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Background: Double coronary culprit lesions in ST-segment elevation myocardial infarction (STEMI) is uncommon. Despite successful primary percutaneous coronary intervention (PPCI) in all culprit lesions, the clinical outcome remains unfavorable and the possible factors for the outcome are not fully understood.Cases Presentation: We reported four cases of double culprit lesions STEMI underwent PPCI. Patient A, a 62 y.o. male with extensive anterior-inferior STEMI, had total occlusion (TO) at both proximal left anterior descending (LAD) and mid right coronary artery (RCA). Patient B, a 42 y.o. male with extensive anterior-inferior STEMI, had subtotal occlusion (STO) at proximal RCA and TO at proximal LAD. Both of them had RBBB ECG pattern. Patient C, a 67 y.o. male with inferior STEMI had 90% thrombus occlusion at proximal–mid LAD and TO at proximal RCA. Patient D, a 65 y.o. male with anteroseptal STEMI, had STO at proximal LAD and 80% thrombus occlusion at mid left circumflex. The cardiomyocyte infarction biomarkers increased in all patients. Although all of them underwent successful PPCI in all of culprit lesions, they suffered from acute heart failure and two of them experienced recurrent ventricular arrhythmia episodes. One of them (patient A) died two days post PPCI. He was only patient who suffering from total occlusion in LAD and RCA with TIMI thrombus 5 and experienced a total atrioventricular block post-PPCI.Conclusion: STEMI with coronary double culprits have severe clinical outcome, regardless of the successful PCI. The degree of coronary occlusions might be linked to the patient clinical outcome.

Background: Central obesity stands for the corner-stone of cardio-metabolic health, while nitric oxide (NO) is a major regulator of cardiovascular function. To day, the correlation between serum NO metabolites nitrate/nitrite and the obesity components in young adults remains elusive. Thus, this current study was conducted to know the correlation between serum NO metabolites levels and body fat percentage, waist circumference (WC) as well as body mass index (BMI) in young adults with central obesity.Materials and Methods: A cross-sectional study was conducted in Riau, Indonesia, involving 79 young adults aged 18-25 years, composing of 39 and 40 subjects with and without central obesity, respectively. Anthropometric measurements were performed to assess WC and BMI. Body fat percentage was measured using bioelectrical impedance analysis and serum NO metabolites levels were assessed using Griess methods.Results: Levels of serum NO metabolites were significant higher in the subjects with central obesity (168.41±12.64 μmol/L) than that of normal subjects (70.57±44.99 μmol/L, p

Serum uric acid (UA) is taken up by endothelial cells and reduces the level of nitric oxide (NO) by inhibiting its production and accelerating its degradation. Cytosolic and plasma xanthine oxidase (XO) generates superoxide and also decreases the NO level. Thus, hyperuricemia is associated with impaired endothelial function. Hyperuricemia is often associated with vascular diseases such as chronic kidney disease (CKD) and cardiovascular disease (CVD). It has long been debated whether hyperuricemia is causally related to the development of these diseases. The 2020 American College of Rheumatology Guideline for the Management of Gout (ACR2020) does not recommend pharmacological treatment of hyperuricemia in patients with CKD/CVD. In contrast, the Japanese Guideline on Management of Hyperuricemia and Gout (JGMHG), 3rdedition, recommends pharmacological treatment of hyperuricemia in patients with CKD. In a FREED study on Japanese hyperuricemic patients with CVD, an XO inhibitor, febuxostat, improved the primary composite endpoint of cerebro-cardio-renovascular events, providing a rationale for the use of urate-lowering agents (ULAs). Since a CARES study on American gout patients with CVD treated with febuxostat revealed increased mortality, ACR2020 recommends switching to different ULAs. However, there was no difference in the mortality of Japanese patients between the febuxostat-treated group and the placebo or allopurinol-treated groups in either the FEATHER or FREED studies.

Serum uric acid level above 7 mg/dl is defined as hyperuricemia, which gives rise to the monosodium urate (MSU), causing gout and urolithiasis. Hyperuricemia is an independent risk factor as well as a marker for hypertension, heart failure, atherosclerosis, atrial fibrillation, and chronic kidney disease. MSU crystals, soluble uric acid (UA), or oxidative stress derived from xanthine oxidoreductase (XOR) might be plausible explanations for the association of cardio-renovascular diseases with hyperuricemia. In macrophages, MSU activates the Nod-like receptor family, pyrin domain containing 3(NLRP3) inflammasome, and proteolytic processing mediated by caspase-1 with enhanced interleukin (IL)-1β and IL-18 secretion. Soluble UA accumulates intracellularly through UA transporters (UAT) in vascular and atrial myocytes, causing endothelial dysfunction ad atrial electrical remodeling. XOR generates reactive oxygen species (ROS) that lead to cardiovascular diseases. Since it remains unclear whether asymptomatic hyperuricemia could be a risk factor for cardiovascular and kidney diseases, European and American guidelines do not recommend pharmacological treatment for asymptomatic patients with cardio-renovascular diseases. The Japanese guideline, on the contrary, recommends pharmacological treatment for hyperuricemia with CKD to protect renal function, and it attaches importance of the cardio-renal interaction for the treatment of asymptomatic hyperuricemia patients with hypertension and heart failure.

