scholarly journals Remote Hind-Limb Ischemia Mechanism of Preserved Ejection Fraction During Heart Failure

2021 ◽  
Vol 12 ◽  
Author(s):  
Rubens P. Homme ◽  
Yuting Zheng ◽  
Irina Smolenkova ◽  
Mahavir Singh ◽  
Suresh C. Tyagi
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Bone Marrow ◽  
Ejection Fraction ◽  
Hind Limb ◽  
Vena Cava ◽  
Vascular Density ◽  
Preserved Ejection Fraction ◽  
Sympathetic Activation ◽  
Contraction And Relaxation

During acute heart failure (HF), remote ischemic conditioning (RIC) has proven to be beneficial; however, it is currently unclear whether it also extends benefits from chronic congestive, cardiopulmonary heart failure (CHF). Previous studies from our laboratory have shown three phases describing CHF viz. (1) HF with preserved ejection fraction (HFpEF), (2) HF with reduced EF (HFrEF), and (3) HF with reversed EF. Although reciprocal organ interaction, ablation of sympathetic, and calcium signaling genes are associated with HFpEF to HFrEF, the mechanism is unclear. The HFrEF ensues, in part, due to reduced angiogenesis, coronary reserve, and leakage of endocardial endothelial (EE) and finally breakdown of the blood-heart barrier (BHB) integrity. In fact, our hypothesis states that a change in phenotype from compensatory HFpEF to decompensatory HFrEF is determined by a potential decrease in regenerative, proangiogenic factors along with a concomitant increase in epigenetic memory, inflammation that combinedly causes oxidative, and proteolytic stress response. To test this hypothesis, we created CHF by aorta-vena-cava (AV) fistula in a group of mice that were subsequently treated with that of hind-limb RIC. HFpEF vs. HFrEF transition was determined by serial/longitudinal echo measurements. Results revealed an increase in skeletal muscle musclin contents, bone-marrow (CD71), and sympathetic activation (β2-AR) by RIC. We also observed a decrease in vascular density and attenuation of EE-BHB function due to a corresponding increase in the activity of MMP-2, vascular endothelial growth factor (VEGF), caspase, and calpain. This decrease was successfully mitigated by RIC-released skeletal muscle exosomes that contain musclin, the myokine along with bone marrow, and sympathetic activation. In short, based on proteome (omics) analysis, ∼20 proteins that appear to be involved in signaling pathways responsible for the synthesis, contraction, and relaxation of cardiac muscle were found to be the dominant features. Thus, our results support that the CHF phenotype causes dysfunction of cardiac metabolism, its contraction, and relaxation. Interestingly, RIC was able to mitigate many of the deleterious changes, as revealed by our multi-omics findings.

Prognostic role of sonographic decongestion in patients with acute heart failure with reduced and preserved ejection fraction: a multicentre study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N.R Pugliese ◽  
M Mazzola ◽  
G Bandini ◽  
G Barbieri ◽  
S Spinelli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Events ◽  
Ejection Fraction ◽  
Acute Heart Failure ◽  
Vena Cava ◽  
Composite Endpoint ◽  
Clinical Findings ◽  
Preserved Ejection Fraction ◽  
Net Reclassification Improvement ◽  
B Lines

Abstract Aims Our aim was to assess the dynamic changes of pulmonary congestion (PC) through variations of sonographic B-lines, in addition to conventional clinical, biohumoral and echocardiographic findings, to improve prognostic stratification of patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF). Methods In this multicenter, prospective, observational study, lung ultrasound was performed in all patients at admission and before discharge by trained investigators, blinded to clinical findings and outcomes. Results We enrolled 208 consecutive patients admitted for acute heart failure (125 HFrEF, 83 HFpEF, mean age 75.9±11.7 years, 36% females, mean ejection fraction 38%). After 180-day follow-up, 38 composite endpoint events occurred (cardiovascular deaths or HF re-hospitalisations). In a multivariate model, B-lines at discharge had independent prognostic value in the overall population together with NT-proBNP, moderate-to-severe mitral regurgitation (MR) and inferior vena cava diameter at admission. When dividing the population in HFrEF and HFpEF, B-lines at discharge was the only independent parameter to predict events in all subgroups. At ROC analysis, a cut-off of B-lines>15 at discharge displayed the highest accuracy in predicting adverse events (AUC=0.80, p<0.0001). The identification of patients unable to halve B-lines during hospitalization (ΔB-lines%), in addition to B-lines >15 at discharge, improved event classification (integrated discrimination improvement=4%, p=0.01; continuous net reclassification improvement=22.8%, p=0.04). Conclusions The presence of residual subclinical sonographic PC at discharge predicts adverse events in the whole spectrum of acute HF patients, independently of conventional biohumoral and echocardiographic parameters. The dynamic evaluation of pulmonary decongestion during hospital stay can further improve patient risk stratification. Funding Acknowledgement Type of funding source: None

scholarly journals Skeletal muscle (dys)function in heart failure with preserved ejection fraction

