Immunometabolism mRNA expression phenotypes and reprogramming of CD14 in T2DM with or without CVD.

BACKGROUND/AIM: Type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) have a significant impact on the expression of genes in peripheral blood mononuclear cells (PBMCs). The primary objective of this study was to investigate the role of two signaling pathways, STAT1/6, and two important modulators of immunometabolism, leptin and PPARs, in the development of T2DM with and without CVD. Furthermore, the study aimed to assess the correlation between these factors and the dynamics of CD14 in PBMCs. This research was conducted within the context of a growing body of literature on the complex pathophysiology of T2DM and its association with CVD. Prior studies have indicated that T2DM is characterized by an imbalance in immunometabolism and the involvement of various signaling pathways. MATERIALS AND METHODS: Blood samples were collected from a total of 47 subjects, including 7 healthy volunteers, 20 individuals diagnosed with diabetes and cardiovascular disease (D.CVD) and another 20 individuals diagnosed with diabetes only (D). PBMCs were isolated from these samples, and the expression levels of leptin, PPARγ, PPARα, and CD14 genes were measured using Real-Time PCR. RESULTS: The most relevant result showed that diabetic patients with CVD had significantly higher levels of leptin expression, which was positively correlated with STAT1 (r = 0.7497, p = 0.0001). On the other hand, diabetic patients without CVD had elevated PPARγ expression, which was strongly correlated with STAT6 (r = 0.8437, p = 0.0001). Interestingly, we found a significant increase in the PPARγ/ PPARα ratio in the D.CVD group compared to the D group (4.273 ± 0.9531; 7.52 ± 3.556, p = 0.0479). Moreover, CD14 expression was significantly reduced in this group compared to diabetic patients without CVD. CONCLUSION: These findings suggested that the immunometabolic imbalance in T2DM was driven by a STAT1/Leptin phenotype in diabetic patients with CVD and by a STAT6/PPARγ phenotype in diabetic patients without CVD. Taking into account STAT1/Leptin and STAT6/PPARγ profiling could help clinicians identify novel therapeutic targets for T2DM and other related diseases.

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.

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.

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.

STAT1 and STAT6 Act as Antagonistic Regulators of PPARγ in Diabetic Patients with and without Cardiovascular Diseases.

BACKGROUND: The processes that mediate an inflammatory environment and increase atherosclerosis in diabetes are not well understood. Peroxisome proliferator-activated receptors (PPARs) are a subgroup of the nuclear hormone receptor superfamily of ligand-activated transcription factors which play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and atherosclerosis. PPARγ promotes changes in lipid metabolism, especially in fatty acid (FA) trafficking, and the activity of PPARγ could be modulated by diabetes phenotype patients. Fatty acid translocase CD36 is one of the advanced PPARγ targets to arbitrate this action. In the current study, we investigated the potential role of signal transducer and activator of transcription STAT1 and STAT6 signaling linked to PPARγ and its implication in the modulation of lipid metabolism. METHODS: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to quantify target genes in Peripheral Blood Mononuclear Cells (PBMCs) isolated from two diabetic groups: diabetic patients with cardiovascular diseases (D.CVD) and without cardiovascular diseases (D). RESULTS: We demonstrated that PPARγ and CD36 mRNA expressions were downregulated along D.CVD compared to D (p = 0.002; p = 0.04; respectively). Decreased CD36 was accompanied by elevated levels of plasma triglyceride (TG) concentrations, 0.83 ± 0.29 vs. 2.46 ± 0.22), respectively. Furthermore, STAT1 was significantly more expressed in D.CVD (p = 0.01). On the other hand, we demonstrated that STAT6 induces a significant level of PPARγ mRNA expression in D patients (p = 0.01). CONCLUSIONS: Our results suggest that the expression and activity of PPARγ mediates CD36 in PBMCs and varies with respect to STAT6 and STAT1 trafficking in diabetic patients with and without cardiovascular diseases.

[In hospital mortality of ST segment elevation myocardial infarction treated with primary angioplasty: monocentric Tunisian study of 250 patients]. / Mortalité intra-hospitalière de l'infarctus du myocarde avec sus-décalage persistant du segment ST traité par angioplastie primaire: étude monocentrique tunisienne de 250 patients.

