scholarly journals Chronic Kidney Disease as a Risk Factor for Heart Failure With Preserved Ejection Fraction: A Focus on Microcirculatory Factors and Therapeutic Targets

2019 ◽  
Vol 10 ◽  
Author(s):  
Jens van de Wouw ◽  
Michelle Broekhuizen ◽  
Oana Sorop ◽  
Jaap A. Joles ◽  
Marianne C. Verhaar ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Therapeutic Targets ◽  
Preserved Ejection Fraction

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 Angiotensin-Neprilysin Inhibition and Renal Outcomes in Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (13) ◽  
pp. 1236-1245 ◽  
Author(s):  
Finnian R. Mc Causland ◽  
Martin P. Lefkowitz ◽  
Brian Claggett ◽  
Nagesh S. Anavekar ◽  
Michele Senni ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Renal Outcome ◽  
Preserved Ejection Fraction ◽  
Double Blind ◽  
Prospective Comparison ◽  
Patients With Heart Failure ◽  
Neprilysin Inhibition

Background: In patients with heart failure, chronic kidney disease is common and associated with a higher risk of renal events than in patients without chronic kidney disease. We assessed the renal effects of angiotensin/neprilysin inhibition in patients who have heart failure with preserved ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction). Methods: In this randomized, double-blind, event-driven trial, we assigned 4822 patients who had heart failure with preserved ejection fraction to receive sacubitril/valsartan (n=2419) or valsartan (n=2403). Herein, we present the results of the prespecified renal composite outcome (time to first occurrence of either: ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease, or death from renal causes), the individual components of this composite, and the influence of therapy on eGFR slope. Results: At randomization, eGFR was 63±19 mL·min –1 ·1.73 m – 2. At study closure, the composite renal outcome occurred in 33 patients (1.4%) assigned to sacubitril/valsartan and 64 patients (2.7%) assigned to valsartan (hazard ratio, 0.50 [95% CI, 0.33–0.77]; P =0.001). The treatment effect on the composite renal end point did not differ according to the baseline eGFR (<60 versus ≥60 mL·min –1 ·1.73 m –2 ( P -interaction=0.92). The decline in eGFR was less for sacubitril/valsartan than for valsartan (–2.0 [95% CI, –2.2 to –1.9] versus –2.7 [95% CI, –2.8 to –2.5] mL·min –1 ·1.73 m –2 per year). Conclusions: In patients with heart failure with preserved ejection fraction, sacubitril/valsartan reduced the risk of renal events, and slowed decline in eGFR, in comparison with valsartan. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920711.

scholarly journals Features of the structural and functional condition of the myocardium in patients with chronic kidney disease and chronic heart failure

2019 ◽  
Vol 11 (3) ◽  
pp. 79-84
Author(s):  
Dmitrij S. Frolov ◽  
Vladimir V. Salukhov ◽  
Sergej B. Shustov ◽  
Tat'yana R. Lokshina ◽  
Elizaveta A. Izilyaeva ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Chronic Heart Failure ◽  
Kidney Disease ◽  
Left Ventricle ◽  
Ejection Fraction ◽  
Chronic Kidney Disease Stage ◽  
Functional Condition ◽  
Disease Stage ◽  
Preserved Ejection Fraction

Relevance. The results of the structural and functional condition of the heart in patients with chronic heart failure with mid-range ejection fraction and heart failure with preserved ejection fraction and chronic kidney disease stage 3 were analyzed. Purpose. To study clinical and laboratory parameters, as well as the structural and functional condition of the myocardium in patients with chronic kidney disease stage 3 and chronic heart failure with mid-range ejection fraction and heart failure with preserved ejection fraction. Materials and methods. A total of 41 patients with chronic stage 3 kidney disease and chronic heart failure with mid-range ejection fraction and heart failure with preserved ejection fraction were examined. Structural and functional changes in the myocardium were estimated by means of echocardiography and tissue Doppler imaging. Results and conclusion. In patients with chronic heart failure with mid-range ejection fraction and heart failure with preserved ejection fraction, the presence of chronic kidney disease stage 3b in comparison with stage 3a is characterized by a more significant interatrial conduction abnormality, AV-node and bundle of the His, and also more significant violation of systolic function, not only the left, but also right ventricles. In the patients with chronic heart failure with mid-range ejection fraction and heart failure with preserved ejection fraction and the presence of chronic kidney disease stage 3a, diastolic dysfunction of the left ventricle of the I type prevails significantly more often. In the patients with chronic kidney disease of 3b stage diastolic dysfunction of the left ventricle type II is more common.

scholarly journals Does Chronic Kidney Disease Facilitate Malignant Myocardial Fibrosis in Heart Failure with Preserved Ejection Fraction of Hypertensive Origin?

