scholarly journals Mechanistic dissection of global proteomic changes in rats with heart failure and preserved ejection fraction

2021 ◽  
Author(s):  
Daniel Soetkamp ◽  
Aleksandra Binek ◽  
Romain Gallet ◽  
Geoffrey de Couto ◽  
Peter Kilfoil ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Therapeutic Effects ◽  
Preserved Ejection Fraction ◽  
Salt Diet ◽  
Upstream Regulators

Introduction: Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction, pulmonary congestion and exercise intolerance. Previous preclinical studies show that treatment with cardiosphere-derived cells (CDCs) improves diastolic function, attenuates arrhythmias and prolongs survival in a rat HFpEF model. Here we characterize the myocardial proteome and diastolic function in HFpEF, with and without CDC therapy. As an initial strategy for identifying pathways worthy of further mechanistic dissection, we correlated CDC-responsive proteomic changes with functional improvements. Methods and Results: Dahl salt-sensitive rats fed high-salt diet, with verified diastolic dysfunction, were randomly assigned to intracoronary CDCs or placebo. Dahl rats fed a low salt diet served as controls. Phenotyping was by echocardiography (E/A ratio) and invasive hemodynamic monitoring (time constant of relaxation Tau, and left ventricular end-diastolic pressure [LVEDP]). CDC treatment improved diastolic function as indicated by a normalized E/A ratio, a 33.3% reduction in Tau, and a 47% reduction of LVEDP. Mass spectrometry of left ventricular tissues (n=6/group) revealed changes in transcription and translation pathways in this rat HFpEF model and was also recapitulated in human HFpEF. These pathways were enhanced following CDC treatment in the animal model (205 proteins and 32 phosphorylated residues accounting for 37% and 19% of all changes, respectively). Among all CDC-sensitive pathways, 65% can be linked to at least 1 of 7 upstream regulators, among which several are of potential relevance for regulating protein expression. To probe newly-synthesized proteins AHA labeling was carried out in isolated rat cardiomyocytes obtained from HFpEF groups, with and without CDC therapy. Five of the initial upstream regulators (HNF4A, MTOR, MYC, TGFβ1, and TP53) were linked to proteins expressed exclusively (or increased) with CDC treatment. All 32 phosphorylated residues of proteins involved in transcription/translation altered specifically by CDC treatment had predicted kinases (Protein kinase C (PKC) being the most dominant) and known to be regulated by MYC, TGFβ1 and/or TP53. Western blot analysis of those 5 upstream regulators showed that TGFβ1, TP53, and Myc were significantly decreased in LV from CDC treated animals, whereas MTOR and HNF4A showed a significant increase compared to HFpEF alone. The cellular quantities of several upstream regulator correlated with indices of diastolic function (E/A ratio, Tau and/or LVEDP). Since CDCs act via the secretion of exosomes laden with signaling cargo, it is relevant that all 7 upstream regulators could, in principle, be regulated by proteins or miRNA that are present in CDC-derived exosomes. Conclusion: We identified key cellular regulators of transcription and translation that underlie the therapeutic effects of CDCs in HFpEF, whose levels correlate quantitatively with measures of diastolic function. Among the multifarious proteomic changes associated with rat model of HFpEF which were also observed in human HFpEF samples, we propose that these regulators, and downstream effector kinases, be prioritized for further dedicated mechanistic dissection.

scholarly journals Validation of the 2016 ASE/EACVI Guideline for Diastolic Dysfunction in Patients With Unexplained Dyspnea and a Preserved Left Ventricular Ejection Fraction

2021 ◽  
Author(s):  
Arno A. van de Bovenkamp ◽  
Vidya Enait ◽  
Frances S. de Man ◽  
Frank T. P. Oosterveer ◽  
Harm Jan Bogaard ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Diagnostic Performance ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Ventricular Ejection Fraction