BACKGROUND: Myocardial reperfusion is the « corner stone ¼ in the treatment of myocardial infarction. Primary percutaneous coronary intervention has proved its superiority upon intravenous thrombolysis. aim: To evaluate in hospital mortality of acute myocardial infarction treated with primary angioplasty and to determine its predictive factors. METHODS: We performed a retrospective study including 250 patients admitted to Mongi Slim university Hospital at la Marsa between January the 1st, 2006 and June the 30th, 2011. All these patients had an ST segment elevation myocardial infarction and underwent primary percutaneous coronary intervention within 24 hours after symptom onset. RESULTS: In our study, males were predominant with a sex-ratio of 4.55. Our patients were aged 59.8± 11.19 years old. Diabetes mellitus was present in 42% of our population. In 60.4% of the cases, myocardial infarction was located in the anterior wall. Cardiogenic shock was present in 13.6% of patients. The culprit coronary artery was the left anterior descending artery in 57.6% of the cases. The coronary flow in the culprit artery was TIMI 0 in 64% of the patients and TIMI 1 in 13.2% of the patients. Angiographic success (TIMI 3 flow and residual stenosis <20%) was achieved in 84% of cases. Our in-hospital mortality rate (cardiogenic shock excluded) was 6.9%. Predictive factors of in-hospital mortality were: female gender, diabetes mellitus, hypertension, renal failure, multi-vessel lesion,TIMI flow before percutaneous coronary intervention, proximal left anterior descending artery lesion, initial cardiogenic shock and acute stent thrombosis. CONCLUSION: In our local context, primary percutaneous coronary intervention is an efficient and safe treatment of myocardial infarction with persistent ST-segment elevation.

[Results of cardiac pacing: report of 188 patients]. / Résultats de la stimulation cardiaque définitive: a propos de 188 malades.

BACKGROUND: Indications for permanent pacing are currently well codified. This treatment may, however, present complications AIM: To report the results of cardiac pacing and to identify predictive factors of pacing's complication. METHODS: We conducted a retrospective study of 188 consecutive patients admitted to the cardiology department of Mongi Slim university hospital in La Marsa between January 2005 and June 2011 and implanted with a single or dual chamber pacemaker. RESULTS: In our study, we had 92 men and 96 women (sexratio= 0.95). The mean age was 70.21 ± 13 years. The indication for cardiac pacing was a high degree heart block in 74.46% of cases and a sick sinus syndrome in 15.95% of cases. The degeneration conduction tissue was the main etiology (72.34% of patients). Success implantation was obtained in 98.4%of cases. The main operative complication was the pneumothorax in 3 patients (1.59% of cases). At Long term, cumulative survival rate was 78.95%. Only operating time affects significantly the rate of early complications (p<0.001). Late complications were related to the valvular heart disease (p = 0.007), the ischemic etiology (p = 0.05), the oral antivitamine K treatment (p = 0.04) and the occurrence of early complication (p = 0.002). CONCLUSION: Our hospital, which is considered as a small Center of cardiac pacing (less than 80 procedures/year) had a low complication rate as well as big centers.

[Non alcoholic fatty liver disease: a new risk factor for cardiovascular disease?]. / La stéatose hépatique non alcoolique : Un nouveau facteur de risque cardio-vasculaire?

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is frequently diagnosed in daily practice. This condition is represented by a large spectrum of chronic liver diseases going from pure hepatic steatosis to cirrhosis and its complications, including hepatocellular carcinoma. NAFLD is usually associated to glucose and lipoproteins metabolism increasing the cardiovascular risk. AIM: To review new advances in the knowledge of the pathophysiological links between NAFLD and cardiovascular risk, evaluation of cardiovascular risk in this special situation and the different therapeutics proposed. METHODS: Systematic review of the literature using medical data bases (Medline) with the following key words: non-alcoholic fatty liver disease, hepatic steatosis, cardiovascular risk, metabolic syndrome. RESULTS: We'll report pathophysiological links between NAFLD and cardiovascular risk, propose an evaluation of cardiovascular risk in this special situation and expose a therapeutic strategy. CONCLUSION: The discovery of a non alcoholic fatty liver disease should lead to a cardiovascular risk evaluation.

[Sudden cardiac death of rhythmic origin in athletes: literature review]. / La mort subite d'origine rythmique chez le sportif: revue de la littérature.

