GDF-15: a novel biomarker of heart failure predicts short-term and long-term heart-failure rehospitalization and short-term mortality in patients with acute heart failure syndrome.

BACKGROUND: Acute heart failure (AHF) is a potentially life-threatening clinical syndrome, usually requiring hospital admission. Growth Differentiation Factor-15 (GDF-15) is a distant member of the transforming growth factor-ß. The increased expression of GDF-15 has been observed during heart failure (HF) and is associated with worse outcomes. However, the relationship between GDF-15 and AHF is not well understood with limited evidence among Thai patients. PURPOSE: Investigate the correlation between biomarker levels (measured upon admission and discharge) and short- and long-term adverse outcomes, encompassing all-cause mortality and heart-failure (HF) rehospitalization (at 30, 90, and 180 days, as well as throughout the entire follow-up duration) in individuals experiencing acute HF. METHODS: This is a prospective single-center investigation involving patients admitted for AHF. Biomarkers, including GDF-15, high-sensitivity troponin T (hsTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were assessed upon admission and discharge. Outcomes, including all-cause mortality and HF rehospitalization, were examined. Logarithmic transformations were applied to the biomarker variables for subsequent analysis. Univariate and multivariate analyses of cause-specific hazards were conducted using the Cox proportional hazards regression model, while subdistribution hazards were assessed using the Fine-Gray regression model to evaluate outcomes. RESULTS: A total of 84 patients were enrolled (mean age of 69 years, 52% females). The GDF-15 level significantly decreased during admission (median at the time of admission 6,346 pg/mL, median at the time of discharge 5,711 pg/mL; p < 0.01). All-cause mortality at 30 days and 180 days were 6.0% and 16.7%, respectively. HF rehospitalization at 30 days and 180 days were 15.5% and 28.6%, respectively. Univariate analysis showed that total orthoedema congestion score (p = 0.02) and admission GDF-15 level (p = 0.01) were associated with 30-day all-cause mortality, whereas hsTnT or NT-proBNP levels did not show significant associations. However, higher levels of NT-proBNP upon admission were associated with all-cause mortality when considering the entire follow-up period (p < 0.01). Both univariate and multivariate analyses demonstrated that lower discharge GDF-15 levels and a greater reduction in GDF-15 levels from admission to discharge were associated with a lower risk of 30-day rehospitalization. Similarly, univariate analysis revealed that a greater reduction in NT-proBNP levels from admission to discharge was associated with lower 30-day rehospitalization rates. At 180 days, a greater reduction in GDF-15 levels remained associated with lower hazards and incidence of rehospitalization. CONCLUSION: The significant decrease in Growth Differentiation Factor-15 (GDF-15) levels during hospitalization suggests its potential as a dynamic marker reflecting the course of AHF. Importantly, higher GDF-15 levels at admission were associated with an increased risk of 30-day all-cause mortality, highlighting its prognostic value in this patient population. Moreover, lower discharge GDF-15 levels, reductions in GDF-15 from admission to discharge, and decreases in NT-proBNP from admission to discharge were associated with a reduced risk of 30-day rehospitalization.

Phase II prefusion non-stabilised Covid-19 mRNA vaccine randomised study.

ChulaCov19 mRNA vaccine demonstrated promising phase 1 results. Healthy adults aged 18-59 years were double-blind randomised 4:1 to receive two intramuscular doses of ChulaCov19 50 µg or placebo. Primary endpoints were safety and microneutralization antibody against-wild-type (Micro-VNT50) at day 50. One hundred fifty adults with median (IQR) age 37 (30-46) years were randomised. ChulaCov19 was well tolerated, and most adverse events were mild to moderate and temporary. Geometric mean titres (GMT) of neutralizing titre against wild-type for ChulaCov19 on day 50 were 1367 IU/mL. T-cell IFN-γ-ELISpot showed the highest responses at one week (Day29) after dose 2 then gradually declined. ChulaCov19 50 µg is well tolerated and elicited high neutralizing antibodies and strong T-cell responses in healthy adults.Trial registration number: ClinicalTrials.gov Identifier NCT04566276, 28/09/2020.

Enhanced external counterpulsation, focusing on its effect on kidney function, and utilization in patients with kidney diseases: a systematic review.

