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.

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.

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).

The Influence of Special Military Training on Left Ventricular Adaptation to Exercise in Elite Air Force Soldiers.

Purpose: The purpose of this study was to observe the influence of level physical training intensity on left ventricular (LV) adaptation in elite air force soldiers compared to regular basic military training. Methods: The LV adaptation of special military physical training for elite air force soldiers was compared with basic military training for regular troops. A group of the nonmilitary subject was also evaluated as a control group. The presence of LV adaptation was evaluated using some echocardiography parameters, including LV mass index (LVMI), LV ejection fraction (LVEF), global longitudinal strain (GLS), and myocardial work index. The parameters of the myocardial work index include global constructive work (GCW), global wasted work (GWW), global work index (GWI), and global work efficiency (GWE). Results: Forty-three elite air force soldiers underwent special military training, 43 regular troops underwent basic military training, and 23 nonmilitary subjects as a control group. Age, heart rate, blood pressure, and Cooper test results significantly differed among the three groups. Multivariate analysis among all groups showed that the level of physical training was associated with the LVMI (coefficient ß = 6.061; 95% confidence interval [CI] = 1.91-10.22; P = 0.005), LVEF (coefficient ß = -1.409; 95% CI = -2.41-[-0.41]; P = 0.006), LVGLS (coefficient ß = 1.726; 95% CI = 1.20-2.25; P < 0.001), GWW (coefficient ß = -13.875; 95% CI = -20.88-[-6.87]; P < 0.001), GWE (coefficient ß = 0.954; 95% CI = 0.62-1.26; P < 0.001), GCW (coefficient ß = 176.128; 95% CI = 121.16-231.10; P < 0.001), and GWI (coefficient ß = 196.494; 95% CI = 144.61-248.38; P < 0.001). Conclusions: Higher intensity of physical training observed in a special military training is associated with higher LV GLS, GWE, GCW, GWI, and lower GWW value suggesting greater physiological adaptation than the lower intensity training.

Smartphone-Based Cardiac Rehabilitation Program Improves Functional Capacity in Coronary Heart Disease Patients: A Systematic Review and Meta-Analysis.

Cardiac rehabilitation (CR) reduces mortality and morbidity in coronary heart disease (CHD); however, patients show a lack of adherence to CR. Alternatively, telehealth interventions have shown promising results for improving target outcomes in CR. This study aimed to review the effect of smartphone-based CR on the functional capacity of CHD patients. A literature search was performed using PubMed, MEDLINE, Embase, and Cochrane Library on 21 March, 2022 to find randomised controlled trials on smartphone usage in CR to improve functional capacity. Outcomes included maximal oxygen consumption (VO2 max), a 6-min walk test (6-MWT), quality of life, smoking cessation, and modifiable risk factors. Eleven trials recruiting CHD patients were reviewed. Wearable devices connected to smartphone- or chat-based applications were commonly used for CR delivery. Most trials managed to provide exercise prescriptions, education on medication adherence and controlling risk factors, and psychosocial counselling through the intervention. Functional capacity improved significantly following smartphone-based CR in CHD patients compared to control groups, as measured by VO2 max and 6-MWT; patients were more likely to quit smoking. Compared to traditional care, smartphones that delivered CR to CHD patients demonstrate superior outcomes regarding increasing functional capacity. There is no significant improvement on lipid profile, blood pressure, HbA1C, body mass index, and quality of life. It can be used either alone or as an adjunct. Ultimately, the patients' preferences and circumstances should be considered.

Plasma brain derived neurotrophic factor level as a modifying factor for trans fat intake and hypertension.

