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)

HMG CoA reductase inhibitors (statins) have an established place in the treatment of coronary artery disease. However, their role in the treatment of heart failure (HF), including HF due to coronary artery disease, has been controversial since beneficial as well as possible harmful effects may occur. Several recent studies lend support for a beneficial effect of the statins in HF. These include: (i) post hoc subgroup analyses of prospective randomized clinical trials of statin therapy among patients with stable coronary artery disease where statins reduce the incidence of new HF; (ii) subgroup analysis of the evidence of statin use in large HF trails with different medication and medical devices; (iii) retrospective observational studies of statin use in HF; and (iv) prospective randomized clinical trials of statins in non-ischemic. Beneficial effects include attenuation of cardiac hypertrophy, improvement in endothelial function, anti-inflammatory effects, reduction in the activity of matrix metalloproteinases, reduction in apoptosis, interference with neurohormones, and improved homeostasis. However, there are also theoretical concerns about statins in HF, and existing literature for their safety and efficacy in HF patients has been limited by the retrospective or observational nature of these analyses, examination of incompletely validated surrogate endpoints and small prospective studies in subgroups of HF subjects. In contrast with the normal population, low concentrations of LDL and total cholesterol are associated with a worse prognosis in HF patients and a possible mechanism is reduction in ubiquinone (coenzyme Q10) levels, which is required for oxidative phosphorylation in cells. The safety aspect of these drugs in HF patients needs to be answered before statins can be recommended as a routine drug. For the moment there are several large-scale prospective outcome studies in HF which probably will give us more definitive answers.
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PMID:The role of statins in heart failure. 1800 20

Although linked with cardiac dysfunction, the association of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and pulmonary artery hypertension (PAH) has not been previously described. PAH and right ventricular heart failure were identified by echocardiography in a 3-year-old boy with a history of hypotonia, microcephaly and developmental delay. He initially presented with a 10-day history of dyspnoea, dependent oedema and reduced oral intake. Lactic acidosis was noted on serial arterial blood sampling and cerebrospinal fluid. Muscle biopsy demonstrated cytochrome-c oxidase-positive 'ragged-red' fibres consistent with MELAS; subsequent analyses revealed the m.3243A>G point mutation most commonly associated with MELAS. The mutation was heteroplasmic, representing 92% of the total mtDNA from a lung sample. Nitric oxide and epoprostenol were administered without significant clinical or echocardiographic improvement of his PAH. A 'mitochondrial cocktail' including biotin, riboflavin, carnitine and coenzyme Q10 also was provided. Five months after presentation, he developed seizures; MRI imaging of his brain demonstrated multiple focal lesions. His clinical status worsened with increasing cardiopulmonary failure. He died two months later. Although therapy for both MELAS and PAH remains limited, recent investigations suggest a beneficial role for l-arginine in both conditions, implying a possible common pathophysiology. Mitochondrial diseases such as MELAS should be considered in cases of idiopathic PAH, particularly when associated with multisystem involvement including short stature, hearing loss, renal dysfunction, retinopathy, diabetes mellitus, migraines, seizures, ophthalmoplegia, fatigability and weakness.
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PMID:Pulmonary artery hypertension in a child with MELAS due to a point mutation of the mitochondrial tRNA((Leu)) gene (m.3243A>G). 1818 Oct 29

This report describes the normalization of left ventricular ejection fraction and resolution of signs and symptoms of chronic and severe heart failure in both male and female patients (mean age 54 years) treated with standard medical therapy. These observations were made in 11 patients with idiopathic dilated cardiomyopathy treated in a single cardiology practice, who had evidence of myocardial "viability" (dysfunctional but noncontractile myocardium that has the potential for improvement in function) as assessed by cardiac magnetic resonance imaging, low-dose dobutamine echocardiography, or nuclear imaging. These patients were treated with standard available therapies including beta-blockers, angiotensin-converting enzyme inhibitors, digoxin, and potassium and non-potassium-sparing diuretics. The average ejection fraction at presentation was 17% +/- 9% which improved to 59% +/- 5%. All patients improved to New York Heart Association functional class I with available therapy. The majority of patients received micronutrient supplementation with coenzyme Q10, vitamin B1, and amino acids, which target the pathways of cardiac metabolism and may aid in the restoration of cardiac function. This case series demonstrates that normalization of cardiac function is possible with standard therapy and the importance of assessing myocardial viability in all patients with heart failure and reduced ejection fraction. Given the unique metabolic needs of the failing heart, the role of micronutrients in combination with standard therapy warrants further investigation.
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PMID:Normalization of ejection fraction and resolution of symptoms in chronic severe heart failure is possible with modern medical therapy: clinical observations in 11 patients. 1849 57

