Predictive value of Systematic Coronary Risk Evaluation 2-Diabetes risk model and arterial stiffness for cardiovascular events in the Asian population with type 2 diabetes mellitus.

AIMS/INTRODUCTION: Individuals with diabetes are at high risk of developing cardiovascular events. The present study investigated the predictive value of the cardio-ankle vascular index (CAVI) when added to the Systematic Coronary Risk Evaluation 2-Diabetes (SCORE2-Diabetes) risk algorithm to predict cardiovascular events in the Asian population. MATERIALS AND METHODS: The SCORE2-Diabetes risk was assessed in 1,502 patients with diabetes, aged 40-69 years. Then, we further stratified each 10-year risk category with a CAVI value of 9.0. The primary outcomes (composite of all causes of death, myocardial infarction, stroke and hospitalization for heart failure) were assessed over 5 years. RESULTS: The mean age of the population was 59.8 ± 6.4 years. The proportion of 10-year risk according to the SCORE2-Diabetes risk of low, moderate, high and very high risk identified at 7.2, 30.0, 27.2 and 35.6%, respectively. The mean CAVI value was 8.4 ± 1.4, and approximately 35.4% of the patients had CAVI ≥9.0. The SCORE2-Diabetes risk algorithm independently predicted the primary outcomes in patients with diabetes (hazard ratio 1.18, 95% confidence interval [CI] 1.13-1.22), whereas CAVI did not (hazard ratio 1.03, 95% CI 0.89-1.18). The C-index for the primary outcomes of the SCORE2-Diabetes risk algorithm alone was 0.72 (95% CI 0.67-0.77). The combination of SCORE2-Diabetes and CAVI, both in the continuous value and risk groups, did not improve discrimination (C-index 0.72, 95% CI 0.67-0.77 and 0.68, 95% CI 0.64-0.74, respectively). CONCLUSIONS: Adding the CAVI to the SCORE2-Diabetes risk algorithm did not improve individual risk stratification in patients with diabetes.

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.

BACKGROUND: We aimed to compare the changes in blood metabolomes and cardiac parameters following doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients. Additionally, the potential roles of changes in blood metabolomes as severity and prognostic markers of doxorubicin-induced cardiotoxicity were determined. METHODS: HER2-positive (n = 37) and HER2-negative (n = 37) breast cancer patients were enrolled. Cardiac function assessment and blood collection were performed at baseline and 2 weeks after completion of doxorubicin treatment in all patients, as well as at three months after completion of doxorubicin treatment in HER2-negative breast cancer patients. Blood obtained at all three-time points was processed for measuring cardiac injury biomarkers. Blood obtained at baseline and 2 weeks after completion of doxorubicin treatment were also processed for measuring systemic oxidative stress and 85 metabolome levels. RESULTS: Cardiac injury and systolic dysfunction 2 weeks after completion of doxorubicin treatment were comparable between these two groups of patients. However, only HER2-negative breast cancer patients exhibited increased systemic oxidative stress and cardiac autonomic dysfunction at this time point. Moreover, 33 and 29 blood metabolomes were altered at 2 weeks after completion of doxorubicin treatment in HER2-positive and HER2-negative breast cancer patients, respectively. The changes in most of these metabolomes were correlated with the changes in cardiac parameters, both at 2 weeks and 3 months after completion of doxorubicin treatment. CONCLUSIONS: The changes in blood metabolomes following doxorubicin treatment were dependent on HER2 status, and these changes might serve as severity and prognostic markers of doxorubicin-induced cardiotoxicity. TRIAL REGISTRATION: The study was conducted under ethical approval from the Institutional Review Board of the Faculty of Medicine, Chiang Mai University (Registration number: MED-2563-07001; Date: April 28, 2020). The study also complied with the Declaration of Helsinki.

Mitochondrial dysfunction is associated with the severity of liver fibrosis in patients after the Fontan operation.

