National Tunisian Study of Cardiac Implantable Electronic Devices: Design and Protocol for a Nationwide Multicenter Prospective Observational Study.

BACKGROUND: In Tunisia, the number of cardiac implantable electronic devices (CIEDs) is increasing, owing to the increase in patient life expectancy and expanding indications. Despite their life-saving potential and a significant reduction in population morbidity and mortality, their increased numbers have been associated with the development of multiple early and late complications related to vascular access, pockets, leads, or patient characteristics. OBJECTIVE: The study aims to identify the rate, type, and predictors of complications occurring within the first year after CIED implantation. It also aims to describe the demographic and epidemiological characteristics of a nationwide sample of patients with CIED in Tunisia. Additionally, the study will evaluate the extent to which Tunisian electrophysiologists follow international guidelines for cardiac pacing and sudden cardiac death prevention. METHODS: The Tunisian National Study of Cardiac Implantable Electronic Devices (NATURE-CIED) is a national, multicenter, prospectively monitored study that includes consecutive patients who underwent primary CIED implantation, generator replacement, and upgrade procedure. Patients were enrolled between January 18, 2021, and February 18, 2022, at all Tunisian public and private CIED implantation centers that agreed to participate in the study. All enrolled patients entered a 1-year follow-up period, with 4 consecutive visits at 1, 3, 6, and 12 months after CIED implantation. The collected data are recorded electronically on the clinical suite platform (DACIMA Clinical Suite). RESULTS: The study started on January 18, 2021, and concluded on February 18, 2023. In total, 27 cardiologists actively participated in data collection. Over this period, 1500 patients were enrolled in the study consecutively. The mean age of the patients was 70.1 (SD 15.2) years, with a sex ratio of 1:15. Nine hundred (60%) patients were from the public sector, while 600 (40%) patients were from the private sector. A total of 1298 (86.3%) patients received a conventional pacemaker and 75 (5%) patients received a biventricular pacemaker (CRT-P). Implantable cardioverter defibrillators were implanted in 127 (8.5%) patients. Of these patients, 45 (3%) underwent CRT-D implantation. CONCLUSIONS: This study will establish the most extensive contemporary longitudinal cohort of patients undergoing CIED implantation in Tunisia, presenting a significant opportunity for real-world clinical epidemiology. It will address a crucial gap in the management of patients during the perioperative phase and follow-up, enabling the identification of individuals at particularly high risk of complications for optimal care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05361759; https://classic.clinicaltrials.gov/ct2/show/NCT05361759. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/47525.

Nurse-led home-based detection of cardiac dysfunction by ultrasound: results of the CUMIN pilot study.

Aims: Access to echocardiography is a significant barrier to heart failure (HF) care in many low- and middle-income countries. In this study, we hypothesized that an artificial intelligence (AI)-enhanced point-of-care ultrasound (POCUS) device could enable the detection of cardiac dysfunction by nurses in Tunisia. Methods and results: This CUMIN study was a prospective feasibility pilot assessing the diagnostic accuracy of home-based AI-POCUS for HF conducted by novice nurses compared with conventional clinic-based transthoracic echocardiography (TTE). Seven nurses underwent a one-day training program in AI-POCUS. A total of 94 patients without a previous HF diagnosis received home-based AI-POCUS, POC N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, and clinic-based TTE. The primary outcome was the sensitivity of AI-POCUS in detecting a left ventricular ejection fraction (LVEF) <50% or left atrial volume index (LAVI) >34 mL/m2, using clinic-based TTE as the reference. Out of seven nurses, five achieved a minimum standard to participate in the study. Out of the 94 patients (60% women, median age 67), 16 (17%) had an LVEF < 50% or LAVI > 34 mL/m2. AI-POCUS provided an interpretable LVEF in 75 (80%) patients and LAVI in 64 (68%). The only significant predictor of an interpretable LVEF or LAVI proportion was the nurse operator. The sensitivity for the primary outcome was 92% [95% confidence interval (CI): 62-99] for AI-POCUS compared with 87% (95% CI: 60-98) for NT-proBNP > 125 pg/mL, with AI-POCUS having a significantly higher area under the curve (P = 0.040). Conclusion: The study demonstrated the feasibility of novice nurse-led home-based detection of cardiac dysfunction using AI-POCUS in HF patients, which could alleviate the burden on under-resourced healthcare systems.

