370 Increase Inflammation, Oxidative Stress and Basal Peripheral Arterial Blood Flow in Ambulatory Patients Suffering from Heart Failure With Preserved Ejection Fraction

Background. Changes in cardiopulmonary reserve and biomarkers related to wall stress, inflammation, and oxidative stress concomitantly with the evaluation of peripheral arterial blood flow have not been investigated in patients with heart failure with preserved ejection fraction (HFpEF) compared with healthy subjects (CTL).Methods and Results. Eighteen HFpEF patients and 14 CTL were recruited. Plasma levels of inflammatory and oxidative stress biomarkers were measured at rest. Brain natriuretic peptide (BNP) was measured at rest and peak exercise. Cardiopulmonary reserve was assessed using an exercise protocol with gas exchange analyses. Peripheral arterial blood flow was determined by strain gauge plethysmography. Peak VO2(12.0±0.4versus19.1±1.1 mL/min/kg,P<0.001) and oxygen uptake efficiency slope (1.55±0.12versus2.06±0.14,P<0.05) were significantly decreased in HFpEF patients compared with CTL. BNP at rest and following stress, C-reactive-protein, interleukin-6, and TBARS were significantly elevated in HFpEF. Both basal and posthyperemic arterial blood flow were not significantly different between the HFpEF patients and CTL.Conclusions. HFpEF exhibits a severe reduction in cardiopulmonary reserve and oxygen uptake efficiency concomitantly with an elevation in a broad spectrum of biomarkers confirming an inflammatory and prooxidative status in patients with HFpEF.

Download Full-text

Abstract 500: Basal Peripheral Arterial Blood Flow Increases Concomitantly with Decreased Cardiopulmonary Reserve and Biomarkers Activation in Patients with Heart Failure and Preserved Ejection Fraction

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a500 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Damien Vitiello ◽

François Harel ◽

Rhian M Touyz ◽

Martin G Sirois ◽

Joel Lavoie ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Blood Flow ◽

Arterial Blood Flow ◽

Subclinical Inflammation ◽

Preserved Ejection Fraction ◽

Arterial Function ◽

Arterial Blood ◽

Peripheral Arterial ◽

And Oxidative Stress

Background The underlying pathophysiology of heart failure with preserved ejection fraction (HFpEF) remains poorly understood. Changes in peripheral arterial function concomitantly with the evaluation of cardiopulmonary reserve and biomarkers related to wall stress, extra-cellular matrix turnover (ECM), subclinical inflammation and oxidative stress have not been investigated in patients with HFpEF nor compared with age-matched healthy volunteers (HV). We hypothesized that patients with HFpEF would have impairments in cardiac reserve with reduced peripheral arterial function associated with broad-spectrum biomarkers activation. Methods Eighteen male and female HFpEF patients (aged 70 ± 9 yr) NYHA class II and III were recruited. Data from patients were compared with those from 14 age and sex matched HV. A maximal exercise testing with gas exchange analysis was completed on a treadmill using a RAMP protocol and heart rate recovery (HRR) was measured at 1 and 2 minutes following exercise. Peripheral arterial function was assessed using near infrared radionuclide plethysmography. Biomarkers included BNP, NT-proBNP, hsCRP, TBARS, 8-epi-prostaglandin F2α, MMP 1, 2, 9 and TIMP 1, 2, 3, 4) were analyzed. Results Selected data are presented in the Table 1 and 2. Conclusions Compared to healthy volunteers, patients with HFpEF demonstrated a significant decrease in aerobic capacity but an increase in basal peripheral arterial blood flow, subclinical inflammation and oxidative stress. The increase in resting arterial blood flow may be a compensatory mechanism for the decrease in cardiac reserve and the pro-inflammatory/oxidant milieu in these patients.

Download Full-text

Reduced peripheral arterial blood flow with preserved cardiac output during submaximal bicycle exercise in elderly heart failure

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/1532-429x-11-48 ◽

2009 ◽

Vol 11 (1) ◽

pp. 48 ◽

Cited By ~ 23

Author(s):

Chirapa Puntawangkoon ◽

Dalane W Kitzman ◽

Stephen B Kritchevsky ◽

Craig A Hamilton ◽

Barbara Nicklas ◽

...

