Clopidogrel utilization in patients with coronary artery disease and diabetes mellitus: should we determine CYP2C19*2 genotype?

PURPOSE: Clopidogrel non-responsiveness is multifactorial; several genetic and non-genetic factors may contribute to impaired platelet inhibition. The goal of this study is to determine the effect of the cytochrome P450 CYP2C19*2 polymorphism on the platelet response to clopidogrel in patients with and without diabetes mellitus (DM). METHODS: We conducted an observational study in patients with coronary artery disease and consequent exposure to clopidogrel therapy (75 mg/day for at least 7 consecutive days). We have analyzed two groups of patients: group I (DM patients) and group II (non-diabetes mellitus patients). Platelet reactivity was assessed by the VerifyNow P2Y12 assay and high on clopidogrel platelet reactivity (HPR) was defined as P2Y12 reaction units (PRU) ≥ 208. Genotyping for CYP2C19*2 polymorphism was performed by PCR-RFLP. RESULTS: We have included 150 subjects (76 DM and 74 non-diabetes mellitus patients). The carriage of CYP2C19*2 allele, in DM patients, was significantly associated to HPR (odds ratio (OR) 4.437, 95% confidence interval (CI) 1.134 to 17.359; p = 0.032). Furthermore, 8.4% of the variability in percent inhibition by clopidogrel could be attributed to CYP2C19*2 carrier status. However, in non-diabetes mellitus patients, there was no significant difference in platelet response to clopidogrel according to the presence or absence of CYP2C19*2 allele carriage (OR 1.260, 95% CI 0.288 to 5.522; p = 0.759). CONCLUSIONS: Our study suggests that the carriage of CYP2C19*2 polymorphism, in DM patients, might be a potential predictor of persisting HPR in these high-risk individuals. TRIAL REGISTRATION: Clinical Trials.gov NCT03373552 (Registered 13 December 2017).

PCSK9 polymorphism in a Tunisian cohort: identification of a new allele, L8, and association of allele L10 with reduced coronary heart disease risk.

The c.61_63dupCTG (L10) allele of rs72555377 polymorphism in PCSK9 has been reported to be associated with low-density lipoprotein-cholesterol (LDL-C) levels and with a decreased risk of coronary artery disease (CAD). We investigated the effect of two known alleles for rs72555377, L10 and L11, on the risk of CAD in a Tunisian cohort (218 patients diagnosed by angiography and 125 control subjects). Two subgroups of patients were defined by their level of stenosis: ≥50% for CAD and <50% for no-CAD. The genotypes were obtained by the size measurement of fluorescent-labeled PCR products. We identified a novel allele for the rs72555377 polymorphism: an in-frame deletion, c.61_63delCTG (L8). The frequency of the L10 allele was significantly higher in the no-CAD subgroup than in the CAD subgroup (0.210 vs 0.114, p = 0.045), and than in the subgroup of CAD patients presenting a stenosis ≥50% in two or three major coronary arteries (0.210 vs 0.125, p = 0.028). Multiple regression analysis showed that the L10 allele was significantly associated with a reduced risk of CAD (p = 0.049, OR = 0.51[0.26-1.00]), and with its reduced severity (p = 0.045, OR = 0.44[0.20-0.98]). The L10 allele is associated with a reduced risk and severity of CAD, seemingly independently of its LDL-lowering effect, suggesting a direct effect of PCSK9 on atherogenesis.

Modern approaches to the management of homozygous familial hypercholesterolemia in the Middle East and North Africa.

Homozygous familial hypercholesterolaemia (HoFH) is a severe form of FH in which inheritance of two defective or null mutations in genes associated with metabolism of low-density lipoprotein cholesterol (LDL-C) results in extremely high LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) and mortality. Treatment of HoFH comprises a multi-modal approach of statins, ezetimibe, lipoprotein apheresis; and inhibitors of proprotein convertase subtilisin/kexin type, angiopoietin-like protein 3 (ANGPTL3) and microsomal triglyceride transfer protein. These treatments are generally costly, and patients also often require treatment for ASCVD consequent to HoFH. Therefore, in the interests of both economics and preservation of life, disease prevention via genetic screening and counselling is rapidly becoming a key element in the overall management of HoFH. Guidelines are available to assist diagnosis and treatment of HoFH; however, while advancements have been made in the management of the disease, there has been little systematic attention paid to prevention. Additionally, the Middle East/North Africa (MENA) region has a higher prevalence of HoFH than most other regions - chiefly due to consanguinity. This has led to the establishment of regional lipid clinics and awareness programs that have thrown education and awareness of HoFH into sharp focus. Incorporation of principles of prevention, education, awareness, and data from real-world use of existing therapeutics will significantly enhance the effectiveness of future guidelines for the management of HoFH, particularly in the MENA region.

