Abstract 12897: Coenzyme Q10 in the Treatment of Heart Failure With Preserved Ejection Fraction: A Prospective, Randomized, Double-blind Trial

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tal Y Samuel ◽  
Tal Hasin ◽  
Israel Gotsman ◽  
Tanya Weitsman ◽  
Fanny Ben Ivgi ◽  
...  

Background: Heart failure with preserved ejection fraction (HFpEF) is the most common form of heart failure (HF) in the elderly and is increasing in prevalence. No specific treatment for this condition appears to be effective. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production and reduced levels have been noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF in particular in the elderly. Aim: To evaluate the effect of CoQ10 supplementation on diastolic function in patients with HFpEF. Methods: A prospective, randomized, double-blind, placebo-controlled trial. Inclusion criteria were age > 50 years, New York Heart Association class II-IV, ejection fraction > 50%, and evidence of impaired diastolic function defined as lateral e' < 0.09 cm/sec, average E/e' > 13 or average E/e' > 8 with additional markers of impaired diastolic function such as delayed relaxation (E/A < 0.5), elevated left atrial volume index (> 40ml / m 2 ) elevated left ventricular mass index ( > 122 gr/ m 2 ♀ or 149 gr/ m 2 ♂) or pulmonary hypertension. Patients with other forms of cardiomyopathies or treated with chronic renal replacement therapy were excluded. Echocardiographic studies and levels of N-terminal pro-B type natriuretic peptide (NT-proBNP) were completed at baseline and following 4 months of CoQ10 (300 mg daily) or placebo supplementation. Results: A total of 39 patients were enrolled, 19 patients in the CoQ10 and 20 patients in the placebo group. Groups were similar in baseline clinical characteristics. Compliance was high and similar between groups (average 208 ± 108 mg/day for the CoQ10 versus 212 ± 95 mg/day for the placebo group). No significant effect was observed on indices of diastolic function or NT-proBNP levels following 4 months of CoQ10 use. Conclusions: Treatment with CoQ10 did not affect indices of diastolic function or NT-proBNP levels in patients with HFpEF. Our study does not support the routine use of CoQ10 in patients with HFpEF.

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
K Liang ◽  
R Hearse-Morgan ◽  
S Fairbairn ◽  
Y Ismail ◽  
AK Nightingale

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND The recent Heart Failure Association (HFA) of the European Society of Cardiology (ESC) consensus guidelines on diagnosis of heart failure with preserved ejection fraction (HFpEF) have developed a simple diagnostic algorithm for clinical use. PURPOSE To assess whether echocardiogram (echo) parameters needed to assess diastolic function are routinely collected in patients referred for assessment of heart failure symptoms. METHODS Retrospective analysis of echo referrals in January 2020 were assessed for parameters of diastolic function as per step 2 of the HF-PEFF diagnostic algorithm.  Echo images and clinical reports were reviewed. Electronic records were utilised to obtain clinical history, blood results (NT-proBNP) and demographic data. RESULTS 1330 patients underwent an echo in our department during January 2020. 83 patients were referred with symptoms of heart failure without prior history of cardiac disease; 20 patients found to have impaired left ventricular (LV) function were excluded from analysis. Of the 63 patients with possible HFpEF, HF-PEFF score was low in 18, intermediate in 33 and high in 12. Median age was 68 years (range 32 to 97 years); 25% had a BMI &gt;30. There was a high prevalence of hypertension (52%), diabetes (19%) and atrial fibrillation (40%) (cf. Table 1). Body surface area (BSA) was documented in 65% of echo reports. Most echo parameters were recorded with the exception of global longitudinal strain (GLS) and indexed LV mass (cf. image 1). NT-proBNP was recorded in only 20 patients (31.7%). 12 patients with an intermediate HF-PEFF score could have been re-categorised to a high score depending on GLS and NT-proBNP (which were not recorded). CONCLUSION More than three quarters of echoes acquired in our department obtained the relevant parameters to assess diastolic function. The addition of BSA, and inclusion of NT-proBNP, and GLS would have been additive to a third of ‘intermediate’ patients to determine definite HFpEF. Our study demonstrates that the current HFA-ESC diagnostic algorithm and HF-PEFF scoring system are easy to use, highly relevant and applicable to current clinical practice. Age &gt;70 years 29 (46.0%) Obesity (BMI &gt;30) 16 (25.4%) Diabetes 12 (19%) Hypertension 33 (52.4%) Atrial Fibrillation 25 (39.7%) ECG abnormalities 18 (28.5%) Table 1. Prevalence of Clinical Risk Factors Abstract Figure. Image 1. HFPEFF score & echo parameters