Low-Dose Colchicine in Patients With Type 2 Diabetes and Recent Myocardial Infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).

OBJECTIVE: The cardiovascular benefits of low-dose colchicine have been demonstrated in patients with coronary disease. Its effects were evaluated in this prespecified analysis in patients with type 2 diabetes (T2D) from the Colchicine Cardiovascular Outcomes Trial (COLCOT). RESEARCH DESIGN AND METHODS: COLCOT was a randomized, double-blinded trial of colchicine, 0.5 mg daily, versus placebo initiated within 30 days after a myocardial infarction. RESULTS: There were 959 patients with T2D enrolled and monitored for a median of 22.6 months. A primary end point event occurred in 8.7% of patients in the colchicine group and in 13.1% in the placebo group (hazard ratio 0.65; 95% CI 0.44-0.96; P = 0.03). Nausea was reported in 2.7% and 0.8% in the study groups (P = 0.03), and pneumonia occurred in 2.4% and 0.4% (P = 0.008). CONCLUSIONS: Among patients with T2D and a recent myocardial infarction, colchicine, 0.5 mg daily, leads to a large reduction of cardiovascular events. These results support the conduct of the COLCOT-T2D trial in primary prevention.

Clinical features, socioeconomic status, management, short and long-term outcomes of patients with acute myocardial infarction: Phase I results of PEACE MENA registry.

BACKGROUND: The Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa (PEACE MENA) is a prospective registry program in Arabian countries that involves in patients with acute myocardial infarction (AMI) or acute heart failure (AHF). METHODS: This prospective, multi-center, multi-country study is the first report of the baseline characteristics and outcomes of inpatients with AMI who were enrolled during the first 14-month recruitment phase. We report the clinical characteristics, socioeconomic, educational levels, and management, in-hospital, one month and one-year outcomes. RESULTS: Between April 2019 and June 2020, 1377 patients with AMI were enrolled (79.1% males) from 16 Arabian countries. The mean age (± SD) was 58 ± 12 years. Almost half of the population had a net income < $500/month, and 40% had limited education. Nearly half of the cohort had a history of diabetes mellitus, hypertension, or hypercholesterolemia; 53% had STEMI, and almost half (49.7%) underwent a primary percutaneous intervention (PCI) (lowest 4.5% and highest 100%). Thrombolytics were used by 36.2%. (Lowest 6.45% and highest (90.9%). No reperfusion occurred in 13.8% of patients (lowest was 0% and highest 72.7%).Primary PCI was performed less frequently in the lower income group vs. high income group (26.3% vs. 54.7%; P<0.001). Recurrent ischemia occurred more frequently in the low-income group (10.9% vs. 7%; P = 0.018). Re-admission occurred in 9% at 1 month and 30% at 1 year, whereas 1-month mortality was 0.7% and 1-year mortality 4.7%. CONCLUSION: In the MENA region, patients with AMI present at a young age and have a high burden of cardiac risk factors. Most of the patients in the registry have a low income and low educational status. There is heterogeneity among key performance indicators of AMI management among various Arabian countries.

