Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenital cardiac malformations are often associated with pulmonary hypertension and structural changes of both, the larger and smaller vessels of the pulmonary circulation. Approximately 5 to 10 % of adults with congenital heart disease, surgically treated or untreated, develop pulmonary arterial hypertension of variable severity from mild to severe (Eisenmenger reaction). Until recently, medical treatment options for the affected patients were very limited. Meanwhile, the advent of new pulmonary vasoactive and antiproliferative substances (including endothelin receptor antagonists, phosphodiesterase-5-inhibitors, prostanoids) offer the option to correct abnormalities in pulmonary endothelial function and to improve the outcome of affected patients. Even patients with severe congenital cardiac malformations and Fontan-type circulation or patients with pulmonary atresia and aorto-pulmonary collaterals may benefit from these new treatment strategies. In any case, the complexity of congenital cardiac malformations when associated with abnormalities in the pulmonary circulation and/or pulmonary arterial hypertension, requires medical care and follow-up in specialized centers for (adult) congenital heart disease.
 ...
PMID:[Pulmonary hypertension and pulmonary circulation in congenital heart disease]. 1971 8

Acute heart failure (AHF) is a major cause of hospitalizations. Severe dyspnea, pulmonary congestion and low cardiac output with peripheral vasoconstriction and renal hypoperfusion is a main form of clinical presentation. Most patients with acute worsening have a pre-existing decompensated chronic heart failure (ADCHF), but AHF may also occur as a first manifestation of a previously unknown heart disease. Myocardial ischemia, cardiac arrhythmias, non-compliance with medication and infections are frequent precipitating factors. Management of AHF depends on the underlying heart disease and cause of decompensation. In patients with ADCHF vasodilators and iv diuretics are first-line drugs for rapid reduction of dyspnea and congestion. In patients with signs of low cardiac output and oliguria, inotropic agents are also often administered to prevent further deterioration. Beta-adrenergic agents and phosphodiesterase inhibitors correct the hemodynamic disturbance, but may also induce arrhythmias and worsen myocardial ischemia. Inotropic therapy therefore remains controversial. A novel class of drugs, the calcium sensitizers, represent a new therapeutic option. Levosimendan was shown to improve myocardial contractility without increasing oxygen requirements and to produce peripheral and coronary vasodilation. Its therapeutic effects and tolerance have been tested in several trials. The present review focuses on the clinical pharmacology and therapeutic utility of levosimendan in patients with ADCHF.
 ...
PMID:Newer treatments for decompensated heart failure: focus on levosimendan. 1992 Sep 23

Patients with Eisenmenger syndrome form a small percentage of congenital heart disease patients. The rarity of this syndrome, combined with its complex pathophysiology, account for the insufficient understanding of the principles underlying its proper treatment. The main clinical symptoms are: cyanosis due to secondary erythrocytosis, resulting in increased blood viscosity, iron deficiency anemia (enhanced by unnecessary phlebotomies), blood clotting disturbances, heart failure and serious supraventricular and ventricular arrhythmias. Recent decades have seen developments in pulmonary hypertension pathophysiology which have led to the introduction of new groups of drugs: prostacycline analogs (Epoprostenol, Treprostinil, Beraprost, Illoprost), phosphodiesterase inhibitors (Sildenafil, Tadalafil), endothelin receptor antagonists (Bosentan, Sitaxantan, Ambrisentan) and nitric oxide. These drugs should be administered to patients in III-IV NYHA class. Despite successful early results, the therapeutic effect on patients with Eisenmenger syndrome has not been conclusively established. Our therapeutic efforts should be directed mainly towards preventing complications. As a rule, we should avoid agents with no established therapeutic efficacy and try to alleviate symptoms without any additional risk, so as not to disrupt the existing clinical balance.
 ...
PMID:Therapeutic methods used in patients with Eisenmenger syndrome. 1995 85