Lomitapide for the treatment of paediatric patients with homozygous familial hypercholesterolaemia (APH-19): results from the efficacy phase of an open-label, multicentre, phase 3 study.

BACKGROUND: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder characterised by extremely high concentrations of LDL cholesterol, leading to early-onset atherosclerosis. Lomitapide is an orally administered microsomal triglyceride transfer protein (MTP) inhibitor that effectively lowers LDL cholesterol and is approved for adults with HoFH. We aimed to investigate the efficacy and safety of lomitapide in paediatric patients with HoFH receiving standard-of-care lipid-lowering therapy. METHODS: APH-19 is an open-label, single-arm, phase 3 trial performed at 12 study centres in Germany, Israel, Italy, Saudi Arabia, Spain, and Tunisia. A 6-week run-in period was followed by a 24-week efficacy phase and an 80-week safety phase. Patients aged 5-17 years, on stable lipid-lowering therapy, with HoFH diagnosed using the criteria from the 2014 European Atherosclerosis Society Consensus Panel on HoFH were titrated to maximum tolerated doses of oral lomitapide, starting at 2 mg (patients aged 5-15 years) or 5 mg (patients aged 16-17 years). The primary endpoint was the percentage change from baseline to week 24 in LDL cholesterol, which was assessed in patients who had received at least one dose of lomitapide, and who had a baseline and at least one post-baseline measurement. The secondary outcomes were the percentage change from baseline at week 24 in total cholesterol, non-HDL cholesterol, VLDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a). Safety was assessed in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04681170. FINDINGS: Between Dec 20, 2020, and Oct 16, 2022, 43 patients were included and treated (24 [56%] were female and 19 [44%] were male, and median age was 10·7 years [7·0-14·0]). Mean change from baseline in LDL cholesterol at week 24 was -53·5% (95% CI -61·6 to -45·4, p<0·0001). Mean percentage reductions were observed at week 24 for non-HDL cholesterol (-53·9%, 95% CI -61·7 to -46·1, p<0·0001), total cholesterol (-50·0%, 95% CI -57·6 to -42·4, p<0·0001), VLDL cholesterol (-50·2%, -59·1 to -41·2, p<0·0001), apolipoprotein B (-52·4%, -60·3 to -44·5, p<0·0001), triglycerides was -49·9% (-58·8 to -41·0, p<0·0001), and lipoprotein(a) (-11·3%, -32·9 to 10·3 [in 21 patients with measurements in mg/dL]; -23·6%, -38·2 to -9·0 [in 22 patients with measurements in nmol/L]; p=0·0070 combined). Adverse events were mostly mild, and gastrointestinal and hepatic in nature. Adverse events of special interest were reported for five (12%) patients (gastrointestinal in two patients and hepatic in three). One serious treatment-emergent adverse event was reported (also classed as an adverse event of special interest): an increase in hepatic enzymes, resulting in two dose interruptions, two dose reductions, and a repeated dose escalation. INTERPRETATION: Lomitapide provided a significant, clinically meaningful LDL cholesterol reduction and has the potential to be an efficient, LDL receptor-independent option for paediatric patients with HoFH. FUNDING: Amryt Pharmaceuticals.

ST-segment Elevation Myocardial Infarction in North African Women: Results From a Twenty-year Experience.

