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Coenzyme Q10 Therapy Blocks the Vicious Metabolic Cycle in Chronic Heart Failure
The 17th Annual Scientific Meeting
HFSA
S25
067 Coenzyme Q10 Therapy Blocks the Vicious Metabolic Cycle in Chronic Heart Failure Svend A. Mortensen1, Franklin Rosenfeldt2, Adarsh Kumar3, Peter Dolliner4, Krzysztof J. Filipiak5, Daniel Pella6, Urban Alehagen7, Gian P. Littarru8; 1 Heart Center, Copenhagen University Hospital, Copenhagen, Denmark; 2Cardiac Surgical Research Unit, Alfred Hospital, Melbourne, Victoria, Australia; 3The Department of Cardiology, Govt. Medical College/G.N.D Hospital, Amritsar, India; 4The University Clinic of Internal Medicine, Vienna, Austria; 5Medical University of Warsaw, Warsaw, Poland; 6University of Kosice, Kosice, Slovakia; 7 The University Hospital, Link€oping, Sweden; 8Institute of Biochemistry, Ancona, Italy Energy starvation of the myocardium is a dominant feature of heart failure (HF) leading to an important role for agents that can enhance myocardial metabolism and augment energy production. Coenzyme Q10 (CoQ10) fulfils this role with previous double-blind trials though positive have been underpowered to detect major clinical endpoints such as mortality. Q-SYMBIO is the first double-blind trial of CoQ10 in HF addressing survival. Methods: Patients in NYHA Class III or IV HF who were receiving optimal pharmacologic therapy were randomly assigned to either CoQ10 100 mg three times daily or placebo. The primary long-term endpoint was composite MACE (major adverse cardiovascular events) including unplanned hospitalisations due to worsening heart failure, cardiovascular death, urgent cardiac transplantation and mechanical support, using a time to first event analysis. Results: A total of 420 patients from 17 international centres were enrolled with a follow-up time of 2 years. There was a significantly greater improvement of NYHA Class in the CoQ10 group compared to placebo (p50.047). The primary endpoint was reached by 14% of the patients in the CoQ10 group vs. 25% of patients in the placebo group; HR CoQ10 vs. placebo 2.0(CI 1.3-3.2); p50.003 by intention to treat analysis. CoQ10 treated patients had lower cardiovascular mortality: 8% vs. 15% (p50.02) and lower incidence of hospitalisations for HF (p50.05). All cause mortality was also lower in the CoQ10 group: 9% vs. 17%; HR CoQ10 vs. placebo 2.1(CI 1.2-3.8); p50.01. There were fewer adverse events in the CoQ10 group compared to placebo (p50.073). Conclusions: CoQ10 supplementation in patients with moderate to severe HF receiving optimal conventional therapy: is safe; improves survival due to reductions in cardiovascular- and all-cause mortality; is associated with reduction in symptoms and hospitalisations for worsening HF. Thus it represents an important advance in therapy.
068 Treating Anemia in Older Adults with Heart Failure with a Preserved EF (HFPEF) with Epoetin Alfa: A Per Protocol Analysis of the Data Sirish Vullaganti, Sergio Teruya, Julissa Alvarez, Jeff Goldsmith, Stephen Helmke, Mathew Maurer; New York Presbyterian-Columbia University Medical Center, New York, NY
066 Effect of CPAP Treatment on EKG Parameters in Patients with Significant Obstructive Sleep Apnea Wissam I. Khalife1, Sharon Onguti2, Ahmad Almomani2, Ali Charif1; 1University of Texas Medical Branch, Galveston, TX; 2University of Texas Medical Branch, Galveston, TX Background: Obstructive sleep apnea (OSA) is a well established risk of cardiovascular morbidity and mortality. The effect of OSA on EKG has not been well studied. The aim of our study is to investigate the impact of continuous positive airway pressure (CPAP) on EKG in patients with significant OSA. Methodology: We conducted a retrospective study using the sleep lab database in our academic center. 700 patients with OSA were randomly selected, of which 243 patients had moderate or severe OSA and prescribed CPAP, 337 patients had mild OSA, and 120 had normal study. Using T test we compared different EKG parameters in patients with moderate or severe OSA before and 6 to 12 months after the initiation of the CPAP treatment. From the 243 patients, 148 have documentation of CPAP compliance. The rest of the patients with no or questionable compliance were excluded. Results: Mean PR interval has dropped significantly in the study group from (123.34624.95) before CPAP treatment to (85.46640.99) after being complaint with the CPAP treatment for 6 to 12 months (p5 0.01). Similar trend was noticed in the QRS and QTc durations, but without being statistically significant. When comparing other EKG parameters, there was no statistically significant difference. Conclusion: CPAP treatment was associated with significant reduction is the PR interval duration in patients with moderate to severe OSA compliant with the treatment. The rest of the parameters were not statistically significant. A larger sample size is needed to confirm other relations observed in the study population.
