ubiquinone and Cardiomyopathy--Dilated

The dystrophinopathies include Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XLDCM). In recent years, co-ordinated multidisciplinary management for these diseases has improved the quality of care, with early corticosteroid use prolonging independent ambulation, and the routine use of non-invasive ventilation signficantly increasing survival. The next target to improve outcomes is optimising treatments to delay the onset or slow the progression of cardiac involvement and so prolong survival further.. To assess the effects of interventions for preventing or treating cardiac involvement in DMD, BMD, and XLDCM, using measures of change in cardiac function over six months.. On 16 October 2017 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase, and on 12 December 2017, we searched two clinical trials registries. We also searched conference proceedings and bibliographies.. We considered only randomised controlled trials (RCTs), quasi-RCTs and randomised cross-over trials for inclusion. In the Discussion, we reviewed open studies, longitudinal observational studies and individual case reports but only discussed studies that adequately described the diagnosis, intervention, pretreatment, and post-treatment states and in which follow-up lasted for at least six months.. Two authors independently reviewed the titles and abstracts identified from the search and performed data extraction. All three authors assessed risk of bias independently, compared results, and decided which trials met the inclusion criteria. They assessed the certainty of evidence using GRADE criteria.. We included five studies (N = 205) in the review; four studies included participants with DMD only, and one study included participants with DMD or BMD. All studied different interventions, and meta-analysis was not possible. We found no studies for XLDCM. None of the trials reported cardiac function as improved or stable cardiac versus deteriorated.The randomised first part of a two-part study of perindopril (N = 28) versus placebo (N = 27) in boys with DMD with normal heart function at baseline showed no difference in the number of participants with a left ventricular ejection fraction (LVEF%) of less than 45% after three years of therapy (n = 1 in each group; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.07 to 15.77). This result is uncertain because of study limitations, indirectness and imprecision. In a non-randomised follow-up study, after 10 years, more participants who had received placebo from the beginning had reduced LVEF% (less than 45%). Adverse event rates were similar between the placebo and treatment groups (low-certainty evidence).A study comparing treatment with lisinopril versus losartan in 23 boys newly diagnosed with Duchenne cardiomyopathy showed that after 12 months, both were equally effective in preserving or improving LVEF% (lisinopril 54.6% (standard deviation (SD) 5.19), losartan 55.2% (SD 7.19); mean difference (MD) -0.60% CI -6.67 to 5.47: N = 16). The certainty of evidence was very low because of very serious imprecision and study limitations (risk of bias). Two participants in the losartan group were withdrawn due to adverse events: one participant developed an allergic reaction, and a second exceeded the safety standard with a fall in ejection fraction greater than 10%. Authors reported no other adverse events related to the medication (N = 22; very low-certainty evidence).A study comparing idebenone versus placebo in 21 boys with DMD showed little or no difference in mean change in cardiac function between the two groups from baseline to 12 months; for fractional shortening the mean change was 1.4% (SD 4.1) in the idebenone group and 1.6% (SD 2.6) in the placebo group (MD -0.20%, 95% CI -3.07 to 2.67, N = 21), and for ejection fraction the mean change was -1.9% (SD 9.8) in the idebenone group and 0.4% (SD 5.5) in the placebo group (MD -2.30%, 95% CI -9.18 to 4.58, N = 21). The certainty of evidence was very low because of study limitations and very serious imprecision. Reported adverse events were similar between. Based on the available evidence from RCTs, early treatment with ACE inhibitors or ARBs may be comparably beneficial for people with a dystrophinopathy; however, the certainty of evidence is very low. Very low-certainty evidence indicates that adding eplerenone might give additional benefit when early cardiomyopathy is detected. No clinically meaningful effect was seen for growth hormone or idebenone, although the certainty of the evidence is also very low.

Topics: Adolescent; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiovascular Agents; Child; Disease Progression; Eplerenone; Human Growth Hormone; Humans; Lisinopril; Losartan; Male; Muscular Dystrophy, Duchenne; Non-Randomized Controlled Trials as Topic; Perindopril; Placebos; Randomized Controlled Trials as Topic; Stroke Volume; Ubiquinone; Young Adult