Background: Coronary artery disease remains the most common cause of morbidity and mortality in the general population. Several studies in developed countries have reported a gender-related difference in ST-segment elevation myocardial infarction (STEMI) in terms of risk factors, clinical presentation, delays in management, therapeutic modalities, and in-hospital as well as one-year outcomes. Data from non-developed countries about women with STEMI remain rare. We therefore aimed through this study to investigate the baseline characteristics of STEMI in Tunisian women compared to men and to determine the impact of gender difference on STEMI complications, in-hospital mortality, and one-year follow-up outcomes. Methods: All patients presenting to our center for STEMI between January 2001 and January 2021 were retrospectively enrolled in this analysis. Clinical features, therapeutic management, and in-hospital as well as one-year outcomes were compared between women and men. Predictive factors of in-hospital mortality in women were determined. Results: Out of 1670 STEMI hospitalizations, 359 (21.4%) were female. Compared to male, female had higher rates of hypertension (51.5% vs. 24.4%, p < 0.001), diabetes (50.1% vs. 32.2%, p < 0.001), and obesity (63.8% vs. 55%, p = 0.003). The clinical presentation was characterized by less prevalent inaugural chest pain (58.8% vs. 68.6%, p < 0.001). Atypical symptoms were significantly higher in women compared to men (55.2% vs. 5%, p<0.001). On admission, women had higher prevalence of anemia, renal failure, and hyperglycemia compared to men. Primary percutaneous coronary intervention (pPCI) was the reperfusion strategy of choice in 37.9% of women vs. 33.1% of men (p=0.02). Women were significantly less likely to receive thrombolysis (p = 0.004), with a significantly less prevalent successful thrombolysis (55.6% vs. 67.2%, p=0.013). In-hospital mortality was markedly higher in women compared to men (12.8% vs. 7.3%, p=0.001). Compared to surviving women (n = 313), those who died (n = 46) frequently had more diabetes and hypertension (65.2% vs. 47.9%, p= 0.02 and 67.4% vs. 49.2%, p = 0.02, respectively). New-onset atrial fibrillation, acute left heart failure, cardiogenic shock, ventricular tachycardia, and atrioventricular block markedly occurred in women who died (52.2% vs. 23.3%, p=<0.001; 17.4% vs. 1.9%, p < 0.001; 19.6% vs. 8.3%, p = 0.016; 15.2% vs. 1.6%, p < 0.001 and 34.8% vs. 10.2%, p < 0.001, respectively). Conclusion: Compared to men, Tunisian women presenting for STEMI had higher prevalence of risk factors and atypical symptoms. Women had more in-hospital complications and mortality.

Cardiac iron overload detection using longitudinal strain in asymptomatic children with beta thalassemia major.

Cardiomyopathy mediated by iron disposition in cardiomyocytes is a dreadful cause of morbidity and mortality in patients with beta thalassemia major (BTM). Conventional transthoracic echocardiography (TTE) parameters are preserved at late stages of cardiomyopathy induced by iron overload. Therefore, cardiac imaging modalities based on myocardial deformation such as strain imaging are used for early detection of cardiac iron overload. To demonstrate the contribution of longitudinal strain (LS) in early detection of cardiac iron overload in children with BTM. Sixty children (30 children with BTM and 30 healthy controls) were enrolled in this study. Conventional TTE study was performed in both patient and control groups. LV regional longitudinal strain (RLS) were determined and compared between the two study groups. Mean age was 10.4 ± 5 years in BTM group compared to 10.2 ± 5 years in control group (p = 0.876). Compared to control group, there was no significant difference in conventional TTE parameters except for indexed left atrium (LA) area and volume. LA was significantly larger in BTM children (27.59 ± 13.1 ml/m2 vs. 18.23 ± 4.33 ml/m2, p = 0.001). RLS was lower in anterior, septal and inferior walls in basal and middle segments of LV in BTM group while there was no significant difference in RLS in apical segment between the two groups (- 27.30 ± 5.1 vs.- 28.83 ± 4.33, p = 0.22). In asymptomatic BMT children with normal conventional TTE parameters, LS could be used for the detection of subclinical myocardial dysfunction.

Mid-term subclinical myocardial injury detection in patients who recovered from COVID-19 according to pulmonary lesion severity.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) may cause damage to the cardiovascular system during the acute phase of the infection. However, recent studies reported mid- to long-term subtle cardiac injuries after recovering from acute coronavirus disease 2019 (COVID-19). This study aimed to determine the relationship between the severity of chest computed tomography (CT) lesions and the persistence of subtle myocardial injuries at mid-term follow-up of patients who recovered from COVID-19 infection. Methods: All patients with COVID-19 were enrolled prospectively in this study. Sensitive troponin T (hsTnT) and chest CT scans were performed on all patients during the acute phase of COVID-19 infection. At the mid-term follow-up, conventional transthoracic echocardiograph and global longitudinal strain (GLS) of the left and right ventricles (LV and RV) were determined and compared between patients with chest CT scan lesions of < 50% (Group 1) and those with severe chest CT scan lesions of greater or equal to 50% (Group 2). Results: The mean age was 55 ± 14 years. Both LV GLS and RV GLS values were significantly decreased in group 2 (p = 0.013 and p = 0.011, respectively). LV GLS value of more than -18 was noted in 43% of all the patients, and an RV GLS value of more than -20 was observed in 48% of them. The group with severe chest CT scan lesions included more patients with reduced LV GLS and reduced RV GLS than the group with mild chest CT scan lesions [(G1:29 vs. G2:57%, p = 0.002) and (G1:36 vs. G2:60 %, p = 0.009), respectively]. Conclusion: Patients with severe chest CT scan lesions are more likely to develop subclinical myocardial damage. Transthoracic echocardiography (TTE) could be recommended in patients recovering from COVID-19 to detect subtle LV and RV lesions.