There are several animal models for studying human pulmonary hypertension (PH). An increased flow model in pigs was developed at the University Hospital in Heidelberg in order to simulate congenital heart disease. The high pulmonary blood flow is achieved by installation of a Blalock-Taussig anastomosis. In order to further improve this model by adding a pressure component, the left pulmonary artery is ligated. An acute model, which is used at the Innsbruck Medical University, addresses another disease entity. Human meconium is placed deeply into the trachea of the pigs in order to induce an acute respiratory distress syndrome-like response in the lungs. Animals were randomly assigned to four treatment groups. Inhaled iloprost, due to its pulmonary and intrapulmonary selectivity, was the only substance that significantly reduced intrapulmonary shunt volumes. In humans, PH encompasses multiple disease subtypes. Pulmonary arterial hypertension (PAH) accounts for only 6% of PH cases, however, all existing treatments are indicated only for PAH. This means that for 94% of patients with PH, no specific medication is available. Therefore, huge efforts have been made to better understand the pathophysiology of PH and to detect new signalling pathways that may allow new compounds to be developed that will ultimately improve the prognosis of PAH and non-PAH PH patients. Promising new substances include riociguat, a stimulator of the soluble guanylate cyclase (sGC), as well as cinaciguat, a sGC activator, and an elastase inhibitor. Riociguat (BAY 63-2521) is an oral agent that targets the intact/native form of sGC. It enhances the sensitivity of sGC to low levels of bioavailable nitric oxide (NO) and is also capable of stimulating native sGC independently of NO. Thus, unlike phosphodiesterase-5 inhibitors, the effect of riociguat is not limited by low NO levels. In a multicentre open-label phase II study, riociguat exerted strong and significant effects on pulmonary haemodynamics and exercise capacity in patients with PAH and in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Riociguat is currently being evaluated in phase III clinical trials both in PAH and in CTEPH patients. Clinical studies with riociguat in earlier development stages have addressed PH in lung diseases and systolic left ventricular failure. An elastase inhibitor is currently being investigated in phase I clinical trials in patients with PH owing to chronic obstructive pulmonary disease.
 ...
PMID:Animal models related to congenital heart disease and clinical research in pulmonary hypertension. 2042 48

Pulmonary hypertension is a serious complication of a number of lung and heart diseases that is characterized by peripheral vascular structural remodeling and loss of vascular tone. Nitric oxide can modulate vascular injury and interrupt elevation of pulmonary vascular resistance selectively; however, it can also produce cytotoxic oxygen radicals and exert cytotoxic and antiplatelet effects. The balance between the protective and adverse effects of nitric oxide is determined by the relative amount of nitric oxide and reactive radicals. Nitric oxide has been shown to be clinically effective in the treatment of congenital heart disease, mitrial valvular disease combined with pulmonary hypertension and in orthotropic cardiac transplantation patients. Additionally, new therapeutic modalities for the treatment of pulmonary hypertension, phosphodiesterase inhibitors, natriuretic peptides and aqueous nitric oxide are also effective for treatment of elevated pulmonary vascular resistance.
 ...
PMID:Nitric oxide and pulmonary hypertension. 2049 5

Pulmonary hypertension is a heterogeneous hemodynamic and pathophysiological state that is observed in a number of clinical conditions, which have been divided into six diagnostic groups. Although the increase in pulmonary pressure observed in these clinical groups may be similar, underlying disease mechanisms, diagnostic methods, and prognostic and therapeutic consequences are completely different. Pulmonary arterial hypertension is associated with several rare conditions that have comparable clinical and hemodynamic characteristics and exhibit virtually identical anatomical and pathological alterations in the lung microcirculation. These conditions include idiopathic and familial forms of the disease and disease forms associated with connective tissue disease, congenital heart defects involving systemic-to-pulmonary arterial shunts, portal hypertension, and HIV infection. It has been shown that treatment with specific drugs (e.g. prostanoids, endothelin-receptor antagonists and phosphodiesterase type-5 inhibitors) is effective in these patients and that these drugs can also be administered in various combinations. An evidence-based treatment algorithm has been developed for these patients. In patients with pulmonary hypertension due to left heart disease or lung disease, treatment focuses on the underlying condition and there is no convincing evidence that agents approved for pulmonary arterial hypertension are effective. For patients with chronic thromboembolic pulmonary hypertension, the treatment of choice is pulmonary endarterectomy. However, drugs intended specifically for the treatment of pulmonary arterial hypertension may be considered in inoperable cases or after suboptimal surgery.
 ...
PMID:Current therapeutic approaches to pulmonary arterial hypertension. 2051 28

Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH). The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings.
 ...
PMID:Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension. 2053 62