Background: Enhanced external counterpulsation (EECP) is provided by a noninvasive device positively affecting cardiovascular function via mechanisms called diastolic augmentation and systolic unloading. The renal aspects of EECP therapy have not been extensively investigated. Objectives: To assess the effect of EECP on renal function and to determine the application in patients with kidney disease. Methods: MEDLINE, EMBASE, SCOPUS, and Cochrane CENTRAL databases were searched for all studies involving EECP treatments. The title and abstract of all searched literatures were screened, and those focusing on renal outcome or conducting in kidney disease patients were selected. Results: Eight studies were included in the qualitative analysis. EECP increases stroke volume, mean arterial pressure, renal artery blood flow, renal plasma flow, glomerular filtration rate (GFR), plasma atrial natriuretic peptide, urine volume, and urinary sodium chloride excretion, but reduces the plasma concentration of renin and endothelin-1 in healthy subjects. A single session of EECP after radioactive contrast exposure could provide increased contrast clearance, and this reduces contrast-induced kidney injury in patients, irrespective of previous kidney function. Thirty-five-hour sessions of EECP treatment were illustrated to increase long-term estimated GFR in patients with chronic angina and heart failure. In cirrhotic patients, EECP fails to improve GFR and renal vascular resistance. EECP device could maintain blood pressure, decrease angina symptoms, and increase cardiac perfusion in hemodialysis patients. Conclusion: EECP treatment potentially increases renal perfusion and prevents kidney injury in several conditions. EECP possibly provides beneficial effects on hemodynamics and cardiac function in hemodialysis patients.

The decline in kidney function after heart transplantation and its impact on survival.

BACKGROUND: Evidence of decline in native renal function after heart transplantation (HTx) in the Asian population is limited. This study determined the incidence and risk factors associated with declining kidney function after HTx and its impact on survival. METHODS: A retrospective study of consecutive adult heart transplant patients was conducted in a single center between 2010 and 2020. The decline in kidney function was defined as the presence of one of the following criteria, including a ≥ 40% decline in eGFR, absolute value <15 mL/min/1.73 m2 (calculated by the CKD-EPI method), doubling of serum creatinine, or dialysis. RESULTS: A total of 79 patients (77% male, mean age 44.5 ± 11.53 years, with a mean eGFR at discharge from the heart transplant admission of 87.9 ± 25.48 mL/min/1.73 m2 ) were included. During the median follow-up of 42 months, the rate of decline in eGFR was 3.9 mL/min/1.73 m2 per year, with a cumulative probability of decline in kidney function of 22% at 1 year and 43% at 5 years. The need for dialysis was 2.5% at 1 year and 5% at 5 years. The decline in kidney function within 1 year after discharge (hazard ratio (HR), 22.24; p = .007) and pre-HTx diabetes mellitus (DM) (HR, 8.99; p = .034) were independently associated with the need for dialysis. Post-HTx dialysis predicted all-cause mortality (HR, 4.47; p = .017). CONCLUSIONS: Approximately 20% of HTx patients developed a decline in kidney function within 1 year after discharge. These individuals and pre-HTx DM patients needed preventive measures to prevent progression to chronic dialysis, which impacted survival. (thaiclinicaltrials.org number, TCTR20230620004).

Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial.

OBJECTIVE: To compare the efficacy of curcumin versus omeprazole in improving patient reported outcomes in people with dyspepsia. DESIGN: Randomised, double blind controlled trial, with central randomisation. SETTING: Thai traditional medicine hospital, district hospital, and university hospitals in Thailand. PARTICIPANTS: Participants with a diagnosis of functional dyspepsia. INTERVENTIONS: The interventions were curcumin alone (C), omeprazole alone (O), or curcumin plus omeprazole (C+O). Patients in the combination group received two capsules of 250 mg curcumin, four times daily, and one capsule of 20 mg omeprazole once daily for 28 days. MAIN OUTCOME MEASURES: Functional dyspepsia symptoms on days 28 and 56 were assessed using the Severity of Dyspepsia Assessment (SODA) score. Secondary outcomes were the occurrence of adverse events and serious adverse events. RESULTS: 206 patients were enrolled in the study and randomly assigned to one of the three groups; 151 patients completed the study. Demographic data (age 49.7±11.9 years; women 73.4%), clinical characteristics and baseline dyspepsia scores were comparable between the three groups. Significant improvements were observed in SODA scores on day 28 in the pain (-4.83, -5.46 and -6.22), non-pain (-2.22, -2.32 and -2.31) and satisfaction (0.39, 0.79 and 0.60) categories for the C+O, C, and O groups, respectively. These improvements were enhanced on day 56 in the pain (-7.19, -8.07 and -8.85), non-pain (-4.09, -4.12 and -3.71) and satisfaction (0.78, 1.07, and 0.81) categories in the C+O, C, and O groups, respectively. No significant differences were observed among the three groups and no serious adverse events occurred. CONCLUSION: Curcumin and omeprazole had comparable efficacy for functional dyspepsia with no obvious synergistic effect. TRIAL REGISTRATION NUMBER: TCTR20221208003.

High-Sensitivity Troponins and Subclinical Coronary Atherosclerosis Evaluated by Coronary Calcium Score Among Older Asians Living With Well-Controlled Human Immunodeficiency Virus.