Real time PCR for fast detection of the angiotensinogen polymorphisms.

OBJECTIVE: to develop a rapid and reliable real-time PCR to detect polymorphisms of angiotensinogen (AGT), to compare the two methods of MS-PCR (Mutagenically Separated PCR) and real-time PCR to determine three polymorphisms of the angiotensinogen gene M235T, the A (-6) G and A (-20) C. METHODS: the method of real-time PCR was developed on the PLC Roche LightCycler1 with SYBR Green I. We used two sense primers and a primer nonsense. Detection of polymorphisms of angiotensinogen gene was performed by comparing the melting curves. RESULTS: the DNA samples were analyzed by two methods: real-time PCR and MS-PCR. In our study, no differences were found between the two techniques. DISCUSSION: The real-time PCR is a rapid and reliable method for detecting gene polymorphisms on the AGT M235T, the A (-6) G and A (-20) C. CONCLUSION: this method of real-time PCR is a reliable genetic test, which is fast and cheap and can be used in practice to study particular polymorphisms of AGT gene associated with cardiovascular disease.

Left atrial appendage closure with Watchman device: Insights from the first-ever Tunisian experience and six-year follow-up.

BACKGROUND: Stroke is a major complication of nonvalvular atrial fibrillation (AF). Despite its proven efficacy in stroke prevention, oral anticoagulation (OAC) is associated to a significant increase in bleeding complications. New techniques such as percutaneous left atrial appendage (LAA) closure were developed. AIM: To evaluate immediate, mid- and long-term outcomes after percutaneous LAA closure in Tunisian patients presenting with nonvalvular AF. METHODS AND RESULTS: Nineteen patients with nonvalvular AF were prospectively enrolled for percutaneous LAA closure between February 2013 and June 2014. The Watchman device was used in all LAA closure procedures. Clinical and echocardiographic follow-up were carried-out at 1, 6, 12 months and six years in all patients. Mean age was 68.4 ± 7.5 years. Thirteen patients were female, 16 had hypertension, 12 had diabetes mellitus and seven had a history of stroke or transient ischemic attack (TIA). Average CHA2DS2VASc (Congestive Heart Failure/Left Ventricular Dysfunction, Hypertension, Age≥75, Diabetes mellitus, Stroke/Transient Ischemic Attack/Thromboembolic event, Vascular disease,Age≥65, Sex category) score was 4.2 ± 1.5 and HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding tendency, Labile INR, Age≥65, Drugs) score was 3.5 ± 1. Ten patients had a history of severe bleeding. Procedural success was achieved in all patients. Pericardial effusion with tamponade was reported in one case. No post-procedural death was reported. Regular follow-up at 1, 6 and12 months then every year up to 6 years reported no stroke, no thromboembolic event, no Watchman device thrombosis and three cases of death caused by a respiratory problem and cancers. CONCLUSION: According to this study, LAA closure with Watchman device was safe and effective in preventing stroke in patients with nonvalvular AF and contra indication to OAC.

Long-term predictors of death among Tunisian patients presenting for non ST-elevation acute coronary syndrome.

BACKGROUND: Coronary artery disease is the leading cause of death in emerging countries. Contemporary data about clinical profile and prognosis in Tunisian patients presenting for non ST-elevation acute coronary syndrome (NSTE-ACS) are lacking. AIM: We sought to study the risk profile and 3-year mortality predictors in Tunisian patients presenting for NSTE-ACS in the contemporary setting. METHODS: In this single center study, data about all consecutive patients presenting to our center for NSTE-ACS from April 2014 to July 2016 were extracted and outcomes exhaustively updated. 3-year mortality predictors were determined by multivariable survival analysis. RESULTS: A total of 340 patients were included, of which 204 (61.8%) were male. Mean age was 63.6 ± 10.3 years. Prevalence of diabetes mellitus, hypertension and smoking was 57.3%, 62.4%, and 45.3%, respectively. In-hospital, 6, 12 and 36-month mortality rate was 2.3%, 3.2%, 7.1% and 15.2%, respectively. In multivariable survival analysis, independent predictors of death were age >75 (HR=5.45, 95% CI: 2.9-10.03, p<0.001), ST-segment deviation (HR=1.86, 95% CI: 1.04-3.33, p=0.036), anemia (HR=2.56, 95% CI: 1.41-4.67, p=0.002), left ventricular ejection fraction (LVEF) <40% (HR=3.5, 95% CI: 1.84-6.67, p<0.001) and a Global Registry of Acute Coronary Events (GRACE) score ≥140 (HR=2.38, 95% CI: 1.02-5.57, p=0.044). CONCLUSION: In Tunisian patients presenting for NSTE-ACS, long-term mortality was high. Advanced age, ST-segment deviation, anemia, LVEF <40% and a GRACE score ≥140 were independent long-term predictors of death.