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Eng Leng Saw ◽  
Swetha Ramachandran ◽  
Maria Valero-Muñoz ◽  
Flora Sam
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Preserved Ejection Fraction

scholarly journals Skeletal Muscle Function, Structure, and Metabolism in Patients With Heart Failure With Reduced Ejection Fraction and Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 13 (12) ◽  
Author(s):  
Tarek Bekfani ◽  
Mohamed Bekhite Elsaied ◽  
Steffen Derlien ◽  
Jenny Nisser ◽  
Martin Westermann ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Ejection Fraction ◽  
Oral Anticoagulation ◽  
Muscle Function ◽  
Muscle Endurance ◽  
Acid Oxidation ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction

Background: Reduced exercise capacity in patients with heart failure (HF) could be partially explained by skeletal muscle dysfunction. We compared skeletal muscle function, structure, and metabolism among clinically stable outpatients with HF with preserved ejection fraction, HF with reduced ejection fraction, and healthy controls (HC). Furthermore, the molecular, metabolic, and clinical profile of patients with reduced muscle endurance was described. Methods: Fifty-five participants were recruited prospectively at the University Hospital Jena (17 HF with preserved ejection fraction, 18 HF with reduced ejection fraction, and 20 HC). All participants underwent echocardiography, cardiopulmonary exercise testing, 6-minute walking test, isokinetic muscle function, and skeletal muscle biopsies. Expression levels of fatty acid oxidation, glucose metabolism, atrophy genes, and proteins as well as inflammatory biomarkers were assessed. Mitochondria were evaluated using electron microscopy. Results: Patients with HF with preserved ejection fraction showed compared with HF with reduced ejection fraction and HC reduced muscle strength (eccentric extension: 13.3±5.0 versus 18.0±5.9 versus 17.9±5.1 Nm/kg, P =0.04), elevated levels of MSTN-2 (myostatin-2), FBXO-32 (F-box only protein 32 [Atrogin1]) gene and protein, and smaller mitochondrial size ( P <0.05). Mitochondrial function and fatty acid and glucose metabolism were impaired in HF-patients compared with HC ( P <0.05). In a multiple regression analysis, GDF-15 (growth and differentiation factor 15), CPT1B (carnitine palmitoyltransferase IB)-protein and oral anticoagulation were independent factors for predicting reduced muscle endurance after adjusting for age (log10 GDF-15 [pg/mL] [B, −54.3 (95% CI, −106 to −2.00), P =0.043], log10 CPT1B per fold increase [B, 49.3 (95% CI, 1.90–96.77), P =0.042]; oral anticoagulation present [B, 44.8 (95% CI, 27.90–61.78), P <0.001]). Conclusions: Patients with HF with preserved ejection fraction have worse muscle function and predominant muscle atrophy compared with those with HF with reduced ejection fraction and HC. Inflammatory biomarkers, fatty acid oxidation, and oral anticoagulation were independent factors for predicting reduced muscle endurance.

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 15025: Visceral Adiposity and Muscle Composition in Heart Failure With Preserved Ejection Fraction and Association With Exercise Tolerance

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Wendy Ying ◽  
Kavita Sharma ◽  
Lisa R Yanek ◽  
Dhananjay Vaidya ◽  
Michael Schar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Exercise Tolerance ◽  
Nyha Class ◽  
Well Being ◽  
Liver Fat ◽  
Exercise Intolerance ◽  
Preserved Ejection Fraction ◽  
Intermuscular Fat