Relationship between serum interleukin-6 levels and severity of coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Cytokines play a potential role in atherosclerosis pathogenesis and progression. We investigated the association of interleukin-6 (IL-6) with the angiographic severity of coronary artery disease (CAD). METHODS: Three hundred ten angiografically diagnosed CAD patients and 210 controls were enrolled in this study. CAD patients were stratified according to IL-6 cut-off value into high levels IL-6 group (≥ 9.5 pg/mL) and low levels IL-6 group (< 9.5 pg/mL). The severity of CAD was assessed according to Gensini score (GS), artery stenosis degree and the number of vessels involved. The mean age was 60.3 ± 11.0 years. RESULTS: The level of IL-6 in patients was increased compared to controls and ranged from 1.5 to 3640.0 pg/mL. High levels of IL-6 were significantly associated with high levels of GS (> 40) but not with stenosis degree and vessel score. GS levels were significantly more elevated in patients with high levels of IL-6 group than in low IL6 levels patients (60.6 ± 39.5 vs 46.7 ± 37.2; p = 0.027). The analysis of the ROC curve performed in myocardial infarction patients showed that IL-6 (AUC: 0.941 (CI 95% 0.886, 0.997; p < 0.001) could be a powerful predictor marker in evaluating the infarct size after myocardial infarction when compared to myonecrosis biomarkers. CONCLUSIONS: IL-6 levels were associated with the severity of CAD assessed by the GS. Based on the highest levels of IL-6 measured in patients with STEMI, our study strongly suggests that IL-6 could be a powerful marker in evaluating the myocardial necrosis. TRIAL REGISTRATION: ClinicalTrials.gov Number: NCT03075566 (09/03/2017).

Reproducibility of transthoracic 3D echocardiography in the assessment of mitral valve area in patients with rheumatic mitral stenosis: real time versus ECG-gated 3D echocardiography.

PURPOSE: To assess reproducibility of Real time 3D echocardiography (RT3D) and ECG-gated 3D echocardiography (EG3D) when measuring the mitral valve area (MVA) in rheumatic mitral stenosis (MS). METHODS: MVA was assessed by three operators in 68 MS patients using RT3D and EG3D. Reproducibility of each technique was determined by calculating the standard error of measurements (SEM). RESULTS: SEM was similar between RT3D and EG3D. MVA variability was of 0.4 cm² or 30% of any RT3D or EG3D measured MVA. The minimal change in MVA above which two measurements should be considered to differ significantly for the same operator was of 0.4 cm² for RT3D and 0.5 cm² for EG3D. For two different operators making successive measurements, the minimum significant change was of 0.5 cm² for RT3D and 0.6 cm² for EG3D. The minimum significant difference when switching from RT3D to EG3D or vice versa is of 0.6 cm². Low temporal resolution of 6 Hz has the least variability when using RT3D (0.19 cm² vs. 0.26 cm², p = 0.009) but significantly underestimated MVA (1.3 ± 0.4 cm² vs. 1.4 ± 0.4 cm², p < 10- 3) when compared to EG3D. MVA variability was significantly higher in mild MS when compared to severe MS whether it is RT3D (0.23 cm² vs. 0.18 cm², p = 0.02) or EG3D (0.27 cm² vs. 0.16 cm², p < 0.001). CONCLUSION: RT3D and EG3D are equally reproducible in the assessment of MVA in patients with MS. Further measurements standardization is required to have a clinically acceptable estimations of the true 3D MVA and minimal detectable differences.

[Pulmonary embolism: the Pulmonary Embolism Severity Index (PESI) score and mortality predictors]. / Embolie pulmonaire: indice de sévérité de l'embolie pulmonaire (ISEP) score et facteurs prédictifs de mortalité.

Introduction: pulmonary embolism is a real public health problem because of its high morbidity and mortality rate. The purpose of this study is to evaluate the impact of PESI score on the prognosis of pulmonary embolism. Methods: we conducted a retrospective study of 146 cases of formally confirmed embolism. Pulmonary embolism severity index (PESI) score was calculated for the entire study population. The patients were divided into 2 groups: a low-risk group (LR) comprising patients in risk classes I and II: 83 patients; a high-risk group (HR) comprising patients in risk classes III, IV and V: 63 patients; the primary endpoint of the study (MACE) was the occurrence of shock, the need for mechanical ventilation, and the occurrence of in-hospital death. Results: total in-hospital mortality was 15.1%, significantly higher in the HR group (25.4% versus 7.2%, p=0.001). In logistic regression analysis, being in the HR group (OR=5.1; 95% CI: [1,637 - 16,093]; p=0.005)) and having renal impairment (OR=4.5; 95% CI: [1.457 - 14.075]; p=0.009) were the independent factors for the occurrence of MACE. After a mean follow-up of 18 ± 8 months, there were more deaths in the HR group (68.4% versus 33%, p=0.004). Conclusion: the results of our study show that the PESI score is correlated with the severity of PE. This should encourage the widespread use of this risk score.