Background: Elevated levels of high-sensitivity cardiac troponin (hs-cTn) are suggestive of myocardial cell injury and coronary artery disease. We explored the association between hs-cTn and subclinical arteriosclerosis using coronary artery calcification (CAC) scoring among 337 virally suppressed patients with human immunodeficiency virus (HIV) who were ≥50 years old and without evidence of known coronary artery disease. Methods: Noncontrast cardiac computed tomography and blood sampling for hs-cTn, both subunit I (hs-cTnI) and subunit T (hs-cTnT), were performed. The relationship between CAC (Agatston score) and serum hs-cTn levels was analyzed using Spearman correlation and logistic regression models. Results: The patients, of whom 62% were male, had a median age of 54 years and had been on antiretroviral therapy for a median of 16 years; the CAC score was >0 in 50% of patients and ≥100 in 16%. Both hs-cTn concentrations were positively correlated with the Agatston score, with correlation coefficients of 0.28 and 0.27 (P < .001) for hs-cTnI and hs-cTnT, respectively. hs-cTnI and hs-cTnT concentrations of ≥4 and ≥5.3 pg/mL, respectively, provided the best performance for discriminating patients with Agatston scores ≥100, with a sensitivity and specificity of 76% and 60%, respectively, for hs-cTnI and 70% and 50% for hs-cTnT. In multivariable logistic regression analysis, each log unit increase in hs-cTnI level was independently associated with increased odds of having an Agatston score ≥100 (odds ratio, 2.83 [95% confidence interval, 1.69-4.75]; P <.001). Although not an independent predictor, hs-cTnT was also associated with an increased odds of having an Agatston score ≥100 (odds ratio, 1.58 [95% confidence interval, .92-2.73]; P = .10). Conclusions: Among Asians aged ≥50 years with well-controlled HIV infection and without established cardiovascular disease, 50% had subclinical arteriosclerosis. Increasing hs-cTnI and hs-cTnT concentrations were associated with an increased risk of severe subclinical arteriosclerosis, and hs-cTn may be a potential biomarker to detect severe subclinical arteriosclerosis.

Self-enhancement lateral flow immunoassay for COVID-19 diagnosis.

Equipment-free colorimetric-based lateral flow immunoassay (LFIA) is the most convenient and popular tool for various applications, including diagnostic tools requiring high sensitivity for the detection of pathogens. Thus, improvements and developments of LFIA are constantly being reported. Herein, we enriched the sensitivity of LFIA using the gold enhancement principle, emphasizing needlessly complicated apparatus, only one step for the strip test operation, and typical time incubation (15 min) process. Self-enhanced LFIA was then executed for subsequent flows by overlapping the additionally enhanced pad composed of gold ions and reducing agent on the conjugate pad and the sample pad. Self-enhanced LFIA was performed to detect SARS-CoV-2 antigens in saliva. The obtained result depicted that the achieved sensitivity was up to tenfold compared with that of conventional LFIA by visual measurements. The detection limits of self-enhanced LFIA detecting nucleocapsid protein antigens in the saliva sample was 0.50 and 0.10 ng/mL employed by naked eye detection and calibration curve-based calculation, respectively. When the proposed device was applied to 207 human saliva samples, the diagnostic performance presented a 96.10 % sensitivity and 99.23 % specificity. This self-enhanced LFIA could be implemented in large-scale production and demonstrates higher sensitivity with effortless use, which meets the requirements for point-of-care testing and on-field mass screening.

Metabolic-Associated Fatty Liver Disease (MAFLD) is associated with immune activation, increased epicardial fat volume, and steatohepatitis among people with HIV in a Thai cohort.

INTRODUCTION: A change in terminology from fatty liver disease to metabolic-associated fatty liver disease (MAFLD), along with modified diagnostic criteria, was proposed in 2020, and data regarding MAFLD burden in people living with HIV are limited. We investigated associations between MAFLD and immune activation, cardiovascular disease (CVD) risks including epicardial fat volume, and steatohepatitis in an Asian cohort. METHODS: We evaluated CVD risk (epicardial fat tissue, coronary artery calcium [CAC] score, and 10-year atherosclerotic CVD [ASCVD] score) in people living with HIV aged >50 years. Individuals with excessive alcohol consumption and viral hepatitis infections were excluded. MAFLD diagnosis was based on 2020 International Consensus criteria. Non-alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis was defined as FibroScan-aspartate aminotransferase (FAST) score ≥0.67 and >0.35. Multivariate logistic regression models were used to investigate factors associated with MAFLD and NASH with significant activity and liver fibrosis. RESULTS: The median age was 54 years (interquartile range [IQR] 52-60) and current CD4 count was 613 (IQR 467-804) cells/mm3 . A total of 37% were female, and most (98%) people living with HIV were virally suppressed. The prevalence of MAFLD and non-alcoholic fatty liver disease was 35% and 38%, respectively. In multivariate analyses, higher body mass index, albumin, epicardial fat volume, and liver stiffness were significantly associated with MAFLD. A higher CD4/CD8 ratio was associated with a lower risk of MAFLD. People with HIV with MAFLD had higher odds of having NASH with significant activity and liver fibrosis (adjusted odds ratio 3.3; 95% confidence interval 1.6-6.6), and similar associations were also observed among different MAFLD categories. CONCLUSIONS: The complex relationship between MAFLD and immune activation, steatohepatitis, and epicardial fat tissue suggests an increased risk of advanced liver disease and CVDs beyond the traditional risk factors in people living with HIV with fatty liver disease.

