Polypill with or without Aspirin in Persons without Cardiovascular Disease.

BACKGROUND: A polypill comprising statins, multiple blood-pressure-lowering drugs, and aspirin has been proposed to reduce the risk of cardiovascular disease. METHODS: Using a 2-by-2-by-2 factorial design, we randomly assigned participants without cardiovascular disease who had an elevated INTERHEART Risk Score to receive a polypill (containing 40 mg of simvastatin, 100 mg of atenolol, 25 mg of hydrochlorothiazide, and 10 mg of ramipril) or placebo daily, aspirin (75 mg) or placebo daily, and vitamin D or placebo monthly. We report here the outcomes for the polypill alone as compared with matching placebo, for aspirin alone as compared with matching placebo, and for the polypill plus aspirin as compared with double placebo. For the polypill-alone and polypill-plus-aspirin comparisons, the primary outcome was death from cardiovascular causes, myocardial infarction, stroke, resuscitated cardiac arrest, heart failure, or revascularization. For the aspirin comparison, the primary outcome was death from cardiovascular causes, myocardial infarction, or stroke. Safety was also assessed. RESULTS: A total of 5713 participants underwent randomization, and the mean follow-up was 4.6 years. The low-density lipoprotein cholesterol level was lower by approximately 19 mg per deciliter and systolic blood pressure was lower by approximately 5.8 mm Hg with the polypill and with combination therapy than with placebo. The primary outcome for the polypill comparison occurred in 126 participants (4.4%) in the polypill group and in 157 (5.5%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.63 to 1.00). The primary outcome for the aspirin comparison occurred in 116 participants (4.1%) in the aspirin group and in 134 (4.7%) in the placebo group (hazard ratio, 0.86; 95% CI, 0.67 to 1.10). The primary outcome for the polypill-plus-aspirin comparison occurred in 59 participants (4.1%) in the combined-treatment group and in 83 (5.8%) in the double-placebo group (hazard ratio, 0.69; 95% CI, 0.50 to 0.97). The incidence of hypotension or dizziness was higher in groups that received the polypill than in their respective placebo groups. CONCLUSIONS: Combined treatment with a polypill plus aspirin led to a lower incidence of cardiovascular events than did placebo among participants without cardiovascular disease who were at intermediate cardiovascular risk. (Funded by the Wellcome Trust and others; TIPS-3 ClinicalTrials.gov number, NCT01646437.).

The effect of resistance training on PCSK9 levels in patients undergoing cardiac rehabilitation after coronary artery bypass grafting: a randomized study.

BACKGROUND: Resistance training is commonly recommended as part of secondary prevention for post-coronary artery bypass graft (CABG) patients in conjunction with aerobic exercise. Despite its potential benefits, there is currently a lack of studies investigating the impact of resistance training on proprotein convertase subtilisin kexin 9 (PCSK9). AIM: To evaluate the effect of intensive resistance training on proprotein convertase subtilisin kexin 9 (PCSK9) levels among post-CABG patients undergoing cardiac rehabilitation (CR). METHODS: In this prospective, open-label, randomized trial, 87 post-coronary artery bypass graft (CABG) patients were randomly assigned into two groups: moderate to high intensity resistance training and aerobic training (n = 44) or aerobic training alone (n = 43) for a total of 12 sessions. Changes in PCSK9 levels was determined as a primary endpoint, while secondary endpoints included changes in the six-minute walk test (6-MWT) results, aerobic capacity, WHO-5 well-being index, fasting blood glucose, and lipid profile. Both groups underwent intention-to-treat analysis. RESULTS: Following completion of cardiac rehabilitation program, the intervention group demonstrated a significant decrease in mean PCSK9 levels when compared to the control group (ß = -55 ng/ml, 95% CI -6.7 to -103.3, p = 0.026), as well as significant improvements in the 6-MWT result (ß = 28.2 m, 95% CI 2.4-53.9, p = 0.033), aerobic capacity (ß = 0.9 Mets, 95% CI 0.1-1.7, p = 0.021), and WHO-5 well-being index (ß = 8.1, 95% CI 2.0-14.4, p = 0.011) in patients who received resistance and aerobic training. No statistically significant changes were observed in fasting blood glucose, cholesterol, LDL-C, HDL-C, and triglyceride levels. CONCLUSION: Resistance training in CR significantly reduced PCSK-9 levels and increases patient's functional capacity and quality of life. (NCT02674659 04/02/2016).