Patients with CHF, NYHA class IV, often fail to achieve adequate plasma CoQ10 levels on supplemental ubiquinone at dosages up to 900 mg/day. These patients often have plasma total CoQ10 levels of less than 2.5 microg/ml and have limited clinical improvement. It is postulated that the intestinal edema in these critically ill patients may impair CoQ10 absorption. We identified seven patients with advanced CHF (mean EF 22%) with sub-therapeutic plasma CoQ10 levels with mean level of 1.6 microg/ml on an average dose of 450 mg of ubiquinone daily (150-600 mg/day). All seven of these patients were changed to an average of 580 mg/day of ubiquinol (450-900 mg/day) with follow-up plasma CoQ10 levels, clinical status, and EF measurements by echocardiography. Mean plasma CoQ10 levels increased from 1.6 microg/ml (0.9-2.0 microg/ml) up to 6.5 microg/ml (2.6-9.3 microg/ml). Mean EF improved from 22% (10-35%) up to 39% (10-60%) and clinical improvement has been remarkable with NYHA class improving from a mean of IV to a mean of II (I to III). Ubiquinol has dramatically improved absorption in patients with severe heart failure and the improvement in plasma CoQ10 levels is correlated with both clinical improvement and improvement in measurement of left ventricular function.
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PMID:Supplemental ubiquinol in patients with advanced congestive heart failure. 1909 7

Reactive oxygen species seem to play an important role in vascular homeostasis. In conditions of high oxidative stress, such as chronic heart failure and multiple coronary risk factors, the rate of inactivation of nitric oxide to peroxynitrite by superoxide anions may be reduced by CoQ10, which can also protect against nitrosative damage. CoQ10 may also influence vascular function indirectly via inhibition of oxidative damage to LDL. Patients with lower levels of extracellular superoxide dismutase (ecSOD) demonstrate greater improvements than patients with normal ec-SOD levels, suggesting that the higher the oxidative stress the greater the improvement in the endothelium-dependent relaxation after the administration of a compound with antioxidant properties like CoQ10. Future studies are needed to inquire whether these effects may translate into benefits in clinical practice.
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PMID:Oxidative stress, endothelial function and coenzyme Q10. 1909 8

It is well known that by improving mitochondrial bioenergetics, Coenzyme Q10 improves the systolic function in heart failure. The aim of this study was to see whether it benefits the diastolic dysfunction in hypertrophic cardiomyopathy (HCM) cases since diastolic relaxation also requires energy like the systole. 200 mg/day of CoQ10 was added to the conventional treatment in 46 patients with HCM diagnosed clinically and by echocardiography and by excluding cases of long standing hypertension. A comparable group of 41 age/sex matched cases received only conventional therapy. There was a significant improvement in the parameters like NYHA class > or = 1, in quality of life (QOL) on 6 minutes walk test, in diastolic dysfunction by > or = 1 parameter and in MR > or = 1 grade. Post treatment echocardiogram showed significant reduction in left ventricular outflow tract (LVOT) gradient > or = 15 mm Hg in obstructive cases (12 out of 46) in the treatment group. The mean interventricular septal thickness (IVS) showed a 22.4% reduction (p < 0.005). The mean posterior wall thickness showed a 23.1% reduction (p < 0.005). No patient in the treatment Group had ventricular tachycardia (VT) whereas 4 cases in the control group had VT. In both groups 1 patient was lost due to sudden cardiac death (SCD).
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PMID:Coenzyme Q10 (CoQ10) in isolated diastolic heart failure in hypertrophic cardiomyopathy (HCM). 1909 10