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Cytochrome b Group; Diagnosis, Differential; DNA, Mitochondrial; Genetic Therapy; Heart Transplantation; Humans; Mitochondrial Myopathies; Mutation; RNA; RNA, Mitochondrial; RNA, Transfer; Ubiquinone

beta-Methyl-p-(123I)-iodophenyl pentadecanoic acid (BMIPP) is one of the branched-chain free fatty acids, which has suitable characteristics for myocardial SPECT because of higher uptake and longer retention in the myocardium. Recent advances of BMIPP myocardial SPECT for evaluating cardiomyopathy were reviewed. BMIPP defects were observed in 80% patients with hypertrophic cardiomyopathy (HCM). Moreover, BMIPP uptake was reduced at sites that corresponded with hypertrophic areas, where thallium uptake was increased. The correlations between severity score and septal wall thickness and LV function were better with BMIPP SPECT, suggesting that BMIPP is more suitable for the assessment of myocardial integrity in HCM. The dissociation between BMIPP and thallium defects was not observed frequently in dilated cardiomyopathy (DCM). We carried out BMIPP myocardial SPECT to evaluate the therapeutic effects of co-enzyme Q10 on DCM patients. Hearts to the mediastinum ratio and BMIPP defect scores were significantly decreased after co-enzyme Q10 treatment. BMIPP myocardial SPECT was confirmed to be sensitive in evaluating the therapeutic effect for the perspective of metabolic SPECT imaging. Recently, a lack of myocardial uptake of BMIPP has been found in a small subset of patients (0.3%-1.2%). Cardiac radionuclide imaging using BMIPP and 18F-FDG were performed on patients with type I CD36 deficiency. The percent dose uptake of 18F-FDG was significantly higher than in normal controls. CD functions as a major myocardial long-chain fatty acid transporter and its absence may lead to a compensatory upregulation of myocardial glucose uptake. An increased frequency of CD36 deficiency was demonstrated in cardiomyopathy. Therefore, fatty acid transport proteins and their related gene defects in relation to BMIPP uptake may become an important issue in the future.

Topics: Antioxidants; Cardiomyopathies; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; CD36 Antigens; Coenzymes; Fatty Acids; Humans; Iodine Radioisotopes; Iodobenzenes; Tomography, Emission-Computed, Single-Photon; Ubiquinone

We aimed to determine the effect of supplementation with coenzyme Q10 on conventional therapy of children with cardiac failure due to idiopathic dilated cardiomyopathy. In a prospective, randomized, double-blinded, placebo-controlled trial, we randomized 38 patients younger than 18 years with idiopathic dilated cardiomyopathy to receive either coenzyme Q10, chosen for 17 patients, or placebo, administered in the remaining 21. Echocardiographic systolic and diastolic function parameters were determined for every patient at baseline, and after 6 months of supplementation. The index score for cardiac failure in children as established in New York was used for assessing the functional class of the patients. After 6 months supplementation, 10 patients randomized to receive coenzyme Q10 showed improvements in the grading of diastolic function, this being significantly more than that achieved by those randomized to the placebo group (p value = 0.011). The mean score for the index of cardiac failure index for those receiving coenzyme Q10 was also lower than the control group (p value = 0.024).Our results, therefore, indicate that administration of coenzyme Q10 is useful in ameliorating cardiac failure in patients with idiopathic dilated cardiomyopathy through its significant effect on improving diastolic function.

Topics: Adolescent; Cardiomyopathy, Dilated; Child; Child, Preschool; Double-Blind Method; Heart Failure; Humans; Infant; Prospective Studies; Ubiquinone; Vitamins

Several noninvasive studies have shown the effect on heart failure of treatment with coenzyme Q10. In order to confirm this by invasive methods we studied 22 patients with mean left ventricular (LV) ejection fraction 26%, mean LV internal diameter 71 mm and in NYHA class 2-3. The patients received coenzyme Q10 100 mg twice daily or placebo for 12 weeks in a randomized double-blinded placebo controlled investigation. Before and after the treatment period, a right heart catheterisation was done including a 3 minute exercise test. The stroke index at rest and work improved significantly, the pulmonary artery pressure at rest and work decreased (significantly at rest), and the pulmonary capillary wedge pressure at rest and work decreased (significantly at 1 min work). These results suggest improvement in LV performance. Patients with congestive heart failure may thus benefit from adjunctive treatment with coenzyme Q10.

Topics: Adult; Aged; Antioxidants; Blood Pressure; Cardiac Catheterization; Cardiac Output; Cardiomyopathy, Dilated; Coenzymes; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Ubiquinone; Ventricular Function, Left

To evaluate therapeutic effects of Cenzyme Q10 (CoQ10), 15 patients with dilated cardiomyopathy were investigated by 123I-BMIPP myocardial single photon emission computed tomography (SPECT). The BMIPP defect score was determined semiquantitatively by using representative short and long axial SPECT images. Mean BMIPP defect score with CoQ10 treatment was significantly low, 7.7 +/- 6.1 compared to 12.7 +/- 7.4 without CoQ10 treatment. On the other hand, in 8 patients of dilated cardiomyopathy, % fractional shortening using echocardiography was not different before and after CoQ10 treatment. In conclusion, 123I-BMIPP myocardial SPECT was proved to be sensitive to evaluate the therapeutic effects of CoQ10, which improve myocardial mitochondrial function, in the cases of dilated cardiomyopathy.