Background: Iron overload can cause DNA oxidation which increase TGF β1, type 1 fibrilarprotein and myocardium fibrosis. Myocardium fibrosis is the main cause of death on the state of iron overload. The iron influx towards the cell during iron overload is still unknown, some research suggested LTCC acts as iron influx. This research aims to investigate the role of azelnidipine as type L calcium channel blocker, lowering TGF β1, collagen and myocardium fibrosis. Method: The research subjects consisted of 25 male Balb-C mice(8 weeks, 30-40mg) divided into 5 groups. Group 1 (NaCl+S) 0,3 cc Na Cl 0,9% (I.P) and drug solvent (Aquabidest, CMC and Nipagin) orally. Group 2Fe+S) 0.3 cc 1,5 mg Fe+sucrose (Venofer®) (I.P) and drug solvent (Aquabidest, CMC and Nipagin) orally. Group 3 (Fe+Dfx) 1,5 mg Fe+sucrose (Venofer®) (I.P) and deferasirox 20 mg/kg body weight/day orally, group 4 (Fe+Azl) 1,5 mg Fe+sucrose (Venofer®) (I.P) and azelnidipine 14 mg/day orally and group 5 (Fe+Dfx-Azl) 1,5 mg Fe+sucrose (Venofer®) (I.P) and mixture of deferasirox 20 mg/kg body weight/day and azelnidipine 14 mg/day orally. Fe-sucorse was diluted with NaCl 0.9 %. Intraperitoneal injection were administered intermittently for 60 days of treatment. Result: The highest Expression of TGF β, collagen I and fibrosis area fractions are in group Fe+S. The result of Post Hoc test between 2 treatment groups indicated that there were no difference in TGF β expression between groups NaCl+S with Fe+Dfx (P>0.05) , Fe+Dzl (P>0.05). There are no significant in collagen expression between groups NaCl+S with Fe+Dfx (P > 0.05) ,Fe+Dzl (P>0.05). Conclusion: Azelnidipine, LTCC have roles on the influx of iron into the myocardium, lowering TGF β, collagen Iexpressionsand myocardium fibrosis. Bangladesh Journal of Medical Science Vol.19(2) 2020 p.223-228

The mechanism of cardiac-troponin elevation after exercise remains unclear. Studies have reported that leucocyte ratios are related to coronary artery disease. The present study explored the relationship between leucocyte ratios, exercise intensity, and post-exercise cardiac-troponin I (cTnI) levels. Ninety-two participants in a long-distance cycling tour were included in this study. Baseline and post-exercise blood samples were collected to determine cTnI concentrations. Biochemical parameters and leucocyte ratios were measured at baseline. Exercise intensity was examined by recording the heart rate (HR). Exercise intensity was determined as the percentage of peak HR to maximal predicted HR. Based on clinical cutoff points of the cTnI assay, cTnI levels were defined as

BACKGROUND: Inflammation plays an important role in the atherosclerotic process. High-sensitivity C-reactive-protein (hs-CRP) is commonly used as inflammatory biomarker. It is well known that regular physical activity lowers hs-CRP levels, while prolonged exercise induces hs-CRP elevations. However, the relationship of training and exercise characteristics with hs-CRP levels remains not well elucidated. We evaluated baseline and post-exercise hs-CRP levels and its association with training and exercise characteristics.METHODS: Eighty-eight male endurance cyclists were involved. Demographic data, health condition and training characteristics were collected. Baseline and postexercise blood-samples were collected to determine hsCRP concentrations. A hs-CRP cut-off point of 3 mg/L was used. Blood-cell count and biochemical parameters were measured at baseline. Heart rate (HR) was measured during exercise.RESULTS: Cyclists performed 7.3 hours (interquartilerange (IQR) = 5.4-7.5) of endurance exercise at intensity of 81.8 % (IQR = 74.9-85.8). Cyclists with baseline hsCRP ≥ 3 mg/L reported higher body mass, body mass index (BMI), waist-circumference and total-cholesterol. An increase in hs-CRP was following endurance exercise. Cyclists with any elevation of hs-CRP reported a higher BMI, HR during exercise and exercise intensity. Binary logistic regression analysis showed BMI (OR = 1.24, 95% CI = 1.04-1.48) and cycling distance (OR = 0.22, 95% CI = 0.06-0.76) were associated with post-exercise hs-CRP elevations.CONCLUSION: Body mass, BMI, waist-circumference, total- and HDL-cholesterol are associated with baseline hsCRP, whereas BMI and cycling distance were associated with hs-CRP elevations. These findings suggest that anthropometry parameters and lipid levels attributed to baseline hs-CRP, while anthropometry parameters and cycling intensity attributed to post-exercise hs-CRP elevations.KEYWORDS: C-reactive-protein, exercise, endurancecycling, inflammation, acute-phase-response