Background: Previous data from a recently conducted prospective, single blind randomized clinical trial among community dwelling older patients with HFPEF and anemia randomized to treatment with epoetin alfa (ESA) vs. placebo did not demonstrate significant benefits of therapy regarding left ventricular (LV) structure, functional capacity, or quality of life. However, unresponsiveness to ESA therapy may have confounded these results as some patients randomized to receive ESA had suboptimal increases in hemoglobin. All patients in the trial also received oral iron, which could have contributed to increases in hemoglobin observed in those receiving placebo. Accordingly, we performed a per-protocol analysis in order to determine if measured improvement in anemia would have any effect on clinical endpoints. Methods: A total of 56 patients (age 77611 years, 68% female) were recruited who had anemia defined as a hemoglobin of # 12 g/dl (average hemoglobin of 10.461 g/dl) with HFPEF defined as having NHANES-CHF criteria score of $ 3 and an ejection fraction of O 40% (average EF 5 63615%) and were randomly allocated to receive either ESA or placebo. In the per protocol analysis, a responder was defined as a patient with an increase of 1 g/dl in the first 4 weeks of the trial. 19 subjects were classified as responders (12 were in ESA group) compared to 33 non-responders (12 were in ESA group). Results: The average hemoglobin increased significantly at the end of 6 months for responders (1.860.3 vs. 0.860.2 g/dl, p50.004). LV function was unchanged in responders with differences in stroke volume (0.169.5 vs. -0.6610.2 ml, p50.82), ejection fraction (3.4%610.0 vs. 0.9%67.4, p50.32), and end diastolic volume (-5.7616.1 vs. -3.2614.8 ml, p50.59). ESA responders also showed no significant functional improvements with a 6-minute walk test or peak VO2. Though quality of life (QOL) improved significantly within each group by the Kansas City Cardiomyopathy Questionnaire, there was no difference between the two. Similar analyses with varying cutoffs for hemoglobin and time points to define a responder also yielded no considerable differences in endpoints. Conclusion: A per protocol analysis does not demonstrate differences in LV remodeling, functional status, peak VO2, or QOL. Thus, treating anemia in older adult subjects with HFPEF does not appear to have clinical benefits.
HFSA
S25
067 Coenzyme Q10 Therapy Blocks the Vicious Metabolic Cycle in Chronic Heart Failure Svend A. Mortensen1, Franklin Rosenfeldt2, Adarsh Kumar3, Peter Dolliner4, Krzysztof J. Filipiak5, Daniel Pella6, Urban Alehagen7, Gian P. Littarru8; 1 Heart Center, Copenhagen University Hospital, Copenhagen, Denmark; 2Cardiac Surgical Research Unit, Alfred Hospital, Melbourne, Victoria, Australia; 3The Department of Cardiology, Govt. Medical College/G.N.D Hospital, Amritsar, India; 4The University Clinic of Internal Medicine, Vienna, Austria; 5Medical University of Warsaw, Warsaw, Poland; 6University of Kosice, Kosice, Slovakia; 7 The University Hospital, Link€oping, Sweden; 8Institute of Biochemistry, Ancona, Italy Energy starvation of the myocardium is a dominant feature of heart failure (HF) leading to an important role for agents that can enhance myocardial metabolism and augment energy production. Coenzyme Q10 (CoQ10) fulfils this role with previous double-blind trials though positive have been underpowered to detect major clinical endpoints such as mortality. Q-SYMBIO is the first double-blind trial of CoQ10 in HF addressing survival. Methods: Patients in NYHA Class III or IV HF who were receiving optimal pharmacologic therapy were randomly assigned to either CoQ10 100 mg three times daily or placebo. The primary long-term endpoint was composite MACE (major adverse cardiovascular events) including unplanned hospitalisations due to worsening heart failure, cardiovascular death, urgent cardiac transplantation and mechanical support, using a time to first event analysis. Results: A total of 420 patients from 17 international centres were enrolled with a follow-up time of 2 years. There was a significantly greater improvement of NYHA Class in the CoQ10 group compared to placebo (p50.047). The primary endpoint was reached by 14% of the patients in the CoQ10 group vs. 25% of patients in the placebo group; HR CoQ10 vs. placebo 2.0(CI 1.3-3.2); p50.003 by intention to treat analysis. CoQ10 treated patients had lower cardiovascular mortality: 8% vs. 15% (p50.02) and lower incidence of hospitalisations for HF (p50.05). All cause mortality was also lower in the CoQ10 group: 9% vs. 17%; HR CoQ10 vs. placebo 2.1(CI 1.2-3.8); p50.01. There were fewer adverse events in the CoQ10 group compared to placebo (p50.073). Conclusions: CoQ10 supplementation in patients with moderate to severe HF receiving optimal conventional therapy: is safe; improves survival due to reductions in cardiovascular- and all-cause mortality; is associated with reduction in symptoms and hospitalisations for worsening HF. Thus it represents an important advance in therapy.