Topics: Aged; Cardiomyopathy, Dilated; Coenzymes; Fatty Acids; Female; Humans; Iodine Radioisotopes; Iodobenzenes; Japan; Male; Middle Aged; Tomography, Emission-Computed, Single-Photon; Ubiquinone

We have already proved that the mitochondrial membrane-phospholipid (MMP) injury changes of peripheral lymphocytes in patients with heart failure can be used as an injury indicator of myocardia, and are related to the long-term prognosis. In the present study, MMP localization of the peripheral lymphocytes was performed by modified Demer's tricomplex flocculation method, and we compared the changes, after classification, between the pre-treatment and the 12-week post-treatment, of coenzyme Q10 (Co.Q10) and captopril in 61 hospitalized patients with dilated cardiomyopathy (DCM). They were followed up for 16.1 +/- 7.8 months (mean). The results showed that compared with the placebo, Co.Q10 and captopril could significantly protect against and repair MMP injury and improve the heart function of patients with DCM after 12 weeks, and the 2-year survival rate rose significantly by 72.7% for Co.Q10, and 64.0% for captopril, vs 24.7% for placebo. As for Longrank test, X2 equals 4.660 and 6.318, respectively, with both p < 0.05. The aforementioned results indicate that MMP injury of peripheral lymphocytes can predict the prognosis of the patients with DCM, thus the protection and repairment of MMP injury can improve the life-quality and prolong the life-span of the patients.

Topics: Antihypertensive Agents; Biomarkers; Captopril; Cardiomyopathy, Dilated; Cell Membrane; Coenzymes; Female; Humans; Lymphocytes; Male; Mitochondria; Phospholipids; Prognosis; Ubiquinone

Over an eight year period (1985-1993), we treated 424 patients with various forms of cardiovascular disease by adding coenzyme Q10 (CoQ10) to their medical regimens. Doses of CoQ10 ranged from 75 to 600 mg/day by mouth (average 242 mg). Treatment was primarily guided by the patient's clinical response. In many instances, CoQ10 levels were employed with the aim of producing a whole blood level greater than or equal to 2.10 micrograms/ml (average 2.92 micrograms/ml, n = 297). Patients were followed for an average of 17.8 months, with a total accumulation of 632 patient years. Eleven patients were omitted from this study: 10 due to non-compliance and one who experienced nausea. Eighteen deaths occurred during the study period with 10 attributable to cardiac causes. Patients were divided into six diagnostic categories: ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), primary diastolic dysfunction (PDD), hypertension (HTN), mitral valve prolapse (MVP) and valvular heart disease (VHD). For the entire group and for each diagnostic category, we evaluated clinical response according to the New York Heart Association (NYHA) functional scale, and found significant improvement. Of 424 patients, 58 per cent improved by one NYHA class, 28% by two classes and 1.2% by three classes. A statistically significant improvement in myocardial function was documented using the following echocardiographic parameters: left ventricular wall thickness, mitral valve inflow slope and fractional shortening. Before treatment with CoQ10, most patients were taking from one to five cardiac medications. During this study, overall medication requirements dropped considerably: 43% stopped between one and three drugs. Only 6% of the patients required the addition of one drug. No apparent side effects from CoQ10 treatment were noted other than a single case of transient nausea. In conclusion, CoQ10 is a safe and effective adjunctive treatment for a broad range of cardiovascular diseases, producing gratifying clinical responses while easing the medical and financial burden of multidrug therapy.

Topics: Cardiomyopathy, Dilated; Cardiovascular Agents; Cardiovascular Diseases; Coenzymes; Diastole; Drug Therapy, Combination; Echocardiography; Female; Follow-Up Studies; Heart Function Tests; Heart Valve Diseases; Humans; Hypertension; Male; Middle Aged; Mitral Valve Prolapse; Myocardial Ischemia; Treatment Outcome; Ubiquinone

Using a placebo-controlled, double-blind cross-over study the potential therapeutic effect of ubiquinone (coenzyme Q10) was investigated in 25 patients suffering from idiopathic dilated cardiomyopathy (New York Heart Association functional classification I, II and III). Over an initial period of 4 months, 15 patients were administered verum (3 x 33.3 mg coenzyme Q10 x day-1 p.o.) and subsequently given a placebo during the ensuing 4 months (V/P). The sequence of treatment was reversed within the remaining 10 patients (P/V). Therapeutic efficacy was assessed by means of echocardiogram, chest X-ray, radionuclide ventriculography in combination with exercise test and impedance cardiography. Control values for left ventricular function parameters were similar in both groups; left ventricular ejection fraction: 39.5 +/- 11.5% (P/V), 37.6 +/- 17.0% (V/P); left ventricular end-diastolic diameter: 65 +/- 9 mm (P/V), 67 +/- 8 mm (P/V); and cardiac output: 5.1 +/- 1.41 x min-1 (P/V), 5.1 +/- 1.11 x min-1 (V/P). Chronic treatment with ubiquinone had no influence on haemodynamic parameters, electrocardiogram, incidence of ventricular arrhythmias or on exercise tolerance. It was therefore impossible to demonstrate any therapeutic effect of ubiquinone in patients suffering from idiopathic dilated cardiomyopathy.