BACKGROUND & AIM: Long-term consumption of trans-fat has been linked with its incorporation in brain neural membrane that could lead into alteration of signalling pathways, including Brain Derived Neurotrophic Factor (BDNF). As an ubiquitous neurotrophin, BDNF is believed to play a role in the regulation of blood pressure yet prior studies shown conflicting results to its effect. Moreover, direct effect of trans fat intake to hypertension has not yet been elucidated. This study aimed to investigate the role of BDNF and its association between trans-fat intake and hypertension. MATERIALS & METHODS: We conducted a population study in Natuna Regency which once reportedly has the highest prevalence of hypertension from Indonesian National Health Survey. Subjects with hypertension and those without hypertension were recruited for the study. Demographic data, physical examination, and food recall were collected. The level of BDNF from all subjects were obtained through analysis of blood samples. RESULTS: A total of 181 participants were included in this study, comprising 134 (74%) hypertensive subjects and 47 (26%) normotensive subjects. Median of daily trans-fat intake of hypertensive subjects was higher compared to normotensive subjects (0,013 [0,0003-0,07] vs 0,010 [0,0006-0,06] % of total energy/day, p = 0,021). Interaction analysis showed significant results for plasma BDNF level in relationship of trans-fat intake and hypertension (p = 0,011). Trans-fat intake association to hypertension in overall subjects showed odds ratio (OR) of 1,85 95%CI 1,05-3,26 (p = 0,034), while in those with low-middle tercile BDNF level the OR was 3,35 95%CI 1,46-7,68 (p = 0,004). CONCLUSION: Plasma BDNF level has a modifying effect in the association between trans-fat intake and hypertension. Subjects with high trans-fat intake, while having low BDNF level, have the highest probability for hypertension.

Interhospital Transfer versus Direct Admission in Patients with Acute ST-Segment Elevation Myocardial Infarction.

There is concern whether patients with ST-segment elevation myocardial infarction (STEMI) who admitted to a percutaneous coronary intervention (PCI) center from interhospital transfer is associated with longer reperfusion time compared with direct admission. We evaluated the reperfusion delays in patients with STEMI who admitted to a primary PCI center through interhospital transfer or direct admission. We retrospectively analyzed 6,494 consecutive STEMI patients admitted between 2011 and 2019. Compared with direct admission ( n = 4,121; 63%), interhospital transferred patients ( n = 2,373) were younger (55 ± 10 vs. 56 ± 10 years, p < 0.001), had similar gender (85.6 vs. 86% male, p = 0.67), greater proportion of off-hour admission (65.2 vs. 48.3%, p < 0.001), less diabetes mellitus (28 vs. 30.8%, p = 0.019), and received more primary PCI (70.5 vs. 48.7%, p < 0.001). Interhospital transferred patients who received primary PCI ( n = 3,677) or fibrinolytic ( n = 238) had longer symptom-to-PCI center admission time (median, 360 vs. 300 minutes, p < 0.001), shorter door-to-device (DTD) time for primary PCI (median, 74 vs. 87 minutes, p < 0.001), and longer total ischemic time (median, 465 vs. 414 minutes, p < 0.001). Logistic regression in interhospital transferred patients showed that delay in door-in-to-door-out (DI-DO) time at the first hospital was strongly associated with prolonged total ischemic time (adjusted odds ratio = 3.92; 95% confidence interval: 3.06-5.04, p < 0.001). This study suggests that although interhospital transferred patients received more primary PCI with shorter DTD time, interhospital transfer creates longer total ischemic time that associates with the delay in DI-DO time at the first hospital that should be improved.

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.

External Counterpulsation Improves Angiogenesis by Preserving Vascular Endothelial Growth Factor-A and Vascular Endothelial Growth Factor Receptor-2 but Not Regulating MicroRNA-92a Expression in Patients With Refractory Angina.

