Abstract MP228: The Role Of Gut Microbiome Secreted Short Chain Fatty Acids In The Development Of Heart Failure With Preserved Ejection Fraction HFpEF

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Jomana Hatahet ◽  
Raiza Bonomo ◽  
Tyler Cook ◽  
Chelsea R White ◽  
Chaitanya Gavini ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acids ◽  
Left Ventricle ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Gut Microbiome ◽  
Cardiac Dysfunction ◽  
Longitudinal Strain ◽  
Preserved Ejection Fraction ◽  
Fecal Matter

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

scholarly journals Association of polymorphism of the endothelial NO synthase gene (NOS3–786T>C) with severity of left ventricle diastolic dysfunction and pulmonary hypertension in patients with heart failure and preserved ejection fraction

2019 ◽  
Vol 26 (1) ◽  
pp. 51-60 ◽  
Author(s):  
K. M. Amosova ◽  
K. I. Cherniaieva ◽  
Yu. V. Rudenko ◽  
L. V. Natrus ◽  
A. B. Bezrodnyi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Left Ventricle ◽  
Ejection Fraction ◽  
Arterial Hypertension ◽  
Diastolic Dysfunction ◽  
Elastic Properties ◽  
Preserved Ejection Fraction ◽  
Artery Disease ◽  
Lv Diastolic Dysfunction

The aim – to determine polymorphisms of the nitric oxide synthase gene -786T>C rs 2070744 and the association of the corresponding genotypes with the severity of left ventricle (LV) diastolic dysfunction (DD), pulmonary hypertension (PH) and elastic properties of the arteries in patients with arterial hypertension (AH) and heart failure (HF) with preserved ejection fraction (EF). Materials and methods. We included 69 patients (pts) with AH and HF with preserved EF (31 female (41.9 %) and 33 male (58.1 %)), aged 67.4±10.2 years; II–III class NYHA, hemodynamically stable. According to Shah’s criteria, the «aging» phenotype was identified in 11 (15.9 %) pts, «obesity» – 14 (20.3 %) pts, «coronary artery disease» – 16 (23.2 %) pts, «pulmonary hypertension» – 17 (24.6 %) pts (with a significant predominance of patients with CC genotype), «arterial hypertension» – 17 (24.6 %) pts. Results and discussion. «Wild» homozygous TT genotype was found in 34 pts (49.3 %, TT group), heterozygous TC genotype – in 21 pts (30.4 %, TC group) and «mutant» homozygous CC genotype – in 14 pts (20.3 %, CC group). The groups did not differ in gender (male 19 or 55.9 %, 12 or 60 % and 11 or 61.1 %, p>0.05) and average age (67.1±8.9, 65.4±10.6 and 64.9±10.3 years p>0.05), and in prevalence of comorbidities. The worst result of 6-minute walk test was in the CC group compared with TT and TC (371.8±77.7, 385.7±85.4 and 314.3±69.1, p>0.05), as well as higher NT-proBNP level (668.1±317.8, 636.9±433.2 and 806.9±369.7, p>0.05), greater LVMI (187.4±37.1, 182.2±25.7 and 195.2±28.5, p>0.05). There was markedly more pronounced DD LV in the CC group compared with TT and TC, according to average e’ (p>0.05) and E/e’ (p>0.05). SPAP was the highest in the CC group (p>0.05), as well as PCWP and TPG (p>0.05). Patients of the CC group had worse elastic properties of arteries according to AIx75 (p>0.001) and PWVc-f (p>0.05), with a decrease in SAC (by 38.2 and 29 % compared to TT and TC (p>0.05) and an increase in Ea, respectively, by 21 and 9 % (p>0.05). According to the cuff test in patients of the CC group, compared with those in the TT and TC groups, worsening of endotelium-dependent vasodilation, respectively by 19.8 and 17.3 % (p>0.05) was revealed. Conclusions. Compared to other polymorphisms, the CC genotype of the NOS3 rs 2070744 gene is associated with greater severity of DD LV, LH and impaired LV diastolic function and elastic properties of systemic arteries, according to pulse wave analysis in patients with AH and HF with preserved EF.

scholarly journals Heart failure with preserved ejection fraction – onset

2021 ◽  
Vol 27 (2) ◽  
pp. 17-36
Author(s):  
Branimir Kanazirev
Keyword(s):  
Heart Failure ◽  
Left Ventricle ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Systolic Function ◽  
Diastolic Heart Failure ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Rich Variety ◽  
Patients With Heart Failure