2019 ◽  
Vol 28 (01) ◽  
pp. 044-049
Author(s):  
Sidhi Purwowiyoto ◽  
Budhi Purwowiyoto ◽  
Amiliana Soesanto ◽  
Anwar Santoso

Exercise improves morbidity, fatality rate, and quality of life in heart failure with low ejection fraction, but fewer data available in heart failure with preserved ejection fraction (HFPEF).The purpose of this study is to test the hypothesis that exercise training might improve the longitudinal intrinsic left ventricular (LV) function in HFPEF patients.This quasi-experimental study had recruited 30 patients with HFPEF. Exercise training program had been performed for a month with a total of 20 times exercise sessions and evaluated every 2 weeks. Echocardiography was performed before sessions, second week and fourth week of exercise training. Six-minute walk tests (6MWTs) and quality-of-life variables using Minnesota living with HF scoring and the 5-item World Health Organization Well-Being Index scoring were measured before and after exercise as well.Left ventricular filling pressure, represented by the ratio of early diastolic mitral flow velocity/early diastolic annular velocity and left atrial volume index, improved during exercise. The longitudinal intrinsic LV function, represented by four-chamber longitudinal strain, augmented during exercise (p < 0.001). Aerobic capacity, measured by 6MWT, increased significantly (p = 0.001). Quality of life improved significantly during exercise (p < 0.001).Exercise training was suggested to improve the longitudinal intrinsic LV function and quality of life in HFPEF. Clinical Trial Registration: ACTRN12614001042639.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M S Dzeshka ◽  
E Shantsila ◽  
V A Snezhitskiy ◽  
G Y H Lip

Abstract Introduction Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist. AF is associated with left atrial (LA) and ventricular (LV) myocardial fibrosis, contributing to diastolic dysfunction in HFpEF. Many profibrotic pathways have been studied in AF and HFpEF, but scarce data are available on the role of circulating microparticles (MPs). Purpose To evaluate association of circulating biomarkers of fibrosis and MPs subsets with Doppler-derived parameters of diastolic function in AF and HFpEF. Methods We studied 274 patients with non-valvular AF and HFpEF (median age 62 years, 37% females). Paroxysmal AF was diagnosed in 150 patients (55%) and non-paroxysmal AF (persistent or permanent) in 124 (45%). Median CHA2DS2-VASc score was 3 in males and 4 in females. Transthoracic echocardiography was performed to assess LV diastolic function, including early mitral inflow velocity (E), E/A velocities ratio (on sinus rhythm), early mitral annular diastolic velocity (E') for LV septal and lateral basal regions, E/E' ratio, LA maximum volume index (LAVi), E-wave velocity deceleration time (DT), flow propagation velocity (Vp). Average values from ten consecutive cardiac cycles were calculated. E/E' ratio was chosen as valid and reproducible index of diastolic function in AF patients for regression analysis. Blood levels of galectin 3, interleukin-1 receptor-like 1 (ST2), transforming growth factor beta 1 (TGF-β1), procollagen type III aminoterminal propeptide (PIIINP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), angiotensin II and aldosterone level were assayed as surrogate biomarkers of myocardial fibrosis and profibrotic signaling. Using microflow cytometry, numbers of platelet-derived (CD42b+), monocyte-derived (CD14+), endothelial (CD144+), and apoptotic MPs (Annexin V+) were quantified in plasma samples. Linear regression was used to reveal parameters associated with diastolic function assessed as E/E' ratio. Data were normalized with Box-Cox transformation. Results Grade I diastolic dysfunction was found in 149 (54%); 94 (34%), and 31 (11%) patients had grade II and grade III diastolic dysfunction, respectively. On univariate analysis, age (β=0.23, p=0.0001); male gender (β=-0.19, p=0.02); history of hypertension (β=0.15, p=0.02); AF type, i.e. progression from paroxysmal to permanent (β=0.14, p=0.02); AnV+ MPs (β=0.19, p=0.01); angiotensin II (β=0.13, p=0.04); ST2 (β=0.1, p=0.04); and TIMP-1 (β=0.13, p=0.03) were associated with E/E' ratio. Using stepwise multivariate regression, AnV+ MPs (β=0.15, p=0.01) and TIMP-1 (β=0.3, p=0.04) remained significant predictors of E/E' ratio, adjusted for age, gender, hypertension and AF type. Relation of E/E' to TIMP-1 and AnV+ MPs Conclusion Apoptotic (AnV+) MPs and TIMP-1 were independently associated with diastolic dysfunction in AF and HFpEF. These may contribute to the pathophysiology of AF and HFpEF, and complications related to the presence of both. Acknowledgement/Funding ESC Research Grant, EHRA Academic Research Fellowship Programme