Spontaneous Hemopericardium Complicated by Tamponade in a Child With Moderate Hemophilia A: Case-Based Review.

Hemophilia A is the most common severe innate bleeding disorder. It is an X-linked recessive inherited bleeding disorder characterized by a qualitative and/or quantitative deficiency of factor VIII. The clinical manifestation of this disease is hemorrhaging that can affect every organ, in particular joints (hemarthrosis) and muscles (hematoma). Some serious but rare hemorrhages can be life-threatening, in particular hemorrhage of the central nervous system and hemopericardium. We report a rare case of spontaneous hemopericardium complicated by tamponade in a child with moderate hemophilia A treated with Factor VIII replacement infusion and pericardial drainage, with a favorable outcome. To our knowledge, this is the second case described in the literature of spontaneous hemopericardium occurring in a child with hemophilia A. Our case suggests that a dose of 50 IU/kg/8 h of factor VIII maintained for up to one day after removal of the pericardial drain seems to be sufficient to ensure correct hemostasis, though further evidence is needed to confirm this impression.

Clinical Features, Socioeconomic Status, Management, and Outcomes of Acute Heart Failure: PEACE MENA Registry Phase I Results.

INTRODUCTION: PEACE MENA (Program for the Evaluation and Management of Cardiac Events in the Middle East and North Africa) is a prospective registry in Arab countries for in-patients with acute myocardial infarction (AMI) or acute heart failure (AHF). Here, we report the baseline characteristics and outcomes of in-patients with AHF who were enrolled during the first 14 months of the recruitment phase. METHODS: A prospective, multi-centre, multi-country study including patients hospitalized with AHF was conducted. Clinical characteristics, echocardiogram, BNP (B-type natriuretic peptide), socioeconomic status, management, 1-month, and 1-year outcomes are reported. RESULTS: Between April 2019 and June 2020, a total of 1258 adults with AHF from 16 Arab countries were recruited. Their mean age was 63.3 (±15) years, 56.8% were men, 65% had monthly income ≤US$ 500, and 56% had limited education. Furthermore, 55% had diabetes mellitus, 67% had hypertension; 55% had HFrEF (heart failure with reduced ejection fraction), and 19% had HFpEF (heart failure with preserved ejection fraction). At 1 year, 3.6% had a heart failure-related device (0-22%) and 7.3% used an angiotensin receptor neprilysin inhibitor (0-43%). Mortality was 4.4% per 1 month and 11.77% per 1-year post-discharge. Compared with higher-income patients, lower-income patients had a higher 1-year total heart failure hospitalization rate (45.6 vs 29.9%, p=0.001), and the 1-year mortality difference was not statistically significant (13.2 vs 8.8%, p=0.059). CONCLUSION: Most of the patients with AHF in Arab countries had a high burden of cardiac risk factors, low income, and low education status with great heterogeneity in key performance indicators of AHF management among Arab countries.