During these more than 20 years of evolution in understandings of the mechanisms of heart failure (HF) with preserved fractional ejection, there has been a rich variety of terminology, including „diastolic heart failure“, „heart failure with preserved systolic function“ and „heart failure with preserved fraction“. By defi nition, the latter term “ejection fraction-induced heart failure” proved to be the most appropriate and was accepted as the most correct, as the presence of diastolic dysfunction is not unique only to this group and exists in these patients, albeit subclinically and discrete disturbance in the longitudinal systolic function of the left ventricle against the background of the preserved ejection fraction. The problem, however, is not in the value of the ejection fraction or in the paradox of the combination of a well-functioning left ventricle and classic symptoms of heart failure, but in the non-infl uence of the prognosis of these patients in the way it is in patients with suppressed EF. Unlike patients with heart failure with a reduced ejection fraction, the prognosis and results in patients with HF with preserved EF do not mark the expected results and so far there are not enough effective and promising therapies.

scholarly journals Opportunistic screening models for high-risk men and women to detect diastolic dysfunction and heart failure with preserved ejection fraction in the community

2018 ◽  
Vol 26 (6) ◽  
pp. 613-623 ◽  
Author(s):  
Aisha Gohar ◽  
Rogier F Kievit ◽  
Gideon B Valstar ◽  
Arno W Hoes ◽  
Evelien E Van Riet ◽  
...  
Keyword(s):  
Heart Failure ◽  
High Risk ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Men And Women ◽  
Ventricular Diastolic Dysfunction

Background The prevalence of undetected left ventricular diastolic dysfunction is high, especially in the elderly with comorbidities. Left ventricular diastolic dysfunction is a prognostic indicator of heart failure, in particularly of heart failure with preserved ejection fraction and of future cardiovascular and all-cause mortality. Therefore we aimed to develop sex-specific diagnostic models to enable the early identification of men and women at high-risk of left ventricular diastolic dysfunction with or without symptoms of heart failure who require more aggressive preventative strategies. Design Individual patient data from four primary care heart failure-screening studies were analysed (1371 participants, excluding patients classified as heart failure and left ventricular ejection fraction <50%). Methods Eleven candidate predictors were entered into logistic regression models to be associated with the presence of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in men and women separately. Internal-external cross-validation was performed to develop and validate the models. Results Increased age and β-blocker therapy remained as predictors in both the models for men and women. The model for men additionally consisted of increased body mass index, moderate to severe shortness of breath, increased pulse pressure and history of ischaemic heart disease. The models performed moderately and similarly well in men (c-statistics range 0.60–0.75) and women (c-statistics range 0.51–0.76) and the performance improved significantly following the addition of N-terminal pro b-type natriuretic peptide (c-statistics range 0.61–0.80 in women and 0.68–0.80 in men). Conclusions We provide an easy-to-use screening tool for use in the community, which can improve the early detection of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in high-risk men and women and optimise tailoring of preventive interventions.

scholarly journals Early Diastolic Longitudinal Strain Rate at MRI and Outcomes in Heart Failure with Preserved Ejection Fraction

Radiology ◽  
2022 ◽  
Vol 302 (1) ◽  
pp. E5-E5
Author(s):  
Jian He ◽  
Wenjing Yang ◽  
Weichun Wu ◽  
Shuang Li ◽  
Gang Yin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Strain Rate ◽  
Longitudinal Strain ◽  
Preserved Ejection Fraction ◽  
Longitudinal Strain Rate

scholarly journals Features of heart failure with preserved ejection fraction (HFpEF) in diabetic patients with resistant hypertension

2021 ◽  
Vol 24 (4) ◽  
pp. 304-314
Author(s):  
M. A. Manukyan ◽  
A. Y. Falkovskaya ◽  
V. F. Mordovin ◽  
T. R. Ryabova ◽  
I. V. Zyubanova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Blood Pressure ◽  
Blood Flow ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Resistant Hypertension ◽  
Diabetic Patients ◽  
Preserved Ejection Fraction