Topics: Cardiomyopathy, Dilated; Double-Blind Method; Female; Humans; Male; Middle Aged; Time Factors; Ubiquinone; Ventricular Function, Left

We compared the effect of oral administration of taurine (3 g/day) and coenzyme Q10 (CoQ10) (30 mg/day) in 17 patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy, whose ejection fraction assessed by echocardiography was less than 50%. The changes in echocardiographic parameters produced by 6 weeks of treatment were evaluated in a double-blind fashion. In the taurine-treated group significant treatment effect was observed on systolic left ventricular function after 6 weeks. Such an effect was not observed in the CoQ10-treated group.

Topics: Administration, Oral; Cardiomyopathy, Dilated; Chronic Disease; Coenzymes; Coronary Disease; Double-Blind Method; Drug Evaluation; Echocardiography; Female; Heart Failure; Humans; Male; Stroke Volume; Taurine; Ubiquinone; Ventricular Function, Left

During 1982-86, 43/137 patients with cardiomyopathy, Classes II, III and IV, had ejection fractions (EF) below 40%, and a mean EF of 25.1 +/- 10.3%. During treatment of these 43 patients with coenzyme Q10 (CoQ10), EF increased to 41.6 +/- 14.3% (p less than 0.001) over a mean period of 3 months (range, 2-4 months). At four subsequent periods up to 36 months. EF ranged from 43.1 +/- 13.3 to 49.7 +/- 6.4% (each period, p less than 0.001). The mean CoQ10 control blood level was 0.85 +/- 0.26 micrograms/ml which increased on treatment to 1.7 to 2.3 micrograms/ml for five periods up to 36 months (each period, p less than 0.001). The survival rates for all 137 patients treated with CoQ10 and for the 43 patients with EF below 40% were both about 75%/46 months. These two survival rates were comparable between 24 and 46 months, which is of extraordinary significance and importance when compared to survival of about 25%/36 months for 182 patients with EF below 46% on conventional therapy without CoQ10. The improved cardiac function and pronounced increase of survival show that therapy with CoQ10 is remarkably beneficial due to correction of CoQ10 deficiency in mechanisms of bioenergetics.

Topics: Aged; Cardiomyopathy, Dilated; Coenzymes; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Survival Rate; Ubiquinone

In a chronic, placebo-controlled, double-blind cross-over study a potential therapeutic effect of coenzyme Q10 (ubiquinone) was investigated in 25 patients suffering from dilative cardiomyopathy (NYHA functional class I, II, III). During a period of four months patients were treated with 3x 33.3 mg of coenzyme Q10 per day, given orally, 15 patients received verum during the first four months and placebo during the following four months (V/P). In the second group of patients (n = 10) the sequence of treatment was reversed (P/V). Therapeutic effect was assessed by means of echocardiogram, chest x-ray, radionuclide ventriculography combined with exercise test and impedance cardiography. Control values for left ventricular function parameters were similar in both groups (left ventricular ejection fraction: 39.5 +/- 11.5% (P/V), 37.6 +/- 17.0% (V/P); left ventricular enddiastolic diameter: 65 +/- 9 mm (P/V), 67 +/- 8 mm (V/P); Cl: 5.1 +/- 1.4 l/min (P/V), 5.1 +/- 1.1 l/min (V/P]. Chronic treatment by coenzyme Q10 did not exhibit any influence on hemodynamic parameters, on the electrocardiogram, on incidence of ventricular arrhythmias, or on exercise tolerance. It was not possible to demonstrate any therapeutic effect of coenzyme Q10 in patients with dilative cardiomyopathy.

Topics: Adult; Aged; Cardiomyopathy, Dilated; Clinical Trials as Topic; Double-Blind Method; Drug Therapy, Combination; Female; Hemodynamics; Humans; Male; Middle Aged; Myocarditis; Random Allocation; Ubiquinone

Coenzyme Q10 (CoQ10) is indispensable in mitochondrial bioenergetics and for human life to exist. 88/115 patients completed a trial of therapy with CoQ10 for cardiomyopathy. Patients were selected on the basis of clinical criteria, X-rays, electrocardiograms, echocardiography, and coronary angiography. Responses were monitored by ejection fractions, cardiac output, and improvements in functional classifications (NYHA). Of the 88 patients 75%-85% showed statistically significant increases in two monitored cardiac parameters. Patients with the lowest ejection fractions (approx. 10%-30%) showed the highest increases (115 delta %-210 delta %) and those with higher ejection fractions (50%-80%) showed increases of approx. 10 delta %-25 delta % on therapy. By functional classification, 17/21 in class IV, 52/62 in class III, and 4/5 in class II improved to lower classes. Clinical responses appeared over variable times, and are presumably based on mechanisms of DNA-RNA-protein synthesis of apoenzymes which restore levels of CoQ10 enzymes in a deficiency state. 10/21 (48%) of patients in class IV, 26/62 (42%) in class III, and 2/5 (40%) in class II had exceptionally low control blood levels of CoQ10. Clinical responses on therapy with CoQ10 appear maximal with blood levels of approx. 2.5 micrograms CoQ10/ml and higher during therapy.