Retrospective Study of the Association Between Platelet-to-Lymphocyte Ratio in Patients with Acute Coronary Syndrome on Admission to a Rural Referral Center in East Java, Indonesia, and the Incidence of New Symptomatic Heart Failure at 6 Months.

BACKGROUND This was a retrospective study conducted at a rural referral center in East Java, Indonesia, to evaluate the association between the platelet-to-lymphocyte ratio (PLR) on hospital admission and the incidence of new symptomatic heart failure (HF) within 6 months in patients with acute coronary syndrome (ACS). MATERIAL AND METHODS The study population consisted of all ACS patients who were hospitalized between 1 January and 31 December 2018 at a non-percutaneous coronary intervention-capable secondary referral hospital and came for a routine follow-up until 6 months afterwards. The diagnosis of new symptomatic HF was based on International Classification of Diseases 10th revision code I50.9. RESULTS From 126 hospitalized patients, 92 patients were included in the analysis. The incidence rate of new symptomatic HF at 6 months was 70.65%. High PLR upon initial admission was significantly associated with new symptomatic HF incidence (odds ratio=1.70, P<0.001). PLR was also able to discriminate new symptomatic HF incidence at 6 months with area under the curve of 0.83 (P=0.001). Multivariate Cox regression analysis showed that PLR was an independent predictor for new symptomatic HF incidence (hazard ratio=4.5, P=0.001). CONCLUSIONS In a rural center in Indonesia, the PLR was independently correlated with the onset of new symptomatic HF in patients with ACS 6 months after hospital admission. The PLR may be a supplementary biomarker for clinical outcomes in patients with ACS for use in resource-limited regions.

Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis.

Background: In this systematic review and meta-analysis, we aimed to explore the association between cardiac injury and mortality, the need for intensive care unit (ICU) care, acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19) in patients with COVID-19 pneumonia. Methods: We performed a comprehensive literature search from several databases. Definition of cardiac injury follows that of the included studies, which includes highly sensitive cardiac troponin I (hs-cTnl) >99th percentile.The primary outcome was mortality, and the secondary outcomes were ARDS, the need for ICU care, and severe COVID-19. ARDS and severe COVID-19 were defined per the World Health Organization (WHO) interim guidance of severe acute respiratory infection (SARI) of COVID-19. Results: There were a total of 2389 patients from 13 studies. This meta-analysis showed that cardiac injury was associated with higher mortality (RR 7.95 [5.12, 12.34], p < 0.001; I2: 65%). Cardiac injury was associated with higher need for ICU care (RR 7.94 [1.51, 41.78], p = 0.01; I2: 79%), and severe COVID-19 (RR 13.81 [5.52, 34.52], p < 0.001; I2: 0%). The cardiac injury was not significant for increased risk of ARDS (RR 2.57 [0.96, 6.85], p = 0.06; I2: 84%). The level of hs-cTnI was higher in patients with primary + secondary outcome (mean difference 10.38 pg/mL [4.44, 16.32], p = 0.002; I2: 0%). Conclusion: Cardiac injury is associated with mortality, need for ICU care, and severity of disease in patients with COVID-19.

Sodium-glucose cotransporter 2 inhibitors at the intersection of cardiovascular, renal and metabolic care: an integrated and multidisciplinary approach to patient-centered care.

PURPOSE OF REVIEW: The management of individuals who live with type 2 diabetes requires an integrated and multifaceted approach. RECENT FINDINGS: Sodium-glucose cotransporter 2 inhibitors effectively prevent and treat cardiorenal complications in the presence of type 2 diabetes. They also reduce death and disease progression in those with established heart failure (with reduced ejection fraction) in the absence of diabetes. SUMMARY: Close collaborations between primary care physicians, cardiovascular specialists, endocrinologists and nephrologists are necessary to optimize cardiovascular, renal and metabolic risk reduction in their shared patients.

Association of plasma pentraxin 3 concentration with angiographic and clinical outcomes in patients with acute ST-segment elevation myocardial infarction treated by primary angioplasty.