068 Treating Anemia in Older Adults with Heart Failure with a Preserved EF (HFPEF) with Epoetin Alfa: A Per Protocol Analysis of the Data Sirish Vullaganti, Sergio Teruya, Julissa Alvarez, Jeff Goldsmith, Stephen Helmke, Mathew Maurer; New York Presbyterian-Columbia University Medical Center, New York, NY
066 Effect of CPAP Treatment on EKG Parameters in Patients with Significant Obstructive Sleep Apnea Wissam I. Khalife1, Sharon Onguti2, Ahmad Almomani2, Ali Charif1; 1University of Texas Medical Branch, Galveston, TX; 2University of Texas Medical Branch, Galveston, TX Background: Obstructive sleep apnea (OSA) is a well established risk of cardiovascular morbidity and mortality. The effect of OSA on EKG has not been well studied. The aim of our study is to investigate the impact of continuous positive airway pressure (CPAP) on EKG in patients with significant OSA. Methodology: We conducted a retrospective study using the sleep lab database in our academic center. 700 patients with OSA were randomly selected, of which 243 patients had moderate or severe OSA and prescribed CPAP, 337 patients had mild OSA, and 120 had normal study. Using T test we compared different EKG parameters in patients with moderate or severe OSA before and 6 to 12 months after the initiation of the CPAP treatment. From the 243 patients, 148 have documentation of CPAP compliance. The rest of the patients with no or questionable compliance were excluded. Results: Mean PR interval has dropped significantly in the study group from (123.34624.95) before CPAP treatment to (85.46640.99) after being complaint with the CPAP treatment for 6 to 12 months (p5 0.01). Similar trend was noticed in the QRS and QTc durations, but without being statistically significant. When comparing other EKG parameters, there was no statistically significant difference. Conclusion: CPAP treatment was associated with significant reduction is the PR interval duration in patients with moderate to severe OSA compliant with the treatment. The rest of the parameters were not statistically significant. A larger sample size is needed to confirm other relations observed in the study population.
Background: Previous data from a recently conducted prospective, single blind randomized clinical trial among community dwelling older patients with HFPEF and anemia randomized to treatment with epoetin alfa (ESA) vs. placebo did not demonstrate significant benefits of therapy regarding left ventricular (LV) structure, functional capacity, or quality of life. However, unresponsiveness to ESA therapy may have confounded these results as some patients randomized to receive ESA had suboptimal increases in hemoglobin. All patients in the trial also received oral iron, which could have contributed to increases in hemoglobin observed in those receiving placebo. Accordingly, we performed a per-protocol analysis in order to determine if measured improvement in anemia would have any effect on clinical endpoints. Methods: A total of 56 patients (age 77611 years, 68% female) were recruited who had anemia defined as a hemoglobin of # 12 g/dl (average hemoglobin of 10.461 g/dl) with HFPEF defined as having NHANES-CHF criteria score of $ 3 and an ejection fraction of O 40% (average EF 5 63615%) and were randomly allocated to receive either ESA or placebo. In the per protocol analysis, a responder was defined as a patient with an increase of 1 g/dl in the first 4 weeks of the trial. 19 subjects were classified as responders (12 were in ESA group) compared to 33 non-responders (12 were in ESA group). Results: The average hemoglobin increased significantly at the end of 6 months for responders (1.860.3 vs. 0.860.2 g/dl, p50.004). LV function was unchanged in responders with differences in stroke volume (0.169.5 vs. -0.6610.2 ml, p50.82), ejection fraction (3.4%610.0 vs. 0.9%67.4, p50.32), and end diastolic volume (-5.7616.1 vs. -3.2614.8 ml, p50.59). ESA responders also showed no significant functional improvements with a 6-minute walk test or peak VO2. Though quality of life (QOL) improved significantly within each group by the Kansas City Cardiomyopathy Questionnaire, there was no difference between the two. Similar analyses with varying cutoffs for hemoglobin and time points to define a responder also yielded no considerable differences in endpoints. Conclusion: A per protocol analysis does not demonstrate differences in LV remodeling, functional status, peak VO2, or QOL. Thus, treating anemia in older adult subjects with HFPEF does not appear to have clinical benefits.