Topics: Adult; Aged; Aged, 80 and over; Cardiac Output; Cardiomyopathies; Cardiomyopathy, Dilated; Clinical Trials as Topic; Coenzymes; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Stroke Volume; Ubiquinone

Pediatric dilated cardiomyopathy (PDCM) is a life-threatening type of cardiac muscle dysfunction in children. Ubiquinone is a lipid-soluble nutrient that participates in energy synthesis. Recently, a novel hydrophilic ubiquinol supplement was developed. The purpose of this study was to assess the effect of liquid ubiquinol supplementation (10 mg/kg body weight/day) on cardiac function in children with PDCM.. Ten children diagnosed with PDCM were recruited to this study and administered with liquid ubiquinol for 24 weeks. The cardiac function was measured by echocardiography. The New York Heart Association (NYHA) functional classification was used to assess symptoms of heart failure. Plasma coenzyme Q10 levels were measured during the study.. Ejection fraction (EF) and fractional shortening (FS) were significantly higher than the baseline values until week 16 of supplementation. Subjects who had higher plasma coenzyme Q10 concentration had significantly better EF and FS values. In addition, 30% of the subjects showed improvement in the NYHA classification after 24 weeks of supplementation.. Liquid ubiquinol supplementation is associated with an increase the level of coenzyme Q10 to complementary improve cardiac function (particularly EF and FS) and ameliorate the symptoms of heart failure in children with PDCM.

Topics: Adolescent; Anthropometry; Cardiomyopathy, Dilated; Child; Child, Preschool; Dietary Supplements; Dose-Response Relationship, Drug; Echocardiography; Female; Humans; Male; Pilot Projects; Ubiquinone

Topics: Angiotensin-Converting Enzyme Inhibitors; Bundle-Branch Block; Cardiac Resynchronization Therapy; Cardiomyopathy, Dilated; Defibrillators, Implantable; Echocardiography; Echocardiography, Doppler; Echocardiography, Three-Dimensional; Electrocardiography; Heart Failure; Humans; Male; Myotonic Dystrophy; Stroke Volume; Tachycardia, Ventricular; Ubiquinone; Vitamins; Young Adult

The inability of heart muscle to generate ventricular pressure to adequately propel blood through the cardiovascular system is a primary defect associated with congestive heart failure (CHF). Force-frequency relationship (FFR) is one of the main cardiac defects associated with congestive heart failure. Thus FFR is a convenient methodological tool for evaluating the severity of muscle contractile dysfunction and the effectiveness of therapeutic agents. Papillary muscle isolated from BIO TO-2 cardiomyopathic Syrian hamsters (CMSHs), show a depressed FFR and represents an animal model of human idiopathic dilated cardiomyopathy. In the present study we investigated the effect of CoQ10, omega-3 fatty acids, propionyl-L-carnitine (PLC) and a combination of these 3 agents (formulation HS12607) on FFR in 8 month old BIO TO-2 CMSHs. Papillary muscles isolated from the anesthetized animals were placed in an incubation bath and attached to an isometric force transducer. A digital computer with an analog/digital interface allowed control of both muscle developed force and electrical stimulus parameters. Force-frequency response was evaluated, at Lmax, with increasing frequencies: 0.06, 0.12, 0.25, 0.5, 1, 2 and 4 Hz. HS12607-treatment produced a positive inotropic effect resulting in a significant enhancement (p < 0.05) of the peak force at the highest frequencies (1-4 Hz). In the range of frequency of 1-4 Hz also CoQ10 and omega-3 significantly (p < 0.05) attenuated the fractional decline in developed force. The significant improvement (p < 0.05) of the timing parameter peak rate of tension rise (+ T') and peak rate of tension fall (-T') indicating a faster rate of muscle contraction and relaxation respectively, found in CoQ10, omega-3 and PLC-treated CMSHs, may be due to the positive effects of these substances on sarcoplasmic reticulum functions. These findings suggest that naturally occurring CoQ10, omega-3 and PLC, particularly when administered together in a coformulation, might be a valid adjuvant to conventional therapy in dilated cardiomyopathy especially when considering that they are natural substances, devoid of side effects.