OBJECTIVE: To evaluate the association of plasma long pentraxin 3 (PTX3) concentration with angiographic and clinical outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI) treated by primary angioplasty. BACKGROUND: Whether concentration of PTX3, a sensitive marker of inflammation, associates with angiographic and clinical outcomes in STEMI patients treated by primary angioplasty is unknown. METHODS: We prospectively enrolled 335 consecutive patients with acute STEMI undergoing primary angioplasty. Blood samples for plasma PTX3 measurement were drawn in all patients at the emergency department before primary angioplasty, and were measured by ELISA method. RESULTS: The median PTX3 concentrations were higher in patients with thrombus burden grade 4 and 5 versus grade <4 on initial coronary angiogram (0.29 ng/ml vs. 0.24 ng/ml, p = .02), thrombolysis in myocardial infarction (TIMI) grade <3 vs. TIMI grade-3 flow after primary angioplasty (0.31 ng/ml vs. 0.24 ng/ml, p < .001), incomplete versus complete ST-segment resolution within 12 hr after angioplasty (0.29 ng/ml vs. 0.22 ng/ml, p = .001) and in patients who did not survive versus those who survived at 30 days (0.44 ng/ml vs. 0.26 ng/ml, p = .001). A linear correlation was observed between PTX3 concentration and baseline leukocyte count (Spearman correlation = 0.21, p < .001). After adjustment for laboratory and selected clinical variables, patients in the highest quartile of PTX3 concentration (≥0.4 ng/ml) were associated with increased risk of 30-day mortality (hazard ratio = 11.83; 95% confidence interval = 1.52-92.27, p = .01). CONCLUSION: This study suggests that higher plasma PTX3 concentration associates with worse angiographic and clinical outcomes in STEMI patients treated by primary angioplasty.

May Measurement Month 2018: an analysis of blood pressure screening results from Indonesia.

Elevated blood pressure (BP) is a significant burden worldwide, leading to high cardio-cerebro-reno-vascular morbidity and mortality. For the second year of the May Measurement Month (MMM) campaign in Indonesia in 2018, we recruited 174 sites in 31 out of 34 provinces in Indonesia and screened through convenience sampling in public areas and rural primary health centres. Hypertension was defined as systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or both, or on the basis of receiving antihypertensive medication. Blood pressure was measured three times followed the standard global MMM protocol, multiple imputation was used to estimate the mean of the 2nd and 3rd BP readings if these were not recorded. A total of 91 222 individuals were screened, and after multiple imputations, 27 331 (30.0%) had hypertension. Of individuals not receiving antihypertensive medication, 14 367 (18.4%) were hypertensive. Among the 47.4% of hypertensive individuals on antihypertensive medication, 10 106 (78.0%) had uncontrolled BP. MMM17 and MMM18 were still the most extensive standardized screening campaigns for BP measurement in Indonesia. Compared to the previous study, the proportion with uncontrolled BP on medication was significantly higher and provided the substantial challenges in managing hypertension in the rural community.

Combined transepicardial and transseptal implantation of autologous CD 133+ bone marrow cells during bypass grafting improves cardiac function in patients with low ejection fraction.

OBJECTIVES: Autologous CD133+ bone marrow stem cells may improve cardiac function. This randomized, single-blind clinical trial inquired whether a combined transepicardial and transseptal implantation of CD133+ stem cells during coronary artery bypass grafting (CABG) improve cardiac function with ejection fraction (EF) changes as a primary endpoint in patients with low EF. METHODS: Thirty patients with coronary heart disease and EF <35% were randomized to undergo CABG alone or CABG with transseptal and transepicardial implantation of CD133+. Cardiac function was evaluated using cardiac magnetic resonance imaging (MRI) before and 6 months after CABG. RESULTS: Preoperative EF was lower in the intervention group (25.88% ± 5.66%) than in the control group (30.18% ± 3.85%; P = .04). The adverse event incidence was similar between both groups. At 6 months, EF changes were significantly higher (8.69% ± 9.49; P = .04) in the CD133+ group than in the CABG-only group. Compared to the control group, significant improvements were seen in the wall motion score index (P = .003) and scar size proportion (P = .047) in the CD133+ group. The quality of life (QOL), assessed by a 6-minute walking test, showed considerable improvement in the CD133+ group compared to that in the control group (P = .03). The Minnesota Living with Heart Failure Questionnaire (MLHFQ) scale did not show improvement in the intervention group (P = .09, vs control). CONCLUSION: Combined transepicardial and transseptal autologous CD133+ BMC implantation during bypass grafting improved cardiac function in low EF coronary artery disease patients.

