scholarly journals Association of Chronic Kidney Disease with Preserved Ejection Fraction Heart Failure Is Independent of Baseline Cardiac Function

2019 ◽  
Vol 44 (5) ◽  
pp. 1247-1258 ◽  
Author(s):  
Thomas A. Mavrakanas ◽  
Aisha Khattak ◽  
Wei Wang ◽  
Karandeep Singh ◽  
David M. Charytan
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Left Ventricular Mass Index ◽  
Secondary Analysis ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Left Atrial Diameter

Background/Aims: Chronic kidney disease (CKD) is common among patients with heart failure with preserved ejection fraction (HFpEF) and is associated with worse clinical outcomes. This study aims to identify whether the association of CKD with HFpEF is independent of underlying echocardiographic abnormalities. Materials: We conducted a retrospective cohort study including patients without prevalent heart failure referred for echocardiography. Patients with serial echocardiograms, baseline left ventricular ejection fraction (LVEF) ≥50% and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 were matched 1:1 with patients with eGFR <60 mL/min/1.73 m2 for age (±5 years), sex, history of hypertension or diabetes, use of renin-angiotensin inhibitors, and LVEF (±5%). A secondary analysis included patients with preserved LVEF and normal left ventricular mass index matched for the same parameters except use of renin-angiotensin inhibitors. Results: Patients with CKD were at increased risk for HFpEF admission: crude hazard ratio (HR) 1.79 (95% confidence interval [CI] 1.38–2.32, p < 0.001) and adjusted HR (for coronary disease, loop diuretics, left atrial diameter) 1.64 (95% CI 1.22–2.21, p = 0.001). LVEF and left ventricular diameter decreased over time in both groups but no difference was observed in rate of dropping. Results were similar in the secondary analysis (crude HR 1.99, 95% CI 1.07–3.71, p = 0.03 and HR adjusted for left atrial diameter 1.98, 95% CI 1.05–3.75, p = 0.04). Rate of change was similar for LVEF, pulmonary artery pressure, and left ventricular mass index in both groups. Conclusion: CKD is independently associated with incident HFpEF despite a similar change in relevant echocardiographic parameters in patients with or without CKD.

P0736A NOVEL MODEL OF CHRONIC KIDNEY DISEASE AND HEART FAILURE WITH PRESERVED EJECTION FRACTION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Alejandro Chade ◽  
Maxx Williams ◽  
Jason Engel ◽  
Michael Hall
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Inflammatory Cytokines ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Tnf Α ◽  
Novel Model

Abstract Background and Aims Patients with chronic kidney disease (CKD) have a significantly higher cardiovascular risk that non-CKD patients, and over 50% of CKD patients die of cardiovascular events. We recently developed a model of CKD that displays major pathological features of clinical CKD: GFR of about 60 ml/min (stage 2-3a), significant renal inflammation, fibrosis, microvascular dysfunction and remodeling, and hypertension. The current study aims to define the cardiac phenotype of this model and, if cardiac abnormalities are present, the potential pathological traits involved. Method CKD was induced in 6 pigs via bilateral renovascular disease and dyslipidemia and observed for 14 weeks. After 14 weeks, renal hemodynamics (RBF, GFR) were quantified using multi-detector CT and echocardiographic assessment (morphology and function) performed using ultrasound-doppler. Mean arterial pressure (MAP) was continuously measured by telemetry. Blood was collected to measure circulating inflammatory cytokines (TNF-α, MCP-1, IL-6) and biomarkers of heart failure (ANP, BNP, NT-proBNP). Animals were then euthanized and kidneys and hearts collected for ex vivo studies. Normal pigs were used as time-matched controls. Results Loss of renal function in CKD was accompanied by left ventricular hypertrophy, left atrial dilatation, diastolic dysfunction (E/A ratio) with preserved ejection fraction (pEF), elevated ANP, BNP, and NT-proBNP, and hypertension (average MAP of 131.2 mm/Hg, p&lt;0.05 vs. normal). CKD also increased renal (but not cardiac) mRNA expression of TNF-α, MCP-1, IL-6, accompanied by increased circulating inflammatory cytokines (Figure). Conclusion This study shows that CKD in the swine model leads to cardiac hypertrophy and diastolic dysfunction (with pEF) and increased biomarkers of heart failure, meeting the criteria for a potential novel model of heart failure with pEF (HFpEF). Our data also suggest that hypertension and inflammatory mediators (possibly originated in the kidney) target the heart and may contribute to HFpEF pathophysiology. HFpEF is considered the largest unmet need in cardiology with no specific treatments and associates with CKD in about 50% of cases. Thus, our study offers a promising new experimental platform to increase our understanding of CKD-HFpEF and to test new treatments in a translational fashion.