Objective: External counterpulsation (ECP) provides long-term benefits of improved anginal frequency and exercise tolerance in patients with refractory angina (RA). This is postulated as a result of improved angiogenesis and endothelial function through an increase in shear stress. Angiogenesis is mainly represented by vascular endothelial growth factor-A (VEGF-A) and its receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). The microRNA-92a (miR-92a) is a flow-sensitive miRNA that regulates atherosclerosis and angiogenesis in response to shear stress. Thus, ECP beneficial effect might be achieved through interaction between VEGF-A, VEGFR-2, and miR-92a. This study aims to evaluate the ECP effect on VEGF-A, VEGFR-2, and miR-92a in patients with RA in a sham-controlled manner. Methods: This was a randomized sham-controlled trial, enrolling 50 patients with RA who have coronary artery disease (CAD). Participants were randomized (1:1 ratio) to 35 sessions of either ECP (n = 25) or sham (n = 25), each session lasting for 1 h. Plasma levels of VEGF-A and VEGFR-2 were assayed by the ELISA technique. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure miR-92a circulating levels in plasma. Result: External counterpulsation significantly preserved VEGF-A and VEGFR-2 level compared to sham [ΔVEGF-A: 1 (-139 to 160) vs.-136 (-237 to 67) pg/ml, p = 0.026; ΔVEGFR-2: -171(-844 to +1,166) vs. -517(-1,549 to +1,407) pg/ml, p = 0.021, respectively]. Circulating miR-92a increased significantly in ECP [5.1 (4.2-6.4) to 5.9 (4.8-6.4), p < 0.001] and sham [5.2 (4.1-9.4) to 5.6 (4.8-6.3), p = 0.008] post-intervention. The fold changes tended to be higher in ECP group, although was not statistically different from sham [fold changes ECP = 4.6 (0.3-36.5) vs. sham 2.8 (0-15), p = 0.33)]. Conclusion: External counterpulsation improved angiogenesis by preserving VEGF-A and VEGFR-2 levels. Both ECP and sham increased miR-92a significantly, yet the changes were not different between the two groups. (Study registered on www.clinicaltrials.gov, no: NCT03991871, August 8, 2019, and received a grant from the National Health Research and Development of Ministry of Health of Indonesia, No: HK.02.02/I/27/2020).

Determinants and Prediction Equations of Six-Minute Walk Test Distance Immediately After Cardiac Surgery.

Background: To date, there is no reference for a 6-min walk test distance (6-MWD) immediately after cardiac surgery. Therefore, this study aimed to identify the determinants and to generate equations for prediction reference for 6-MWD in patients immediately after cardiac surgery. Methods: This is a cross-sectional study of the 6-min walk test (6-MWT) prior to participation in the cardiac rehabilitation (CR) program of patients after coronary artery bypass surgery (CABG) or valve surgery. The 6-MWT were carried out in a gymnasium prior to the CR program immediately after the cardiac surgery. Available demographic and clinical data of patients were analyzed to identify the clinical determinants of 6-MWD. Results: This study obtained and analyzed the data of 1,509 patients after CABG and 632 patients after valve surgery. The 6-MWD of all patients was 321.5 ± 73.2 m (60-577). The distance was longer in the valve surgery group than that of patients in the CABG group (327.75 ± 70.5 vs. 313.59 ± 75.8 m, p < 0.001). The determinants which significantly influence the 6-MWD in the CABG group were age, gender, diabetes, atrial fibrillation, and body height, whereas in the valve surgery group these were age, gender, and atrial fibrillation. The multivariable regression models generated two formulas using the identified clinical determinants for patients after CABG: 6-MWD (meter) = 212.57 + 30.47 (if male gender) - 1.62 (age in year) + 1.09 (body height in cm) - 12.68 (if with diabetes) - 28.36 (if with atrial fibrillation), and for patients after valve surgery with the formula: 6-MWD (meter) = 371.05 + 37.98 (if male gender) - 1.36 (age in years) - 10.61 (if atrial with fibrillation). Conclusion: This study identified several determinants for the 6-MWD and successively generated two reference equations for predicting 6-MWD in patients after CABG and valve surgery.

Randomised controlled trial into the role of ramipril in fibrosis reduction in rheumatic heart disease: the RamiRHeD trial protocol.

INTRODUCTION: Rheumatic heart disease (RHD) is a major burden in developing countries and accounts for 80% of all people living with the disease, where it causes most cardiovascular morbidity and mortality in children and young adults. Chronic inflammation and fibrosis of heart valve tissue due to chronic inflammation in RHD will cause calcification and thickening of the impacted heart valves, especially the mitral valve. This fibrogenesis is enhanced by the production of angiotensin II by increased transforming growth factor ß expression and later by the binding of interleukin-33, which is known to have antihypertrophic and antifibrotic effects, to soluble sST2. sST2 binding to this non-natural ligand worsens fibrosis. Therefore, we hypothesise that ACE inhibitors (ACEIs) would improve rheumatic mitral valve stenosis. METHODS AND ANALYSIS: This is a single-centre, double-blind, placebo-controlled, randomised clinical trial with a pre-post test design. Patients with rheumatic mitral stenosis and valve dysfunction will be planned for cardiac valve replacement operation and will be given ramipril 5 mg or placebo for a minimum of 12 weeks before the surgery. The expression of ST2 in the mitral valve is considered to be representative of cardiac fibrosis. Mitral valve tissue will be stained by immunohistochemistry to ST2. Plasma ST2 will be measured by ELISA. This study is conducted in the Department of Cardiology and Vascular Medicine, Universitas Indonesia, National Cardiac Center Harapan Kita Hospital, Jakarta, Indonesia, starting on 27 June 2019. ETHICS AND DISSEMINATION: The performance and dissemination of this study were approved by the ethics committee of National Cardiovascular Center Harapan Kita with ethical code LB.02.01/VII/286/KEP.009/2018. TRIAL REGISTRATION NUMBER: NCT03991910.