Topics: Animals; Cardiomyopathies; Cardiomyopathy, Dilated; Carnitine; Cricetinae; Fatty Acids, Omega-3; Male; Mesocricetus; Models, Animal; Myocardial Contraction; Papillary Muscles; Stimulation, Chemical; Ubiquinone

Cardiomyopathy (CMP) is a common debilitating illness, associated with a high mortality and poor quality of life. There is extensive evidence from in vitro and animal experiments that CMP is a state of increased oxidative stress. Coenzyme Q10 (CoQ10) and high-sensitivity C-reactive protein (hs-CRP) are important markers to evaluate the oxidative stress and inflammatory status of patients with CMP.. A total of 28 patients with chronic stable heart failure (21 men and 7 women, ages 18-76 years) were included in the study. Causes of heart failure were ischemic CMP in 17 patients and idiopathic dilated CMP in 11 patients. A total of 28 patients (12 men and 16 women; ages 30-71 years) with normal coronary angiography were enrolled as a control group. Levels of CoQ10, albumin, total thiol groups (T-SH), bilirubin, uric acid as plasma antioxidants, hs-CRP as an inflammation marker and lipid profile were studied in patients and controls.. Plasma CoQ10, T-SH and albumin levels were significantly decreased in patients compared to controls. Uric acid, bilirubin and hs-CRP levels were found to be significantly increased compared to controls.. In this study, evidence of decreased antioxidant status was determined in CMP patients together with vascular inflammation. CoQ10, other plasma antioxidants and hs-CRP measured routinely can reflect decreased antioxidant status and inflammatory process in patients with dilated CMP. These markers can be used to monitor the status of patients with CMP.

Topics: Adolescent; Adult; Aged; Antioxidants; Biomarkers; C-Reactive Protein; Cardiomyopathy, Dilated; Case-Control Studies; Female; Humans; Ischemia; Male; Middle Aged; Substrate Specificity; Ubiquinone

Mechanisms underlying dilated cardiomyopathy (DCM) are poorly understood and effective therapy is still unavailable. The aim of this study was to examine the heart ultrastructure and dynamic of BIO T0-2 cardiomyopathic hamsters, an animal model of DCM, and to study in these animals, the effects of a co-formulation (HS12607) of propionyl-L-carnitine, coenzyme Q(10) and omega-3 fatty acids on cardiac mechanical parameters. Sarcomere length, Frank-Starling mechanism and force-frequency relations were studied on isolated ventricular papillary muscle from age-matched BIO F1B normal Syrian hamsters, BIO T0-2 control and BIO T0-2 HS12607-treated cardiomyopathic Syrian hamsters. At the optimum length to maximum active force, electron microscopy of left ventricular papillary muscle revealed that seven out of ten muscles studied showed shorter sarcomeres (1.20 +/- 0.29 microm), and the remaining three showed longer sarcomeres (2.80 +/- 0.13 microm), compared to those of normal hamsters (2.05 +/- 0.06 microm, n = 10). Severe alterations of the Frank-Starling mechanism, force-frequency relations and derivative parameters of contractile waves were also observed in vitro in the BIO T0-2 control hamsters. Long-term (8 weeks) treatment with HS12607 prevented alterations in sarcomere length in the BIO T0-2 cardiomyopathic hamsters; the Frank-Starling mechanism and force-frequency relations were also significantly (P < 0.05) improved in these hamsters. Therefore results of the present study strongly suggest the need for clinical studies on metabolic therapeutic intervention in the effort to stop the progression of dilated cardiomyopathy.

Topics: Animals; Cardiomyopathy, Dilated; Carnitine; Cricetinae; Disease Models, Animal; Electric Stimulation; Fatty Acids, Omega-3; Male; Mesocricetus; Myocardial Contraction; Papillary Muscles; Sarcomeres; Ubiquinone

Friedreich ataxia (FRDA), a progressive neurodegenerative disorder associated with cardiomyopathy, is caused by severely reduced frataxin, a mitochondrial protein involved in Fe-S cluster assembly. We have recently generated mouse models that reproduce important progressive pathological and biochemical features of the human disease. Our frataxin-deficient mouse models initially demonstrate time-dependent intramitochondrial iron accumulation, which occurs after onset of the pathology and after inactivation of the Fe-S dependent enzymes. Here, we report a more detailed pathophysiological characterization of our mouse model with isolated cardiac disease by echocardiographic, biochemical and histological studies and its use for placebo-controlled therapeutic trial with Idebenone. The Fe-S enzyme deficiency occurs at 4 weeks of age, prior to cardiac dilatation and concomitant development of left ventricular hypertrophy, while the mitochondrial iron accumulation occurs at a terminal stage. From 7 weeks onward, Fe-S enzyme activities are strongly decreased and are associated with lower levels of oxidative stress markers, as a consequence of reduced respiratory chain activity. Furthermore, we demonstrate that the antioxidant Idebenone delays the cardiac disease onset, progression and death of frataxin deficient animals by 1 week, but does not correct the Fe-S enzyme deficiency. Our results support the view that frataxin is a necessary, albeit non-essential, component of the Fe-S cluster biogenesis, and indicate that Idebenone acts downstream of the primary Fe-S enzyme deficit. Furthermore, our results demonstrate that Idebenone is cardioprotective even in the context of a complete lack of frataxin, which further supports its utilization for the treatment of FRDA.