Epidemiological characteristics, management, and outcomes of atrial fibrillation in TUNISIA: Results from the National Tunisian Registry of Atrial Fibrillation (NATURE-AF).

BACKGROUND: Contemporary registries on atrial fibrillation (AF) are scare in North African countries. HYPOTHESIS: In the context of the epidemiological transition, prevalence of valvular AF in Tunisia has decreased and the quality of management is still suboptimal. METHODS: NATURE-AF is a prospective Tunisian registry, involving consecutive patients with AF from March 1, 2017 to May 31, 2017, with a one-year follow-up period. All the patients with an Electrocardiogram-documented AF, confirmed in the year prior to enrolment were eligible. The epidemiological characteristics and outcomes were described. RESULTS: A total of 915 patients were included in this study, with a mean age of 64.3 ± 22 years and a male/female sex ratio of 0.93. Valvular AF was identified in 22.4% of the patients. The mean CHA2 DS2 VASC score in nonvalvular AF was 2.4 ± 1.6. Monotherapy with antiplatelet agents was prescribed for 13.8% of the patients. However, 21.7% of the subjects did not receive any antithrombotic agent. Oral anticoagulants were prescribed for half of the patients with a low embolic risk score. In 341 patients, the mean time in therapeutic range was 48.87 ± 28.69%. Amiodarone was the most common antiarrhythmic agent used (52.6%). During a 12-month follow-up period, 15 patients (1.64%) had thromboembolism, 53 patients (5.8%) had major hemorrhage, and 52 patients (5.7%) died. CONCLUSIONS: NATURE-AF has provided systematic collection of contemporary data regarding the epidemiological and clinical characteristics as well as the management of AF by cardiologists in Tunisia. Valvular AF is still prevalent and the quality of anticoagulation was suboptimal.

Relationship between high sensitivity C-reactive protein and angiographic severity of coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) remains a leading cause of morbidity and mortality. Cytokines play a potential role in atherosclerosis pathogenesis and progression. We investigated the association between high sensitive C-reactive protein (hsCRP) and severity of CAD. METHODS: CAD patients were stratified according to hsCRP cut-off value into high levels hsCRP group (≥ 8.4 mg/L) and low levels hsCRP group (< 8.4 mg/L). Severity of CAD was assessed according to artery stenosis degree and the number of vessel involved. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS, version 23.0). RESULTS: The mean age was 60.3 ± 11.0 years. The level of hsCRP was increased and ranged from 0.2 to 1020.0 mg/L. Biochemical risk factors and severity of CAD didn't show significant differences between the two groups. In multivariate linear analysis, cardiac troponin I (cTnI) and serum amyloid A (SAA) were predictors of hsCRP. As shown in receiver operating characteristic (ROC) curve analysis performed in patients with ST-segment elevation myocardial infarction (STEMI) and compared to myonecrosis biomarkers, hsCRP (area under the curve (AUC): 0.905; 95%CI: 0.844-0.966; P < 0.001) could be a powerful predictor marker in evaluating the infarct size after myocardial infarction but not better than cTnI. CONCLUSIONS: HsCRP levels were not associated with the severity of CAD but could be useful in the evaluation of myocardial necrosis in patients with STEMI.

Association of the methylene-tetrahydrofolate reductase gene rs1801133 C677T variant with serum homocysteine levels, and the severity of coronary artery disease.