Significance of the echocardiographic evaluation of left atrial myocardial strain for early diagnosis of heart failure with preserved ejection fraction

Kardiologiia ◽  
2021 ◽  
Vol 61 (8) ◽  
pp. 68-75
Author(s):  
E. K. Serezhina ◽  
A. G. Obrezan
Keyword(s):  
Heart Failure ◽  
Early Diagnosis ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Myocardial Dysfunction ◽  
Systolic Dysfunction ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Echocardiographic Evaluation

This systematic review is based on 19 studies from Elsevier, PubMed, Embase, and Scopus databases, which were found by the following keywords: LA strain (left atrial strain), STE (speckle tracking echocardiography), HF (heart failure), and HFpEF (heart failure with preserved ejection fraction). The review focuses on results and conclusions of studies on using the 2D echocardiographic evaluation of left atrial (LA) myocardial strain for early diagnosis of HFpEF in routine clinical practice. Analysis of the studies included into this review showed a significant decline of all LA functions in patients with HFpEF. Also, multiple studies have reported associations between decreased indexes of LA strain and old age, atrial fibrillation, left ventricular hypertrophy, left and right ventricular systolic dysfunction, and LV diastolic dysfunction. Thus, the review indicates significant possibilities of using indexes of LA strain in evaluation of early stages of both systolic and diastolic myocardial dysfunction. Notably, LA functional systolic and diastolic indexes are not sufficiently studied despite their growing significance for diagnosis and prognosis of patients with HFpEF. For this reason, in addition to existing models for risk stratification in this disease, including clinical characteristics and/or echocardiographic data, future studies should focus on these parameters. 

Abstract 471: Combination of Allogeneic Mesenchymal and Kidney Stem Cells Ameliorates Chronic Kidney Disease Induced Heart Failure With Preserved Ejection Fraction

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Angela C Castellanos ◽  
Bryon A Tompkins ◽  
Makoto Natsumeda ◽  
Victoria Florea ◽  
Monisha Banerjee ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Cell Therapy ◽  
Renal Artery ◽  
Preserved Ejection Fraction ◽  
Kidney Stem Cells

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition involving multiple comorbidities. Phenotypic classification of HFpEF associated with chronic kidney disease (CKD) manifests worse outcomes, compared to other HFpEF phenotypes. Few treatments improve morbidity and mortality in HFpEF. Stem cell therapy promotes cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that allogeneic stem cell treatment ameliorates HFpEF in a large animal model of CKD. Methods: Yorkshire pigs (n=26) underwent 5/6 embolization-mediated nephrectomy and 4-weeks later received either: allogeneic mesenchymal stem cells (MSCs) (10х10 6 ), Kidney stem cells (KSC; 10х10 6 ), combination (ACCT; MSC+KSC; 1:1 ratio [5х10 6 each]), or placebo (n=6-7/ group). Cell therapy was delivered via the patent renal artery of the remnant kidney. RNAsec analysis compared placebo and ACCT groups. Results: Mean arterial pressure increased significantly in the placebo- (21.89±6.05 mmHg, p<0.0001) compared to the ACCT-group (p=0.04) at 12 weeks. Glomerular filtration rate improved significantly in the ACCT group (p=0.002). RNAseq analysis revealed a significant decrease in genes normally increased during kidney transplant rejection (q<10 -6 , NES = -2.32) in ACCT. Consistent with these results, there was a downregulation of canonical drivers of tubular damage and regeneration, including SOX9 (-2.39 fold, p=0.0004) and apoptosis of kidney cell types (-24.89 fold, p=0.004), including podocytes (-2.065 fold, p=0.04) with ACCT. ACCT administration also downregulated genes related to oxidative stress (-4.6 fold, p<0.0001), fibrosis, inflammatory response (-4.760 fold, p=<0.05), and renin-angiotensin signaling (-3.162 fold, p=0.024), which are related to cardiac hypertrophy pathways (-7.23, fold, p<0.0001). EDPVR improved in with ACCT (p=0.003), indicating decreased ventricular stiffness. Ejection fraction, relative wall thickness, and left ventricular mass did not differ between groups at 12 weeks. Conclusion: Intra-renal artery allogeneic cell therapy was safe. Beneficial effects were observed in the ACCT and MSC groups in the kidney and heart. These findings have important implications on the use of cell therapy for HFpEF and cardiorenal syndrome.

scholarly journals MO062CHRONIC KIDNEY DISEASE, INFLAMMATION, AND HEART FAILURE WITH PRESERVED EJECTION FRACTION: A RENAL-CARDIO AXIS?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Alejandro Chade ◽  
Maxx Williams ◽  
Jason Engel ◽  
Gene Bidwell
Keyword(s):  
Heart Failure ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Left Ventricular ◽  
Swine Model ◽  
Preserved Ejection Fraction ◽  
Renal Inflammation ◽  
Tnf Α