Nutrition impairment commonly occurs in patients with heart failure and affects disease progression. Vitamin and mineral deficiencies are associated with early mortality, particularly in patients classified as cachectic. Guideline-based therapies approved for heart failure, such as loop diuretics, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, aldosterone antagonists, and beta-adrenergic blockers, can lead to electrolyte abnormalities and predispose to some vitamin and micronutrient deficits. Clinical trial evidence in support of supplementary vitamin and mineral therapies for heart failure patients is limited with the exception of documented calcium and possibly vitamin D, thiamine, and coenzyme Q10 deficiencies. This area is gaining significant attention, and research is ongoing. The clinician can help minimize morbidity from nutrition impairment through appropriate monitoring and correction of baseline and medication-induced electrolyte imbalances, in addition to vitamin and mineral supplementation when appropriate.
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PMID:Nutrition and heart failure: impact of drug therapies and management strategies. 1924 50

Statins and coenzyme Q10 are both used as adjuncts in the treatment of chronic heart failure (CHF) due to their anti-inflammatory and antioxidant effects, respectively. And both have been variously shown to improve cardiac function in patients with CHF. The two agents interact in two ways; statins inhibit coenzyme Q10 synthesis through inhibition of HMG-CoA reductase, the rate limiting step in cholesterol synthesis, also shared by coenzyme Q10. Secondly, they both exhibit their antioxidant effects through activation of the enzyme superoxide dismutase, the rate limiting step in nitric oxide metabolism and main antioxidant mechanism of coenzyme Q10. We hypothesize that the interaction between statins and coenzyme Q10 is more than just a replacement, but a synergistic interaction on superoxide dismutase that could result in better cardiac function, improvement in patient symptoms, shortening of duration of hospital stay and improvement in patient quality of life.
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PMID:Combined statin/coenzyme Q10 as adjunctive treatment of chronic heart failure. 1940 11

Coenzyme Q10 (ubiquinone) is a mitochondrial coenzyme which is essential for the production of ATP. Being at the core of cellular energy processes it assumes importance in cells with high energy requirements like the cardiac cells which are extremely sensitive to CoQ10 deficiency produced by cardiac diseases. CoQ10 has thus a potential role for prevention and treatment of heart ailments by improving cellular bioenergetics. In addition it has an antioxidant, a free radical scavenging and a vasodilator effect which may be helpful in these conditions. It inhibits LDL oxidation and thus the progression of atherosclerosis. It decreases proinflammatory cytokines and decreases blood viscosity which is helpful in patients of heart failure and coronary artery disease. It also improves ischemia and reperfusion injury of coronary revascularisation. Significant improvement has been observed in clinical and hemodynamic parameters and in exercise tolerance in patients given adjunctive CoQ10 in doses from 60 to 200 mg daily in the various trials conducted in patients of heart failure, hypertension, ischemic heart disease and other cardiac illnesses. Recently it has been found to be an independent predictor of mortality in congestive heart failure. It has also been found to be helpful in vertigo and Meniere-like syndrome by improving the immune system. Further research is going on to establish firmly its role in the therapy of cardiovascular diseases.
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PMID:Role of coenzyme Q10 (CoQ10) in cardiac disease, hypertension and Meniere-like syndrome. 1963 84

Ubidecarenone (coenzyme Q10) has been widely used as a complementary therapy in heart failure and as a dietary supplement for over two decades. Ubidecarenone is manufactured by organic synthesis, yeast (non-Saccharomyces cerevisiae) fermentation, or bacteria fermentation. There are many reports on the safety of ubidecarenone. However, genotoxicity of ubidecarenone manufactured by bacteria fermentation has not been reported. We carried out genotoxicity evaluation of ubidecarenone manufactured by bacteria fermentation through the bacterial reverse mutation test (Ames test) and in vitro chromosome aberration test in compliance with the Japanese guidelines on genotoxicity testing of pharmaceuticals and the Organization for Economic Co-operation and Development (OECD) guidelines for testing chemicals. The results indicate neither increase of revertant colonies nor chromosome aberration, suggesting that the ubidecarenone manufactured by bacteria fermentation has no genotoxic activities under the condition of this study.
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PMID:Genotoxicity studies of ubidecarenone (coenzyme Q10) manufactured by bacteria fermentation. 1965 61


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