Factors associated with bleeding events from enoxaparin used for patients with acute coronary syndrome.

BACKGROUND: Low molecular weight heparins (LMWHs) are the mainstay of treatment for acute coronary syndrome (ACS). However, bleeding, the main side effect, is associated with prolonged hospitalization and mortality. Therefore, assessment of the incidence of bleeding and associated risk factors is crucial in developing an appropriate treatment plan to prevent bleeding. METHODS: A retrospective cohort study was conducted in patients with ACS admitted to a university hospital in Bangkok, Thailand between 2011 and 2015 and received enoxaparin. To estimate the incidence of bleeding events, patients were followed up for 30 days from the first enoxaparin dose. Multiple logistic regression was used to determine factors associated with bleeding events. RESULTS: From a total of 602 patients, the incidence of bleeding was 15.8%, of which 5.7% involved major bleeding. The risk factors for any form of bleeding were aged at least 65 years (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.18 to 3.36), history of bleeding (OR, 3.79; 95% CI, 1.24 to 11.55), and history of oral anticoagulant exposure (OR, 4.73; 95% CI, 1.74 to 12.86). CONCLUSION: ACS patients treated with enoxaparin had an increased risk of bleeding if they were aged 65 years or older, had a history of bleeding events, and had a history of taking oral anticoagulants.

Immunogenicity of a fractional or full third dose of AZD1222 vaccine or BNT162b2 messenger RNA vaccine after two doses of CoronaVac vaccines against the Delta and Omicron variants.

OBJECTIVES: The study aimed to compare the immunogenicity and safety of fractional (half) third doses of heterologous COVID-19 vaccines (AZD1222 or BNT162b2) to full doses after the two-dose CoronaVac and when boosting after three different extended intervals. METHODS: At 60-<90, 90-<120, or 120-180 days intervals after the two-dose CoronaVac, participants were randomized to full-dose or half-dose AZD1222 or BNT162b2, followed up at day 28, 60, and 90. Vaccination-induced immune responses to Ancestral, Delta, and Omicron BA.1 strains were evaluated by antispike, pseudovirus, and microneutralization and T cell assays. Descriptive statistics and noninferiority cut-offs were reported as geometric mean concentration or titer and concentration or titer ratios comparing baseline to day 28 and day 90 and different intervals. RESULTS: No safety concerns were detected. All assays and intervals showed noninferior immunogenicity between full doses and half doses. However, full-dose vaccines and/or longer 120-180-day intervals substantially improved the immunogenicity (measured by antispike or measured by pseudotyped virus neutralizing titers 50; P <0.001). Seroconversion rates were over 90% against the SARS-CoV-2 strains by all assays. Immunogenicity waned more quickly with half doses than full doses but remained high against the Ancestral or Delta strains. Against Omicron, the day 28 immunogenicity increased with longer intervals than shorter intervals for full-dose vaccines. CONCLUSION: Immune responses after day 28 when boosting at longer intervals after the two-dose CoronaVac was optimal. Half doses met the noninferiority criteria compared with the full dose by all the immune assays assessed.

Primary isolated right ventricular failure after heart transplantation: prevalence, right ventricular characteristics, and outcomes.