Abstract Background and Aims Inflammation contributes to progressive renal dysfunction and increases cardiovascular mortality of patients with chronic kidney disease (CKD). The association of CKD and heart failure with preserved ejection fraction (HFpEF) is observed in up to 50%, suggesting the possibility of a shared pathophysiology. CKD and HFpEF are commonly associated with inflammation. Using a novel swine model of CKD and HFpEF, we propose that a renal-cardio inflammatory axis drives diastolic dysfunction and HFpEF in CKD and that targeting renal inflammation will improve cardiac health and reduce cardiovascular risk. Methods We developed a biopolymer-fused peptide of nuclear-factor kappa (NFk)B (ELP-p50i) that we show it blocks its activity in vitro and in vivo. NFkB is a key pro-inflammatory transcription factor that is upregulated in CKD. To test our hypothesis, we induced CKD in 10 pigs via bilateral renovascular disease and dyslipidemia. Pigs were observed for 6 weeks, renal hemodynamics quantified (multi-detector CT), then randomized to single intra-renal ELP-p50i or placebo (n=5 each), and studies repeated 8 weeks later accompanied by echocardiographic assessment. Blood pressure was continuously measured (telemetry). Blood was collected to measure circulating TNF-α and biomarkers of HF (ANP, BNP). Furthermore, kidneys and hearts were used to quantify expression of factors involved in NFkB signaling. Results CKD led to a significant loss of renal function, accompanied by left ventricular hypertrophy and diastolic dysfunction with pEF, increased renal mRNA expression of TNF-α and canonical and non-canonical mediators of NFkB signaling, and elevated systemic TNF-α, ANP, and BNP, indicating renal and cardiac dysfunction. Most of these changes were improved after intra-renal ELP-p50i, although cardiac inflammatory signaling was unchanged (Figure) suggesting the kidney as a source of inflammation that can target the heart in CKD. Conclusion We show that a renal anti-inflammatory strategy via targeted inhibition of renal NFkB improves renal and cardiac function in CKD, suggesting an inflammatory renal-cardio axis. The translational pathological features of CKD and HFpEF combined with the predictive power of the model may contribute to advance the field towards new treatments targeting renal inflammation to reduce cardiovascular risk in CKD.

scholarly journals The risks and benefits of spironolactone use in heart failure with a reduced left ventricular ejection fraction and chronic kidney disease

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
O Obertynska
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Left Ventricular Ejection Fraction ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Public Institution ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

Abstract Purpose Mineralocorticoid receptor antagonists (MRAs) remain underused in cases of heart failure with a reduced left ventricular ejection fraction (HFrEF) and chronic kidney disease (CKD), largely due to the fear of inducing worsening of renal function (RF) and hyperkalemia (HK), particularly in combination with renin angiotensin inhibitors. The aim was to investigate the safety use of spironolactone (SP) in patients with HFrEF (ejection fraction &lt;40%) and CKD and determine predictors of worsening of RF and developing HK. Methods 208 patients with HFrEF (on top of standard therapy including ACE-I or an ARB) and CKD (baseline eGFR between 30 and 60 ml/min) were included in the study. The potassium (K) and creatinine (C) levels, plasma aldosterone (AS) and NT-proBNP were estimated at baseline and at week 12. After biochemical evaluation, 101 patients started on SP treatment with a median dose of 23 mg daily (titrated). K and RF were checked at weeks 1, 2, 4, 6, 8, 12. Results K and C levels increased significantly after start of SP: mean K levels increased from 4.47±0.59 to 5.23±0.57 mEq/l, (P&lt;0.01) and was dose dependent. After 12 weeks of treatment the incidence of severe HK (K+ ≥6.0 mmol/L) was &lt;5%, K 5.5–5.9 mmol/L occurred in 13 patients (13%) and it was predicted by baseline eGFR≤35 ml/min/1.73 m2. and K ≥5.0 mmol/L/. Subsequently, these patients required a prescription of K binders. Mean eGFR on SP decreased from 48.34±2.23 to 42.19±2.65 ml/min/1.73 m2 (P&lt;0.01) and a significant decrease in GFR was observed only during the first month (P &lt;0.01) with not significant increasing to 6 and 12 weeks after the start of SP. Five patients (5%) on SP experienced significant decline of RF result in withdrew SP. Age, NT-proBNP concentration &gt;1550 ng/L and eGFR ≤35 ml/min/1.73 m2 at baseline had modest discriminative powers for predicting decline of RF (0.456, P&lt;0.01; 0.542, P&lt;0.001; 0.712, P&lt;0.001; respectively). At baseline in patients with HFrEF was an inverse correlation between GFR and NT-proBNP level (r=−0.298, p&lt;0.001). The SP treatment resulted in significantly reduced NT-proBNP and AS (P&lt;0.01; P&lt;0.05 respectively). By linear regression analysis in SP group the eGFR was associated with NT-proBNP change (0.362, P&lt;0.05). Conclusion In patient with HFrEF and CKD the risk-benefit ratio of spironolactone with respect to renal failure appears favourable due to improvement of the neurohumoral profile. Although the renal disfunction and hyperkalemia on spironolactone are common: approximately 18% patients required the prescription of K binders and 5% required the withdrew SP duo to decline RF, the occurrence of hyperkalemia was predicted by baseline potassium level and eGFR. Age, higher level of NT-proBNP and eGFR were identified as potential predictors of worsening of RF. So, caution should be advised when using spironolactone in HFrEF with CKD and potassium of ≥5.0 mmol/L and eGFR ≤35 ml/min/1.73 m2 and NT-proBNP concentration &gt;1550 ng/L for safety reasons. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): National Medical University

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