Predictive value of heart rate variability on long-term mortality in end-stage kidney disease on hemodialysis.

Autonomic disturbance is common in end-stage kidney disease (ESKD). Heart rate variability (HRV) is a useful tool to assess autonomic function. We aimed to evaluate the predictive value of HRV on all-cause mortality and explore the proper timing of HRV assessment. This prospective cohort study enrolled 163 ESKD on hemodialysis patients from April-December 2018. HRV measurements were recorded ten minutes before hemodialysis, four hours during hemodialysis, and ten minutes after hemodialysis. Clinical parameters and all-cause mortality were recorded. Cox-proportional hazard regression was used for statistical analysis. After a median follow up of 40 months, 37 (22.7%) patients died. Post-dialysis HRV parameters including higher very low frequency (VLF) (hazard ratio [HR], 0.881; 95%confidence interval [CI], 0.828-0.937; p<0.001), higher normalized low frequency (nLF) (HR, 0.950; 95%CI, 0.917-0.984; p = 0.005) and higher LF/HF ratio (HR, 0.232; 95%CI, 0.087-0.619; p = 0.004) were the independent predictors associated with lower risk for all-cause mortality. Higher post-dialysis normalized high frequency (nHF) increased risk of mortality (HR, 1.051; 95%CI, 1.015-1.089; p = 0.005). HRV parameters at pre-dialysis and during dialysis were not predictive for all-cause mortality. The area under receiver operating characteristic curve (AuROC) of VLF for survival was highest compared to other HRV parameters at post-dialysis period (AuROC 0.71; 95% CI; 0.62-0.79; p<0.001). In conclusion, post-dialysis HRV parameters predicted all-cause mortaliy in ESKD. VLF measured at post-dialysis exhibited best predictive value for survival in chronic hemodialysis patients

Effect of renin angiotensin system inhibitors on long-term major cardiovascular outcomes in patients with high atherosclerotic cardiovascular risk

Abstract The advantage of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) in patients with preserved LV systolic function is uncertain. We aimed to investigate the effects of ACEI/ARB in high atherosclerotic risk patients without overt heart failure (HF) on long-term major cardiovascular outcomes (MACEs). The Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) registry is a prospective, multicenter, observational, longitudinal study of Thai patients with high atherosclerotic risk. The patients with ejection fraction < 50% were excluded. Among 8513 recruited patients, there were 4246 patients included into final analysis after propensity score matching. At 5-years follow-up, Cox regression analysis showed that ACEI/ARB was significantly associated with reduced risk of all-cause mortality or non-fatal myocardial infarction, non-fatal stroke and HF hospitalization (HR 0.82, 95% CI 0.70–0.96, P = 0.011). The benefit was driven by the reduced all-cause mortality and HF. Subgroup analysis demonstrated that ACEI/ARB decreased risk of long-term MACEs in patients with diabetes (HR 0.77, 95% CI 0.63–0.94, P = 0.011) and patients not taking statin (HR 0.57, 95% CI 0.40–0.82, P = 0.002). We demonstrated that the use of ACEI/ARB was associated with reduced risk of long-term MACEs in a large cohort of high atherosclerotic risk patients. Reduction of all-cause mortality and HF were likely the main contributors to the benefit of ACEI/ARB

Aspirin for primary prevention in patients with high cardiovascular risk: insights from CORE-Thailand registry

Abstract Aspirin may be considered for primary prevention in non-elderly patients with high cardiovascular risk. However, contemporary management aimed at aggressive cardiovascular risk factor control may alter benefit-risk ratio of aspirin. Therefore, we aimed to examine the effect of aspirin for primary prevention on the long-term MACEs in a large cohort registry. Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) registry is a prospective, multicenter, observational, longitudinal study of Thai patients with high atherosclerotic risk. Patients with established atherosclerotic cardiovascular diseases were excluded. Among 4259 patients with multiple cardiovascular risk factors, 1945 (45.7%) patients used aspirin. After propensity score matching, there were 3228 patients remained in post-matching analysis. During the median follow-up period of 58.2 months, we demonstrated that aspirin use increased risk of long-term MACEs in pre-matching cohort (unadjusted HR 1.76, 95% CI 1.43–2.17, P < 0.001) and post-matching cohort (HR 1.66 (1.31–2.10), P < 0.001). In addition, patients taking aspirin had a higher risk of bleeding than non-aspirin users in pre-matching cohort (unadjusted HR 2.28, 95% CI 1.09–4.75, P = 0.028). We demonstrated that aspirin was associated with increased risk of long-term MACEs in patients with multiple cardiovascular risk factors. Due to the non-randomized design, our results should be interpreted with caution

Effects of metformin and donepezil on the prevention of doxorubicin-induced cardiotoxicity in breast cancer: a randomized controlled trial

Abstract Doxorubicin (DOX) causes deleterious cardiotoxicity. We aimed to investigate the protective roles of metformin and donepezil against DOX-induced cardiotoxicity. In this randomized-controlled trial, 143 female breast cancer patients were enrolled. Metformin (n = 43), donepezil (n = 52), or placebo (n = 48) were prescribed during DOX treatment. The primary endpoint was a proportion of patients with high sensitivity troponin-I (hsTnI) more than the 99th percentile value (> 15.6 ng/L) after DOX treatment. The secondary outcomes were the changes in the hsTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and peripheral blood mononuclear cells analysis for mitochondrial respiration. Baseline characteristics were similar between the groups. The primary endpoint occurred in 58.54% of metformin group, 76.92% in donepezil group, and 69.77% in placebo group (p = 0.215). The level of hsTnI increased after receiving DOX with subsequent decline in LVEF and GLS. Metformin and donepezil did not attenuate hsTnI elevation, LVEF or GLS reduction. There was no significant change in NT-proBNP level. Mitochondrial respiratory dysfunction was observed in the placebo and donepezil groups. However, metformin preserved mitochondrial respiration during DOX therapy. In conclusion, co-treatment with metformin or donepezil did not prevent myocardial injury. Metformin had a favorable mitochondrial outcome and warranted future studies

Additional file 1 of Changes in blood metabolomes as potential markers for severity and prognosis in doxorubicin-induced cardiotoxicity: a study in HER2-positive and HER2-negative breast cancer patients

Additional file 1: Fig. S1. Study protocol. Fig. S2. Absolute changes in LVEF (A), LF/HF ratio (B), plasma troponin I (C), plasma NT-proBNP (D), and cellular oxidative stress in peripheral blood mononuclear cells (E) at 2 weeks after completion of doxorubicin treatment in HER2-positive versus HER2-negative breast cancer patients. Table S1. Lists of eighty-five targeted plasma metabolomes and the chromatographic technique for each metabolome. Table S2. Patients’ characteristics at baseline. Table S3: Baseline plasma metabolome levels in HER2-positive versus HER2-negative breast cancer patients. Table S4. Plasma metabolome levels in HER2-positive breast cancer patients at baseline versus at 2 weeks after completion of doxorubicin treatment. Table S5. Plasma metabolome levels in HER2-negative breast cancer patients at baseline versus at 2 weeks after completion of doxorubicin treatment. Table S6. The top five plasma metabolomes that their alterations were significantly correlated with the changes in each cardiac parameter of HER2-positive and HER2-negative breast cancer patients at 2 weeks after completion of doxorubicin treatment