Search

Unchalee Permsuwan,1 Arintaya Phrommintikul,2 Voratima Silavanich1 1Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand; 2Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, ThailandCorrespondence: Voratima SilavanichDepartment of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Suthep Road, Muang District, Chiang Mai 50200, ThailandTel +66 89-430-6510Fax +66 5-322-2741Email voratima.silavanich@gmail.comBackground: Cardiac resynchronization therapy (CRT) improves symptoms and survival in patients with heart failure (HF). However, the CRT devices are costly and can impose a significant burden to the relatively constrained health budgets of middle-income countries such as Thailand. The aim of this study was to analyze the cost-effectiveness of CRT in combination with optimal medical therapy (OMT) relative to patients with OMT alone.Methods: A two-component model was used to analyze lifetime costs and quality-adjusted life-years (QALYs) from a healthcare perspective. Clinical inputs were mostly obtained from meta-analysis of landmark trials. All cost-related data, risk of non-cardiovascular death and readmission rate were based on Thai HF data. Costs and QALYs were discounted at 3%. Findings were reported as an incremental cost-effectiveness ratio (ICER). A variety of sensitivity analyses were also performed.Results: CRT plus OMT costs more than OMT (123,279 vs 11,165 THB or 3,972.90 vs 359.81 USD), and is more effective (3.57 QALYs vs 2.49 QALYs), yielding an ICER of 104,325 THB per QALY (3,362.07 USD per QALY). CRT was cost-effective at the Thai willingness to pay threshold of 160,000 THB per QALY (5,156.30 USD per QALY). The results were sensitive to cost of CRT maintenance.Conclusion: The use of CRT was associated with a cost-effectiveness ratio below generally accepted benchmarks for therapeutic interventions of 160,000 THB per QALY (5,156.30 USD per QALY). This suggests that the clinical benefits of CRT can be achieved at a reasonable cost in Thai HF patients.Keywords: cost-effectiveness, quality-adjusted life-years, cardiac resynchronization therapy, heart failure, Thailand

Abstract Prior research has demonstrated an association between sodium-glucose cotransporter 2 (SGLT2) inhibitor and a reduced incidence of atrial fibrillation (AF). Given the established link between mitochondrial dysfunction and AF, this study aimed to explore the impact of SGLT2 inhibitors on AF burden and plausible antiarrhythmic mechanisms in patients with cardiovascular implantable electronic devices (CIEDs). Patients with atrial high-rate episodes (AHREs) detected by CIEDs were randomized to receive either 10 mg of dapagliflozin or a placebo for 3 months. AF burdens were quantified via CIEDs interrogations as AHREs duration, percentage, and number of episodes at baseline and after 3 months of treatment. Mitochondrial parameters, cellular oxidative stress, and norepinephrine levels were measured in peripheral blood mononuclear cells (PBMCs). A total of 54 patients with CIEDs were enrolled in the study. Among them, 36 patients (66.7%) had a history of clinical AF, and 9 patients (16.7%) had diabetes mellitus. After 3 months of the assigned treatment, the median longest AHRE duration decreased similarly in both the dapagliflozin and placebo groups (-77.0 vs. -162.0 min, p = 0.442). Clinical AF, as opposed to subclinical AF, was independently linked to decreased basal respiration and adenosine triphosphate (ATP) production. Although the changes in AHREs burden over the 3 months did not significantly differ between the dapagliflozin and placebo groups, dapagliflozin significantly decreased the number of AHREs per month by 2.2 episodes among patients with clinical AF, whereas the placebo group experienced an increase of 0.6 episodes (p = 0.048). Additionally, dapagliflozin significantly reduced cellular oxidative stress (from 26840 to 18164 arbitrary units, p = 0.049) and improved mitochondrial spare respiratory capacity (SRC) percentage (from 166 to 202%, p = 0.016) in patients with clinical AF. Dapagliflozin did not significantly reduce the longest AHRE duration in patients with CIED. However, in the subgroup of patients with clinical AF, dapagliflozin reduced the number of AHREs potentially via reduction of cellular oxidative stress and enhancement of mitochondrial function. The study protocol was registered at the Thai Clinical Trials Registry (TCTR identification number TCTR20210315003) on March 15, 2021.

Abstract The gut microbiota metabolite trimethylamine-N-oxide (TMAO)—derived from dietary phosphatidylcholine—is mechanistically linked to cardiovascular disease (CVD) and increased cardiovascular risk. This study examined the relationship between fasting plasma TMAO levels and 5-year all-cause mortality in a cohort of patients at high risk of cardiovascular events (CORE-Thailand Registry). Of the 134 patients, 123 (92%) had established cardiovascular disease, and 11 (8%) had multiple risk factors. Fasting plasma TMAO levels were measured using nuclear magnetic resonance spectroscopy. Within this prospective cohort study, the median TMAO was 3.81 μM [interquartile range (IQR) 2.89–5.50 μM], with a mean age of 65 ± 11 years; 61% were men, and 39.6% had type II diabetes. Among 134 patients, 65 (49%) were identified as the high-TMAO group (≥ 3.8 μM), and 69 (51%) were identified as the low-TMAO group (

Abstract 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.