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Soeren Jan Backhaus ◽  
Torben Lange ◽  
Elisabeth George ◽  
Kristian Hellenkamp ◽  
Roman Gertz ◽  
...  

Introduction: Invasive right heart catherization (RHC) using exercise-stress is the reference-standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF) but carries the risk of the procedure. Real-time cardiovascular magnetic resonance (RT-CMR) imaging allows bicycle exercise CMR with unprecedented temporal and spatial resolution and may represent a novel non-invasive alternative. Methods: The HFpEF stress trial (NCT03260621) prospectively included 75 patients with echocardiographic signs of diastolic dysfunction and dyspnoea on exertion (E/E’>8, NYHA≥II) who underwent echocardiography, RHC and RT-CMR at rest and exercise-stress. HFpEF was defined according to pulmonary capillary wedge pressure (PCWP ≥15mmHg at rest or ≥25mmHg during exercise stress). RT-CMR functional assessments included time-volume-curves for total and early (1/3) diastolic left ventricular (LV) filling or left atrial (LA) emptying and LV/LA long axis strain (LAS). Results: HFpEF patients (n=34, mean PCWP rest 13mmHg, stress 27mmHg) had higher E/e’ (12.5 vs 9.15), NT-proBNP (255 vs 75ng/l) and LA volume index (43.8 vs 36.2ml/m 2 ) compared to non-HFpEF patients (n=34, rest 8mmHg, stress 18mmHg, p≤0.001 for all). There were no differences in RT-CMR LV total and early diastolic filling at rest and during exercise-stress (p≥0.164). In contrast, RT-CMR revealed impaired stress LA total (p=0.033) and early (p<0.001) diastolic emptying in HFpEF. LA LAS was the only impaired parameter at rest (p<0.001) and emerged as the best predictor for the presence of HFpEF during exercise-stress testing (AUC rest 0.82 vs stress 0.93, p=0.029). Conclusions: RT-CMR allows highly accurate identification of HFpEF during physiological exercise and may establish itself as a novel non-invasive diagnostic alternative for routine clinical use.


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Jenna C Edwards ◽  
Madeleine Dionne ◽  
T. D Olver ◽  
Jan R Ivey ◽  
Pamela K Thorne ◽  
...  