BACKGROUND: It is expected that a steady increase in the incidence of diabetes and resistant hypertension (RHTN), along with an increase in life expectancy, will lead to a noticeable increase in the proportion of patients with heart failure with preserved ejection fraction (HFpEF). At the same time, data on the frequency of HFpEF in a selective group of patients with RHTN in combination with diabetes are still lacking, and the pathophysiological and molecular mechanisms of its formation have not been yet studied sufficiently.AIM: To assess the features of the development HFpEF in diabetic and non-diabetic patients with RHTN, as well as to determine the factors associated with HFpEF.MATERIALS AND METHODS: In the study were included 36 patients with RHTN and type 2 diabetes mellitus (DM) (mean age 61.4 ± 6.4 years, 14 men) and 33 patients with RHTN without diabetes, matched by sex, age and level of systolic blood pressure (BP). All patients underwent baseline office and 24-hour BP measurement, echocardiography with assess diastolic function, lab tests (basal glycemia, HbA1c, creatinine, aldosterone, TNF-alpha, hsCRP, brain naturetic peptide, metalloproteinases of types 2, 9 (MMP-2, MMP-9) and tissue inhibitor of MMP type 1 (TIMP-1)). HFpEF was diagnosed according to the 2019 AHA/ESC guidelines.RESULTS: The frequency of HFpEF was significantly higher in patients with RHTN with DM than those without DM (89% and 70%, respectively, p=0.045). This difference was due to a higher frequency of such major functional criterion of HFpEF as E/e’≥15 (p=0.042), as well as a tendency towards a higher frequency of an increase in left atrial volumes (p=0.081) and an increase in BNP (p=0.110). Despite the comparable frequency of diastolic dysfunction in patients with and without diabetes (100% and 97%, respectively), disturbance of the transmitral blood flow in patients with DM were more pronounced than in those without diabetes. Deterioration of transmitral blood flow and pseudo-normalization of diastolic function in diabetic patients with RHTN have relationship not only with signs of carbohydrate metabolism disturbance, but also with level of pulse blood pressure, TNF-alfa, TIMP-1 and TIMP-1 / MMP-2 ratio, which, along with the incidence of atherosclerosis, were higher in patients with DM than in those without diabetes.CONCLUSIONS: Thus, HFpEF occurs in the majority of diabetic patients with RHTN. The frequency of HFpEF in patients with DN is significantly higher than in patients without it, which is associated with more pronounced impairments of diastolic function. The progressive development of diastolic dysfunction in patients with diabetes mellitus is associated not only with metabolic disorders, but also with increased activity of chronic subclinical inflammation, profibrotic state and high severity of vascular changes.

scholarly journals Preload-corrected dynamic Starling mechanism in patients with heart failure with preserved ejection fraction

2018 ◽  
Vol 124 (1) ◽  
pp. 76-82 ◽  
Author(s):  
Michinari Hieda ◽  
Erin Howden ◽  
Shigeki Shibata ◽  
Takashi Tarumi ◽  
Justin Lawley ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Pressure ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Dynamic Modulation ◽  
Power Spectral ◽  
Ventricular Diastolic Dysfunction

The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume (SV) because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. The purpose of this study was to test whether the LVEDP-SV relationship remained impaired in heart failure with preserved ejection fraction (HFpEF) patients after normalization of LVEDP. Right heart catheterization and model-flow analysis of the arterial pressure waveform were performed while preload was manipulated using lower-body negative pressure to alter LVEDP. The DSM was compared at similar levels of LVEDP between HFpEF patients ( n = 10) and age-matched healthy controls ( n = 12) (HFpEF vs. controls: 10.9 ± 3.8 vs. 11.2 ± 1.3 mmHg, P = 1.00). Transfer function analysis between diastolic pulmonary artery pressure (PAD) representing dynamic changes in LVEDP vs. SV index was applied to obtain gain and coherence of the DSM. The DSM gain was significantly lower in HFpEF patients than in the controls, even at a similar level of LVEDP (0.46 ± 0.19 vs. 0.99 ± 0.39 ml·m−2·mmHg−1, P = 0.0018). Moreover, the power spectral density of PAD, the input variability, was greater in the HFpEF group than the controls (0.75 ± 0.38 vs. 0.28 ± 0.26 mmHg2, P = 0.01). Conversely, the power spectral density of SV index, the output variability, was not different between the groups ( P = 0.97). There was no difference in the coherence, which confirms the reliability of the linear transfer function between the two groups (0.71 ± 0.13 vs. 0.77 ± 0.19, P = 0.87). The DSM gain in HFpEF patients is impaired compared with age-matched controls even at a similar level of LVEDP, which may reflect intrinsic LV diastolic dysfunction and incompetence of ventricular-arterial coupling. NEW & NOTEWORTHY The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. Although the DSM gain is impaired in heart failure with preserved ejection fraction (HFpEF) patients, it is not clear whether this is because of higher LVEDP or left-ventricular diastolic dysfunction. The DSM gain in HFpEF patients is severely impaired, even at a similar level of LVEDP, which may reflect intrinsic left-ventricular diastolic dysfunction.

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