The gold standard for determining the severity of liver disease in Fontan patients is now liver biopsy. Since it is an invasive procedure, this study determined the possibility of applying mitochondrial function from isolated peripheral blood mononuclear cells (PBMCs) as a non-invasive indicator of liver fibrosis. Fontan patients (n = 37) without known liver disease were analysed cross-sectionally. Patients were classified according to their histology using the METAVIR score as follows; F0/F1-no/mild fibrosis; F2-moderate fibrosis; and F3/F4-cirrhosis. Peripheral blood mononuclear cells were assessed for mitochondrial activity and apoptosis. This study did not find any significant differences in cardiac function among the groups according to liver histology. Interestingly, our findings indicated a significant decrease in maximal respiration and spare respiratory capacity, in both the moderate (F2) and cirrhosis (F3/F4) groups compared with the group without significant fibrosis (F0/F1). Moreover, the cirrhosis group exhibited higher levels of apoptosis and lower levels of live cells, compared with both the moderate and no significant fibrosis groups. In conclusion, the degree of liver fibrosis in Fontan patients is strongly correlated with mitochondrial dysfunction in PBMCs. Mitochondrial function and apoptosis could potentially serve as novel markers for tracking the progression of liver fibrosis in these patients.

Reference-range of arterial stiffness by cardio-ankle vascular index in normal pregnancy.

OBJECTIVE: To establish the arterial stiffness, represented by the cardio-ankle vascular index (CAVI) at various gestational ages among low-risk pregnant women. The second objective is to construct the reference range of mean arterial pressure and maternal heart rate during pregnancy. METHODS: This cross-sectional study was conducted on low risk pregnant Thai women, meeting the following inclusion criteria: 1) singleton pregnant women aged 18 years old or over; 2) gestational age between 11 and 40 weeks; 3) low-risk pregnancy without any underlying medical diseases; and 4) known final pregnancy outcomes. Pregnancy-induced hypertension, gestational diabetes and fetal growth restriction were excluded. The mean CAVI, mean arterial pressure (MAP), and heart rate were measured at each gestational age. RESULTS: A total of 329 measurements for each parameter were available for analysis. CAVI was significantly correlated with gestational age with the best fitted model: CAVI = 6.952 - 0.076(GA) + 0.001(GA)2; SD = 0.742 (R2 = 0.049; p-value < 0.001). The maternal age and pre-pregnancy BMI were correlated with CAVI. CAVI gradually increased with maternal age and decreased with increasing body mass index (BMI). The MAP and heart rate of normal pregnancy in each gestation were conducted. CONCLUSION: The reference range of CAVI in normal pregnancies as a function of gestational age and the model for predicting CAVI based on multiple regression analysis are constructed and presented. These reference ranges may be useful in predicting risk of cardiovascular disorders during pregnancy.

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

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.

Prognostic Value of Ankle-Brachial Index in Prediction of Cardiovascular Events in an Asian Population with Multiple Atherosclerotic Risk Factors.

We aimed to evaluate the incremental prognostic value after incorporation of the ankle-brachial index (ABI) into the 10-year pool cohort equation (PCE) risk model in patients with multiple risk factors (MRFs). A total of 4332 MRFs patients were divided into 2 groups as ABI ≤.9 or >.9. The primary outcome was hard cardiovascular events (hCVE: including cardiovascular death, myocardial infarction, or ischemic stroke) over a median follow-up of 36 months. The Cox proportional hazards survival model, C-statistic, and net reclassification indices (NRI) were used. The occurrence of the primary outcome in the ABI ≤.9 group (3.7%) was significantly greater than in the ABI > .9 group (1.3%), P < .001. ABI is an independent predictor of hCVE in addition to the variables in the standard risk model (age, gender, and smoking status). ABI modestly improved the C-index when added to the PCE risk model (PCE .70 vs ABI+PCE .74). The addition of ABI to the PCE risk model did not significantly improve the classification of patients (NRI -.029; 95% CI: -.215 to .130). Despite ABI being one of the independent predictors of hCVE, integration of ABI into the PCE model did not improve the efficacy of risk reclassification in patients with MRFs.