Introduction: Heart failure with preserved ejection fraction (HFpEF) is clinically characterized by an increased incidence in females and many comorbidities including type 2 diabetes (T2D) and obesity. Animal models accurately representing clinical HFpEF are lacking; thus, the purpose of this study was to examine left ventricular (LV) mechanics in a novel Ossabaw swine model of chronic pressure-overload (aortic-banding; AB) and T2D (Western diet; WD) using two dimensional speckle tracking echocardiography (2D-STE). We hypothesized that global LV strain would be decreased primarily in the longitudinal direction in WD-AB animals. Methods: Female Ossabaws were randomly divided into 2 groups: CON (n=5) and WD-AB (n=5). LV function and strain were measured at 1 year of age after 6 mo. of AB and 9 mo. of WD via pressure-volume relations and 2D-STE. Significance was set at P < 0.05 using t-test vs. CON. Results: In the WD-AB group, ejection fraction (EF%) and end diastolic volume were normal (>50%), and observed in parallel with increased LV weight, lung weight, and LV diastolic wall thickness (i.e. concentric hypertrophy). WD-AB group had increased HOMA-IR and body surface area, two common features in T2D. In WD-AB animals, although global longitudinal systolic strain rate and end systolic displacement were increased, stroke volume index was decreased. Early diastolic rotation rate was decreased, while global longitudinal late diastolic strain rate was increased in the WD-AB group. These changes, considered in parallel with an increased end diastolic pressure-volume relationship in WD-AB animals, are consistent with diastolic dysfunction. In contrast, longitudinal, radial, and circumferential early diastolic strain rates increased in the WD-AB group. Conclusion: Contrary to our hypothesis, LV longitudinal strain was increased during both systole and diastole, and observed in parallel with decreased early diastolic untwisting in WD-AB animals. Our results suggest alterations to LV mechanics do not preserve normal systolic and diastolic cardiac function, despite normal resting EF%, in this novel translational model of pressure-overload HF with potential relevance to human HFpEF including associated clinical comorbidities (sex, obesity, and T2D).


2019 ◽  
Vol 10 ◽  
pp. 204201881986159 ◽  
Author(s):  
Gaurav S. Gulsin ◽  
Prathap Kanagala ◽  
Daniel C. S. Chan ◽  
Adrian S. H. Cheng ◽  
Lavanya Athithan ◽  
...  

Background: Attempts to characterize cardiac structure in heart failure with preserved ejection fraction (HFpEF) in people with type 2 diabetes (T2D) have yielded inconsistent findings. We aimed to determine whether patients with HFpEF and T2D have a distinct pattern of cardiac remodelling compared with those without diabetes and whether remodelling was related to circulating markers of inflammation and fibrosis and clinical outcomes. Methods: We recruited 140 patients with HFpEF (75 with T2D and 65 without). Participants underwent comprehensive cardiovascular phenotyping, including echocardiography, cardiac magnetic resonance imaging and plasma biomarker profiling. Results: Patients with T2D were younger (age 70 ± 9 versus 75 ± 9y, p = 0.002), with evidence of more left ventricular (LV) concentric remodelling (LV mass/volume ratio 0.72 ± 0.15 versus 0.62 ± 0.16, p = 0.024) and smaller indexed left atrial (LA) volumes (maximal LA volume index 48 ± 20 versus 59 ± 29 ml/m2, p = 0.004) than those without diabetes. Plasma biomarkers of inflammation and extracellular matrix remodelling were elevated in those with T2D. Overall, there were 45 hospitalizations for HF and 22 deaths over a median follow-up period of 47 months [interquartile range (IQR) 38–54]. There was no difference in the primary composite endpoint of hospitalization for HF and mortality between groups. On multivariable Cox regression analysis, age, prior HF hospitalization, history of pulmonary disease and LV mass/volume were independent predictors of the primary endpoint. Conclusions: Patients with HFpEF and T2D have increased concentric LV remodelling, smaller LA volumes and evidence of increased systemic inflammation compared with those without diabetes. This suggests the underlying pathophysiology for the development of HFpEF is different in patients with and without T2D. ClinicalTrials.gov identifier: NCT03050593.


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