Background: Coronary collateral circulation (CCC) is linked to myocardial remodeling severity in patients with chronic ischaemic heart disease (IHD). However its effect on left ventricular reverse remodeling (LVRR) in patients with chronic IHD underwent coronary artery bypass surgery (CABG) has never been reported. Purpose of this study was to investigate the effect of CCC grade on the LVRR event in patients with chronic IHD underwent CABG. Methods: This prospective cohort study was performed in patients with chronic IHD underwent CABG. The CCC was classified using Rentrop collateral score, i.e low CCC grade (Rentrop score 0 and 1) and high CCC grade (Rentrop score 2 and 3). LVRR event was defined as a reduction in left ventricular end systolic volume (LVESV) of 10% or more, measured by a 3D echocardiography at 1.5 months post CABG compared to the baseline before CABG. Results: A total of 22 patients (81.8% male) with mean of age 58.6 years old were enrolled. LVRR occurred in 50% patients. LVRR event was significantly higher in the patients with high CCC grade than the low CCC grade patients (p=0.009). The high CCC grade increased LVRR event independently (odds ratio=26.67; relative risk=6.93). Conclusions: High coronary collateral circulation may increase left ventricular reverse remodeling event in patients with chronic ischemic heart disease underwent coronary artery bypass surgery. Keywords: coronary collateral circulation; left ventricular reverse remodeling; chronic ischaemic heart disease; coronary artery bypass surgery; 3D echocardiography.

Background: To date, the mechanisms of post-exercise cardiac troponin elevation are debatable. Previous studies have reported that oxidative stress happens after extended exercise. Objectives: This study purposed to establish the association between the elevation of malondialdehyde (MDA), which is a marker of oxidative stress, and cardiac troponin-I (cTn-I) after prolonged cycling. Methods: Ninety-two males in Indonesian cycling tours participated in the present study. Baseline and post-exercise blood specimens were obtained to define MDA and cTn-I levels. The elevations of MDA and cTn-I were determined as positive differences of post-cycling MDA and cTn-I levels to the baseline, respectively. Results: Eighty-eight participants (age, mean = 45.3 years old, [SD]:11.47; body mass index (BMI), mean=24.2 kg/m2, [SD]: 3.03) finished the cycling tours. Subjects’ characteristics were comparable based on the touring category, except for the family history of coronary artery disease, high-density lipoprotein cholesterol level, neutrophil count, resting heart rate, exercise intensity, and cTn-I elevation. MDA significantly escalated at the level of 210.90 µmol/mL at post-exercise, from 190.18 µmol/mL at baseline. cTn-I also increased at the level of 13.65 ng/dL from 5.16 ng/dL. The elevation of MDA was related to the elevation of cTn-I. Elevation of cTn-I after prolonged cycling was contributed by elevation of MDA and exercise intensity. Conclusions: The present findings support existing confirmation that cTn-I elevation after prolonged exercise is related to oxidative stress and exercise intensity.

