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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary pulmonary hypertension is a rare disease of unknown etiology, whereas secondary pulmonary hypertension is a complication of many pulmonary, cardiac and extrathoracic conditions. Chronic obstructive pulmonary disease, left ventricular dysfunction and disorders associated with hypoxemia frequently result in pulmonary hypertension. Regardless of the etiology, unrelieved pulmonary hypertension can lead to right-sided heart failure. Signs and symptoms of pulmonary hypertension are often subtle and nonspecific. The diagnosis should be suspected in patients with increasing dyspnea on exertion and a known cause of pulmonary hypertension. Two-dimensional echocardiography with Doppler flow studies is the most useful imaging modality in patients with suspected pulmonary hypertension. If pulmonary hypertension is present, further evaluation may include assessment of oxygenation, pulmonary function testing, high-resolution computed tomography of the chest, ventilation-perfusion lung scanning and cardiac catheterization. Treatment with a continuous intravenous infusion of prostacyclin improves exercise capacity, quality of life, hemodynamics and long-term survival in patients with primary pulmonary hypertension. Management of secondary pulmonary hypertension includes correction of the underlying cause and reversal of hypoxemia. Lung transplantation remains an option for selected patients with pulmonary hypertension that does not respond to medical management.
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PMID:Diagnosis and treatment of pulmonary hypertension. 1135 91

With advanced diagnostic and therapeutic techniques in pediatric cardiology and cardiac surgery, pregnancy can be an option for patients with congenital heart disease. A low overall maternal mortality and a healthy pregnancy require interdisciplinary cooperation between the cardiologist, obstetrician and general practitioner caring for the mother. Treatment and outcome will depend on the type of cardiac malformation, on the functional impairment of the maternal heart (heart failure and/or cyanosis) and on the status of the fetus, with evidence of a better outcome for patients treated in specialized centers. However, even with recent advances in treatment, for women with primary pulmonary hypertension, Eisenmenger's syndrome, left heart obstruction of Marfan syndrome, pregnancy remains associated with a high maternal mortality. Therefore, these are conditions in which pregnancy is still absolutely contraindicated and a patient should be counselled to terminate the pregnancy. The risk of an inherited recurrence of a congenital heart disease is difficult to assess in an individual case because the majority of cardiac malformations are caused by multifactored variables. But for some types of malformations (i.e., atrioventricular canal, Morbus Fallot) the incidence of cardiac malformation in the offspring of affected parents is slightly higher compared to the general population. Consequently, all patients with congenital heart disease should be offered genetic counselling and fetal echocardiography. In general, pregnancy in women with congenital heart disease has no significant long-term adverse effects and a second pregnancy is possible in the majority of the cases.
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PMID:[Pregnancy and congenital heart defects]. 1137 41

Atrial flutter is an uncommon arrhythmia in children. The presenting features and treatment responses of two fetuses and six children with atrial flutter were presented. Two patients were diagnosed prenatally at 31 and 35 weeks' gestation. One patient was successfully controlled in utero by maternal administration of digoxin and the other by direct current cardioversion after delivery. Two fetuses and 2 of 6 children had normal cardiac structure by echocardiogram. Three patients had right atrial enlargement due to atrial primun septal defect, secundum atrial septal defect with primary pulmonary hypertension, and endomyocardial fibrosis. One patient developed atrial flutter with sinus node dysfunction after surgical correction of total anomalous pulmonary venous connection. Four cases presented as atrial flutter with regular atrioventricular conduction (2:1 or 3:1 conduction) while the remainder presented with irregular atrioventricular conduction. Heart failure was presented in two patients and improved after the arrhythmias were controlled. Successful termination of atrial flutter was accomplished by using DC cardioversion in 4 patients and one patient converted to normal sinus rhythm following combination of digoxin and amiodarone administration. Digoxin was administered for one year as the prophylactic medication in six patients. None had recurrence of atrial flutter during the follow-up period of one to four years. Two patients required chronic digoxin and amiodarone therapy. We concluded that atrial flutter in fetuses and early childhood carries a good prognosis. Acute treatment with direct current cardioversion is sufficient in most patients, combination of digoxin and amiodarone may be an alternative therapy to convert atrial flutter.
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PMID:Atrial flutter in fetuses and early childhood: a report of eight cases. 1152 63

Pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD). The increase in pulmonary artery pressures is often mild to moderate, but some patients may suffer from severe pulmonary hypertension, and present with a progressively downhill clinical course because of right-sided heart failure added to ventilatory handicap. The cause of pulmonary hypertension in COPD is generally assumed to be hypoxic pulmonary vasoconstriction leading to permanent medial hypertrophy. However, recent pathological studies point, rather, to extensive remodeling of the pulmonary arterial walls, with prominent intimal changes. These aspects account for minimal reversibility with supplemental oxygen. There may be a case for pharmacological treatment of pulmonary hypertension in selected patients with advanced COPD and right-sided heart failure. Candidate drugs include prostacyclin derivatives, endothelin antagonists and inhaled nitric oxide, all of which have been reported of clinical benefit in primary pulmonary hypertension. However, it will be a challenge for randomized controlled trials to overcome the difficulties of the diagnosis of right ventricular failure and the definition of a relevant primary endpoint in pulmonary hypertensive COPD patients.
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PMID:Pulmonary hypertension associated with COPD. 1173 25

The pathogenesis of primary pulmonary hypertension is still unclear. The case of a 68-yr-old female patient who complained of recurrent dizzy spells and collapses over a period of 6 weeks and died of global cardiac failure is presented. Autopsy revealed severe pulmonary hypertension, slight chronic bronchitis, and bronchiolitis as well as intra-alveolar accumulation of macrophages. Chlamydiae were detected within the pulmonary arteries and in intramural and intra-alveolar macrophages by immunofluorescence, confocal laser scanning microscopy, scanning and transmission electron microscopy. Nested-polymerase chain reaction (PCR) and nonradioactive deoxyribonucleic acid (DNA) hybridization of PCR products from pulmonary arteries revealed Chlamydia pneumoniae DNA. Chlamydia pneumoniae has already been detected in atherosclerosis and in pulmonary emphysema. It can induce proliferation of smooth muscle cells. Chlamydia pneumoniae might be relevant in aggravation of primary pulmonary hypertension and might perhaps be a trigger factor in some cases.
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PMID:Detection of Chlamydia pneumoniae in unexplained pulmonary hypertension. 1184 18

Vascular endothelial growth factor (VEGF) plays a central role in the life and death of pulmonary vascular endothelial cells. Treatment of neonatal or adult rats with a VEGF receptor blocker destroys lung capillaries by inducing endothelial cell apoptosis and causes emphysema. Human lung tissue samples from patients with endstage emphysema have decreased levels of VEGF messenger RNA and protein and have decreased expression of kinase insert domain-containing receptor (VEGF receptor II). These decreases are associated with a high rate of alveolar septal cell apoptosis, indicating perhaps that decreased VEGF and kinase insert domain-containing receptor expression impairs endothelial cell survival in emphysematous lungs. Combination of VEGF receptor blockade with chronic hypoxia (3-wk exposure) results in obliteration of small precapillary pulmonary arteries by proliferating endothelial cells, severe pulmonary hypertension, and death caused by right-side heart failure. We propose that 1) VEGF receptor blockade causes endothelial cell apoptosis, 2) hypoxic vasoconstriction (shear stress) selects apoptosis-resistant endothelial cells that proliferate and obliterate the lumen, and 3) the vascular remodeling observed is relevant to the structural alterations that characterize severe pulmonary hypertension (including primary pulmonary hypertension) in humans. The endovascular cell growth in human disease and in our model exhibits some similarities with neoplastic cell growth. Chemotherapy strategies can now be employed in the animal model in an attempt to treat established vascular-obliterative lung disease.
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PMID:Janus face of vascular endothelial growth factor: the obligatory survival factor for lung vascular endothelium controls precapillary artery remodeling in severe pulmonary hypertension. 1200 44

The peptide endothelin plays a significant role in a wide array of pathological conditions, including primary pulmonary hypertension and pulmonary arterial hypertension associated with collagen vascular disease. These are life-threatening conditions that can severely compromise the function of the lungs and heart. Inhibiting the actions of endothelin by blockade of its receptors provides a new and effective approach to therapy for patients with these conditions. Bosentan (Tracleer ) is the first orally-active dual endothelin receptor antagonist and has recently been approved in the US, Canada, Switzerland and the EU for the treatment of pulmonary arterial hypertension. Bosentan significantly improves exercise capacity, symptoms and functional status in patients with this disease and also slows clinical deterioration, which may be indicative of a delay of disease progression. Results from large-scale studies of bosentan in patients with pulmonary arterial hypertension and chronic heart failure have established its long-term safety and tolerability profiles. The introduction of the dual endothelin receptor antagonist bosentan has provided an essential treatment for pulmonary arterial hypertension and ongoing trials are evaluating its potential role in the management of other endothelin-mediated disease states.
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PMID:Bosentan: a dual endothelin receptor antagonist. 1208 9