To determine the prevalence, right ventricular (RV) characteristics, and outcomes of primary isolated RV failure (PI-RVF) after heart transplant (HTX). PI-RVF was defined as (1) the need for mechanical circulatory support post-transplant, or (2) evidence of RVF post-transplant as measured by right atrial pressure (RAP) > 15 mmHg, cardiac index of < 2.0 L/min/m2 or inotrope support for < 72 h, pulmonary capillary wedge pressure < 18 mmHg, and transpulmonary gradient < 15 mmHg with pulmonary systolic pressure < 50 mmHg. PI-RVF can be diagnosed from the first 24-72 h after completion of heart transplantation. A total of 122 consecutive patients who underwent HTX were reviewed. Of these, 11 were excluded because of secondary causes of graft dysfunction (GD). PI-RVF was present in 65 of 111 patients (59%) and 31 (48%) met the criteria for PGD-RV. Severity of patients with PI-RVF included 41(37%) mild, 14 (13%) moderate, and 10 (9%) severe. The median onset of PI-RVF was 14 (0-49) h and RV recovery occurred 5 (3-14) days after HTX. Severe RV failure was a predictor of 30-day mortality (HR 13.2, 95% CI 1.6-124.5%, p < 0.001) and post-transplant dialysis (HR 6.9, 95% CI 2.0-257.4%, p = 0.001). Patients with moderate PI-RVF had a higher rate of 30-day mortality (14% vs. 0%, p = 0.014) and post-operative dialysis (21% vs. 2%, p = 0.016) than those with mild PI-RVF. Among patients with mild and moderate PI-RVF, patients who did not meet the criteria of PGD-RV had worsening BUN/creatinine than those who met the PGD-RV criteria (p < 0.05 for all). PI-RVF was common and can occur after 24 h post-HTX. The median RV recovery time was 5 (2-14) days after HTX. Severe PI-RVF was associated with increased rates of 30-day mortality and post-operative dialysis. Moderate PI-RVF was also associated with post-operative dialysis. A revised definition of PGD-RV may be needed since patients who had adverse outcomes did not meet the criteria of PGD-RV.

Association of Phenotypic Aging Marker with comorbidities, frailty and inflammatory markers in people living with HIV.

BACKGROUND: Aging characteristics in people living with HIV (PLWH) are heterogeneous, and the identification of risk factors associated with aging-related comorbidities such as neurocognitive impairment (NCI) and frailty is important. We evaluated predictors of novel aging markers, phenotypic age (PhenoAge) and phenotypic age acceleration (PAA) and their association with comorbidities, frailty, and NCI. METHODS: In a cohort of PLWH and age- and sex-matched HIV-negative controls, we calculated PhenoAge using chronological age and 9 biomarkers from complete blood counts, inflammatory, metabolic-, liver- and kidney-related parameters. PAA was calculated as the difference between chronological age and PhenoAge. Multivariate logistic regression models were used to identify the factors associated with higher (>median) PAA. Area under the receiver operating characteristics curve (AUROC) was used to assess model discrimination for frailty. RESULTS: Among 333 PLWH and 102 HIV-negative controls (38% female), the median phenotypic age (49.4 vs. 48.5 years, p = 0.54) and PAA (- 6.7 vs. -7.5, p = 0.24) was slightly higher and PAA slightly less in PLWH although this did not reach statistical significance. In multivariate analysis, male sex (adjusted odds ratio = 1.68 [95%CI = 1.03-2.73]), current smoking (2.74 [1.30-5.79]), diabetes mellitus (2.97 [1.48-5.99]), hypertension (1.67 [1.02-2.72]), frailty (3.82 [1.33-10.93]), and higher IL-6 levels (1.09 [1.04-1.15]), but not HIV status and NCI, were independently associated with higher PAA. PhenoAge marker discriminated frailty better than chronological age alone (AUROC: 0.75 [0.66-0.85] vs. 0.65 [0.55-0.77], p = 0.04). In the analysis restricted to PLWH, PhenoAge alone predicted frailty better than chronological age alone (AUROC: 0.7412 vs. 0.6499, P = 0.09) and VACS index (AUROC: 0.7412 vs. 0.6811, P = 0.34) despite not statistically significant. CONCLUSIONS: While PLWH did not appear to have accelerated aging in our cohort, the phenotypic aging marker was significantly associated with systemic inflammation, frailty, and cardiovascular disease risk factors. This simple aging marker could be useful to identify high-risk PLWH within a similar chronological age group.

Outcomes and predictors of one-year mortality in patients hospitalized with Acute Heart Failure.

Background: Registries of patients hospitalized with acute heart failure (AHF) provided useful description of characteristics and outcomes. However, a contemporary registry which provides sufficient evidence on outcomes after discharge is needed. Objective: The study aims to identify 1-year clinical outcomes and prognostic predictors of patients hospitalized with AHF. Method: This is a retrospective registry which enrolled patients who were hospitalized due to a principal diagnosis of AHF in a tertiary care center in Thailand between July 2017 and June 2019. Baseline characteristics and hospital courses between the deceased patients and the survivors at 1 year were compared. Prognostic predictors for 1-year mortality were analyzed using Cox regression model. Results: A total of 759 patients were enrolled (mean age of 68.9 ± 15 years, 49.8% men, mean ejection fraction of 47.1 ± 19.2%, 55.7% heart failure reduced ejection fraction (HFrEF)). Among these, 40.7% had no history of heart failure. The in-hospital and 1-year mortality was 5.8% and 21.5%, respectively. Patients with HFrEF had lower 1-year mortality compared to those without (HR = 0.57, p = 0.04). Age ≥ 70 years, the history of heart failure, prior heart failure hospitalization, cerebrovascular accident (CVA), reactive airway disease, cancer, length of stay > 10 days and NT-proBNP ≥ 10,000 pg/mL were associated with higher 1-year mortality (p < 0.05). The multivariate analysis showed age, CVA and NT-proBNP were independent predictors. Conclusion: Patients with AHF had high mortality after discharge. Patients with poor prognostic predictors, such as elderly, may benefit from continuous care. The study is the most recent registry of patients with AHF in Thailand.

Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial.

Effective mRNA SARS-CoV-2 vaccines are available but need to be stored in freezers, limiting their use to countries that have appropriate storage capacity. ChulaCov19 is a prefusion non-stabilized SARS-CoV-2 spike-protein-encoding, nucleoside-modified mRNA, lipid nanoparticle encapsulated vaccine that we report to be stable when stored at 2-8 °C for up to 3 months. Here we report safety and immunogenicity data from a phase I open-label, dose escalation, first-in-human trial of the ChulaCov19 vaccine (NCT04566276). Seventy-two eligible volunteers, 36 of whom were aged 18-55 (adults) and 36 aged 56-75 (elderly), were enroled. Two doses of vaccine were administered 21 d apart at 10, 25 or 50 µg per dose (12 per group). The primary outcome was safety and the secondary outcome was immunogenicity. All three dosages of ChulaCov19 were well tolerated and elicited robust dose-dependent and age-dependent B- and T-cell responses. Transient mild/moderate injection site pain, fever, chills, fatigue and headache were more common after the second dose. Four weeks after the second dose, in the adult cohort, MicroVNT-50 geometric mean titre against wild-type SARS-CoV-2 was 848 (95% CI, 483-1,489), 736 (459-1,183) and 1,140 (854-1,522) IU ml-1 at 10, 25 and 50 µg doses, respectively, versus 285 (196-413) IU ml-1 for human convalescent sera. All dose levels elicited 100% seroconversion, with geometric mean titre ratios 4-8-fold higher than for human convalescent sera (P < 0.01), and high IFNγ spot-forming cells per million peripheral blood mononuclear cells. The 50 µg dose induced better cross-neutralization against Alpha, Beta, Gamma and Delta variants than lower doses. ChulaCov19 at 50 µg is well tolerated and elicited higher neutralizing antibodies than human convalescent sera, with strong T-cell responses. These antibodies cross-neutralized four variants of concern. ChulaCov19 has proceeded to phase 2 clinical trials. We conclude that the mRNA vaccine expressing a prefusion non-stabilized spike protein is safe and highly immunogenic.

Higher prevalence of QTc interval prolongation among virologically suppressed older people with HIV.

OBJECTIVE: To assess the prevalence, and factors associated with QTc interval prolongation, among 383 virologically suppressed people with HIV (PWH), without evidence of cardiovascular disease and active opportunistic infections in Thailand. DESIGN: Cross-sectional study. METHODS: Resting 12-lead digital ECGs were performed in 2019. QT interval corrected for heart rate (QTc) >450 ms in males and >460 ms in females was defined as QTc interval prolongation. We used multivariable logistic regression to investigate factors associated with QTc interval prolongation. RESULTS: Mean (standard deviation) age was 56 (5.5) years and 42% were female. The median current CD4+ was 619 (interquartile range [IQR] 487, 769) cells/mm 3 . The median duration of antiretroviral therapy (ART) was 11.9 (IQR 7.1-16.1) years. Commonly used ART were rilpivirine (37.9%), efavirenz (20.1%), atazanavir/ritonavir (15.7%), lopinavir/ritonavir (12.3%) and dolutegravir (5%). The prevalence of QTc interval prolongation was 22.7%. In multivariable analysis, older age (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12, P  = 0.005), female sex (OR 1.69, 95% CI 1.01-2.82, P  = 0.046) and increasing BMI (OR 1.08, 95% CI 1.01-1.15, P  = 0.03) were associated with QTc interval prolongation. With every 1-year increase in age, the odds of QTc interval prolongation increased by 7%. CONCLUSIONS: In this well-suppressed aging Asian HIV cohort, the prevalence of QTc interval prolongation was relatively high, and associated with increasing age, female sex, and higher BMI. For PLWH with these characteristics, QTc interval should be monitored before and after initiating any medications known to prolong QTc intervals, to prevent fatal cardiac arrhythmias.

Association of Drug-Metabolizing Enzyme and Transporter Gene Polymorphisms and Lipid-Lowering Response to Statins in Thai Patients with Dyslipidemia.