Effects of aspirin on cardiovascular outcomes in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) carry a high cardiovascular (CV) risk. Since whether this risk is reduced by aspirin is unclear, we examined if the effect of aspirin on cardiovascular outcomes varied by baseline kidney function in a primary cardiovascular disease prevention trial. The International Polycap Study-3 (TIPS-3) trial had randomized people without previous cardiovascular disease to aspirin (75 mg daily) or placebo. We now examined aspirin versus placebo on cardiovascular events in participants grouped by estimated glomerular filtration rate (eGFR), using a threshold of 60 ml/min/1.73 m2, and by using tertiles of eGFR. The primary outcome was a composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. A total of 5712 participants were randomized with a mean follow-up of 4.6 years. Of these, 983 (17.2%) had an eGFR under 60 ml/min/1.73 m2 (mean eGFR 49 ml/min/1.73 m2) and 4,729 over 60 ml/min/1.73 m2 (mean 84 ml/min/1.73 m2). In participants with an eGFR under 60 ml/min/1.73 m2 there were 26 primary outcomes in 502 participants on aspirin and 39/481 on placebo (hazard ratio 0.57; 95% confidence interval 0.34-0.94). In participants with an eGFR over 60 ml/min/1.73 m2 there were 90 primary outcomes in 2357 participants on aspirin and 95/2372 on placebo (0.95; 0.71-1.27). With tertiles of eGFR under 70, 70-90, and over 90 ml/min/1.73 m2, risk reductions with aspirin for the primary outcome were larger at lower eGFR levels (0.62; 0.43-0.91) for the lowest tertile, (0.96; 0.62-1.49) for the middle, and (1.30; 0.77-2.18) for the highest tertile. Thus, our findings support aspirin may reduce cardiovascular events in people with moderate to advanced stage CKD.

Combination Therapy With Nicardipine and Isosorbide Dinitrate to Prevent Spasm in Transradial Percutaneous Coronary Intervention (from the NISTRA Multicenter Double-Blind Randomized Controlled Trial).

Verapamil and nitroglycerin are widely used to prevent radial artery spasm (RAS) during percutaneous cardiovascular procedures. However, these agents are not typically available in most African countries and consequently, isosorbide dinitrate is often the only spasmolytic treatment. Our aim was to compare the efficacy of isosorbide dinitrate alone versus isosorbide dinitrate used together with nicardipine to prevent RAS during transradial coronary procedures. This was a randomized controlled double-blind multicenter trial. Patients (n = 1,523) were randomized to receive either a sole therapy of isosorbide dinitrate (n = 760) or the combination of isosorbide dinitrate and nicardipine (n = 763). Our primary end point was the occurrence of RAS; defined as considerable perceived hindrance of catheter advancement. Our secondary end points were severe RAS; defined as (1) severe arm pain, (2) the need for either morphine or midazolam treatment, and (3) necessity for crossover to the contralateral radial or femoral artery. RAS incidence was reduced with the combination therapy versus isosorbide dinitrate alone (15% vs 25%, p <0.001), with a number needed to treat of 10 patients. There was also a significant reduction in the incidence of the secondary end points with combination therapy (3.6% vs 8.2%, p <0.001), with a number needed to treat of 22 patients. This result was driven by reductions in both femoral crossover (0.5% vs 2.4%, p = 0.003) and the use of morphine or midazolam injections (1.6% vs 3.5%, p = 0.02) with combination therapy. In conclusion, we demonstrated the superiority of the combination therapy of isosorbide dinitrate and nicardipine over isosorbide dinitrate alone in reducing the incidence of RAS.

Impact of dual antiplatelet therapy duration on clinical outcome after coronary bifurcation stenting: results from the EuroBifurcation Club registry.

BACKGROUND: Optimal duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) of a bifurcation stenosis is still debated. We evaluated the impact of DAPT duration on clinical outcomes in all-comers patients undergoing bifurcation PCI included in the European Bifurcation Club (EBC) registry. METHODS: We enrolled 2284 consecutive patients who completed at least 18 months follow-up. The cumulative occurrence of major adverse cardiac and cardiovascular events (MACCE), defined as a composite of overall-death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR) and stroke were evaluated. Bleedings classified as Bleeding Academic Research Consortium (BARC) ≥3 were evaluated too. RESULTS: Patients were divided into 3 groups: short DAPT (<6-months, N.=375); standard DAPT (≥6-months but ≤12-months, N.=636); prolonged DAPT (>12-months, N.=1273). At 24 months follow-up MACCE-free survival was significantly lower in short DAPT patients (Log-Rank: 45.23, P for trend <0.001). MACCE occurred less frequently in the prolonged DAPT group (148 [11.6%]) as compared with both the short (83 [22.1%] HR: 0.48 [0.37-0.63], P<0.001) and standard DAPT groups (137 [21.5%] HR:0.51 [0.41-0.65], P<0.001). These differences remain after propensity score adjustment (respectively, HR: 0.27 [0.20-0.36] and HR: 0.44 [0.34-0.57]). Such finding was consistent in patients presenting with both acute and chronic coronary syndromes. BARC≥3 bleedings were 0.3% in the standard DAPT, 1.6% in short and 1.9% in prolonged DAPT groups. CONCLUSIONS: In the "real-world" EBC registry of patients undergoing PCI of coronary artery bifurcation stenosis, a prolonged DAPT duration was associated with a significantly lower risk of MACCE and a potential increased risk of major bleedings.