This study aimed to investigate whether the single nucleotide polymorphism C677T (rs1801133) of the methylene-tetrahydrofolate reductase (MTHFR) gene was associated with the risk of coronary artery disease (CAD) and circulating homocysteine (Hcy) levels in Tunisian population. 310 angiografically diagnosed CAD patients and 210 controls were enrolled in this study. The MTHFR C677T (rs1801133) polymorphism was genotyped, and the Hcy concentrations were measured. The severity of CAD was evaluated using the Gensini scoring system. Compared to the CC genotype, the TT genotype confers a higher risk for CAD severity with an OR = 9.07 and 95% CI = 3.78-21.8. The T allele was the predisposing allele for CAD and that it was probably associated with CAD severity. The area under the ROC curve for Hcy was 0.764 (95% CI 0.660 to 0.868, p = 0.001). The receiver operating characteristics curve (ROC) for Hcy showed its useful prediction of CAD. Hcy levels were not significantly associated with CAD severity expressed by Gensini Score (GS). The MTHFR C677T (rs1801133) polymorphism influences circulating Hcy levels. The MTHFR C677T polymorphism and hyperhomocysteinemia could have an important role in the prediction of the presence and not the severity expressed by GS of CAD.

Acute coronary syndrome: factors predicting smoking cessation.

BACKGROUND: Few randomized controlled trials have examined the efficacy time of smoking cessation in hospitalized patients with acute coronary syndrome, either during hospitalization or after discharge. AIMS: To assess smoking cessation rates at 24 weeks among patients with acute coronary syndrome. Group A had begun nicotine replacement therapy during hospitalization, and Group B after discharge. We also determined factors predicting success. METHODS: We conducted a randomized controlled trial in the Cardiology Department and Smoking Cessation Service at University Hospital of Monastir, Tunisia from January 2015 to June 2016. Participants were randomly assigned to the above 2 groups. The endpoint assessment was smoking abstinence at 24 weeks, defined as self-reported abstinence in the past week, confirmed by measured exhaled carbon monoxide (CO) ≤ 8 ppm. We analysed data by intention to treat. We used a binary logistic regression model to determine factors predicting abstinence. RESULTS: All participants were male and mean (standard deviation) age was 55 (11) years. At 24 weeks there was no significant difference in smoking cessation rate between the 2 groups: 54.5% [95% confidence interval (CI): 44.7-64.3%] in Group A and 45.5% (95% CI: 35.7-55.3%) in Group B (P = 0.81). High level of nicotine dependence [odds ratio (OR): 0.72; 95% CI: 0.54-0.96) and good compliance during follow-up (OR: 6.56; 95% CI: 2.07-20.78) were predictive factors for abstinence. CONCLUSIONS: Smoking cessation rate after acute coronary syndrome was high regardless of the start date. Good compliance during follow-up was the key predictive factor for success.

Neonatalogist-performed echography in neonatology: a Tunisian experience.

INTRODUCTION: Echocardiography is an important tool for diagnosis of cardiac abnormalities that can impact the management and outcome of the sick newborn in the intensive care unit. A preliminary echocardiogram performed by the neonatologist under the supervision of a paediatric cardiologist for interpretation and review is an alternate when there is not a cardiologist on site. The aim of this study was to evaluate frequency of use, neonatal characteristics, and indications of neonatologist-performed echocardiography in a Tertiary Neonatal Care Centre in Tunisia. METHODS: Prospective observational study in a tertiary Neonatal Intensive Care Unit (NICU) in Monastir (Tunisia) from April 2015 to February 2017.An echocardiography was indicated in these situations: cyanosis, signs of circulatory shock, clinical signs of heart failure, presence of a murmur, arrhythmia, and abnormal pulses in upper and/or lower extremities, suspected persistent pulmonary hypertension in neonates, clinically suspected patent ductus arteriosus, maternal diabetes mellitus and polymalformative syndrome. The findings of echocardiography were confirmed by pediatric cardiologist in case of structural or functional cardiac abnormalities. RESULTS: 675 echocardiography were performed among them 535 were normal and 25 revealed a persistent arterial duct treated with E2 postaglandins (Prostine®) or paracetamol according to a pre-established protocol. 80 Congenital heart diseases were retained, which represented an incidence of 7 ‰ live births. The second time of our work consisted to study the 55 cases of cardiac diseases confirmed after exclusion of atrial communication. The antenatal diagnosis was made in 11% of cases. The main signs indicating the echocardiogram were the heart murmur (22 cases) followed by cyanosis (6 cases). A malformation association and / or a chromosomal aberration have been noted in 36% of cases. For half of the patients, the cardiac ultrasound was performed before the first 24 hours of life. This examination was completed by a thoracic angioscan in 9 patients. 31% of newborns had an infusion of Prostaglandins for an average duration of 11 days [2-60 days]. One-third of newborns (35 cases) required respiratory assistance. A palliative surgery was made in 7 cases and curative one in 4 cases. The average age at the time of the intervention was 20 days. The neonatal mortality rate was 40%. CONCLUSION: Echocardiography is being utilized progressively on the neonatal unit, and has been indicated to have a high return for both structural and functional cardiac abnormalities. It is important to encourage collaboration with pediatric cardiologists to establish standards for training and to develop guidelines for clinical practice in order to improve neonatal care.