The Effects of Aerobic Exercise on N-terminal Pro-B-type Natriuretic Peptide and Cardiopulmonary Function in Patients With Heart Failure: A Meta-Analysis of Randomised Clinical Trials.

BACKGROUND: Aerobic exercise (AEx) improves outcomes in heart failure (HF). N-terminal pro B-type natriuretic peptide (NT-pro-BNP) is a prognosticator in HF. There are few data on the association of AEx, NT-pro-BNP, and cardiopulmonary function; hence, robust evidence is needed. The aim of this study was to measure the effects of AEx on NT-pro-BNP levels and cardiopulmonary function in HF. METHOD: Databases (Pubmed, EMBASE, Medline, Cochrane Central Registry, and Scopus) were systematically searched for randomised controlled trials (RCTs) that assessed the association of AEx with NT-pro-BNP and cardiopulmonary function (VE/VCO2 slope, peak VO2, maximal workload, and left ventricular ejection fraction [LVEF]) in HF. RevMan 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, 2014) was used to produce forest plots, and the random-effect model was applied with the effects measure of weighted mean differences (WMD) and 95% confidence interval (CI). RESULTS: Thirteen (13) RCTs recruited 1,503 patients and 1,494 controls. Aerobic exercise was significant in lowering NT-pro-BNP (pg/mL) compared with control group (WMD=-741.69, 95% CI -993.10 to -490.27 [p<0.00001; I2=63%]). VE/VCO2 slope was also significantly reduced (WMD=-3.57, 95% CI -6.48 to -0.67 [p=0.02; I2=97%]). Peak VO2 (mL/kg/min) significantly improved (WMD=3.68, 95% CI 2.39-4.96 [p<0.00001; I2=96%]). Maximal workload (watt) significantly increased following AEx (WMD=22.80, 95% CI 18.44-27.17 [p<0.00001; I2=78%]). Furthermore, there was a significant enhancement of LVEF (%) in the AEx group (WMD=2.42, 95% CI 0.64-4.19 [p=0.008; I2=71%]). CONCLUSIONS: Aerobic exercise improves the NT-pro-BNP, ventilatory efficiency, aerobic capacity, maximal workload, and the left ventricular function in patients with HF.

May Measurement Month 2017: an analysis of the blood pressure screening campaign results in Indonesia-South-East Asia and Australasia.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. Our previous primary health surveys in 2013 and 2018 show that 25.8% to 34.1% of adults have raised BP, which is associated with cardiovascular, cerebrovascular, and renovascular morbidity and mortality. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. We recruited 292 sites in all 34 provinces in Indonesia, and screened in public areas and offices as well as health centres. A total of 69 307 individuals were screened. After multiple imputation, 23 892 (34.5%) had hypertension. Of individuals not receiving antihypertensive medication, 20.0% were hypertensive. Among individuals receiving antihypertensive medication, 7885 (62.8%) had uncontrolled BP. MMM17 was the largest standardized screening campaign for BP measurement in our country. The proportion of individuals identified with hypertension and the percentage of those with uncontrolled BP on medication provide evidence of the substantial challenges in managing hypertension in the community. These results suggest that opportunistic screening can identify significant numbers of individuals with raised BP.

The International Polycap Study-3 (TIPS-3): Design, baseline characteristics and challenges in conduct.

BACKGROUND: It is hypothesized that in individuals without clinical cardiovascular disease (CVD), but at increased CVD risk, a 50% to 60% reduction in CVD risk could be achieved using fixed dose combination (FDC) therapy (usually comprised of multiple blood-pressure agents and a statin [with or without aspirin]) in a single "polypill". However, the impact of a polypill in preventing clinical CV events has not been evaluated in a large randomized controlled trial. METHODS: TIPS-3 is a 2x2x2 factorial randomized controlled trial that will examine the effect of a FDC polypill on major CV outcomes in a primary prevention population. This study aims to determine whether the Polycap (comprised of atenolol, ramipril, hydrochlorothiazide, and a statin) reduces CV events in persons without a history of CVD, but who are at least at intermediate CVD risk. Additional interventions in the factorial design of the study will compare the effect of (1) aspirin versus placebo on CV events (and cancer), (2) vitamin D versus placebo on the risk of fractures, and (3) the combined effect of aspirin and the Polycap on CV events. RESULTS: The study has randomized 5713 participants across 9 countries. Mean age of the study population is 63.9 years, and 53% are female. Mean INTERHEART risk score is 16.8, which is consistent with a study population at intermediate CVD risk. CONCLUSION: Results of the TIP-3 study will be key to determining the appropriateness of FDC therapy as a strategy in the global prevention of CVD.