Impact of dual antiplatelet therapy duration on clinical outcome after coronary bifurcation stenting: results from the euro bifurcation club registry

BACKGROUND: Optimal duration of Dual Antiplatelet Therapy (DAPT) following percutaneous coronary intervention (PCI) of a bifurcation stenosis is still debated. We evaluated the impact of DAPT duration on clinical outcomes in all-comers patients undergoing bifurcation PCI included in the European Bifurcation Club (EBC) registry. METHODS: We enrolled 2284 consecutive patients who completed at least 18 months follow-up. The cumulative occurrence of Major Adverse Cardiac and Cardiovascular Events (MACCE), defined as a composite of overall-death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR) and stroke were evaluated. Bleedings classified as BARC ≥ 3 were evaluated too. RESULTS: Patients were divided into 3 groups: Short DAPT (<6-months, n=375); Standard DAPT (≥6-months but ≤12-months, n=636); Prolonged DAPT (>12- months, n=1273). At 24 months follow-up MACCE-free survival was significantly lower in Short DAPT patients (Log-Rank: 45.23, p for trend <0.001). MACCE occurred less frequently in the Prolonged DAPT group (148 (11.6%)) as compared with both the Short (83 (22.1%) HR:0.48 (0.37-0.63), p<0.001) and Standard DAPT groups (137 (21.5%) HR:0.51 (0.41-0.65), p<0.001). These differences remain after propensity score adjustment (respectively, HR: 0.27 (0.20-0.36) and HR: 0.44 (0.34-0.57)). Such finding was consistent in patients presenting with both acute and chronic coronary syndromes. BARC ≥ 3 bleedings were 0.3% in the Standard DAPT, 1.6% in Short and 1.9% in Prolonged DAPT groups. CONCLUSIONS: In the "real-world" EBC registry of patients undergoing PCI of coronary artery bifurcation stenosis, a prolonged DAPT duration was associated with a significantly lower risk of MACCE and a potential increased risk of major bleedings.

The cost implications of a polypill for primary prevention in the TIPS-3 trial.

AIMS: The International Polycap Study 3 (TIPS-3) trial demonstrated that a polypill containing cholesterol- and multiple blood-pressure-lowering drugs reduces cardiovascular events by 20% compared with placebo in people without cardiovascular disease. The polypill plus aspirin led to a 31% relative risk reduction in cardiovascular disease events compared with double placebo. We report regional variations in costs and affordability of a polypill based on the TIPS-3 trial. METHODS AND RESULTS: Countries were categorized using World Bank economic groups: lower-middle-income, upper-middle-income, and high-income countries. Country-specific costs were obtained for hospitalization events, procedures, and non-study medications (2019 US dollars). Polypill price was based on the cheapest equivalent substitute (CES) for each component. For the polypill vs. placebo, the difference in cost over the 4.6 years of the trial was $291 [95% confidence interval (CI): $243-339] per participant in lower-middle-income countries, $1068 (95% CI: $992-1144) in upper-middle-income countries, and $48 (95% CI: -$271 to $367) in high-income countries. Results were similar for the polypill plus aspirin vs. a double placebo. In both cases, the polypill was affordable in all groups using monthly household capacity to pay or a threshold of 4% of the gross national income per capita. CONCLUSION: The use of a polypill (CES) in TIPS-3 increases costs in lower-middle-income countries and upper-middle-income countries but is affordable in countries at various economic levels and is cost neutral (dominant) in high-income countries.