PURPOSE: Statins are increasingly widely used in the primary and secondary prevention of cardiovascular disease. However, there is an inter-individual variation in statin response among patients. The study aims to determine the association between genetic variations in drug-metabolizing enzyme and transporter (DMET) genes and lipid-lowering response to a statin in Thai patients with hyperlipidemia. PATIENTS AND METHODS: Seventy-nine patients who received statin at steady-state concentrations were recruited. Serum lipid profile was measured at baseline and repeated after 4-month on a statin regimen. The genotype profile of 1936 DMET markers was obtained using Affymetrix DMET Plus genotyping microarrays. RESULTS: In this DMET microarray platform, five variants; SLCO1B3 (rs4149117, rs7311358, and rs2053098), QPRT (rs13331798), and SLC10A2 (rs188096) showed a suggestive association with LDL-cholesterol-lowering response. HDL-cholesterol-lowering responses were found to be related to CYP7A1 gene variant (rs12542233). Seven variants, SLCO1B3 (rs4149117, rs7311358, and rs2053098); SULT1E1 (rs3736599 and rs3822172); and ABCB11 (rs4148768 and rs3770603), were associated with the total cholesterol-lowering response. One variant of the ABCB4 gene (rs2109505) was significantly associated with triglyceride-lowering response. CONCLUSION: This pharmacogenomic study identifies new genetic variants of DMET genes that are associated with the lipid-lowering response to statins. Genetic polymorphisms in DMET genes may impact the pharmacokinetics and lipid-lowering response to statin. The validation studies confirmations are needed in future pharmacogenomic studies.

Higher epicardial fat in older adults living with HIV with viral suppression and relationship with liver steatosis, coronary calcium and cardiometabolic risks.

OBJECTIVES: HIV infection is associated with ectopic fat deposition, which leads to chronic inflammation and cardiometabolic dysregulation. We assessed the epicardial adipose tissue (EAT) volume and its associated factors among people with HIV (PWH). DESIGN: A cross-sectional study. METHODS: We conducted a cross-sectional study among PWH aged at least 50 years and age-matched and sex-matched HIV-negative older individuals in Bangkok, Thailand. Participants underwent a noncontrast, cardiac computed tomography (CT) scan to assess coronary artery calcium (CAC) score and EAT between March 2016 and June 2017. Multivariate linear regression analyses were used to investigate HIV-related factors, cardiac and metabolic markers associated with EAT volume. RESULTS: Median age was 55 years [interquartile range (IQR) 52-60] and 63% were men. Median duration of antiretroviral therapy (ART) was 16 years with 97% had HIV-1 RNA less than 50 copies/ml and median CD4 + cell count of 617 cells/µl. Median EAT volume was significantly higher in PWH [99 (IQR 75-122) cm 3 ] than HIV-negative individuals [93 (IQR 69-117) cm 3 ], P  = 0.022. In adjusted model, factors associated with EAT volume included male sex ( P  = 0.045), older age ( P  < 0.001), abnormal waist circumference ( P  < 0.001) and HOMA-IR ( P  = 0.01). In addition, higher CAC score was independently associated with EAT volume. Higher mean EAT volume was seen in PWH with severe liver steatosis than those without steatosis ( P  = 0.018). In adjusted PWH-only model, duration of HIV was significantly associated with higher EAT volume ( P  = 0.028). CONCLUSION: In an aging cohort, PWH had higher EAT volume than HIV-negative controls. EAT was also independently associated with central fat accumulation, insulin resistance, liver steatosis and CAC score.

Thyrotoxicosis-Induced Cardiomyopathy Complicated by Refractory Cardiogenic Shock Rescued by Extracorporeal Membrane Oxygenation.

BACKGROUND Thyrotoxicosis-induced cardiomyopathy is a rare but potentially life-threatening condition that occurs in less than 1% of thyrotoxic individuals. Severely impaired left ventricular systolic function can lead to an overt cardiogenic shock requiring mechanical circulatory support. Abnormal cardiac structure and function are potentially reversible after achievement of euthyroid state. CASE REPORT We present a case of a 53-year-old patient with a diagnosis of thyrotoxicosis-induced acute heart failure. Transthoracic echocardiography revealed a mildly dilated left ventricle and severely reduced systolic function with ejection fraction of 20%. Subsequently, the patient developed refractory cardiogenic shock, which was treated with the use of extracorporeal membrane oxygenation (ECMO). After early intensive treatments to achieve euthyroid state, the clinical status significantly improved. Echocardiography prior to discharge showed improvement of left ventricular ejection fraction to 40%. The anti-TSH receptor was positive and Grave's disease was diagnosed. The patient eventually returned to baseline functional status and could return to basic activities of daily living without limitations. CONCLUSIONS Early diagnosis of cardiac involvement in patients with thyrotoxicosis is critical. Promptly delivered intensive treatment with rapid achievement of euthyroid state can reverse cardiac dysfunction and improve patient outcomes. The use of ECMO can be considered as a "bridge" to recovery of cardiac function after restoration of euthyroid state.