Ticagrelor versus clopidogrel in Asian patients with acute coronary syndrome: A retrospective analysis from the Platelet Inhibition and Patient Outcomes (PLATO) Trial.

BACKGROUND: In the PLATO trial, ticagrelor was superior to clopidogrel in reducing cardiovascular events among patients with acute coronary syndrome (ACS) at the expense of increased nonfatal bleeding. Because Asian patients, when compared with non-Asian patients, are believed to be more susceptible to bleeding, we evaluated the effects of ticagrelor compared with clopidogrel in Asian (n=1,106) and non-Asian (n=17,515) patients with acute coronary syndrome enrolled in the PLATO study. METHODS AND RESULTS: Interaction between Asian/non-Asian and primary efficacy end point (a composite of vascular death, myocardial infarction, and stroke) and net clinical benefit (composite of primary efficacy end point and coronary artery bypass graft [CABG] surgery or non-CABG-related major bleeding) were evaluated with a Cox proportional hazards model. Baseline demographics and comorbidities were different between Asians and non-Asians. The overall cardiovascular event rates were higher in Asians, but bleeding rates were similar. Despite these observed differences, the effects of ticagrelor versus clopidogrel were not significantly different between Asians and non-Asians with respect to the primary efficacy outcome (hazard ratio for Asians vs non-Asians, 0.84 [95% CI 0.61-1.17] vs 0.85 [95% CI 0.77-0.93], P=.974), net clinical benefit (0.85 [95% CI 0.65-1.11] vs 0.93 [95% CI 0.86-0.99], P=.521), or individual efficacy end points. There was no significant interaction for bleeding (PLATO major bleeding, 1.02 [95% CI 0.70-1.49] vs 1.04 [95% CI 0.95-1.14], P=.938) and other related adverse events with ticagrelor compared with clopidogrel between Asians and non-Asians. CONCLUSIONS: We observed consistency of effects in Asian patients receiving ticagrelor and clopidogrel in the PLATO study. The relatively modest number of Asian patients in this analysis supports further investigation of larger cohorts to confirm our observations.

Prognostic model of in-hospital ischemic stroke mortality based on an electronic health record cohort in Indonesia.

Stroke patients rarely have satisfactory survival, which worsens further if comorbidities develop in such patients. Limited data availability from Southeast Asian countries, especially Indonesia, has impeded the disentanglement of post-stroke mortality determinants. This study aimed to investigate predictors of in-hospital mortality in patients with ischemic stroke (IS). This retrospective observational study used IS medical records from the National Brain Centre Hospital, Jakarta, Indonesia. A theoretically driven Cox's regression and Fine-Gray models were established by controlling for age and sex to calculate the hazard ratio of each plausible risk factor for predicting in-hospital stroke mortality and addressing competing risks if they existed. This study finally included 3,278 patients with IS, 917 (28%) of whom had cardiovascular disease and 376 (11.5%) suffered renal disease. Bivariate exploratory analysis revealed lower blood levels of triglycerides, low density lipoprotein, and total cholesterol associated with in-hospital-stroke mortality. The average age of patients with post-stroke mortality was 64.06 ± 11.32 years, with a mean body mass index (BMI) of 23.77 kg/m2 and a median Glasgow Coma Scale (GCS) score of 12 and an IQR of 5. Cardiovascular disease was significantly associated with IS mortality risk. NIHSS score at admission (hazard ratio [HR] = 1.04; 95% confidence interval [CI]: 1.00-1.07), male sex (HR = 1.51[1.01-2.26] and uric acid level (HR = 1.02 [1.00-1.03]) predicted survivability. Comorbidities, such as cardiovascular disease (HR = 2.16 [1.37-3.40], pneumonia (HR = 2.43 [1.42-4.15] and sepsis (HR = 2.07 [1.09-3.94, had higher hazards for post-stroke mortality. Contrarily, the factors contributing to a lower hazard of mortality were BMI (HR = 0.94 [0.89-0.99]) and GCS (HReye = 0.66 [0.48-0.89]. In summary, our study reported that male sex, NIHSS, uric acid level, cardiovascular diseases, pneumonia, sepsis. BMI, and GCS on admission were strong determinants of in-hospital mortality in patients with IS.