We studied the role of oxidative stress in the pathogenesis of primary pulmonary hypertension. In patients with primary pulmonary hypertension the content of malonic dialdehyde in the plasma was higher than in healthy volunteers (5.18 0.46 and 2.95 0.14 nmol/liter, respectively, p<0.01). However, glutathione peroxidase activity in the plasma decreased in these patients (0.50 0.17 vs. 1.19 0.14 U/ml in the control, p<0.05). By contrast, glutathione peroxidase activity in erythrocytes from patients surpassed the control (6.13 0.39 and 4.63 0.45 U/h hemoglobin). The increase in malonic dialdehyde content in the plasma and glutathione peroxidase activity in erythrocytes and the decrease in glutathione peroxidase activity in the plasma were most pronounced in patients with severe cardiac insufficiency and pulmonary hypertension. Our results indicate that antioxidant preparations improve the prognosis in patients with primary pulmonary hypertension.
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PMID:Oxidative stress in patients with primary pulmonary hypertension. 1244 71

Endothelins are powerful vasoconstrictor agents produced by endothelial cells and identified by Yanagisawa et al. in 1988. Two types of receptors for endothelins have been identified: ET(A) receptors are located on smooth muscle cells of the vascular wall and are responsible for endothelin-induced vasoconstriction while ET(B) receptors are located on endothelial cells and induce these cells to release NO and prostacyclin. Moreover, these peptides not only cause a potent and prolonged vasoconstriction but are also known to enhance cell proliferation and to stimulate extracellular matrix accumulation. High levels of plasma or tissue endothelins have been found in patients with heart failure, diabetes, stroke, primary pulmonary hypertension, liver cirrhosis and other diseases. Given these effects of endothelins, blocking their receptors might be a new way to reduce blood pressure and to treat other illnesses. Accordingly, many endothelin antagonists have been developed and evaluated in animals and humans. Enrasentan is a mixed ET(A) and ET(B) receptor antagonist with a higher affinity for ET(A) receptors, although it cannot be considered a selective antagonist. In an animal model of hypertension and cardiac hypertrophy the drug has reduced blood pressure, prevented cardiac hypertrophy and preserved myocardial function. In rats with hyperinsulinemia and hypertension enrasentan normalized blood pressure and prevented cardiac and renal damage. In rats with stroke the drug reduced the ischemic area in the brain. Enrasentan has been added to conventional treatment in patients with heart failure (NYHA Class 2-3) and no addictive effect of the drug has been observed. This is in contrast with results obtained in animal models and still has not been explained. In conclusion, many possible clinical applications can be suggested for this drug, but further studies are necessary to better evaluate its therapeutic efficacy.
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PMID:Enrasentan, an antagonist of endothelin receptors. 1259 14

The endothelins are synthesized in vascular endothelial and smooth muscle cells, as well as in neural, renal, pulmonal, and inflammatory cells. These peptides are converted by endothelin-converting enzymes (ECE-1 and -2) from 'big endothelins' originating from large preproendothelin peptides cleaved by endopeptidases. Endothelin (ET)-1 has major influence on the function and structure of the vasculature as it favors vasoconstriction and cell proliferation through activation of specific ET(A) and ET(B) receptors on vascular smooth muscle cells. In contrast, ET(B )receptors on endothelial cells cause vasodilation via release of nitric oxide (NO) and prostacyclin. Additionally, ET(B) receptors in the lung are a major pathway for the clearance of ET-1 from plasma. Indeed, ET-1 contributes to the pathogenesis of important disorders as arterial hypertension, atherosclerosis, and heart failure. In patients with atherosclerotic vascular disease (as well as in many other disease states), ET-1 levels are elevated and correlate with the number of involved sites. In patients with acute myocardial infarction, they correlate with 1-year prognosis. ET receptor antagonists have been widely studied in experimental models of cardiovascular disease. In arterial hypertension, they prevent vascular and myocardial hypertrophy. Experimentally, ET receptor blockade also prevents endothelial dysfunction and structural vascular changes in atherosclerosis due to hypercholesterolemia. In experimental myocardial ischemia, treatment with an ET receptor antagonist reduced infarct size and prevented left ventricular remodeling after myocardial infarction. Most impressively, treatment with the selective ET(A) receptor antagonist BQ123 significantly improved survival in an experimental model of heart failure. In many clinical conditions, such as congestive heart failure, both mixed ET(A/B )as well as selective ET(A) receptor antagonism ameliorates the clinical status of patients, i.e. symptoms and hemodynamics. A randomized clinical trial showed that a mixed ET(A/B) receptor antagonist effectively lowered arterial blood pressure in patients with arterial hypertension. In patients with primary pulmonary hypertension or pulmonary hypertension related to scleroderma, treatment with a mixed ET(A/B) receptor antagonist resulted in an improvement in exercise capacity. ET receptor blockers thus hold the potential to improve the outcome in patients with various cardiovascular disorders. Randomized clinical trials are under way to evaluate the effects of ET receptor antagonism on morbidity and mortality.
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PMID:Therapeutic potential for endothelin receptor antagonists in cardiovascular disorders. 1472 28


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