Circulating growth differentiation factor-15 as a novel biomarker in heart transplant.

AIMS: This study aimed to examine (i) whether circulating growth differentiation factor-15 (GDF-15) is associated with acute cellular cardiac allograft rejection (ACR); (ii) a longitudinal trend of GDF-15 after heart transplantation; and (iii) the prognostic value of GDF-15 in predicting a composite outcome of severe primary graft dysfunction (PGD) and 30 day mortality post-transplant. METHODS AND RESULTS: Serum samples were collected before heart transplantation and at every endomyocardial biopsy (EMB) post-heart transplantation in de novo transplant patients. A total of 60 post-transplant serum samples were matched to the corresponding EMBs. Seven (12%) were considered International Society for Heart Lung Transplantation Grade 1R ACR, and one (2%) was identified as Grade 2R ACR. GDF-15 levels in patients with ACR were not different from those in the non-rejection group (6230 vs. 6125 pg/mL, P = 0.27). GDF-15 concentration gradually decreased from 8757 pg/mL pre-transplant to 5203 pg/mL at 4 weeks post-transplant. The composite adverse outcome of PGD and 30 day mortality was significantly associated with increased post-operative GDF-15 (odds ratio: 40; 95% confidence interval: 2.01-794.27; P = 0.005) and high inotrope score post-transplant (odds ratio: 18; 95% confidence interval: 1.22-250.35; P = 0.01). CONCLUSIONS: Circulating GDF-15 concentration was markedly elevated in patients with end-stage heart failure and decreased after heart transplantation. GDF-15 was significantly associated with post-transplant PGD and mortality. A lack of association between ACR and GDF-15 did not support routine use of GDF-15 as a biomarker to detect ACR. However, GDF-15 may be potentially useful to determine heart transplant recipients at high risk for adverse post-transplant outcomes. We suggest that GDF-15 levels in recipient serum can provide risk stratification for severe PGD including death during post-operative period. This novel biomarker may serve to inform and guide timely interventions against severe PGD and adverse outcomes during the first 4 weeks after transplantation. Further studies to support the utility of GDF-15 in heart transplantation are required.

Home Blood Pressure Control and Drug Prescription Patterns among Thai Hypertensives: A 1-Year Analysis of Telehealth Assisted Instrument in Home Blood Pressure Monitoring Nationwide Pilot Project.

BACKGROUND: Several interventions have been proposed to improve hypertension control with various outcomes. The home blood pressure (HBP) measurement is widely accepted for assessing the response to medications. However, the enhancement of blood pressure (BP) control with HBP telemonitoring technology has yet to be studied in Thailand. OBJECTIVE: To evaluate the attainment of HBP control and drug prescription patterns in Thai hypertensives at one year after initiating the TeleHealth Assisted Instrument in Home Blood Pressure Monitoring (THAI HBPM) nationwide pilot project. METHODS: A multicenter, prospective study enrolled treated hypertensive adults without prior regular HBPM to obtain monthly self-measured HBP using the same validated, oscillometric telemonitoring devices. The HBP reading was transferred to the clinic via a cloud-based system, so the physicians can adjust the medications at each follow-up visit on a real-life basis. Controlled HBP is defined as having HBP data at one year of follow-up within the defined target range (<135/85 mmHg). RESULTS: A total of 1,177 patients (mean age 58 ± 12.3 years, 59.4% women, 13.1% with diabetes) from 46 hospitals (81.5% primary care centers) were enrolled in the study. The mean clinic BP was 143.9 ± 18.1/84.3 ± 11.9 mmHg while the mean HBP was 134.4 ± 15.3/80.1 ± 9.4 mmHg with 609 (51.8%) patients having HBP reading <135/85 mmHg at enrollment. At one year of follow-up after implementing the HBP telemonitoring, 671 patients (57.0%) achieved HBP control. Patients with uncontrolled HBP had a higher prevalence of dyslipidemia and greater waist circumference than the controlled group. The majority of uncontrolled patients were still prescribed only one (36.0%) or two drugs (34.4%) at the end of the study. The antihypertensive drugs were not uptitrated in 136 (24%) patients with uncontrolled HBP at baseline. Calcium channel blocker was the most prescribed drug class (63.0%) followed by angiotensin-converting enzyme inhibitor (44.8%) while the thiazide-type diuretic was used in 18.9% of patients with controlled HBP and 16.4% in uncontrolled patients. CONCLUSION: With the implementation of HBP telemonitoring, the BP control rate based on HBP analysis was still low. This is possibly attributed to the therapeutic inertia of healthcare physicians. Calcium channel blocker was the most frequently used agent while the diuretic was underutilized. The long-term clinical benefit of overcoming therapeutic inertia alongside HBP telemonitoring needs to be validated in a future study.