Left atrium reservoir function is central in patients with rheumatic mitral stenosis.

We investigated the relationship between Left Atrium strain reservoir function and symptoms and its impact on modulating Left Ventricular mechanics, diastolic filling, stroke volume, mean trans-mitral gradient and pulmonary pressure in mitral stenosis (MS) patients. We examined 195 full spectrum MS patients which were divided into two groups: Group 1 (n = 109) included patients with NYHA I & II functional class and group 2 (n = 86) included patients with NYHA III & IV functional class. LA strain reservoir function and classical echocardiographic parameters were calculated. LASr was significantly higher in group 1 versus group 2 in patients with MVA ≤ 1cm2 [8.8(6.0-12.6) vs 6.8(4.1-8.9), p = 0.03) and when 1cm2 < MVA ≤ 1.5 cm2 [10.0 (5.4-13.8) vs 6.7(4.5-9.0), p = 0.02). In patients with Pulmonary Hypertension, group 1 had significantly higher LASr than group 2 [11.1(6.6-14.8) vs 5.9(4.3-9.0), p = 0.002) By multivariate analysis, diabetes (OR = 4.11, 95%CI: 1.6-10.4), stroke (OR = 2.9, 95%CI: 1.1-7.9), LASr (OR = 0.9, 95%CI: 0.80-0.99) and LV ejection fraction (LVEF)(OR = 0.9, 95%CI: 0.91-0.99) were independently associated with NYHA functional class. LASr was significantly and positively correlated to MVA (r = 0.3, p < 10-3), stroke volume (r = 0.25, p = 10-3), mitral inflow (r = 0.4, p < 10-3) and LVEF(r = 0.14, p = 0.05). It was significantly and negatively correlated to left ventricular strain (r = -0.65, p < 10-3), LA indexed volume (r = -0.40, p < 10-3), maximum tricuspid regurgitation velocity (r = -0.25, p = 0.003), MTMG (r = -0.25, p = 10-3), and heart rate (r = -0.4, p < 10-3). We demonstrated a large range of interaction between LASr and mitral valve echocardiographic parameters. This may explain the reasons we identified LASr as an independent factor for MS functional tolerance.

2021 Asian Pacific Society of Cardiology Consensus Recommendations on the Use of P2Y12 Receptor Antagonists in the Asia-Pacific Region: Special Populations.

Advanced age, diabetes, and chronic kidney disease not only increase the risk for ischaemic events in chronic coronary syndromes (CCS) but also confer a high bleeding risk during antiplatelet therapy. These special populations may warrant modification of therapy, especially among Asians, who have displayed characteristics that are clinically distinct from Western patients. Previous guidance has been provided regarding the classification of high-risk CCS and the use of newer-generation P2Y12 inhibitors (i.e. ticagrelor and prasugrel) after acute coronary syndromes (ACS) in Asia. The authors summarise evidence on the use of these P2Y12 inhibitors during the transition from ACS to CCS and among special populations. Specifically, they present recommendations on the roles of standard dual antiplatelet therapy, shortened dual antiplatelet therapy and single antiplatelet therapy among patients with coronary artery disease, who are either transitioning from ACS to CCS; elderly; or with chronic kidney disease, diabetes, multivessel coronary artery disease and bleeding events during therapy.

Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: an individual participant data meta-analysis.