Topics: Animals; Benzoquinones; Cardiomyopathy, Dilated; Disease Models, Animal; Electrocardiography; Frataxin; Friedreich Ataxia; Iron-Binding Proteins; Iron-Sulfur Proteins; Mice; Mitochondria; Myocardium; Oxidative Stress; Ubiquinone

Topics: Age Factors; Antioxidants; Cardiomyopathy, Dilated; Child; Child, Preschool; Coenzymes; Female; Humans; Infant; Male; Ubiquinone

Evidence indicates that nutritional factors may be important in the maintenance of myocyte structure and energetics. The failing myocardium has been reported to exhibit a depletion of several nutrients that are important for the maintenance of intracellular calcium homeostasis and cellular energetics, and levels of oxidative stress. This nutrient depletion may contribute to the progressive deterioration in myocardial structure and function observed in heart failure.. To examine the extent to which advanced cardiomyopathy results in a depletion of nutrients and/or metabolites and antioxidants, and whether supplementation with these nutrients may influence cellular structure or function.. Cardiomyopathic hamsters were randomly placed to one of the three following diet groups: chow; control gelled diet; or a supplemented gelled diet that provided taurine, carnitine, coenzyme Q10, selenium, vitamins E and C, creatine, thiamine and L-cysteine. After approximately three months of supplementation, one group of hamsters underwent functional testing using a modified Langendorff technique with biopsy samples taken for electron microscopy. Myocardial nutrient concentrations were determined in a second group of diseased and nondiseased hamsters of the same age.. Cardiomyopathy resulted in a depletion of vitamin E, creatine, carnitine, taurine and coenzyme Q10. Supplementation resulted in improved cardiac ultrastructure, function and contractility compared with nonsupplemented hamsters.. These studies suggest that heart failure results in 'condition-related nutrient deficiencies' that, once corrected, can significantly impact on heart function and structure.

Topics: Animals; Cardiomyopathy, Dilated; Cricetinae; Dietary Supplements; Heart Function Tests; Male; Mesocricetus; Nutritional Status; Ubiquinone; Vitamin E

Topics: Cardiomyopathy, Dilated; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Prognosis; Randomized Controlled Trials as Topic; Treatment Outcome; Ubiquinone

Topics: Cardiomyopathy, Dilated; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Randomized Controlled Trials as Topic; Treatment Outcome; Ubiquinone

It has been reported that myocardial mitochondrial function can be improved by the administration of co-enzyme Q10 (CoQ10). Recently, iodine-123 labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was developed for metabolic imaging using single-photon emission tomography (SPET). This study was conducted to determine whether the therapeutic effects of CoQ10 on idiopathic dilated cardiomyopathy can be evaluated by BMIPP myocardial SPET. Fifteen patients, comprising 14 men and one woman (mean age: 64+/-12 years), were examined. CoQ10 was administered at 30 mg/day for a period of 35.7+/-12.4 days. BMIPP myocardial SPET was carried out before and after CoQ10 treatment. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated using a region of interest method with anterior planar imaging. Representative short-axis tomograms were divided into 27 segments (three slicesxnine segments). Each segmental score was analysed semiquantitatively using a four-point scoring system (normal=0, mild low uptake=1, severe low uptake=2, defect=3). The H/M ratio showed a significant improvement, from 2.39+/-0.39 to 2.54+/-0.47, after treatment (P<0.05). The BMIPP total defect score after CoQ10 treatment was significantly decreased to 10.1+/-4.3, compared to 13. 9+/-4.5 without CoQ10 treatment (P<0.001). However, the percent fractional shortening measured using echocardiography was not significantly different before and after CoQ treatment (19.2+/-8.1 vs 19.7+/-7.1). BMIPP myocardial SPET was confirmed to be sensitive in evaluating the therapeutic effects of CoQ10 in patients with idiopathic dilated cardiomyopathy. This method is unique, since the therapeutic effects can be estimated from the perspective of metabolic SPET imaging.