Background Echocardiography is considered the cornerstone of the diagnostic workup of heart failure with preserved ejection fraction. Thus far, validation of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) echo‐algorithm for evaluation of diastolic (dys)function in a patient suspected of heart failure with preserved ejection fraction has been limited. Methods and Results The diagnostic performance of the 2016 ASE/EACVI algorithm was assessed in 204 patients evaluated for unexplained dyspnea or pulmonary hypertension with echocardiogram and right heart catheterization. Invasively measured pulmonary capillary wedge pressure (PCWP) was used as the gold standard. In addition, the diagnostic performance of H 2 FPEF score and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) were evaluated. There was a poor correlation between indexed left atrial volume, E/e′ (septal and average) or early mitral inflow (E), and PCWP ( r =0.25–0.30, P values all <0.01). No correlation was found in our cohort between e′ (septal or lateral) or tricuspid valve regurgitation and PCWP. The correlation between diastolic function grades of the ASE/EACVI algorithm and PCWP was poor ( r =0.17, P <0.05). The ASE/EACVI algorithm had a sensitivity and specificity of 35% and 87%, respectively; an accuracy of 67% and an area under the curve of 0.56. Moreover, in 30% of cases the algorithm was not applicable or indeterminate. H 2 FPEF score had a modest correlation with PCWP ( r =0.44, P <0.0001), and accuracy was 73%; NT‐proBNP correlated weakly with PCWP ( r =0.24, P <0.001), and accuracy was 57%. Conclusions The 2016 ASE/EACVI algorithm for the assessment of diastolic function has a limited diagnostic accuracy in patients evaluated for unexplained dyspnea and/or pulmonary hypertension, and especially sensitivity to detect diastolic dysfunction was low.

scholarly journals Opportunistic screening models for high-risk men and women to detect diastolic dysfunction and heart failure with preserved ejection fraction in the community

2018 ◽  
Vol 26 (6) ◽  
pp. 613-623 ◽  
Author(s):  
Aisha Gohar ◽  
Rogier F Kievit ◽  
Gideon B Valstar ◽  
Arno W Hoes ◽  
Evelien E Van Riet ◽  
...  
Keyword(s):  
Heart Failure ◽  
High Risk ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Preserved Ejection Fraction ◽  
Men And Women ◽  
Ventricular Diastolic Dysfunction

Background The prevalence of undetected left ventricular diastolic dysfunction is high, especially in the elderly with comorbidities. Left ventricular diastolic dysfunction is a prognostic indicator of heart failure, in particularly of heart failure with preserved ejection fraction and of future cardiovascular and all-cause mortality. Therefore we aimed to develop sex-specific diagnostic models to enable the early identification of men and women at high-risk of left ventricular diastolic dysfunction with or without symptoms of heart failure who require more aggressive preventative strategies. Design Individual patient data from four primary care heart failure-screening studies were analysed (1371 participants, excluding patients classified as heart failure and left ventricular ejection fraction <50%). Methods Eleven candidate predictors were entered into logistic regression models to be associated with the presence of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in men and women separately. Internal-external cross-validation was performed to develop and validate the models. Results Increased age and β-blocker therapy remained as predictors in both the models for men and women. The model for men additionally consisted of increased body mass index, moderate to severe shortness of breath, increased pulse pressure and history of ischaemic heart disease. The models performed moderately and similarly well in men (c-statistics range 0.60–0.75) and women (c-statistics range 0.51–0.76) and the performance improved significantly following the addition of N-terminal pro b-type natriuretic peptide (c-statistics range 0.61–0.80 in women and 0.68–0.80 in men). Conclusions We provide an easy-to-use screening tool for use in the community, which can improve the early detection of left ventricular diastolic dysfunction/heart failure with preserved ejection fraction in high-risk men and women and optimise tailoring of preventive interventions.

scholarly journals Application of the current HFA-ESC consensus guidelines on diagnosis of heart failure with preserved ejection fraction to a population referred for echocardiography

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
K Liang ◽  
R Hearse-Morgan ◽  
S Fairbairn ◽  
Y Ismail ◽  
AK Nightingale
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Diastolic Function ◽  
Global Longitudinal Strain ◽  
Diagnostic Algorithm ◽  
Left Ventricular ◽  
Lv Function ◽  
Preserved Ejection Fraction ◽  
Consensus Guidelines