The present study aimed to explore the prevalence of isolated systolic hypertension (ISH) and its risk factors among diabetes mellitus (DM) subjects in the community setting study in Indonesia. This cross-sectional study extracted secondary data from basic health survey (Riset Kesehatan Dasar; RISKESDAS) conducted in 2018. DM subjects were defined based on fasting blood glucose level ≥ 126 mg/dL or 2 hours postprandial and random blood glucose level ≥ 200 mg/dL or previously had been diagnosed by a doctor; while ISH was determined based on systolic blood pressure ≥ 140 mmHg and diastolic blood pressure < 90 mmHg. We also observed the subject’s characteristics, such as demography, lipid profile, and subject’s compliance. Data were then analyzed using Chi-square and Binary logistic regression. Study involved 3,911 DM subjects, revealed the overall prevalence of ISH 17.5%. Age category of 35-44 years old (POR= 10.80; 95%CI: 2.595-44.957), 45-54 years old (POR=22.81; 95%CI: 5.616-92.677), 55-64 years old (POR=46.12; 95% CI: 11.393-186.720); 65-74 years old (POR= 81.82; 95% CI: 20.110-332.868); ≥75 years old (POR=109.64; 95% CI: 26.373-455.789), low HDL cholesterol (POR= 0,80; 95% CI: 0.653-0.972); duration of DM (POR= 1.73; 95% CI: 1.257-2.389) were associated with the ISH. The prevalence of ISH among DM subjects was 17.5%. Older DM subjects, low HDL cholesterol, and duration of DM were associated with the ISH, suggesting that modification lipid profile, especially the HDL cholesterol level, is an important measure to delay ISH in elderly and long-duration DM subjects.

BackgroundPrevious studies reported recurrent SARS-CoV-2 RNA positivity in individuals who had recovered from COVID-19 infections. However, little is known regarding the systematic review of recurrent SARS-CoV-2 RNA positivity. The current study conducted a systematic review and meta-analysis, aimed to estimate the incidence of recurrent SARS-CoV-2 RNA positivity after recovery from COVID-19 and to determine the factors associated with recurrent positivity.MethodsWe searched the PubMed, MedRxiv, BioRxiv, the Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry for studies published to June 12, 2020. Studies were reviewed to determine the risk of bias. A random-effects model was used to pool results. Heterogeneity was assessed using I2.ResultsFourteen studies of 2,568 individuals were included. The incidence of recurrent SARS-CoV-2 positivity was 14.81% (95% confidence interval [CI]: 11.44–18.19%). The pooled estimate of the interval from disease onset to recurrence was 35.44 days (95% CI: 32.65–38.24 days), and from the last negative to recurrent positive result was 9.76 days (95% CI: 7.31–12.22 days). Patients with younger age (mean difference [MD]=-2.27, 95% CI: -2.95 to -1.80) and a longer initial illness (MD=8.24 days; 95% CI: 7.54 – 8.95; I2=98.9%) were more likely to experience recurrent SARS-CoV-2 positivity, while patients with diabetes (RR=0.52; 95% CI: 0.30-0.90; I2=53%), severe disease (RR=0.54; 95% CI: 0.35-0.84; I2=70%), and a low lymphocyte count (RR=0.58; 95% CI: 0.39 – 0.86; I2=48%) were less likely to experience recurrent SARS-CoV-2 positivity.ConclusionsThe incidence of recurrent SARS-CoV-2 positivity was 14.81%. The estimated interval from disease onset to repeat positivity was 35.44 days, and the estimated interval from the last negative result to recurrent positive result duration was 9.76 days.

Total-Cholesterol (TC) to HDL-Cholesterol (HDL-C) ratio in athletes is well-known to be better than sedentary people. However, information about comparison of TC/HDL-C in different groups of cyclists based on cycling touring characteristics and anthropometry parameters is lacking. This study aimed to compare TC/HDL-C ratio between groups based on the type of tour in cyclists population. Eighty-eight participants were recruited in this cross-sectional study. Mean differences of parameters between groups was analyzed by One-Way Anova and independent t-test, whereas multivariate analyses was conducted by binary logistic-regression. P value

Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder caused by mutations in UMOD that encodes uromodulin. Topiroxostat, a novel non-purine analog, selectively inhibits xanthine oxidase and reduces the serum uric acid levels and the urinary albuminuria.Genomic DNA of a patient was extracted from peripheral white blood. Exons and flanking sequences of UMOD were amplified by PCR with primers. Mutation analysis was performed by direct sequencing of the PCR products. The wild-type and mutant uromodulin were expressed in HEK293 cells and analyzed by western blotting, immunoprecipitation, immunofluorescence, and flow cytometry.We identified an FJHN patient who carried a novel UMOD mutation G335A (C112Y). The levels of both cytosolic and secreted C112Y protein were significantly decreased compared with the wild-type, whereas the level of ubiquitination was higher in C112Y than that in the wild type. The half-life of C112Y was shortened and it was restored by a proteasome inhibitor MG132. Immunofluorescence revealed decreased levels of C112Y in the Golgi apparatus and on the plasma membrane. Expression of C112Y induced cellular apoptosis as revealed by flow cytometry. Apoptosis induced by C112Y was suppressed by topiroxostat.C112Y causes its protein instability resulting cellular apoptosis which could be suppressed with topiroxostat.