Surarong Chinwong,1 Jayanton Patumanond,2 Dujrudee Chinwong,1 John Joseph Hall,3 Arintaya Phrommintikul4 1Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand; 2Center of Excellence in Applied Epidemiology, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; 3Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health, University of Newcastle, Callaghan, NSW, Australia; 4Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Background: For investigations into cardiovascular disease, the first problematic event (ie, nonfatal acute coronary syndrome (ACS), nonfatal stroke, or all-cause mortality) generally was considered as the primary end point; however, ACS patients often experience subsequent events, which are rarely considered. This study reports an investigation into whether achieving a low-density lipoprotein cholesterol (LDL-C) goal of

Dujrudee Chinwong,1,2 Jayanton Patumanond,3 Surarong Chinwong,1 Khanchai Siriwattana,4 Siriluck Gunaparn,5 John Joseph Hall,6 Arintaya Phrommintikul5 1Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand; 2Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 3Center of Excellence in Applied Epidemiology, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; 4Division of Medicine, Nakornping Hospital, Chiang Mai, Thailand; 5Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 6Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health, University of Newcastle, Callaghan, NSW, Australia Background: Elevated low-density lipoprotein cholesterol (LDL-C) is associated with an increased risk of cardiovascular disease or mortality; however, the LDL-C goal for therapy in acute coronary syndrome (ACS) patients is controversial and varies among guidelines. This study aimed to assess the effect of reaching an LDL-C goal of

Dujrudee Chinwong,1,2 Jayanton Patumanond,3 Surarong Chinwong,1 Khanchai Siriwattana,4 Siriluck Gunaparn,5 John Joseph Hall,6 Arintaya Phrommintikul5 1Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand; 2Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 3Center of Excellence in Applied Epidemiology, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; 4Division of Medicine, Nakornping Hospital, Chiang Mai, Thailand; 5Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 6Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health, University of Newcastle, Callaghan, NSW, Australia Background: Elevated low-density lipoprotein cholesterol (LDL-C) is associated with an increased risk of coronary artery disease. Current guidelines recommend an LDL-C target of

Background Poor adherence to chronic cardiovascular treatments can impede targeted clinical outcomes. This study estimates the potential benefits of improving adherence among patients with cardiovascular disease requiring secondary prevention in Mexico, Thailand, and China. Methods and Results We performed Markov model simulation for patients with cardiovascular disease in 3 countries from health care and societal perspectives over a lifetime horizon. Two scenarios were compared: (1) optimal adherence based on a meta‐analysis of 51 randomized controlled trials and (2) status quo. The association between adherence and cardiovascular disease outcomes derives from a dose–response meta‐analysis of 4 051 338 patients. Outcomes include the accumulated number of cardiovascular events and associated costs in 2022 US dollars, life years, and quality‐adjusted life years. Optimal adherence could prevent 42 (95% credible interval [CrI], 29–56) cardiovascular events in Mexico, 34 (95% CrI, 24–50) in Thailand, and 63 (95% CrI, 43–89) in China per 1000 patients over a lifetime. Incremental effectiveness per patient was 0.60 (95% CrI, 0.47–0.74) life‐years in Mexico, 0.68 (95% CrI, 0.37–0.94) quality‐adjusted life years in Thailand, and 0.93 (95% CrI, 0.44–1.27) quality‐adjusted life years in China. Cost savings from societal perspective amounted to $412 (95% CrI, $211–$723), $316 (95% CrI, $187–$541), and $700 (95% CrI, $355–$1144) per patient for Mexico, Thailand, and China, respectively. Findings remained cost saving in deterministic and probabilistic sensitivity analyses. Conclusions Achieving optimal adherence in patients with cardiovascular disease requiring lipid‐lowering therapy saves costs and improves health outcomes in Mexico, Thailand, and China. These findings support national health care systems implementing strategies to improve adherence in these countries.

Abstract 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.

