Uremic cardiomyopathy is a common complication in chronic kidney disease (CKD) patients, accounting for a high mortality rate. Several mechanisms have been proposed to link CKD and cardiac alterations; however, the early cardiac modifications that occur in CKD that may trigger cardiac remodeling and dysfunction remain largely unexplored. Here, in a mouse model of CKD induced by 5/6 nephrectomy, we first analyzed the early transcriptional and inflammatory changes that occur in the heart. Five days after 5/6 nephrectomy, RNA-sequencing showed the upregulation of 54 genes in the cardiac tissue of CKD mice and the enrichment of biological processes related to immune system processes. Increased cardiac infiltration of T-CD4+ lymphocytes, myeloid cells, and macrophages during early CKD was observed. Next, since CC chemokine ligand-8 (CCL8) was one of the most upregulated genes in the heart of mice with early CKD, we investigated the effect of acute and transient CCL8 inhibition on uremic cardiomyopathy severity. An increase in CCL8 protein levels was confirmed in the heart of early CKD mice. CCL8 inhibition attenuated the early infiltration of T-CD4+ lymphocytes and macrophages to the cardiac tissue, leading to a protection against chronic cardiac fibrotic remodeling, inflammation and cardiac dysfunction induced by CKD. Altogether, our data show the occurrence of transcriptional and inflammatory changes in the heart during the early phases of CKD and identify CCL8 as a key contributor to the early cardiac inflammatory state that triggers further cardiac remodeling and dysfunction in uremic cardiomyopathy.

Early inflammatory changes and CC chemokine ligand-8 upregulation in the heart contribute to uremic cardiomyopathy

Protein acetylation in cardiac aging.

Myocardial extracellular matrix remodeling with the development of pacing induced congestive heart failure contributory mechanisms.

Background: N-terminal pro-brain natural peptide (NT-pro-BNP) is a well-established biomarker of tissue congestion and has prognostic value in patients with heart failure (HF). Nonetheless, there is scarce evidence on its predictive capacity for HF re-admission after an acute coronary syndrome (ACS). We performed a prospective, single-center study in all patients discharged after an ACS. HF re-admission was analyzed by competing risk regression, taking all-cause mortality as a competing event. Results are presented as sub-hazard ratios (sHR). Recurrent hospitalizations were tested by negative binomial regression, and results are presented as incidence risk ratio (IRR). Results: Of the 2133 included patients, 528 (24.8%) had HF during the ACS hospitalization, and their pro-BNP levels were higher (3220 pg/mL vs. 684.2 pg/mL; p < 0.001). In-hospital mortality was 2.9%, and pro-BNP was similarly higher in these patients. Increased pro-BNP levels were correlated to increased risk of HF or death during the hospitalization. Over follow-up (median 38 months) 243 (11.7%) patients had at least one hospital readmission for HF and 151 (7.1%) had more than one. Complete revascularization had a preventive effect on HF readmission, whereas several other variables were associated with higher risk. Pro-BNP was independently associated with HF admission (sHR: 1.47) and readmission (IRR: 1.45) at any age. Significant interactions were found for the predictive value of pro-BNP in women, diabetes, renal dysfunction, STEMI and patients without troponin elevation. Conclusions: In-hospital determination of pro-BNP is an independent predictor of HF readmission after an ACS.

https://www.mdpi.com/2077-0383/10/8/1653/pdf

Predictive Value of Pro-BNP for Heart Failure Readmission after an Acute Coronary Syndrome

Objective To explore the effect of dapagliflozin on the myocardial fibrosis and the levels of inflammatory factors in heart failure patients. Methods 60 patients with T2DM who were diagnosed as acute left heart failure or acute exacerbation of chronic left heart failure in the Department of Cardiology of our hospital from November 1, 2020, to December 31, 2021, during hospitalization were the study subjects. According to the treatment regimen, they were divided into the experimental group (EG) which received dapagliflozin and conventional drugs and the control group (CG) which received conventional drugs, with 30 cases in each group to compare and analyze the clinical indicators such as myocardial fibrosis and inflammatory factors. Results The levels of TNF-α, IL-1β, IL-6, and hs-CRP in the two groups were decreased gradually after treatment, and the levels of TNF-α, IL-1β, IL-6, and hs-CRP in the EG were visibly lower compared with those in the CG at week 4 of treatment (P < 0.05). The cardiac function evaluation of patients showed that the levels of LVEF and LVEDD in both groups were gradually improved after treatment, with a significant difference from the fourth week. In other words, compared with the CG, the LVEF level in the EG was obviously higher (P < 0.05), the LVEDD level was distinctly lower (P < 0.05), and the levels of ST2, BNP, and MCP-1 in the EG were clearly lower at week 4 of treatment (P < 0.05) with a statistical significance in difference. Conclusion Dapagliflozin has a definite curative effect in heart failure patients with type 2 diabetes mellitus, which can effectively reduce the inflammatory response of patients and inhibit the myocardial fibrosis, and has a potential value in improving cardiac function and promoting prognosis.

/pdf/effect-of-dapagliflozin-on-indicators-of-myocardial-fibrosis-3qrrx51k.pdf

Effect of Dapagliflozin on Indicators of Myocardial Fibrosis and Levels of Inflammatory Factors in Heart Failure Patients

Focusing Heart Failure Research on Myocardial Fibrosis to Prioritize Translation

Congestive heart failure and abnormal diastolic function occur both in dilated cardiomyopathy and cardiac hypertrophy However, the mechanisms causing these abnormalities appear to be strikingly different Changes in diastolic function have been ascribed to alterations in ventricular load, the development of left ventricular (LV) hypertrophy, changes in myocardial blood flow, factors extrinsic to the cardiocyte such as the extracellular matrix and factors intrinsic to the cardiocyte such as the intracellular cytoskeleton, calcium concentration, and rate of sequestration, and myofilament response to calcium While any or all of the alterations may be present in a given pathologic entity, recent studies have suggested that in dilated cardiomyopathies, diastolic dysfunction may be most closely related to changes in ventricular loading conditions, systolic contractile state, and ventricular remodeling [1–4]

Francis G. Spinale

Papers

Focusing Heart Failure Research on Myocardial Fibrosis to Prioritize Translation

Diastolic Dysfunction in Tachycardia-Induced Heart Failure