The formula for calculating the predicted value of cardiorespiratory endurance using a foot rest-based cardiorespiratory exercise device.

This study developed a formula for calculating the predicted VO2 max value using a prototype model of foot-based cardiorespiratory exercise. Forty sedentary workers (20 men and 20 women) were enrolled via consecutive sampling. They underwent direct measurement of VO2 max using spiroergometry as the gold standard; the predicted VO2 max value was calculated using a prototype model of foot-based cardiorespiratory exercise, which was performed on consecutive days. Multivariate linear regression analysis was used to formulate the equation for the predicted VO2 max value by including potential contributing variables: gender, body height, body weight and heart rate. Bland-Altman test was used for assessing the agreement level for the predicted VO2 max value. The equation for the predicted VO2 max value was formulated as 3.2 + 0.15 optimal exercise heart rate -5.5 sexes (0 for men, 1 for women). The agreement level for the formula was acceptable in all measurement result ranges. The formula developed in this study can be used to measure the predicted VO2 max value with an acceptable agreement level.

Aerobic exercise prescription in heart failure patients with cardiac resynchronization therapy.

Exercise for heart failure patients had been shown to be beneficial in improving functional status, and was reviewed to be safe. In cases of advanced heart failure, Cardiac Resynchronization Therapy (CRT) is a promising medical option before being a heart transplant candidate. CRT itself is a biventricular pacing device, which could detect electrical aberrance in the failing heart and provide a suitable response. Studies have shown that exercise has clear benefits toward improving an overall exercise capacity of the patients. Despite its impacts, these randomized clinical trials have varying exercise regime, and until now there has not been a standardized exercise prescription for this group of patients. The nature of CRT as a pacemaker, sometimes with defibrillator, being attached to a heart failure patient, each has its own potential exercise hazards. Therefore, providing detailed exercise prescription in adjusting to the medical condition is very essential in the field of physical medicine and rehabilitation. Being classified as a high-risk patient group, exercise challenges for the complex heart failure with CRT patients will then be discussed in this literature review, with a general aim to provide a safe, effective, and targeted exercise regime.

Dyslipidemia Increases the Risk of Severe COVID-19: A Systematic Review, Meta-analysis, and Meta-regression.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate whether dyslipidemia affects the mortality and severity of COVID-19, we also aimed to evaluate whether other comorbidities influence the association. METHODS: A systematic literature search using PubMed, Embase, and EuropePMC was performed on 8 October 2020. This study's main outcome is a poor composite outcome, comprising of mortality and severe COVID-19. RESULTS: There were 9 studies with 3,663 patients. The prevalence of dyslipidemia in this pooled analysis was 18% (4%-32%). Dyslipidemia was associated with increased composite poor outcome (RR 1.39 [1.02, 1.88], p=0.010; I2: 56.7%, p=0.018). Subgroup analysis showed that dyslipidemia was associated with severe COVID-19 (RR 1.39 [1.03, 1.87], p=0.008; I2: 57.4%, p=0.029). Meta-regression showed that the association between dyslipidemia and poor outcome varies by age (coefficient: -0.04, p=0.033), male gender (coefficient: -0.03, p=0.042), and hypertension (coefficient: -0.02, p=0.033), but not diabetes (coefficient: -0.24, p=0.135) and cardiovascular diseases (coefficient: -0.01, p=0.506). Inverted funnel-plot was relatively symmetrical. Egger's test indicates that the pooled analysis was not statistically significant for small-study effects (p=0.206). CONCLUSION: Dyslipidemia potentially increases mortality and severity of COVID-19. The association was stronger in patients with older age, male, and hypertension. PROSPERO REGISTRATION NUMBER: CRD42020213491.