Keyword(s):

Heart Failure ◽

Blood Flow ◽

Cardiac Output ◽

Arterial Blood Flow ◽

Bicycle Exercise ◽

Arterial Blood ◽

Peripheral Arterial

Download Full-text

Immediate Effects of Electrical Stimulation, Diathermy, and Physical Exercise on Lower Limb Arterial Blood Flow in Diabetic Women With Peripheral Arterial Disease: A Randomized Crossover Trial

Journal of Manipulative and Physiological Therapeutics ◽

10.1016/j.jmpt.2014.08.008 ◽

2015 ◽

Vol 38 (3) ◽

pp. 195-202 ◽

Cited By ~ 7

Author(s):

Elaine Caldeira de Oliveira Guirro ◽

Rinaldo Roberto de Jesus Guirro ◽

Almir Vieira Dibai-Filho ◽

Siane Cristina Santarosa Pascote ◽

Delaine Rodrigues-Bigaton

Keyword(s):

Blood Flow ◽

Electrical Stimulation ◽

Peripheral Arterial Disease ◽

Lower Limb ◽

Crossover Trial ◽

Arterial Disease ◽

Arterial Blood Flow ◽

Arterial Blood ◽

Randomized Crossover Trial ◽

Peripheral Arterial

Download Full-text

Low-Sodium Dietary Approaches to Stop Hypertension Diet Reduces Blood Pressure, Arterial Stiffness, and Oxidative Stress in Hypertensive Heart Failure With Preserved Ejection Fraction

Hypertension ◽

10.1161/hypertensionaha.112.202705 ◽

2012 ◽

Vol 60 (5) ◽

pp. 1200-1206 ◽

Cited By ~ 93

Author(s):

Scott L. Hummel ◽

E. Mitchell Seymour ◽

Robert D. Brook ◽

Theodore J. Kolias ◽

Samar S. Sheth ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Blood Pressure ◽

Arterial Stiffness ◽

Ejection Fraction ◽

Preserved Ejection Fraction ◽

Low Sodium ◽

And Oxidative Stress

Download Full-text

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

Diabetes Mellitus ◽

10.14341/dm12732 ◽

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.

Download Full-text

Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Gα oxidation

Cardiovascular Research ◽

10.1093/cvr/cvaa123 ◽

2020 ◽

Cited By ~ 10

Author(s):

Detmar Kolijn ◽

Steffen Pabel ◽

Yanna Tian ◽

Mária Lódi ◽

Melissa Herwig ◽

...

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Ejection Fraction ◽

Linear Regression Analysis ◽

Lipid Peroxide ◽

Dependent Manner ◽

Preserved Ejection Fraction ◽

Human Heart Failure ◽

Stress Dependent

Abstract Aims Sodium-glucose-cotransporter-2 inhibitors showed favourable cardiovascular outcomes, but the underlying mechanisms are still elusive. This study investigated the mechanisms of empagliflozin in human and murine heart failure with preserved ejection fraction (HFpEF). Methods and results The acute mechanisms of empagliflozin were investigated in human myocardium from patients with HFpEF and murine ZDF obese rats, which were treated in vivo. As shown with immunoblots and ELISA, empagliflozin significantly suppressed increased levels of ICAM-1, VCAM-1, TNF-α, and IL-6 in human and murine HFpEF myocardium and attenuated pathological oxidative parameters (H2O2, 3-nitrotyrosine, GSH, lipid peroxide) in both cardiomyocyte cytosol and mitochondria in addition to improved endothelial vasorelaxation. In HFpEF, we found higher oxidative stress-dependent activation of eNOS leading to PKGIα oxidation. Interestingly, immunofluorescence imaging and electron microscopy revealed that oxidized PKG1α in HFpEF appeared as dimers/polymers localized to the outer-membrane of the cardiomyocyte. Empagliflozin reduced oxidative stress/eNOS-dependent PKGIα oxidation and polymerization resulting in a higher fraction of PKGIα monomers, which translocated back to the cytosol. Consequently, diminished NO levels, sGC activity, cGMP concentration, and PKGIα activity in HFpEF increased upon empagliflozin leading to improved phosphorylation of myofilament proteins. In skinned HFpEF cardiomyocytes, empagliflozin improved cardiomyocyte stiffness in an anti-oxidative/PKGIα-dependent manner. Monovariate linear regression analysis confirmed the correlation of oxidative stress and PKGIα polymerization with increased cardiomyocyte stiffness and diastolic dysfunction of the HFpEF patients. Conclusion Empagliflozin reduces inflammatory and oxidative stress in HFpEF and thereby improves the NO–sGC–cGMP–cascade and PKGIα activity via reduced PKGIα oxidation and polymerization leading to less pathological cardiomyocyte stiffness.

Download Full-text