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

Abstract Aims/Introduction High glycated hemoglobin (HbA1c) variability has been reported to be linked with cardiovascular events in type 2 diabetes patients. Only a few studies have been carried out on Asian patients. This study aimed to investigate the association of prediabetes and type 2 diabetes in Asian patients by performing a post‐hoc analysis of a multicenter, prospective, observational study. Materials and methods Data for prediabetes and type 2 diabetes patients were retrieved from a multicenter national registry entitled “CORE‐Thailand study.” The primary outcome was 4P‐MACE (major adverse cardiovascular events, including non‐fatal myocardial infarction, heart failure hospitalization, non‐fatal stroke and all‐cause death). Patients were stratified according to quartiles of HbA1c standard deviation. The Cox proportional hazards regression model was used to estimate the association of HbA1c variability with incident cardiovascular disease. Results A total of 3,811 patients with prediabetes and type 2 diabetes were included. The median follow‐up duration was 54 months. In the fully adjusted model, the highest quartile of HbA1c variability showed a statistically significant association with 4P‐MACE (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.77–4.35), fatal and non‐fatal myocardial infarction (HR 6.91, 95% CI 1.90–25.12), hospitalization for heart failure (HR 3.34, 95% CI 1.20–9.26) and all‐cause death (HR 3.10, 95% CI 1.72–5.57). All these outcomes were statistically significantly different among four quartiles of HbA1c (log‐rank P‐value

Trastuzumab, a monoclonal antibody which works against human epidermal growth factor receptor 2 (HER2), possibly causes cardiotoxicity through mitochondrial dysfunction. The usefulness of isolated peripheral blood mononuclear cells (PBMCs) in the assessment of trastuzumab-induced cardiotoxicity remains uncertain. This study aimed to determine the temporal changes in mitochondrial function, oxidative stress, and cell death in the isolated PBMCs of HER2-positive breast cancer patients during breast cancer treatment and to compare the changes with HER2-negative breast cancer patients who did not receive trastuzumab therapy. Eighteen newly diagnosed HER2-positive breast cancer women who received sequential doxorubicin and trastuzumab were consecutively recruited. Age- and gender-matched controls with HER2-negative breast cancer were selected. Echocardiography was carried out, and blood samples for the study of cardiac biomarkers and PBMCs were collected periodically during treatment. Only one patient in our cohort developed asymptomatic left ventricular dysfunction during trastuzumab treatment. However, trastuzumab following doxorubicin aggravated subclinical cardiac injury, determined by cardiac troponin and echocardiography. Cellular and mitochondrial oxidative stress in isolated PBMCs remained unchanged throughout breast cancer treatment. Regarding mitochondrial respiration, the maximal respiration and spare respiration capacity was significantly increased in controls after doxorubicin treatment but not in patients who received trastuzumab therapy. Moreover, the percentage of apoptosis and necroptosis in isolated PBMCs was dramatically decreased in the control, compared to patients with trastuzumab treatment. In conclusion, trastuzumab caused subtle myocardial injury and impaired mitochondrial respiration and cell viability in isolated PBMCs.

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

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.

Presence of left atrial (LA) fibrosis reflects underlying atrial cardiomyopathy. Interatrial block (IAB) is associated with LA fibrosis in patients with atrial fibrillation (AF). The association of IAB and LA fibrosis in the patients without history of AF is unknown. We examined association of IAB and LA fibrosis in the patients without AF history. This is a retrospective analysis of 229 patients undergoing cardiac magnetic resonance imaging (CMR). LA fibrosis was reported from spatial extent of late gadolinium enhancement of CMR. IAB was measured from 12-lead electrocardiography using digital caliper. Of 229 patients undergoing CMR, prevalence of IAB was 50.2%. Patients with IAB were older (56.9±13.9 years vs. 45.9±19.2 years, p

Purposes: Coronary artery calcium (CAC) score provides a quantification of atherosclerotic plaque within the coronary arteries. This study aimed to examine the prevalence and CAC score distribution and to evaluate the association of each CAC score classifications with major adverse cardiovascular events (MACE) in a Thai clinical cohort. Methods: This study was a retrospective observational cohort. We included patients aged above 35 years who underwent CAC score testing. The absolute and age-sex specific percentile classifications were categorized as 0, 1 to 10, 11 to 100, 101 to 400, and >400 and 0, 90th, respectively. The endpoint was MACE, including cardiovascular death, myocardial infarction, heart failure hospitalization, coronary artery revascularization procedure, and stroke. Multivariable Cox regression was used to estimate the hazard ratios. The discriminative performance between classifications were compared using Harrell's C-statistics. The agreement was assessed via Cohen's Kappa. Results: This study included 440 patients, with approximately 70% of Thai patients exhibiting a CAC score. CAC score distributed higher in male than female and increased with age. Both CAC score classification demonstrated the acceptable predictive performance. However, fair agreement was observed between classifications (Cohen's kappa 0.51, 95%CI 0.42–0.59). Within the absolute classification, a higher CAC score was associated with increased hazard ratios for MACE across stratified age-sex-specific percentile levels. In contrast, the hazard ratios for MACE did not consistently rise with higher age-sex-specific percentile CAC score when stratified by absolute CAC score levels. Conclusions: Both absolute and age-sex-specific percentile CAC score demonstrated acceptable performance in predicting MACE. However, the absolute CAC score classification may be more suitable for risk stratification within the Thai clinical cohort. Our findings offer supportive information that could inform future recommendations for CAC score testing criteria within national clinical practice guidelines.