Causes of pulmonary arterial hypertension (PAH) are similar in adults and children. The main difference is that PAH secondary to congenital heart diseases, is the predominant cause in pediatric patients. Persistent pulmonary hypertension of the newborn shows completely different clinical course and pathophysiological mechanisms. It is usually seen in full term babies with a high morbidity and mortality rate. Improved prognosis has been reported with inhaled nitric oxide (NO) and extracorporeal membrane oxygenation therapy in babies hospitalized in well equipped and experienced newborn centers. Primary pulmonary hypertension and familial pulmonary hypertension are rare in pediatric age group because the diagnosis is initially made in adolescence. The incidence of PAH secondary to congenital heart disease is estimated as 1.6 - 12.5 case/million/year. Eisenmenger syndrome is diagnosed in 1% of patients with PAH. Patients with left to right shunts are the main group who develop pulmonary vascular disease if not treated in the early infancy. Some cyanotic congenital heart diseases are also the causes of PAH. The best treatment of patients at risk for the development of pulmonary vascular disease is prevention by early surgical elimination of defects or repairing the anatomy. Treatment options with vasodilating agents like NO, prostaglandin analogs, phosphodiesterase -5 inhibitors and endothelin receptor antagonists are used to improve survival and quality of life. Heart lung or bilateral lung transplantation is the only surgical option for many of these patients. Results of national and international registries will bring valuable epidemiological and prognostic perspectives to pediatric PAH.
 ...
PMID:[Pediatric pulmonary hypertension and pulmonary arterial hypertension secondary to congenital heart diseases]. 2081 67

Pulmonary arterial hypertension (PAH) is a progressive disease with poor survival outcome. PAH is classified by the 2009 updated clinical classification of pulmonary hypertension and a major subgroup is PAH due to congenital heart disease (CHD) with systemic-to-pulmonary shunt. CHD-PAH is a result of systemic-to-pulmonary shunting and chronic increased flow that ultimately results in adaptations of pulmonary vasculature and endothelial dysfunction. The advanced stage is called Eisenmenger syndrome which forms a small percentage (1%) of all CHD patients. Therapies targeted on PAH symptoms are called primary therapy for PAH, but most CHD-PAH patients progress to advanced therapy which is directed at the PAH itself. In CHD-PAH, advanced therapies are extensively investigated for all three major pathways: endothelin-1 receptor antagonists such as bosentan, prostanoids such as epoprostenol and phosphodiesterase 5 inhibitors such as sildenafil. Endpoints in most trials were catheterization hemodynamics, World Health Organization functional class, six-minute walking distance and patient-focused outcomes, based on quality of life questionnaires and Borg dyspnea index. The BREATHE-5 and EARLY study were two important randomized controlled trials showing efficacy of bosentan at short follow-up. Moreover in patients with Eisenmenger syndrome, one recent survival retrospective study with majority of patients on bosentan showed strong survival benefit over conservative therapy. A diversity of prospective cohort and retrospective studies were performed but all with limited data, due to small numbers and heterogeneity of underlying CHD diagnoses. Further larger studies are needed to determine optimal treatment for adults with CHD-PAH. This review focuses on bosentan in CHD-PAH. In particular, we discuss outcome of various clinical trials and compare efficacy and safety of bosentan to other advanced therapies.
 ...
PMID:Adult patients with pulmonary arterial hypertension due to congenital heart disease: a review on advanced medical treatment with bosentan. 2085 82

There now is strong evidence to recognize the pivotal role of the right ventricle (RV) in heart disease and to establish it as a unique and separate entity than the left ventricle (LV). Here, we summarize the differences between the two ventricles, the diagnosis of RV failure, and the management of acute and chronic RV failure. We review the indices derived by echocardiography used to measure RV function, and novel biomarkers that may play a role diagnosing and prognosticating in RV-specific disease. There are new novel therapies that specifically target the RV in disease. For example, phosphodiesterase type 5 inhibitors improve contractility of the hypertrophied RV while sparing the normal LV in pulmonary arterial hypertension. The metabolism of the hypertrophied RV is another area for therapeutic exploitation by metabolic modulation. We also suggest future potential molecular targets that may be unique to the RV because they are upregulated in RV hypertrophy greater than in LV hypertrophy.
 ...
PMID:Right ventricular failure: a novel era of targeted therapy. 2089 Jul 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>