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND The recent Heart Failure Association (HFA) of the European Society of Cardiology (ESC) consensus guidelines on diagnosis of heart failure with preserved ejection fraction (HFpEF) have developed a simple diagnostic algorithm for clinical use. PURPOSE To assess whether echocardiogram (echo) parameters needed to assess diastolic function are routinely collected in patients referred for assessment of heart failure symptoms. METHODS Retrospective analysis of echo referrals in January 2020 were assessed for parameters of diastolic function as per step 2 of the HF-PEFF diagnostic algorithm.  Echo images and clinical reports were reviewed. Electronic records were utilised to obtain clinical history, blood results (NT-proBNP) and demographic data. RESULTS 1330 patients underwent an echo in our department during January 2020. 83 patients were referred with symptoms of heart failure without prior history of cardiac disease; 20 patients found to have impaired left ventricular (LV) function were excluded from analysis. Of the 63 patients with possible HFpEF, HF-PEFF score was low in 18, intermediate in 33 and high in 12. Median age was 68 years (range 32 to 97 years); 25% had a BMI &gt;30. There was a high prevalence of hypertension (52%), diabetes (19%) and atrial fibrillation (40%) (cf. Table 1). Body surface area (BSA) was documented in 65% of echo reports. Most echo parameters were recorded with the exception of global longitudinal strain (GLS) and indexed LV mass (cf. image 1). NT-proBNP was recorded in only 20 patients (31.7%). 12 patients with an intermediate HF-PEFF score could have been re-categorised to a high score depending on GLS and NT-proBNP (which were not recorded). CONCLUSION More than three quarters of echoes acquired in our department obtained the relevant parameters to assess diastolic function. The addition of BSA, and inclusion of NT-proBNP, and GLS would have been additive to a third of ‘intermediate’ patients to determine definite HFpEF. Our study demonstrates that the current HFA-ESC diagnostic algorithm and HF-PEFF scoring system are easy to use, highly relevant and applicable to current clinical practice. Age &gt;70 years 29 (46.0%) Obesity (BMI &gt;30) 16 (25.4%) Diabetes 12 (19%) Hypertension 33 (52.4%) Atrial Fibrillation 25 (39.7%) ECG abnormalities 18 (28.5%) Table 1. Prevalence of Clinical Risk Factors Abstract Figure. Image 1. HFPEFF score & echo parameters

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

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.

scholarly journals Preload-corrected dynamic Starling mechanism in patients with heart failure with preserved ejection fraction

2018 ◽  
Vol 124 (1) ◽  
pp. 76-82 ◽  
Author(s):  
Michinari Hieda ◽  
Erin Howden ◽  
Shigeki Shibata ◽  
Takashi Tarumi ◽  
Justin Lawley ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Pressure ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Dynamic Modulation ◽  
Power Spectral ◽  
Ventricular Diastolic Dysfunction

The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume (SV) because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. The purpose of this study was to test whether the LVEDP-SV relationship remained impaired in heart failure with preserved ejection fraction (HFpEF) patients after normalization of LVEDP. Right heart catheterization and model-flow analysis of the arterial pressure waveform were performed while preload was manipulated using lower-body negative pressure to alter LVEDP. The DSM was compared at similar levels of LVEDP between HFpEF patients ( n = 10) and age-matched healthy controls ( n = 12) (HFpEF vs. controls: 10.9 ± 3.8 vs. 11.2 ± 1.3 mmHg, P = 1.00). Transfer function analysis between diastolic pulmonary artery pressure (PAD) representing dynamic changes in LVEDP vs. SV index was applied to obtain gain and coherence of the DSM. The DSM gain was significantly lower in HFpEF patients than in the controls, even at a similar level of LVEDP (0.46 ± 0.19 vs. 0.99 ± 0.39 ml·m−2·mmHg−1, P = 0.0018). Moreover, the power spectral density of PAD, the input variability, was greater in the HFpEF group than the controls (0.75 ± 0.38 vs. 0.28 ± 0.26 mmHg2, P = 0.01). Conversely, the power spectral density of SV index, the output variability, was not different between the groups ( P = 0.97). There was no difference in the coherence, which confirms the reliability of the linear transfer function between the two groups (0.71 ± 0.13 vs. 0.77 ± 0.19, P = 0.87). The DSM gain in HFpEF patients is impaired compared with age-matched controls even at a similar level of LVEDP, which may reflect intrinsic LV diastolic dysfunction and incompetence of ventricular-arterial coupling. NEW & NOTEWORTHY The beat-to-beat dynamic Starling mechanism (DSM), the dynamic modulation of stroke volume because of breath-by-breath changes in left-ventricular end-diastolic pressure (LVEDP), reflects ventricular-arterial coupling. Although the DSM gain is impaired in heart failure with preserved ejection fraction (HFpEF) patients, it is not clear whether this is because of higher LVEDP or left-ventricular diastolic dysfunction. The DSM gain in HFpEF patients is severely impaired, even at a similar level of LVEDP, which may reflect intrinsic left-ventricular diastolic dysfunction.

