Abstract P436: The Role of Free Fatty Acids in Patients With Obesity and Heart Failure With Preserved Ejection Fraction: A Post-hoc Analysis of the UFA-preserved Pilot Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Hayley Billingsley ◽  
Justin M Canada ◽  
ROSHANAK MARKLEY ◽  
Brando Rotelli ◽  
Dinesh Kadariya ◽  
...  

Background: Increased circulating free fatty acids (FFA) are associated with an increased risk for heart failure (HF). Interestingly, in the setting of established HF, the failing heart relies heavily on the use of FFA as energetic substrate, and therapeutics aimed at reducing FFA in HF have been found to worsen cardiac performance. A dietary intervention aimed at increasing unsaturated fatty acids (UFA) was associated with favorable changes in cardiorespiratory fitness (CRF) in patients with obesity and HF with preserved ejection fraction (HFpEF) in the UFA-Preserved Pilot Study, although the mechanism remains largely unknown. We hypothesized that dietary UFA supplementation is associated with an increase in circulating FFA and may improve determinants of CRF such as cardiac function and body composition. Methods: Eight subjects with obesity and HFpEF engaged in 12 weeks of UFA supplementation by increasing intake of foods rich in monounsaturated fatty acids (i.e., oleic acid) and polyunsaturated fatty acids (i.e., α-linolenic acid, linoleic acid) under instruction and monitoring of a research dietitian. Measures were performed at baseline and 12 weeks. Subjects underwent venipuncture to measure circulating FFA, plasma biomarkers of UFA consumption, and NT-proBNP.. Bioelectrical impedance analysis was used to estimate skeletal muscle mass (SMM). Maximal cardiopulmonary exercise testing was performed to measure CRF defined as peak oxygen consumption (VO 2 ). Data are presented as median and interquartile range. Within group changes were assessed using Wilcoxon rank test and correlations were performed using Spearman rank test. Results: Five subjects were female and median age was 53 [50-59] years. The dietary intervention resulted in a significant increase in FFA (from 0.29 [0.20-0.43] to 0.37 [0.32-0.73] μmol/L, p=0.012) and plasmatic UFA (from 1319 [1224-1477] to 1620 [1268-2110] μg/mL, p=0.05). Changes in FFA were positively associated with changes in plasmatic UFA (R=+0.74, p=0.035). Changes in FFA were associated with a trend toward improvement in peak VO 2 , although it did not reach statistical significance (R=+0.72, p=0.068). Changes in FFA were also positively and significantly associated with an increase in SMM expressed in kg (R=+0.99, p<0.001) and % of body weight (R=+0.90, p=0.006) and inversely associated with changes in NT-proBNP (R=-0.85, p=0.007). Conclusion: In patients with obesity and HFpEF, dietary UFA supplementation increases FFA, which are associated with favorable changes in cardiac function and body composition. This supports a novel mechanism through which UFA may positively affect CRF. Ongoing randomized controlled trials (NCT03966755) are underway investigating UFA supplementation as a therapeutic strategy to improve CRF in obesity and HFpEF.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Fusako Sera ◽  
Tomohito Ohtani ◽  
kei nakamoto ◽  
Shungo Hikoso ◽  
Daisaku Nakatani ◽  
...  

Introduction: The proposed revision of hemodynamic definition of pulmonary hypertension (PH) adopts a lower threshold of mean pulmonary artery pressure (mPAP) > 20 mmHg. In addition, pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU) is included as the definition of pre-capillary component of PH. Heart failure (HF) with preserved ejection fraction (HFpEF) can develop pre-capillary PH as well as post-capillary PH. We aimed to investigate the impact of the proposed definition of PH on clinical diagnosis of PH associated with HFpEF. Methods: From the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) registry, 225 patients who were hospitalized with HF and underwent right heart catheterization were categorized according to the current guidelines and the proposed definition of PH: non-PH, isolated post-capillary PH (Ipc-PH), pre-capillary PH, and combined pre- and post-capillary PH (Cpc-PH). In the proposed definition, patients with mPAP > 20 mmHg, PVR < 3 WU, and pulmonary artery wedge pressure ≤ 15 mmHg do not meet criteria for any of the above categories and are categorized as “unclassified PH”. Results: Prevalence of PH was significantly increased in the proposed definition compared to that in the current definition (51% vs 29%, p<0.0001), with a doubled frequency of pre-capillary PH (Fig A). Furthermore, 24 patients (11%) were diagnosed as unclassified PH and accounted for 22% of those with PH by the proposed definition. Among the PH categories in the proposed definition, Cpc-PH category was significantly relevant for worse prognosis at 1 year after discharge in patients with HFpEF (p=0.03 vs non-PH by log-rank test with Bonferroni's correction) (Fig 2). Conclusions: The new definition of PH resulted in a remarkable increase of prevalence of PH in HFpEF with a quite a few patients with unclassified PH and doubled frequency of pre-capillary PH.