Abstract Most of the studies about aortic valve calcium (AVC) score in aortic stenosis (AS) were based on degenerative or bicuspid AS but not rheumatic AS. We aimed to study the diagnostic accuracy of AVC score to determine severe AS in various etiologies. Adult patients diagnosed with mild to severe AS were enrolled. AVC score were identified from multi-detector computed tomography (MDCT) scan. The AVC score was highest in bicuspid AS (3211.9 (IQR (1100.0–4562.4) AU) compared to degenerative AS (1803.7 (IQR (1073.6–2550.6) AU)), and rheumatic AS (875.6 (IQR 453.3–1594.0) AU), p 2028.9AU (male) and > 1082.5AU (female) for degenerative AS, and > 2431.8AU (male) and > 1293.5AU (female) for bicuspid AS. In conclusions, AVC score is the accurate test for assessing severity in patients with degenerative and bicuspid AS but performs poorly in rheumatic AS group.

Mitochondrial dysfunction contributes significantly to the development of atrial fibrillation (AF). Conflicting data regarding the atrial pacing and the risk of AF existed, and the impact of atrial pacing on mitochondrial function remains unknown. Therefore, we sought to examine the association between atrial pacing percentage and mitochondrial function in patients with cardiovascular implantable electronic devices (CIEDs) with atrial pacing capability. This is a cross-sectional study involving 183 patients with CIEDs with atrial pacing capability. The oxidative stress and mitochondrial function were determined in peripheral blood mononuclear cells (PBMCs). Among 183 patients, 55.7% had permanent pacemakers, 7.7% had defibrillators, and 36.6% had cardiac resynchronization therapy. Mean age was 67.5 ± 14.7 yr with 51% being male. Mean left ventricular ejection fraction (LVEF) was 53.9 ± 16.8%. We demonstrated that the presence of atrial pacing above 50% correlated with higher levels of mitochondrial spared respiratory capacity (P = 0.043) and coupling efficiency (P = 0.045). After adjusting with multiple linear regression for age, sex, LVEF, history of AF, sick sinus syndrome, comorbidities, estimated glomerular filtration rate (eGFR), cardiac resynchronization therapy (CRT), and percentage of ventricular pacing, our findings revealed a statistically significant association between a higher percentage of atrial pacing and increased spared respiratory capacity (β, 0.217, P = 0.046), lower nonmitochondrial respiration (β, −0.230; P = 0.023), and proton leak (β, −0.247; P = 0.022). We demonstrated that atrial pacing enhances mitochondrial performance in PBMCs and left ventricular contractile performance in patients with CIEDs. This observation may serve as an additional support for the preventive effect of atrial pacing in the prevention of atrial arrhythmia. NEW & NOTEWORTHY: Atrial pacing enhances mitochondrial spare respiratory capacity and reduces proton leak. This finding may provide further evidence supporting the preventive role of atrial pacing in reducing the risk of atrial fibrillation in patients with cardiac implantable electronic devices. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Trastuzumab, a monoclonal antibody which works against human epidermal growth factor receptor 2 (HER2), possibly causes cardiotoxicity through mitochondrial dysfunction. The usefulness of isolated peripheral blood mononuclear cells (PBMCs) in the assessment of trastuzumab-induced cardiotoxicity remains uncertain. This study aimed to determine the temporal changes in mitochondrial function, oxidative stress, and cell death in the isolated PBMCs of HER2-positive breast cancer patients during breast cancer treatment and to compare the changes with HER2-negative breast cancer patients who did not receive trastuzumab therapy. Eighteen newly diagnosed HER2-positive breast cancer women who received sequential doxorubicin and trastuzumab were consecutively recruited. Age- and gender-matched controls with HER2-negative breast cancer were selected. Echocardiography was carried out, and blood samples for the study of cardiac biomarkers and PBMCs were collected periodically during treatment. Only one patient in our cohort developed asymptomatic left ventricular dysfunction during trastuzumab treatment. However, trastuzumab following doxorubicin aggravated subclinical cardiac injury, determined by cardiac troponin and echocardiography. Cellular and mitochondrial oxidative stress in isolated PBMCs remained unchanged throughout breast cancer treatment. Regarding mitochondrial respiration, the maximal respiration and spare respiration capacity was significantly increased in controls after doxorubicin treatment but not in patients who received trastuzumab therapy. Moreover, the percentage of apoptosis and necroptosis in isolated PBMCs was dramatically decreased in the control, compared to patients with trastuzumab treatment. In conclusion, trastuzumab caused subtle myocardial injury and impaired mitochondrial respiration and cell viability in isolated PBMCs. [ABSTRACT FROM AUTHOR]

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