Management of patients with acute ST-elevation myocardial infarction: Results of the FAST-MI Tunisia Registry.

BACKGROUND: The FAST-MI Tunisia registry was set up by the Tunisian Society of Cardiology and Cardiovascular Surgery to assess the demographic and clinical characteristics, management and hospital outcome of patients with ST-elevation myocardial infarction (STEMI). METHODS: Data for 459 consecutive patients (mean age 60.8 years; 88.5% male) with STEMI, treated in 16 public hospitals (representing 72.2% of public hospitals in Tunisia treating STEMI patients), were collected prospectively.The most common risk factors were smoking (63.6%), hypertension (39.7%), diabetes (32%) and dyslipidaemia (18.2%). RESULTS: Among the 459 patients, 61.8% received reperfusion therapy: 30% with primary percutaneous coronary intervention (PPCI) and 31.8% with intravenous fibrinolysis (IF) (28.6% with pre-hospital thrombolysis). The median time from symptom onset to thrombolysis was 185 min and to PPCI was 358 min. In-hospital mortality was 5.3%. Compared with those managed at regional hospitals, patients managed at interventional university hospitals (n = 357) were more likely to receive reperfusion therapy (52.9% vs. 34.1%; p<0.001), with less IF (28.6% vs. 43.1%; p = 0.002) but more PPCI (37.8% vs. 3.9%; p<0.0001). However, in-hospital mortality in the two types of hospitals was similar (5.3% vs. 5.1%; p = 0.866). CONCLUSIONS: Data from the FAST-MI Tunisia registry show that a pharmaco-invasive strategy of management for STEMI should be promoted in non-interventional regional hospitals.

[Abnormalities of the interatrial septum associated with cerebral ischemia in young adults: contribution of trans-oesophageal echocardiography]. / Anomalies du septum inter-auriculaire complique d'ischemie cerebral chez le sujet jeune: apport de l'echographie trans-oesophagienne.

BACKGROUND: About 40% of the mechanism of ischaemic stroke in young adults remains unclear. A paradoxical embolism associated with persistence of a patent foramen ovale and/or the presence of an atrial septal anevrysm are significantly more frequent in patients examined for ischaemic stroke of unknown cause than in control subjects. AIM: was to evaluate the contribution of trans-oesophageal echocardiography to the diagnosis of abnormalities of the interatrial septum and to identify the role played by this condition in unexplained ischemic stroke. METHODS: In 30 consecutive patients, trans-oesophageal echocardiography recording were made during a saline contrast study. RESULTS: Abnormalities of the interatrial septum was diagnosed in 23.3% cases. The proportion of patent foramen ovale was 10% (3 patients); atrial septal anevrysm was detected in 6.6%(2 patients). The prevalence of patent foramen ovale associated with atrial septal anevrysm was 6.6% (2 patients). CONCLUSION: Transesophageal echocardiography with contrast appears to be an effective exam in diagnosis of abnomalities of the interatrial septum and our study was suggestive of their embolic nature.

Prognostic value of hyperglycemia on-admission in diabetic versus non-diabetic patients presenting with ST-elevation myocardial infarction in Tunisia.