Dyslipidemia Increases the Risk of Severe COVID-19: A Systematic Review, Meta-analysis, and Meta-regression.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate whether dyslipidemia affects the mortality and severity of COVID-19, we also aimed to evaluate whether other comorbidities influence the association. METHODS: A systematic literature search using PubMed, Embase, and EuropePMC was performed on 8 October 2020. This study's main outcome is a poor composite outcome, comprising of mortality and severe COVID-19. RESULTS: There were 9 studies with 3663 patients. The prevalence of dyslipidemia in this pooled analysis was 18% (4%-32%). Dyslipidemia was associated with increased composite poor outcome (RR 1.39 [1.02, 1.88], P = .010; I 2: 56.7%, P = .018). Subgroup analysis showed that dyslipidemia was associated with severe COVID-19 (RR 1.39 [1.03, 1.87], P = .008; I 2: 57.4%, P = .029). Meta-regression showed that the association between dyslipidemia and poor outcome varies by age (coefficient: -0.04, P = .033), male gender (coefficient: -0.03, P = .042), and hypertension (coefficient: -0.02, P = .033), but not diabetes (coefficient: -0.24, P = .135) and cardiovascular diseases (coefficient: -0.01, P = .506). Inverted funnel-plot was relatively symmetrical. Egger's test indicates that the pooled analysis was not statistically significant for small-study effects (P = .206). CONCLUSION: Dyslipidemia potentially increases mortality and severity of COVID-19. The association was stronger in patients with older age, male, and hypertension.PROSPERO Registration Number: CRD42020213491.

Availability and delivery of cardiac rehabilitation in South-East Asia: How does it compare globally?

Background: The aims of this study were to establish cardiac rehabilitation (CR) availability and density, as well as the nature of programs in South-East Asian Region (SEAR) countries, and to compare this with other regions globally. Methods: In 2016/2017, the International Council of Cardiovascular Prevention and Rehabilitation engaged cardiac associations to facilitate program identification globally. An online survey was administered to identify programs using REDCap, assessing capacity and characteristics. CR density was computed using Global Burden of Disease study annual ischemic heart disease (IHD) incidence estimates. The program audit was updated in 2020. Results: CR was available in 6/11 (54.5%) SEAR countries. Data were collected in 5 countries (83.3% country response); 32/69 (68.1% response rate from 2016/2017) programs completed the survey. These data were compared to 1082 (32.1%) programs in 93/111 (83.3%) countries with CR. Across SEAR countries, there was only one CR spot per 283 IHD patients (vs. 12 globally), with an unmet regional need of 4,258,968 spots annually. Most programs were in tertiary care centers (n = 25, 78.1%; vs. 46.1% globally, P < 0.001). Most were funded privately (n = 17, 56.7%; vs. 17.9%, P < 0.001), and 22 (73.3%) patients were paying out of pocket (vs. 36.2% globally; P < 0.001). The mean number of staff on the multidisciplinary teams was 5.5 ± 3.0 (vs. 5.9 ± 2.8 globally P = 0.268), offering 8.6 ± 1.7/11 core components (consistent with other countries) over 16.8 ± 12.6 h (vs. 36.2 ± 53.3 globally, P = 0.01). Conclusion: Funded CR capacity must be augmented in SEAR. Where available, services were consistent with guidelines, and other regions of the globe, despite programs being shorter than other regions.

Angiotensin Converting Enzyme Inhibitors (ACEIs) Decrease the Progression of Cardiac Fibrosis in Rheumatic Heart Disease Through the Inhibition of IL-33/sST2.