Abstract 14648: Interleukin-18 Blockade Prevents Diastolic Dysfunction in a Mouse Model of Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jessica A Regan ◽  
Adolofo G Mauro ◽  
Salvatore Carbone ◽  
Carlo Marchetti ◽  
Eleonora Mezzaroma ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Ejection Fraction ◽  
Mouse Model ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Low Dose ◽  
Preserved Ejection Fraction ◽  
Interleukin 18 ◽  
Lv Diastolic Function

Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by elevated left ventricular (LV) filling pressures due to impaired LV diastolic function. Low-dose infusion of angiotensin 2 (AT2) in the mouse induces a HFpEF phenotype without increasing blood pressure. AT2 infusion induces expression of Interleukin-18 (IL-18) in the heart. We therefore tested whether IL-18 mediated AT2-induced LV diastolic dysfunction in this model. Methods: We infused subcutaneously AT2 (0.2 mg/Kg/day) or a matching volume of vehicle via osmotic pumps surgically implanted in the interscapular space in adult wild-type (WT) male mice and IL-18 knock-out mice (IL-18KO). We also treated WT mice with daily intraperitoneal injections of recombinant murine IL-18 binding protein (IL-18bp, a naturally occurring IL-18 blocker) at 3 different doses (0.1, 0.3 and 1.0 mg/kg) or vehicle for 25 days starting on day 3. We performed a Doppler-echocardiography study before implantation and at 28 days to measure LV dimensions, mass, and systolic and diastolic function in all mice. LV catheterization was performed prior to sacrifice to measure LV end-diastolic pressure (LVEDP) using a Millar catheter. Results: AT2 induces a significant increase in isovolumetric relaxation time (IRT) and myocardial performance index (MPI) at Doppler echocardiography and elevation of LVEDP at catheterization, indicative of impaired LV diastolic function, in absence of any measurable effects on systolic blood pressure nor LV dimensions, mass, or systolic function. Mice with genetic deletion of IL-18 (IL-18 KO) or WT mice treated with IL-18bp had no significant increase in IRT, MPI or LVEDP with AT2 infusion. Conclusion: Genetic or pharmacologic IL-18 blockade prevent diastolic dysfunction in a mouse model of HFpEF induced by low dose AT2 infusion, suggesting a critical role of IL-18 in the pathophysiology of HFpEF.

scholarly journals Myocardial hypertrophy and its role in heart failure with preserved ejection fraction

2015 ◽  
Vol 119 (10) ◽  
pp. 1233-1242 ◽  
Author(s):  
Frank R. Heinzel ◽  
Felix Hohendanner ◽  
Ge Jin ◽  
Simon Sedej ◽  
Frank Edelmann
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Clinical Evidence ◽  
Mechanical Load ◽  
Contractile Function ◽  
Surrogate Marker ◽  
Left Ventricular ◽  
Structural Abnormality ◽  
Preserved Ejection Fraction

Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load, and cytokines associated with arterial hypertension, chronic kidney disease, diabetes, and other comorbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood, but may include extracellular matrix changes, vascular dysfunction, as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca2+ turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound comorbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training, on the other hand, in clinical trials improved exercise tolerance and diastolic function, but did not reduce LVH. Thus current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF.

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.

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