BACKGROUND: Hyperglycemia on-admission is a powerful predictor of adverse events in patients presenting for ST-elevation myocardial infarction (STEMI). AIM: In this study, we sought to determine the prognostic value of hyperglycemia on-admission in Tunisian patients presenting with STEMI according to their diabetic status. METHODS: Patients presenting to our center between January 1998 and September 2014 were enrolled. Hyperglycemia was defined as a glucose level ≥11mmol/L. In-hospital prognosis was studied in diabetic and non-diabetic patients. The predictive value for mortality of glycemia level on-admission was assessed by mean of the area under receiver operating characteristic (ROC) curve calculation. RESULTS: A total of 1289 patients were included. Mean age was 60.39±12.8years and 977 (77.3%) patients were male. Prevalence of diabetes mellitus was 70.2% and 15.2% in patients presenting with and without hyperglycemia, respectively (p<0.001). In univariate analysis, hyperglycemia was associated to in-hospital death in diabetic (OR: 8.85, 95% CI: 2.11-37.12, p<0.001) and non-diabetic patients (OR: 2.57, 95% CI: 1.39-4.74, p=0.002). In multivariate analysis, hyperglycemia was independently predictive of in-hospital death in diabetic patients (OR: 9.6, 95% CI: 2.18-42.22, p=0.003) but not in non-diabetic patients (OR: 1.93, 95% CI: 0.97-3.86, p=0.06). Area under ROC curve of glycemia as a predictor of in-hospital death was 0.792 in diabetic and 0.676 in non-diabetic patients. CONCLUSION: In patients presenting with STEMI, hyperglycemia was associated to hospital death in diabetic and non-diabetic patients in univariate analysis. In multivariate analysis, hyperglycemia was independently associated to in-hospital death in diabetic but not in non-diabetic patients.

Design and Rationale of the National Tunisian Registry of Atrial Fibrillation: Protocol for a Prospective, Multicenter Trial.

BACKGROUND: Atrial fibrillation (AF) is an important health problem in Tunisia. A significant change in the epidemiological pattern of heart disease has been seen in the last 3 decades; however, no large prospective multicenter trial reflecting national data has been published so far. Robust data on the contemporary epidemiological profile and management of AF patients in Tunisia are limited. OBJECTIVE: The aim of this study is to analyze, follow, and evaluate patients with AF in a large multicenter nationwide trial. METHODS: A total of 1800 consecutive patients with AF by electrocardiogram, reflecting all populations of all geographical regions of Tunisia, will be included in the study, with the objective of describing the epidemiological pattern of AF. Patients will be officially enrolled in the National Tunisian Registry of Atrial Fibrillation (NATURE-AF) only if an electrocardiogram diagnosis (12-lead, 24-hour Holter, or other electrocardiographic documentation) confirming AF is made. The qualifying episode of AF should have occurred within the last year, and patients do not need to be in AF at the time of enrollment. Patients will be followed for 1 year. Incidence of stroke or transient ischemic attack, thromboembolic events, and cardiovascular death will be recorded as the primary end point, and hemorrhagic accidents, measurement of international normalized ratio, and time in therapeutic range will be recorded as secondary end points. RESULTS: Results will be available at the end of the study; the demographic profile and general risk profile of Tunisian AF patients, frequency of anticoagulation, frequency of effective treatment, and risks of thromboembolism and bleeding will be evaluated according to the current guidelines. Major adverse events will be determined. NATURE-AF will be the largest registry for North African AF patients. CONCLUSIONS: This study would add data and provide a valuable opportunity for real-world clinical epidemiology in North African AF patients with insights into the uptake of contemporary AF management in this developing region. TRIAL REGISTRATION: ClinicalTrials.gov NCT03085576; https://clinicaltrials.gov/ct2/show/NCT03085576 (Archived by WebCite at http://www.webcitation.org/6zN2DN2QX). REGISTERED REPORT IDENTIFIER: RR1-10.2196/8523.

Plasma metalloproteinase-12 and tissue inhibitor of metalloproteinase-1 levels and presence, severity, and outcome of coronary artery disease.

Several matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been implicated in the development and outcome of coronary artery disease (CAD). We investigated whether MMP-12 and TIMP-1 levels were associated with risk, severity, and outcome of CAD. Plasma MMP-12 and TIMP-1 levels are measured in 50 and 44 patients with CAD, respectively, by enzyme-linked immunosorbent assay. Of all patients, 16 were taking statins. Patients who were not on statins were classified into 3 groups according to number of >50% stenotic vessels. Compared with 29 volunteers without CAD, patients without statins (n = 34) had higher MMP-12 concentrations (1.71 vs 1.08 ng/ml, p = 0.021). MMP-12 levels were significantly lower in patients with than in those without statin treatment (0.99 vs 1.71 ng/ml, p = 0.008). There was no association between MMP-12 levels and number of >50% stenotic vessels. MMP-12 concentrations were not associated with outcome of CAD. However, plasma TIMP-1 levels were associated with restenosis independently of number of stenotic vessels and age (p = 0.035) but not with risk or severity of CAD. In conclusion, plasma MMP-12 concentration was associated with the presence of CAD. Statin therapy decreases plasma MMP-12 levels in patients with CAD. Increased TIMP-1 levels may prevent restenosis after angioplasty.