The Effect of Omega-3 Supplementation on Heart Failure Outcome: A Meta-Analysis of Randomized Clinical Trial.

The effect of omega-3 supplementation on cardiovascular (CV) disease has been widely studied in several large clinical trials. However, the evidence of the effect of omega-3 supplementation in patients with heart failure (HF) remains controversial. This meta-analysis investigated the effects of omega-3 supplementation on patients with HF. We conducted a literature search on MEDLINE, Embase, and Cochrane databases for clinical trials and preprints of relevant articles. Following a literature search and critical appraisal, 5 studies were included in the meta-analysis. The pooling of the result of the studies shows that there were no significant association between omega-3 supplementation and CV mortality (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.84-1.05, p=0.16) nor hospitalization due to HF (OR, 0.94; 95% CI, 0.88-1.02; p=0.13). Our systematic review and meta-analysis showed that omega-3 supplementation has no beneficial effect in patients with HF.

Current Evidence and Future Directions of Omega-3 Supplementation and Cardiovascular Disease Risk.

Omega-3 supplementation has a controversial role in the secondary prevention of cardiovascular diseases. Despite large clinical trials published over the years, the evidence of omega-3 in preventing cardiovascular diseases, especially coronary heart disease, is still inconclusive. However, recent clinical trials using higher dose of omega-3 or highly purified esters of omega-3 shows promising result, with reduction in cardiovascular death and incidence of cardiovascular disease. This review aims to summarize the possible mechanism of omega-3 in preventing cardiovascular disease and future directions of research regarding the benefit of omega-3 in cardiovascular disease.

Adherence to penicillin treatment is essential for effective secondary prevention of rheumatic heart disease: a systematic review and meta-analysis.

Background: Penicillin is essential for secondary prevention of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). However, the incidences of ARF recurrence and RHD progression remain high, particularly in endemic countries. This meta-analysis evaluated the effectiveness of penicillin adherence in secondary prevention of ARF recurrence and RHD progression. Methods: The authors included original articles employing an observational study design in which the study population included patients with ARF or RHD and documented adherence to secondary prophylaxis with penicillin for secondary prevention. Systematic searches of the PubMed, Scopus, and Cochrane databases were performed. Moreover, the authors also conducted a snowballing literature search from Europe PMC to expand the included studies. The quality of each study was assessed using the National Institute of Health Quality Assessment Tool. The statistical analyses were conducted using Review Manager 5.4.1 software developed by Cochrane. In addition, the authors utilized pooled odds ratios (ORs) to compare the adherence techniques. Results: A total of 310 studies were identified, of which 57 full-text articles were assessed for eligibility. The authors included six studies with 1364 patients for the qualitative synthesis and meta-analysis. Good adherence to penicillin for the secondary prophylaxis of ARF and RHD, significantly reduced the odds of ARF recurrence or RHD progression by up to 71% compared to that associated with poor adherence [pooled OR 0.29 (0.21-0.40); I²=0% (p=0.56); Z=7.64 (p <0.00001)]. Conclusion: Good adherence to penicillin for secondary prophylaxis in patients with ARF or RHD is essential for reducing the risk of ARF recurrence or RHD progression.

Oral triiodothyronine normalizes triiodothyronine levels after surgery for pediatric congenital heart disease*.

