Search

Background Heart failure with reduced ejection fraction (HFrEF) is a chronic disease with substantial mortality. Management of HFrEF has seen significant breakthrough after the launch of neprilysin inhibitor. The PARADIGM‐HF (Prospective Comparison of ARNI with ACEI to Determine Impacton Global Mortality and Morbidity in Heart Failure) trial showed that sacubitril/valsartan significantly reduces HFrEF mortality and the heart failure hospitalization rate. However, in patients with advanced kidney disease, who have the highest prevalence of heart failure, the efficacy and safety of sacubitril/valsartan remains uncertain. We aim to study the efficiency of sacubitril/valsartan in patients with end‐stage kidney disease. Methods and Results Heart function was screened by echocardiogram among all patients with end‐stage kidney disease in 2 hospitals. Patients with HFrEF received either sacubitril/valsartan or conventional treatment. Fifteen echocardiographic parameters were compared before and after treatment. After 1‐year sacubitril/valsartan treatment, parameters of systolic (left ventricular ejection fraction 31.3% to 45.1%, P

Background Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease. Corin converts proatrial natriuretic peptide into its active form after being activated by PCSK6 (proprotein convertase subtilisin/kexin type 6) protease. It remains unknown whether the PCSK6/corin/atrial natriuretic peptide pathway plays a role in CKD‐induced cardiomyopathy. Methods and Results Serum corin, left ventricular mass index, and corin–left ventricular mass index correlation were compared between outpatients with versus without CKD. Cardiac corin expression and activity as well as serum corin were compared between 5/6 nephrectomy CKD animal models and sham controls. The effects of indoxyl sulfate, a uremic toxin, on cardiomyocytes were examined in vitro in H9c2 cells. A total of 543 patients were enrolled in this study. Serum corin levels were elevated in patients with CKD compared with levels in patients without CKD. Serum corin levels correlated negatively with left ventricular mass index in participants without CKD, but not in patients with CKD. Compared with sham controls, CKD mice had higher serum corin levels and increased cardiac expression of corin but reduced cardiac corin conversion activity. Indoxyl sulfate stimulated corin expression while suppressing serine protease activity in H9c2 cardiomyoblasts. Lower PCSK6 expression in CKD mouse hearts and indoxyl sulfate–treated H9c2 cardiomyoblasts may explain, at least partly, the observed CKD‐associated reduction in corin activity. Conclusions In CKD, cardiac and serum levels of corin are increased, yet corin activity is suppressed. The latter may be attributable to reduced PCSK6 expression. These findings suggest that corin dysfunction may play a significant role in the pathogenesis of CKD‐associated cardiomyopathy.

BackgroundHigher circulatory corin in patients with cardiac diseases is associated with improved cardiovascular outcomes, and chronic cardiac dysfunction is a well‐known cause of progressive renal dysfunction. This study aimed to determine the role of serum corin in predicting short‐term and long‐term renal outcomes after contrast exposure in patients with suspected coronary artery disease. Methods and ResultsFour hundred one patients who had received coronary angiography were enrolled. Serum corin levels were determined before administration of contrast media. Contrast‐induced nephropathy was defined as a rise in serum creatinine of 0.5 mg/dL or a 25% increase from baseline within 48 hours after the procedure. Progressive renal dysfunction was defined as >50% decrease in estimated glomerular filtration rate after discharge. All patients were followed up for at least 1 year or until the occurrence of death after coronary angiography. Overall, contrast‐induced nephropathy occurred in 23 (5.7%) patients. During a median follow‐up of 529 days, 44 (11.0%) cases had subsequent decline in renal function. After adjustment for demographic characteristics, kidney function, traditional risk factors, and medications, lower corin level was found to be independently associated with higher risk for progressive renal dysfunction (hazard ratio, 0.23; 95% confidence interval, 0.12–0.44) but not for contrast‐induced nephropathy. This inverse correlation remained evident in patients with underlying chronic kidney disease, coronary artery disease, or heart failure. ConclusionsLower baseline serum corin was associated with higher risk of renal function decline in patients undergoing coronary angiography. Further studies are needed to verify these results.