Introduction: Visceral adipose tissue (AT) promotes inflammation and adverse metabolic changes that mediate disease progression in heart failure with preserved ejection fraction (HFpEF). Exercise intolerance is a hallmark of HFpEF, but little is known about its relation to the extent and distribution of AT. We characterized regional AT distribution in HFpEF patients and controls and analyzed associations with comorbidities and exercise tolerance. Methods: MRI was performed to quantify epicardial, liver, abdominal and thigh skeletal muscle AT. We assessed NYHA class, 6-minute walk distance (6MWD), and global well-being score (GWBS). Multivariable linear and logistic regression models were used, adjusted for age, sex, and body surface area. Results: We studied 55 HFpEF patients (41 women, mean age 67) and 33 controls (21 women, mean age 57). Epicardial AT (4.6 vs 3.2mm, p = 0.03), thigh intermuscular fat (11.0 vs 5.0cm 2 , p < 0.01) and liver fat fraction (FF) (6.4% vs 4.1%, p = 0.04) were higher in HFpEF patients than controls. Women with HFpEF had higher abdominal (443.9 vs 297.3 cm 2 , p = 0.03) and thigh (228.6 vs 112.3 cm 2 , p < 0.001) subcutaneous AT than men. Higher thigh intermuscular fat was associated with higher blood pressure (β [SE] 14.1 [3.3], p < 0.001) and diabetes (β [SE] 2.6 [1.1], p = 0.02), and liver FF was associated with chronic kidney disease (β [SE] 1.6 [0.6], p = 0.01). Higher thigh intramuscular fat was associated with both higher NYHA class and shorter 6MWD, and higher thigh intermuscular AT FF was associated with higher NYHA class ( Table ). Higher epicardial AT and liver FF were associated with lower GWBS. Conclusions: HFpEF patients have increased epicardial, liver, and skeletal muscle fat compared to controls out of proportion to their body size, and adiposity was associated with worse exercise intolerance in HFpEF. These results provide the basis for further investigation into regional AT distribution in relation to HFpEF symptoms and pathophysiology.

scholarly journals Heart failure with preserved ejection fraction and skeletal muscle physiology

2017 ◽  
Vol 22 (2) ◽  
pp. 141-148 ◽  
Author(s):  
Stephen D. Farris ◽  
Farid Moussavi-Harami ◽  
April Stempien-Otero
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Ejection Fraction ◽  
Muscle Physiology ◽  
Preserved Ejection Fraction

Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction

2015 ◽  
Vol 309 (10) ◽  
pp. H1648-H1654 ◽  
Author(s):  
Sara Leite ◽  
Sara Rodrigues ◽  
Marta Tavares-Silva ◽  
José Oliveira-Pinto ◽  
Mohamed Alaa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Pressure ◽  
Vena Cava ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Stiffness Constant ◽  
Complete Relaxation ◽  
Filling Time ◽  
Wistar Kyoto

Myocardial stiffness and upward-shifted end-diastolic pressure-volume (P-V) relationship (EDPVR) are the key to high filling pressures in heart failure with preserved ejection fraction (HFpEF). Nevertheless, many patients may remain asymptomatic unless hemodynamic stress is imposed on the myocardium. Whether delayed relaxation induced by pressure challenge may contribute to high end-diastolic pressure (EDP) remains unsettled. Our aim was to assess the effect of suddenly imposed isovolumic afterload on relaxation and EDP, exploiting a highly controlled P-V experimental evaluation setup in the ZSF1 obese rat (ZSF1 Ob) model of HFpEF. Twenty-week-old ZSF1 Ob ( n = 12), healthy Wistar-Kyoto rats (WKY, n = 11), and hypertensive ZSF1 lean control rats (ZSF1 Ln, n = 10) underwent open-thorax left ventricular (LV) P-V hemodynamic evaluation under anesthesia with sevoflurane. EDPVR was obtained by inferior vena cava occlusions to assess LV ED chamber stiffness constant β, and single-beat isovolumic afterload acquisitions were obtained by swift occlusions of the ascending aorta. ZSF1 Ob showed increased ED stiffness, delayed relaxation, as assessed by time constant of isovolumic relaxation (τ), and elevated EDP with normal ejection fraction. Isovolumic afterload increased EDP without concomitant changes in ED volume or heart rate. In isovolumic beats, relaxation was delayed to the extent that time for complete relaxation as predicted by 3.5 × monoexponentially derived τ (τexp) exceeded effective filling time. EDP elevation correlated with reduced time available to relax, which was the only independent predictor of EDP rise in multiple linear regression. Our results suggest that delayed relaxation during pressure challenge is an important contributor to lung congestion and effort intolerance in HFpEF.

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