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 Right Ventricular and Right Atrial Function Are Less Compromised in Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction: A Comparison With Pulmonary Arterial Hypertension With Similar Pressure Overload

2021 ◽  
Author(s):  
Jessie van Wezenbeek ◽  
Azar Kianzad ◽  
Arno van de Bovenkamp ◽  
Jeroen Wessels ◽  
Sophia A. Mouratoglou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Ejection Fraction ◽  
Arterial Hypertension ◽  
Vena Cava ◽  
Pressure Overload ◽  
Right Atrial ◽  
Preserved Ejection Fraction ◽  
Pulmonary Arterial

Background: Heart failure with preserved ejection fraction (HFpEF) is a prevalent disorder for which no effective treatment yet exists. Pulmonary hypertension (PH) and right atrial (RA) and ventricular (RV) dysfunction are frequently observed. The question remains whether the PH with the associated RV/RA dysfunction in HFpEF are markers of disease severity. Methods: To obtain insight in the relative importance of pressure-overload and left-to-right interaction, we compared RA and RV function in 3 groups: 1. HFpEF (n=13); 2. HFpEF-PH (n=33), and; 3. pulmonary arterial hypertension (PAH) matched to pulmonary artery pressures of HFpEF-PH (PH limited to mPAP ≥30 and ≤50 mmHg) (n=47). Patients underwent right heart catheterization and cardiac magnetic resonance imaging. Results: The right ventricle in HFpEF-PH was less dilated and hypertrophied than in PAH. In addition, RV ejection fraction was more preserved (HFpEF-PH: 52±11 versus PAH: 36±12%). RV filling patterns differed: vena cava backflow during RA contraction was observed in PAH only. In HFpEF-PH, RA pressure was elevated throughout the cardiac cycle (HFpEF-PH: 10 [8–14] versus PAH: 7 [5–10] mm Hg), while RA volume was smaller, reflecting excessive RA stiffness (HFpEF-PH: 0.14 [0.10–0.17] versus PAH: 0.08 [0.06–0.11] mm Hg/mL). RA stiffness was associated with an increased eccentricity index (HFpEF-PH: 1.3±0.2 versus PAH: 1.2±0.1) and interatrial pressure gradient (9 [5 to 12] versus 2 [−2 to 5] mm Hg). Conclusions: RV/RA function was less compromised in HFpEF-PH than in PAH, despite similar pressure-overload. Increased RA pressure and stiffness in HFpEF-PH were explained by left atrial/RA-interaction. Therefore, our results indicate that increased RA pressure is not a sign of overt RV failure but rather a reflection of HFpEF-severity.

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

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