Topics: Cardiomyopathy, Dilated; Coenzymes; Echocardiography; Fatty Acids; Female; Heart; Humans; Iodine Radioisotopes; Iodobenzenes; Male; Middle Aged; Tomography, Emission-Computed, Single-Photon; Ubiquinone

Coenzyme Q10, a mitoquinone involved in mitochondrial energy synthesis and the removal of free radicals, may be lacking in a number of cardiac pathologies leading to reduced contractile activity. The administration of exogenous coenzyme Q10 may help to improve contractile activity. In order to assess this hypothesis 63 patients suffering from altered myocardial contractile function (29 dilated cardiopathies, 15 valvular cardiopathies, 19 ischemic cardiopathies) which presented a NYHA class above 2 were selected. The study was open and patients were subdivided into two groups, one of which received conventional therapy alone whereas the other also received exogenous coenzyme Q10. After 4 months of follow-up clinical (NYHA class, effort tolerance) and echocardiographical (ventricular diameter and contraction fraction %) parameters were evaluated. In those patients treated with coenzyme Q10 and suffering from dilated cardiomyopathy a significant reduction in the NYHA class and a marked improvement in echocardiographic parameters were observed at the end of this period. The variations observed in other groups of patients treated were less conspicuous and not always statistically significant. The results of this study confirm that the association of coenzyme Q10 and conventional therapy may lad to a marked improvement in contractile function and correlated clinical conditions.

Topics: Adult; Aged; Cardiomyopathy, Dilated; Coenzymes; Female; Heart Valve Diseases; Humans; Male; Middle Aged; Myocardial Contraction; Myocardial Ischemia; Ubiquinone

Twenty years of international open and seven double blind trials established the efficacy and safety of coenzyme Q10 (CoQ10) to treat patients in heart failure. In the U.S., ca. 20,000 patients under 65 years are eligible for transplants, but donors are less than 1/10th of those eligible, and there are many more such patients over 65, both eligible and ineligible. We treated eleven exemplary transplant candidates with CoQ10; all improved; three improved from Class IV to Class I; four improved from Classes III-IV to Class II; and two improved from Class III to Class I or II. After CoQ10, some patients required no conventional drugs and had no limitation in lifestyle. The marked improvement is based upon correcting myocardial deficiencies of CoQ10 which improve mitochondrial bioenergetics and cardiac performance. These case histories, and very substantial background proof of efficacy and safety, justify treating with CoQ10 patients in failure awaiting transplantation.

Topics: Adult; Aged; Cardiomyopathies; Cardiomyopathy, Dilated; Coenzymes; Female; Heart Transplantation; Humans; Male; Middle Aged; Ubiquinone

The authors have tried to study the therapeutic efficacy of coenzyme Q10 (CoQ10) in patients with dilated cardiomyopathy (DCM). In fact, CoQ10 has been shown to be deficient in myocardial tissue biopsies taken from DCM hearts, compared to normal hearts. Thirty patients with histological diagnosis of DCM were orally treated with CoQ10 (100 mg/die) for 2 months. Before and after treatment a clinical examination with determination of NYHA class and an echocardiographic examination with determination of ejection fraction (EF) and of telediastolic (TDV) and telesystolic (TSV) volumes were performed, and blood was drawn for plasma CoQ10 determination. In seven patients the pretreatment endomyocardial level of CoQ10 was also assayed. Seven patients left the study because of poor therapeutic compliance. In 47% of patients the clinical symptomatology regressed, with improvement of NYHA class. The EF improved from 0.31 +/- 0.09 to 0.37 +/- 0.11 (p less than 0.001). The TDV passed from 262.2 +/- 85 ml to 203.3 +/- 83 ml (p less than 0.05), and the TSV from 166.13 +/- 75 ml to 126.9 +/- 56 ml (ns). The CoQ10 plasmatic levels improved in 95% of the patients: from 0.74 +/- 0.37 micrograms/ml to 2.27 +/- 0.99 micrograms/ml (p +/- 0.0001). The CoQ10 myocardial levels did not show univocal values, but the patients with lower myocardial levels seemed to have a better therapeutic response. These data suggest that the CoQ10 deficiency in DCM may be reversible and that the therapeutic effects depend on the basal plasmatic and myocardial levels. Therapy with coenzyme Q10 may be considered to be an efficacious aid in the traditional treatment of chronic cardiac failure.

Topics: Cardiomyopathy, Dilated; Coenzymes; Energy Metabolism; Humans; Myocardium; Ubiquinone

Topics: Adult; Aged; Cardiomyopathy, Dilated; Coenzymes; Female; Humans; Longitudinal Studies; Male; Middle Aged; Stroke Volume; Time Factors; Ubiquinone

Topics: Adult; Cardiomyopathy, Dilated; Coenzymes; Drug Evaluation; Echocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ubiquinone

Topics: Biopsy; Cardiomyopathy, Dilated; Humans; Myocardium; Ubiquinone

Topics: Cardiac Catheterization; Cardiomyopathy, Dilated; Coronary Circulation; Female; Heart Ventricles; Hemodynamics; Humans; Male; Pulmonary Circulation; Ubiquinone

Topics: Biopsy; Cardiomyopathy, Dilated; Endocardium; Fluorescent Antibody Technique; Humans; Immunoglobulins; Ubiquinone