2016 ◽  
Vol 4 (1) ◽  
pp. 56-65 ◽  
Author(s):  
Tobias Daniel Trippel ◽  
Volker Holzendorf ◽  
Martin Halle ◽  
Götz Gelbrich ◽  
Kathleen Nolte ◽  
...  

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Tatsunori Ikeda ◽  
Manabu Fujimoto ◽  
Masakazu Yamamoto ◽  
Kazuyasu Okeie ◽  
Hisayoshi Murai ◽  
...  

Introduction: Central sleep apnea (CSA) is a common complication in heart failure patients (HF) and closely associated with poor prognosis. Adaptive servo-ventilation (ASV) is a new treatment for HF with CSA. Some study indicated ASV might improve cardiac function and its prognosis. However, there was little discussion by each background disease. Methods and Results: We examined 64 HF with CSA patients (involving 15 dilated cardiomyopathy (DCM) patients, 27 ischemic cardiomyopathy (ICM) patients, and 22 heart failure with preserved ejection fraction (HFpEF) patients) treated with ASV who had not been admitted to the hospital due to worsening HF in the 6 months before initiating ASV therapy. During 1 and 6 months observation, apnia-hypopnea index and brain natriuretic peptide were decreased significantly than baseline in all groups. There was similar in left ventricular ejection fraction in ICM and HFpEF groups during observation, however, in DCM group, there was significantly improved (29.3 +/- 14.3 to 36.5 +/- 12.4, and to 40.5 +/- 14.9%, P<0.01 compared with baseline). And left ventricular end systolic diameter was significantly shortened (53.7 +/- 11.1 to 30.4 +/- 11.5, and to 47.6 +/- 12.0 mm, P<0.01 compared with baseline), in spite of left ventricular end diastolic diameter was not changed. Conclusions: These results indicate that ASV is more effective in DCM patient with modifying hemodynamics and cardiac function than ICM and HFpEF patients.


2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Jomana Hatahet ◽  
Raiza Bonomo ◽  
Tyler Cook ◽  
Chelsea R White ◽  
Chaitanya Gavini ◽  
...  

More than 50% of patients with heart failure are diagnosed with heart failure with preserved ejection fraction (HFpEF), and 80% of them are obese. It is a prominent disease with no available treatments. It is characterized by diastolic dysfunction that involves increase in left ventricle stiffness and decrease in its relaxation during diastole. To better understand the pathogenesis of obesity associated HFpEF, our studies focus on the early asymptomatic changes in cardiac mechanics that occurs before the increases in intracardiac pressure. Therefore, we have developed an obesity associated mouse model that we called pre-HFpEF where mice were fed either Normal Chow or Western Diet for 14 weeks. Our echocardiography measurements indicated the presence of early cardiac dysfunction consistent with obesity associated pre-HFpEF phenotype. Mice on WD had decrease in Global Longitudinal Strain (%GLS) and Longitudinal strain rate reverse (LSRr) indicating early signs of systolic and diastolic dysfunction, as well as increase in left ventricle anterior and posterior wall thickness during diastole (LVAWd, LVPWd). Obesity is also known to cause microbiome imbalance, which plays a significant role in the development of cardiovascular diseases through changes in short chains fatty acids, which are products of dietary fiber fermentation by the gut bacteria. In order to study the association between gut microbiome imbalance and HFpEF development, we treated our obese pre-HFpEF mice with fecal matter transplantation (FMT) from either lean or obese mice, and we found that FMT from lean mice led to significant improvements in systolic and diastolic dysfunction by increasing %GLS and LSRr and preventing hypertrophy by decreasing LVAWd and LVPWd. In addition, WD reduced butyrate producing bacteria, however circulating levels of butyrate were significantly increased with lean FMT treatment. Using an in-vitro approach to mimic WD we found butyrate treatment to inhibit the activation of NLRP3 inflammasome and NF-KB. Therefore, since FMT treatment improved cardiac dysfunction in obesity associated pre-HFpEF mice, and that butyrate is increased after FMT and can play a role in metabolic homeostasis, we predict that butyrate could be an important player in FMT improvements through cardiac metabolic regulation and cardiac inflammation suppression


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).


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