels of subtype-specific mRNAs mirror the expression of receptor-subtype proteins in human heart. In a collaborative effort, two different and independent methods, performed in two independent laboratories, reverse transcription followed by polymerase chain reaction (RT-PCR) and RNase protection assays, were used to determine the absolute steady-state levels of beta 1- and beta 2-adrenergic receptor mRNAs in control (NF) and in failing human hearts. As determined by quantitative RT-PCR the beta 1-mRNA was significantly reduced from 0.98 +/- 0.12 (n = 10) to 0.49 +/- 0.11 pg/microgram total RNA in dilated cardiomyopathy (dCMP, n = 7) and to 0.40 +/- 0.11 pg/microgram total RNA in ischemic cardiomyopathy (iCMP, n = 8). The steady-state levels of mRNA specific for beta 2-adrenergic receptors also tended to be decreased but without reaching significance (NF: 0.16 +/- 0.05, dCMP: 0.11 +/- 0.03, iCMP: 0.13 +/- 0.04 pg/microgram total RNA). RNase protection assays revealed similar values. beta 1-mRNA was found to be significantly reduced from 1.22 +/- 0.22 in NF (n = 10) to 0.63 +/- 0.14 pg/microgram total RNA in dCMP (n = 5) and to 0.52 +/- 0.1 pg/microgram total RNA in iCMP (n = 8). The beta 2-mRNA also tended to be lower in dCMP and in iCMP as compared to NF but again without reaching significance (NF: 0.14 +/- 0.02, dCMP: 0.099 +/- 0.02, iCMP 0.107 +/- 0.02 pg/microgram total RNA). This is the first study to demonstrate in parallel by two different methods performed independently in two laboratories that the ratio of beta 1- and beta 2-adrenergic receptor densities in the left ventricle of the normal human heart of about 80/20 is closely related to the absolute steady state concentrations of their specific mRNA. In addition, the magnitude of the decrease in mRNA-levels of beta 1- and beta 2-adrenergic receptors in the failing human heart closely correlates with the decrease of the respective receptor proteins. These data suggest that the predominant regulation of beta-adrenergic receptors occurs at the mRNA level.
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PMID:Differential regulation of mRNA specific for beta 1- and beta 2-adrenergic receptors in human failing hearts. Evaluation of the absolute cardiac mRNA levels by two independent methods. 874 9

The ryanodine-sensitive Ca2+ release channel (RyaCRC) of the sarcoplasmic reticulum plays a key role in the intracellular Ca2+ handling in cardiomyocytes. Altered expression of the RyaCRC has been supposed to contribute to abnormal cellular Ca2+ handling and to myocardial dysfunction in dilated and ischemic cardiomyopathy. In the present study the 3H-ryanodine binding site in human myocardial homogenates was characterized and the density of the RyaCRC (which corresponds to the cardiac ryanodine receptor) was determined in nonfailing and in failing human myocardium. Homogenates were prepared from nonfailing left ventricular myocardium from the hearts of 5 organ donors (NF) and from failing myocardium from 14 explanted hearts of transplant recipients with end-stage heart failure resulting from dilated (DCM, n = 5) or ischemic (ICM, n = 9) cardiomyopathy. Radioligand saturation binding experiments revealed a specific, high-affinity 3H-ryanodine binding site (Kd-values: NF: 0.65 +/- 0.11 nmol/l, DCM: 0.66 +/- 0.09 nmol/l, ICM: 0.88 +/- 0.18 nmol/l; n.s.) in all preparations. Specific 3H-ryanodine binding depended on the free Ca2+ concentration in the assay. It was maximal at 3-100 micro mol/l Ca2+. The binding was inhibited by the RyaCRC antagonists ruthenium red (Ki-value: 0.32 [0.18-0.56] micromol/l, n = 5) and Mg2+ (Ki-value: 2.95 [1.23-7.11] mmol/l, n = 5). The RyaCRC density was 103.5 +/- 11.9 fmol/mg protein in nonfailing myocardium. There was no significant change in the RyaCRC density in dilated or ischemic cardiomyopathy (112.4 +/- 17.1 and 122.7 +/- 13.9 fmol/mg protein) compared to nonfailing control myocardium. In summary, 3H-ryanodine binds specifically and with high-affinity to the RyaCRC in human myocardium. There is no change in the RyaCRC density in failing myocardium of patients with DCM or ICM in comparison to non-failing controls.
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PMID:The ryanodine binding sarcoplasmic reticulum calcium release channel in nonfailing and in failing human myocardium. 875 Sep 20


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