OBJECTIVES: This study was conducted to determine if oral triiodothyronine supplementation could prevent the decrease of serum triiodothyronine levels that commonly occurs after cardiopulmonary bypass for pediatric congenital heart surgery. Secondary objectives included identifying any significant adverse effects of oral triiodothyronine supplementation, including any effects on the thyroid/pituitary axis. DESIGN: Randomized, placebo-controlled, doubleblind clinical trial SETTING: Operating room and ICU. SUBJECTS: Infants and children younger than 2 years of age undergoing congenital heart surgery using cardiopulmonary bypass (n = 43). INTERVENTIONS: Subjects were assigned to placebo (n = 15, group A) or one of two treatment groups: a low-dose group (group B, n = 14, 0.5 mcg/kg triiodothyronine orally every 24 hr for 3 d) or a high-dose group (group C, n = 14, 0.5 mcg/kg triiodothyronine orally every 12 hr for 3 d). MEASUREMENTS AND MAIN RESULTS: Thyroid hormone, including total and free triiodothyronine levels at predetermined time points, potential side effects indicating hyperthyroidism, indicators of the thyroid-pituitary axis, and clinical endpoints. Oral triiodothyronine supplementation twice-daily maintained serum triiodothyronine levels within normal limits in group C, whereas serum levels progressively declined in groups A and B. A statistically significant difference in triiodothyronine levels between the treatment groups occurred between 18 and 36 hours post cross-clamp release, with the largest difference in serum levels between group C and group A noted at 36 hours post cross-clamp release (total triiodothyronine, 0.71 ± 0.15 [0.34-1.08] ng/mL [p < 0.01]; free triiodothyronine, 2.56 ± 0.49 [1.33-3.79] pg/mL [p < 0.01]). There was no evidence of hyperthyroidism or suppression of the pituitary-thyroid axis in either treatment group CONCLUSIONS: Oral triiodothyronine supplementation at a dose of 0.5 mcg/kg every 12 hours for 3 days can maintain total and free triiodothyronine levels within normal limits after open-heart surgery using cardiopulmonary bypass for congenital heart disease.

Cardiology residents' attitudes towards clinical supervision: a multi-centered study.

PURPOSE: Residents' gender, residency level, and hospital types might influence their attitudes towards clinical supervision (CS); however, reports of its impact on cardiology residency are nonexistent. We explore the effect of gender, residency level, and hospital location's effect on Indonesian cardiology trainees' attitudes towards CS. METHODS: A multi-centered, cross-sectional study was conducted. We invited 490 Indonesian cardiology residents in September- October 2019 to complete the Cardiology CS Scale. Residents' attitudes, gender, university, and residency year were expressed using descriptive statistics. A Mann-Whitney test analyzed the gender and university location effect on residents' attitudes. Training year and university's impact were subjected to the Kruskal-Wallis test; a p-value of <0.05 reflected a significant result. RESULTS: A total of 388 residents agreed to participate (response rate=79.18%). Most of them were male (n=229 [59,02%]), attended universities in Java Island (n=262 [67,52%]), and were in their 2nd-3rd year of training (n=95 [24.48%], each). There were no significant differences in residents' attitudes between genders (U [Nmale=229, Nfemale=159]=17,908.50, z=-0.27, p=0.78). Generally, their attitudes were significantly affected by the university (H(7)=47.38, p<0.01). However, the university location (located in Java Island or outside Java Island) does not affect residents' attitude towards CS (U [NJava=262, Nnon-Java=126]=15,237.00, z=-1.23, p=0.22). In addition, the residents' training year also affected the residents' response (H(2)=14.278, p<0.01). CONCLUSION: Cardiology residents' attitudes towards CS are significantly influenced by training year and university but not gender or university location. The results might provide insightful information for further improvement of CS in cardiology training and guide further evaluation.

Intramyocardial Stem Cell Transplantation during Coronary Artery Bypass Surgery Safely Improves Cardiac Function: Meta-Analysis of 20 Randomized Clinical Trials.

IMSC transplantation during CABG is considered one of the most promising methods to effectively deliver stem cells and has been widely studied in many trials. But the results of outcomes and safety of this modality still vary widely. We conducted this meta-analysis of randomized controlled trials (RCTs) to evaluate not only the outcome but also the safety of this promising method. A meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search was undertaken using the PubMed, Scopus, and Cochrane databases. Articles were thoroughly evaluated and analyzed. Twenty publications about IMSC during CABG were included. Primary outcomes were measured using LVEF, LVESV, LVESVI, LVESD, LVEDV, LVEDVI, LVEDD, WMSI, and 6-MWT. Safety measures were depicted by total deaths, MACE, CRD, CVA, myocardial infarction, ventricular arrhythmia, and cardiac-related readmission. IMSC transplantation during CABG significantly improved LVEF (MD = 3.89%; 95% CI = 1.31% to 6.46%; p = 0.003) and WMSI (MD = 0.28; 95% CI = 0.01-0.56; p = 0.04). Most of the other outcomes showed favorable results for the IMSC group but were not statistically significant. The safety analysis also showed no significant risk difference for IMSC transplantation compared to CABG alone. IMSC during CABG can safely improve cardiac function and tend to improve cardiac volumes and dimensions. The analysis and application of influencing factors that increase patients' responses to IMSC transplantation are important to achieve long-term improvement.