Screening modalities for the diagnosis of Fontan-associated liver disease: evidence from the past for future development.

Approximately 70,000 patients who have undergone the Fontan operation worldwide survive into adulthood, however the majority of these patients are faced with long-term post-operative complications due to specific hemodynamic changes. Fontan-associated liver disease (FALD) is a challenging complication characterized by various spectra. Of these, liver congestion and liver fibrosis potentially lead to cirrhosis and liver nodules. The most serious condition associated with the development of liver nodules is hepatocellular carcinoma. Various non-invasive modalities including blood tests, ultrasound scans of the upper abdomen, ultrasound elastography of the liver, computed tomography scans, magnetic resonance imaging and magnetic resonance elastography of the liver have been used as alternatives to liver biopsies for FALD assessment in post-Fontan patients. To date, a detailed understanding of the pathophysiology and natural history of these patients, and the most appropriate modality for the effective investigation of this condition is incomplete. In this comprehensive review, reports regarding the currently available screening modalities used in the detection of FALD are summarized and discussed. The findings of this review, including identification of any current knowledge gaps, can pave the way for the development of effective future strategies in the surveillance and ultimately the treatment of post-Fontan patients.

The cardio-ankle vascular index as a predictor of adverse pregnancy outcomes.

OBJECTIVE: To assess the association between maternal hemodynamic parameters; cardio-ankle vascular index (CAVI), representing arterial stiffness; mean arterial pressure (MAP), uterine artery pulsatility index (Ut-PI), and adverse pregnancy outcomes including preeclampsia (PE), fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). METHODS: A prospective cohort study was conducted on low-risk pregnancies. All were serially measured for the mean CAVI, MAP, and Ut-PI for four times at gestational age (GA) 11-14, 18-22, 28-32, and after 36 weeks. Also, the women were followed up for pregnancy outcomes, focusing on PE, FGR, and GDM. RESULTS: Of 335 recruited cases meeting the inclusion criteria, 16 cases developed PE, 24 cases had FGR, and 83 cases had GDM. Compared to the non-PE group, women developing PE had a significant increase in CAVI at 18-22, 28-32, and after 36 weeks (P-value = 0.021, 0.003, and <0.001, respectively), a significant increase in MAP at all of the four periods (P-value < 0.001, for all periods), and a significant increase in Ut-PI during GA 18-22 weeks (P-value = 0.021). In pregnancies with FGR, there was a significant increase of CAVI at GA 18-22, 28-32 and after 36 weeks (P-value = 0.012, 0.015, and 0.004, respectively), an increase in Ut-PI in all gestational periods (P-value < 0.05) but no changes of MAP throughout pregnancy. In GDM, the three parameters were not significantly different from those in the non-GDM group in all of the four periods. CAVI could predict PE and FGR with AUC of 0.655-0.835 and 0.673-0.760, respectively. CAVI added predictive values when combined with MAP or Ut-PI. CONCLUSION: Increased CAVI, like MAP and Ut-PI, can be used as a predictor of PE and FGR but not GDM. Also, it has an added predictive value when combined with MAP or Ut-PI.

Mechanisms and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs: Insights from in vitro, in vivo, and clinical studies in breast cancer patients.

Breast cancer is the most frequently occurring cancer among women worldwide. Human epidermal growth factor receptor 2 (HER2 or ErbB2) is overexpressed in between 20 and 25% of invasive breast cancers and is associated with poor prognosis. Trastuzumab, an anti-ErbB2 monoclonal antibody, reduces cancer recurrence and mortality in HER2-positive breast cancer patients, but unexpectedly induces cardiac dysfunction, especially when used in combination with anthracycline-based chemotherapy. Novel approved ErbB2-targeting drugs, including lapatinib, pertuzumab, and trastuzumab-emtansine, also potentially cause cardiotoxicity, although early clinical studies demonstrate their cardiac safety profile. Unfortunately, the mechanism involved in causing the cardiotoxicity is still not completely understood. In addition, the use of preventive interventions against trastuzumab-induced cardiac dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, remain controversial. Thus, this review aims to summarize and discuss the evidence currently available from in vitro, in vivo, and clinical studies regarding the mechanism and potential interventions associated with the cardiotoxicity of ErbB2-targeted drugs.