2020 ◽  
Vol 9 (2) ◽  
pp. 404 ◽  
Author(s):  
Rocio Eiros ◽  
Gregorio Romero-González ◽  
Juan Jose Gavira ◽  
Oscar Beloqui ◽  
Inmaculada Colina ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Myocardial Fibrosis ◽  
Collagen Type I ◽  
Type I ◽  
Preserved Ejection Fraction ◽  
Matrix Metalloproteinase 1 ◽  
Carboxy Terminal

In hypertensive patients with heart failure (HF) a serum biomarker combination of high carboxy-terminal propeptide of procollagen type-I (PICP) and low carboxy-terminal telopeptide of collagen type-I to matrix metalloproteinase-1 (CITP:MMP-1) ratio identifies a histomolecular phenotype of malignant myocardial fibrosis (mMF) associated with severe diastolic dysfunction (DD) and poor outcomes. As chronic kidney disease (CKD) facilitates MF and DD, we investigated the influence of CKD on the mMF biomarker combination in HF patients with preserved ejection fraction (HFpEF). Hypertensives (n = 365), 232 non-HF and 133 HFpEF, were studied, and 35% non-HF and 46% HFpEF patients had CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio ≥ 30 mg/g). Specific immunoassays were performed to determine biomarkers. Medians were used to establish the high PICP and low CITP:MMP-1 combination. A comparison with non-HF showed that the biomarker combination presence was increased in HFpEF patients, being associated with CKD in all patients. CKD influenced the association of the biomarker combination and HFpEF (p for interaction ≤ 0.019). The E:e’ ratio was associated with the biomarker combination in CKD patients. Among CKD patients with HFpEF, those with the biomarker combination exhibited higher (p = 0.016) E:e’ ratio than those without the pattern. These findings suggest that CKD facilitates the development of biomarker-assessed mMF and DD in hypertensive HFpEF patients.

Association between use of beta-blockers and mortality/morbidity in patients with heart failure with reduced, midrange or preserved ejection fraction and advanced chronic kidney disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Fu ◽  
A Uijl ◽  
F.W Dekker ◽  
L.H Lund ◽  
G Savarese ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Ejection Fraction ◽  
Beta Blocker ◽  
Beta Blockers ◽  
Preserved Ejection Fraction ◽  
Advanced Chronic Kidney Disease ◽  
Patients With Heart Failure ◽  
All Cause Mortality

Abstract Background Beta-blockers reduce mortality and morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). However, patients with advanced chronic kidney disease (CKD) were underrepresented in landmark trials. Purpose We evaluated if beta-blockers are associated with improved survival and cardiovascular outcomes in patients with HFrEF and advanced CKD, and if potential benefits of beta-blockers would extend also to HFpEF and HFmrEF with advanced CKD. Methods We identified 3906 persons with an ejection fraction &lt;40% and advanced CKD (eGFR &lt;30 mL/min/1.73m2) enrolled in the Swedish Heart Failure Registry during 2001–2016. We did not exclude patients with atrial fibrillation. The associations between beta-blocker use, 5-year all-cause mortality, and the composite of time to cardiovascular (CV) mortality/first HF hospitalization were assessed by multivariable Cox regression. Analyses were adjusted for 36 variables, including demographics, laboratory measures, comorbidities, medication use, medical procedures, and socioeconomic status. To assess consistency, the same analyses were performed in a positive control cohort of 12,673 patients with moderate CKD (eGFR &lt;60–30 mL/min/1.73m2). Analyses were repeated in individuals with HF with preserved ejection fraction (HFpEF; EF ≥50%) or midrange ejection fraction (HFmrEF; EF 40–49%). Results In HFrEF and advanced CKD, 89% received beta-blockers. Overall, median (IQR) age was 81 (74–86) years, 36% were women and median eGFR was 26 (20–28) ml/min/1.73m2. During a median of 1.3 years follow-up, 2086 (53.4%) individuals had a subsequent HF hospitalization, and 2954 (75.6%) individuals died, of which 2089 (70.1%) due to cardiovascular causes. Beta-blocker use was associated with a significant reduction in 5-year all-cause mortality [adjusted hazard ratio (HR) 0.86; 95% confidence interval (CI) 0.76–0.96)] and CV mortality/HF hospitalization (HR 0.87; 95% CI 0.77–0.98). The magnitude of the associations between beta-blocker use and outcomes was similar to that observed for HFrEF patients with mild/moderate CKD [all-cause mortality: 0.85 (95% CI 0.78–0.91); CV mortality/HF hospitalization: 0.88 (95% CI 0.82–0.96)]. Adjusted HRs were 0.88 (95% CI 0.77–1.02) and 1.07 (95% CI 0.92–1.24) for individuals with HFpEF and advanced CKD and 0.95 (95% CI 0.80–1.13) and 1.13 (95% CI 0.94–1.36) for individuals with HFmrEF and advanced CKD, for all-cause mortality and CV mortality/HF hospitalization, respectively. Conclusion Despite lack of trial evidence, the use of beta-blockers in patients with HFrEF and advanced CKD was high in routine Swedish care, and was independently associated with reduced mortality to the same degree as HFrEF with moderate CKD. However, these benefits were not observed in patients with HFpEF or HFmrEF with severe CKD. Funding Acknowledgement Type of funding source: None

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