Effects of switching from sacubitril/valsartan to valsartan alone on plasma levels of natriuretic peptides and myocardial remodeling in heart failure with reduced ejection fraction

Abstract Background We examined the effect of switching from angiotensin receptor-neprilysin inhibitor (ARNI) to angiotensin-receptor blocker (ARB) on plasma levels of natriuretic peptides and myocardial remodeling. Methods This is a prospective study that included 11 patients with heart failure (HF) treated with ARNI. The patients were divided into two groups: 5 patients who continued treatment with sacubitril/valsartan 194/206 mg/day (ARNI-continue group) and 6 patients who were switched to valsartan 160 mg/day (ARB-switch group). The primary endpoint was percent change (%Change) in plasma A-, B-, and N-terminal pro-B-type natriuretic peptide (ANP, BNP, and NT-proBNP) levels from the baseline to week 24. The secondary endpoint was the change in echocardiographic parameters related to myocardial remodeling from the baseline to week 24. Results ANP levels in the ARB-switch group significantly decreased (from 1155.7 ± 592.6 pg/mL to 231.6 ± 233.8 pg/mL, p = 0.035), whereas those in the ARNI-continue group were not significant (p = 0.180). The %Change of decrease in ANP levels was significantly greater in the ARB-switch group than the ARNI-continue group (− 76.9% vs. −9.1%, p = 0.009). BNP levels were not significantly different between the baseline and week 24 in both groups. NT-proBNP levels in the ARB-switch group increased from 1185.3 ± 835.6 pg/mL to 1515.2 ± 1213.5 pg/mL, although the changes were not statistically significant (p = 0.345). The %Change of increase in NT-proBNP levels was significantly greater in the ARB-switch group than the ARNI-continue group (57.9% vs. 17.3%, p = 0.016). In the ARB-switch group, there was a significant increase in left ventricular (LV) end-systolic volume (from 41.3 ± 24.1 mL/m2 to 71.4 ± 8.8 mL/m2, p = 0.043) and LV peak-systolic wall stress (from 187.0 ± 42.7 × 103 dynes/cm2 to 279.7 ± 34.1 × 103 dynes/cm2, p = 0.012) from the baseline to week 24 and a trend toward a decrease in LV ejection fraction (p = 0.080). In the ARNI-continue group, no differences in echocardiographic parameters were observed from the baseline to week 24. Conclusion Switching from ARNI to ARB may worsen HF due to returning to myocardial remodeling induced by a sustained decline in ANP levels

Low-density lipoprotein cholesterol lowering by adding ezetimibe to statin is associated with improvement of postprandial hyperlipidemia in diabetic patients with coronary artery disease

Objective and methods: We investigated the hypothesis that serum low-density lipoprotein cholesterol (LDL-C) reduction by ezetimibe is associated with the improvement in postprandial hyperlipidemia by performing an oral fat loading test before and 24 weeks after ezetimibe treatment in diabetic (n = 29) and non-diabetic (n = 30) male patients with coronary artery disease (CAD). Results: Serum LDL-C levels were significantly reduced by ezetimibe in both groups (diabetic, from 120.3 ± 39.4 to 79.5 ± 23.2 mg/dL, p < 0.001; non-diabetic, from 98.2 ± 41.7 to 76.7 ± 29.2 mg/dL, p < 0.001), and the mean reduction in serum LDL-C was greater in diabetic than non-diabetic patients (−32.0 vs. −19.0%, p = 0.004). The area under the curve (AUC) for triglyceride (TG) and remnant-like particle cholesterol (RLP-C) decreased significantly in both groups. When compared with the reduction before and after treatment in AUC of TG (∆AUC0–6 h TG) and RLP-C (∆AUC0–6 h RLP-C), they were significantly greater in diabetic than non-diabetic patients (∆AUC0–6h TG, −28.9 vs. −12.2%, p = 0.028; ∆AUC0–6h RLP-C, −27.8 vs. −12.3%, p = 0.007). In diabetic patients, ∆AUC0–6 h TG and ∆AUC0–6 h RLP-C in the highest tertile of serum LDL-C reduction were significantly greater than those in the lowest tertile (∆AUC0-6h TG, −34.1 vs. −20.9%, p = 0.012; ∆AUC0-6h RLP-C, −34.5 vs. −15.1%, p = 0.024). Conclusions: These findings suggest that serum LDL-C reduction by ezetimibe might be associated with the improvement of postprandial hyperlipidemia in diabetic patients with CAD

Sudden failure of ventricular pacing and recovery in a patient with cardiac sarcoidosis

A 76-year-old woman with sarcoidosis who had an implantable pacemaker for complete atrioventricular block was admitted with syncope. Electrocardiogram revealed ventricular pacing failure, and a marked rise in the ventricular pacing threshold. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) indicated increased uptake of FDG in the ventricular septum. Three days after steroid therapy, the ventricular pacing threshold reverted to normal, and FDG-PET showed decreased FDG uptake in the ventricular septum. In this case report, we demonstrate that a sudden deterioration in the ventricular pacing threshold due to worsening cardiac sarcoidosis can be reversed with early steroid therapy

Validation of a drug-based score in advanced urothelial carcinoma treated with pembrolizumab

: Aim: To validate a 'drug score' that stratifies patients receiving immunotherapy based on concomitant medications (antibiotics/proton pump inhibitors/corticosteroids) in urothelial carcinoma (UC). Materials &amp; methods: We assessed oncological outcomes according to the drug score in 242 patients with advanced UC treated with pembrolizumab. Results: The drug score classified patients into three risk groups with significantly different survivals. Heterogeneous treatment effect analyses showed that the primary cancer site (bladder UC [BUC] or upper-tract UC [UTUC]) significantly affected the prognostic capability of the drug score; it significantly correlated with survivals in BUC, while there were no such correlations in UTUC. Conclusion: A drug score was examined in advanced UC treated with pembrolizumab and was validated in BUC but not in UTUC