BACKGROUND: In randomised controlled trials, fixed-dose combination treatments (or polypills) have been shown to reduce a composite of cardiovascular disease outcomes in primary prevention. However, whether or not aspirin should be included, effects on specific outcomes, and effects in key subgroups are unknown. METHODS: We did an individual participant data meta-analysis of large randomised controlled trials (each with ≥1000 participants and ≥2 years of follow-up) of a fixed-dose combination treatment strategy versus control in a primary cardiovascular disease prevention population. We included trials that evaluated a fixed-dose combination strategy of at least two blood pressure lowering agents plus a statin (with or without aspirin), compared with a control strategy (either placebo or usual care). The primary outcome was time to first occurrence of a composite of cardiovascular death, myocardial infarction, stroke, or arterial revascularisation. Additional outcomes included individual cardiovascular outcomes and death from any cause. Outcomes were also evaluated in groups stratified by the inclusion of aspirin in the fixed-dose treatment strategy, and effect sizes were estimated in prespecified subgroups based on risk factors. Kaplan-Meier survival curves and Cox proportional hazard regression models were used to compare strategies. FINDINGS: Three large randomised trials were included in the analysis (TIPS-3, HOPE-3, and PolyIran), with a total of 18 162 participants. Mean age was 63·0 years (SD 7·1), and 9038 (49·8%) participants were female. Estimated 10-year cardiovascular disease risk for the population was 17·7% (8·7). During a median follow-up of 5 years, the primary outcome occurred in 276 (3·0%) participants in the fixed-dose combination strategy group compared with 445 (4·9%) in the control group (hazard ratio 0·62, 95% CI 0·53-0·73, p<0·0001). Reductions were also observed for the separate components of the primary outcome: myocardial infarction (0·52, 0·38-0·70), revascularisation (0·54, 0·36-0·80), stroke (0·59, 0·45-0·78), and cardiovascular death (0·65, 0·52-0·81). Significant reductions in the primary outcome and its components were observed in the analyses of fixed-dose combination strategies with and without aspirin, with greater reductions for strategies including aspirin. Treatment effects were similar at different lipid and blood pressure levels, and in the presence or absence of diabetes, smoking, or obesity. Gastrointestinal bleeding was uncommon but slightly more frequent in the fixed-dose combination strategy with aspirin group versus control (19 [0·4%] vs 11 [0·2%], p=0·15). The frequencies of haemorrhagic stroke (10 [0·2%] vs 15 [0·3%]), fatal bleeding (two [<0·1%] vs four [0·1%]), and peptic ulcer disease (32 [0·7%] vs 34 [0·8%]) were low and did not differ significantly between groups. Dizziness was more common with fixed-dose combination treatment (1060 [11·7%] vs 834 [9·2%], p<0·0001). INTERPRETATION: Fixed-dose combination treatment strategies substantially reduce cardiovascular disease, myocardial infarction, stroke, revascularisation, and cardiovascular death in primary cardiovascular disease prevention. These benefits are consistent irrespective of cardiometabolic risk factors. FUNDING: Population Health Research Institute.

Pharmacogenomics of the Efficacy and Safety of Colchicine in COLCOT.

BACKGROUND: The randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine. METHODS: There were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study's primary cardiovascular end point was defined as for the main trial, as time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. The safety end point was time to the first report of gastrointestinal events. Patients' DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients. RESULTS: None of the genetic variants passed the genome-wide association study significance threshold for the primary cardiovascular end point conducted in 702 patients in the colchicine arm who were compliant to medication. The genome-wide association study for gastrointestinal events was conducted in all 767 patients in the colchicine arm and found 2 significant association signals, one with lead variant rs6916345 (hazard ratio, 1.89 [95% CI, 1.52-2.35], P=7.41×10-9) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82-3.47]; P=2.70×10-8), an intronic variant in gene SEPHS1. The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant. CONCLUSIONS: We found 2 genomic regions associated with gastrointestinal events in patients treated with colchicine. Those findings will benefit from replication to confirm that some patients may have genetic predispositions to lower tolerability of treatment with colchicine.

Correction: Acute Myocardial Infarction and Acute Heart Failure in the Middle East and North Africa: Study Design and Pilot Phase Study Results from the PEACE MENA Registry.

[This corrects the article DOI: 10.1371/journal.pone.0236292.].