Rheumatic heart disease (RHD) is common in developing countries and poses a big medical challenge and burden. The pathogenesis of RHD is influenced by the triad of host, agent, and environment. Autoantigens generated from Group A Streptococcus (GAS) infection are captured by the resident dendritic cells (DCs) in the heart's valvular endothelium. DCs differentiate into antigen presenting cells (APC) in the valve interstices. APC induces activation of autoreactive T cells, which triggers inflammation and tissue fibrosis. Cardiac fibrosis is promoted through the activation of Mitogen activated protein kinases (MAPKs) and its downstream signaling, including its interaction with transforming growth factor-ß (TGF-ß) and Smad proteins. TGF-ß-induced phosphorylation of Smad2 complexes with Smad3 and Smad4, and translocates into the nucleus. Angiotensin II enhances the migration, maturation, and presentation of DC. In RHD, Angiotensin II induces fibrosis via the stimulation of TGF-ß, which further increases the binding of IL-33 to sST2 but not ST2L, resulting in the upregulation of Angiotensin II and progression of cardiac fibrosis. This cascade of inflammation and valvular fibrosis causes calcification and stiffening of the heart valves in RHD. Angiotensin converting enzyme inhibitors (ACEIs) inhibit Angiotensin II production, which in turn decreases TGF-ß expression and the onset of overt inflammatory response. This condition leads to a reduction in the sST2 as the decoy receptor to "steal" IL-33, and IL-33 binds to ST2L and results in cardioprotection against cardiac fibrosis in the pathogenesis of RHD.

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.

"Door-In to Door-Out" Delay in Patients with Acute ST-Segment Elevation Myocardial Infarction Transferred for Primary Percutaneous Coronary Intervention in a Metropolitan STEMI Network of a Developing Country.

Background Routine performance measures of primary percutaneous coronary intervention (PCI) within an ST-segment elevation myocardial infarction (STEMI) network are needed to improve care. Objective We evaluated the door-in to door-out (DI-DO) delays at the initial hospitals in STEMI patients as a routine performance measure of the metropolitan STEMI network. Patients and Methods We retrospectively analyzed the DI-DO time from 1,076 patients with acute STEMI who were transferred by ground ambulance to a primary PCI center for primary PCI between 4 October 2014 and 1 April 2019. Correlation analysis between DI-DO times and total ischemia time was performed using Spearman's test. Logistic regression analyses were used to find variables associated with a longer DI-DO time. Results Median DI-DO time was 180 minutes (25th percentile to 75th percentile: 120-252 minutes). DI-DO time showed a positive correlation with total ischemia time ( r = 0.4, p < 0.001). The median door-to-device time at the PCI center was 70 minutes (25th percentile to 75th percentile: 58-88 minutes). Multivariate analysis showed that women patients were independently associated with DI-DO time > 120 minutes (odds ratio 1.55, 95% confidence interval 1.03 to 2.33, p = 0.03). Conclusion The DI-DO time reported in this study has not reached the guideline recommendation. To improve the overall performance of primary PCI in the region, interventions aimed at improving the DI-DO time at the initial hospitals and specific threat for women patients with STEMI are possibly the best efforts in improving the total ischemia time.

Promoting patient utilization of outpatient cardiac rehabilitation: A joint International Council and Canadian Association of Cardiovascular Prevention and Rehabilitation position statement.

BACKGROUND: Cardiac Rehabilitation (CR) is a recommendation in international clinical practice guidelines given its' benefits, however use is suboptimal. The purpose of this position statement was to translate evidence on interventions that increase CR enrolment and adherence into implementable recommendations. METHODS: The writing panel was constituted by representatives of societies internationally concerned with preventive cardiology, and included disciplines that would be implementing the recommendations. Patient partners served, as well as policy-makers. The statement was developed in accordance with AGREE II, among other guideline checklists. Recommendations were based on our update of the Cochrane review on interventions to promote patient utilization of CR. These were circulated to panel members, who were asked to rate each on a 7-point Likert scale in terms of scientific acceptability, actionability, and feasibility of assessment. A web call was convened to achieve consensus and confirm strength of the recommendations (based on GRADE). The draft underwent external review and public comment. RESULTS: The 3 drafted recommendations were that to increase enrolment, healthcare providers, particularly nurses (strong), should promote CR to patients face-to-face (strong), and that to increase adherence part of CR could be delivered remotely (weak). Ratings for the 3 recommendations were 5.95 ±â€¯0.69 (mean ±â€¯standard deviation), 5.33 ±â€¯1.12 and 5.64 ±â€¯1.08, respectively. CONCLUSIONS: Interventions can significantly increase utilization of CR, and hence should be widely applied. We call upon cardiac care institutions to implement these strategies to augment CR utilization, and to ensure CR programs are adequately resourced to serve enrolling patients and support them to complete programs.