Enhancing Knowledge and Self-Care Behavior of Heart Failure Patients by Interactive Educational Board Game.

Objective: To evaluate the effects of an educational board game on heart failure (HF) patients' knowledge and self-care behavior. Methods: In this randomized controlled study with a follow-up of 3 months, 76 patients with HF with reduced ejection fraction, who had been enrolled in our multidisciplinary HF program, were divided into two groups. During their follow-up appointment at the HF clinic usually 2 weeks after discharge, the interventional group participated in an HF educational board game conducted in Thai language, while the control group received the usual care including standard education. The primary outcome was the change of score achieved in the specialized HF knowledge and self-care behavior assessment. Results: In the intervention group, the knowledge and self-care behavior significantly improved (all P < 0.001), whereas both scores were unchanged in the control group (P = 0.09 and P = 0.21). Mean score change for knowledge and self-care behavior showed greater improvement in the intervention group when compared with the control group (P < 0.002 and P < 0.006). Conclusion: Participation in an interactive educational board game resulted in an increase in the HF patients' knowledge and self-care behavior. Practice Implications: An interactive educational board game may be used as an alternative educational tool in HF patients.

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic.

Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications.

Automatic cardiac T2* relaxation time estimation from magnetic resonance images using region growing method with automatically initialized seed points.

BACKGROUND AND OBJECTIVE: Heart failure due to iron-overload cardiomyopathy is one of the main causes of mortality. The cardiomyopathy is reversible if intensive iron chelation treatment is done in time, but the diagnosis is often delayed because the cardiac iron deposition is unpredictable and the symptoms are lately detected. There are many ways to assess iron-overload. However, the widely used and approved method is by using MRI which is performed by calculating the T2* (T2-star). In order to compute the T2* value, the region of interest (ROI) is manually selected by an expert which may require considerable time and skills. The aim of this work is hence to develop the cardiac T2* measurement by using region growing algorithm for automatically segmenting the ROI in cardiac MR images. Mathematical morphologies are also used to reduce some errors. METHODS: Thirty MR images with free-breathing and respiratory-trigger technique were used in this work. The segmentation algorithm yields good results when compared with the manual segmentation performed by two experts. RESULTS: The averages of positive predictive value, the sensitivity, the Hausdorff distance, and the Dice similarity coefficient are 0.76, 0.84, 7.78 pixels, and 0.80 when compared with the two experts' opinions. The T2* values were carried out based on the automatically segmented ROI's. The mean difference of T2* values between the proposed technique and the experts' opinion is about 1.40ms. CONCLUSIONS: The results demonstrate the accuracy of the proposed method in T2* value estimation. Some previous methods were implemented for comparisons. The results show that the proposed method yields better segmentation and T2* value estimation performances.

The mirror image of Gerbode defect: acquired right ventricular-to-left atrial communication.

: Left ventricular-to-right atrial communication, known as Gerbode defect, is rare. However, right ventricular-to-left atrial communication is much rarer. We present a case of a middle-aged woman with a past history of primum atrial septal defect surgery who presented with dyspnea on exertion. Echocardiographic studies showed dehiscence of the pericardial atrial patch from atrioventricular junction, causing a right ventricular-to-left atrial communication with bidirectional shunt. A three-dimensional transesophageal echocardiographic reconstruction revealed a defect of septal tricuspid valve leaflet. In atrioventricular septal defect, the apical displacement of mitral valve insertion, together with a congenital defect of septal tricuspid valve leaflet, contributes to predisposing conditions for this communication.