BACKGROUND The prion protein (PrP) has been reported to serve as a surface maker for isolation of cardiomyogenic progenitors from murine embryonic stem (ES) cells. Although PrP-positive cells exhibited automaticity, their electrophysiological characteristics remain unresolved. The aim of the present study was therefore to investigate the electrophysiological properties of PrP-positive cells in comparison with those of HCN4p-or Nkx2.5-positive cells. METHODS AND RESULTS Differentiation of AB1, HCN5p-EGFP and hcgp7 ES cells into cardiac progenitors was induced by embryoid body (EB) formation. EBs were dissociated and cells expressing PrP, HCN4-EGFP and/or Nkx2.5-GFP were collected via flow cytometry. Sorted cells were subjected to reverse transcriptase-polymerase chain reaction, immunostaining and patch-clamp experiments. PrP-positive cells expressed mRNA of undifferentiation markers, first and second heart field markers, and cardiac-specific genes and ion channels, indicating their commitment to cardiomyogenic progenitors. PrP-positive cells with automaticity showed positive and negative chronotropic responses to isoproterenol and carbamylcholine, respectively. Hyperpolarization-activated cation current (I(f)) was barely detectable, whereas Na(+) and L-type Ca(2+) channel currents were frequently observed. Their spontaneous activity was slowed by inhibition of sarcoplasmic reticulum Ca(2+) uptake and release but not by blocking I(f). The maximum diastolic potential of their spontaneous firings was more depolarized than that of Nkx2.5-GFP-positive cells. CONCLUSIONS PrP-positive cells contained cardiac progenitors that separated from the lineage of sinoatrial node cells. PrP can be used as a marker to enrich nascent cardiac progenitors.

Background: Development of biological pacemaker is a potential treatment for bradyarrhythmias. Pacemaker cells could be extracted from differentiated embryonic stem (ES) cells based on their specific cell marker hyperpolarization-activated cyclic nucleotide-gated (HCN)4. The goal of this study was to develop a method of identification, isolation, and characterization of pacemaking cells derived from differentiated ES cells with GFP driven by HCN4 promoter. Methods and Results: Polymerase chain reaction (PCR) screening and southern blot analysis revealed that HCN4p-EGFP trans-gene was stably integrated into the chromosome of mouse AB1 ES cells. RT-PCR and immunostaining results showed similar expression of the specific cardiac pacemaker markers of the HCN4p-EGFP ES cells and its parental AB1 ES cell lines. Although HCN4p-EGFP trans-gene may have slight effect on the general mesodermal differentiation, it had no effect on the pluripotency of ES cells, on the transcription of cardiac specific factors and cardiac contractile proteins, and on the capability of ES cells to differentiate into pacemaker cells. Electrophysiological study indicated that HCN4p-GFP-positive cells revealed the spontaneous action potential, which was slowed by the treatment with 2 mM Cs+, and expressed the hyperpolarization-activeted cation current If encoded by HCN4 gene. Conclusion: By the approach of using stable transfectant of HCN4p-EGFP gene, the identification, isolation, and characterization of ES cell-derived pacemaking cells could be carried out. PACE 2010; 33:290–303)

Congenital Adrenal Hyperplasia (CAH) is an adrenal disorders due to impaired activity of one of the enzymes required for cortisol and aldosterone biosynthesis. One of the subtypes of CAH is the salt-wasting (SW) form which there is a renal salt loss due to aldosterone deficiency. Plasma Renin Activity (PRA) is the main index used to evaluate the mineralocorticoid control in CAH. PRA testing is almost very rare done for the CAH patients due to high cost, sophisticated laboratory is not available in all region and no compulsary health insurance in Indonesia. The objective of this research was to describe PRA level in patient with Congenital Adrenal Hyperplasia. This study is a part of CAH cohort study in Center for Biomedical Research (CEBIOR), Semarang, Indonesia. Eighteen patients diagnosed as CAH were drawned blood samples for hormonal test, including 17 OHP, Plasma Renin Activity, Cortisol, and Electrolytes. Clinical history and physical examination was performed to each patients. All 18 patients (17 female and 1 male) have high 17-OHP level and normal electrolites levels, but only 14 patients have PRA data. Four patients did not show their PRA level due to fail in too much blood collection. Out of 14 patient, four patients which had history of SW have very high PRA level, while six patients have PRA level more than normal without history of salt wasting. The mean of PRA level in patients with history of SW (47.72 (SD 18.63)) are higher than the patient without history of SW (13.97 (SD 13.3)). This study suggest that PRA level might be useful for evaluating mineralocorticoid level in CAH. It is proposed to the government to subsidize and provide PRA and other hormonal testing for CAH in many regions with affordable cost.