The sudden death in athletes is, in the vast majority of cases, related to ventricular fibrillation, often in a subject with unknown cardiovascular abnormality; this dramatic event has a significant impact on society and the medical profession. We conducted through a literature review an analysis of data on sudden cardiac death of rhythmic origin in athletes; sudden death may be cardiovascular in 95.3% of cases and related to ventricular arrhythmia in 88% cases. The main causes are: hypertrophic cardiomyopathy, congenital anomalies of coronary arteries, and arhythmogenic right ventricular dysplasia for athletes under 35 years, and atherosclerosis beyond 35 years. Prevention is based on three main areas: the medical assessment and screening for cardiovascular disease; the chain of survival; the education of the athlete and the public. All these measures should improve significantly the survival prognosis of patients suffering from these accidents.

Postocclusion hyperemia provides a better estimate of coronary reserve than intracoronary adenosine in patients with coronary artery stenosis.

OBJECTIVE: The aim of this study was to compare the ability of intracoronary adenosine (ADE) and postocclusion hyperemia (PH) to cause maximal hyperemia in humans. BACKGROUND: The current clinical standard for induction of maximal coronary hyperemia is intracoronary ADE. However, animal studies have shown that maximal hyperemia was not achieved by ADE and that PH yielded a higher hyperemic response. METHODS: In 10 stable patients with coronary artery stenosis > or = 80%, basal and peak coronary blood flow velocity (intracoronary Doppler) were measured before and after coronary angioplasty (PTCA), both after an intracoronary bolus of 60 mcg ADE, and after 30-second occlusion of the coronary artery by a balloon angioplasty catheter. Coronary reserve was estimated through coronary flow reserve (CFR = peak-to-resting coronary blood flow velocity), and coronary resistance reserve (CRR = [resting aortic pressure/resting coronary flow velocity]/[aortic pressure at peak velocity/peak coronary flow velocity]). RESULTS: Before PTCA, ADE and PH result in comparable CFR (1.79 +/- 0.65 vs. 1.95 +/- 0.52, respectively; p = 0.0846), but CRR was higher with PH (1.75 +/- 0.52 vs. 2.14 +/- 0.81, respectively; p = 0.0125). After PTCA, CFR and CRR were significantly lower with ADE than with PH (CFR = 2.53 +/- 0.58 vs. 3.31 +/- 0.67, respectively; p = 0.0001, and CRR = 2.58 +/- 0.49 vs. 3.46 +/- 0.79; p = 0.0004, respectively). Lastly, the higher the coronary reserve, the greater the differences between ADE and PH values. CONCLUSIONS: Because intracoronary 60 mcg ADE elicits a lower hyperemic response than PH, intracoronary ADE represents a potential source of error in coronary reserve measurements, and may result in an underestimation of the physiological significance of a coronary artery stenosis.

[A rare cause of myocardial infarction: carbon monoxide intoxication]. / Une cause rare d'infarctus du myocarde: l'intoxication au monoxyde carbone.

We describe a 34-year-old man who suffered an acute myocardial infarction after carbon monoxide domestic exposure. The coronary angiogram was normal. The necrosis is explained in part by a severe coronary spasm. The purpose of this work was to assess the pathophysiology and the treatment of this rare cause of myocardial infarction.

[Pregnancy in patients with prosthetic heart valves]. / Grossesse et prothese valvulaire cardiaque.

In women with prosthetic heart valves, pregnancy carry a risk for both mother and fetus, requiring an obstetrical and cardiological management at an optimal level. We performed a systematic review of the literature to estimate the maternal and fetal complications and in order to offer pregnant women carrying a prosthetic heart valve the most practical approach enabling reduction of these risks. As there are no available controlled clinical trials, larger prospective studies are needed to provide guidelines for effective antithrombotic therapy.

[Prognostic value of high-sensitivity C-reactive protein in assessing intrahospital outcome of unstable angina]. / L'intérêt de la CRP ultrasensible dans l'évaluation du pronostic intrahospitalier de l'angor instable.

Inflammation has been shown to play an important role in the pathogenesis of unstable angina. CRP has been demonstrated to be a reliable marker of prognosis is unstable angina. The aim of this study was to investigate the prognostic value of CRP in assessing short outcome of unstable angina. Our study is a prospective double blinded one. We measured CRP in 33 consecutive patients admitted for unstable angina at the 24th and 48th hour. The mean age is 60 years (30 to 84 years). There were 22 men and 11 women. 8 patients were included in class I of Braunwald classification, 5 were in class II and 20 in class III. 14 patients presented cardiac events. The CRP mean value was significantly higher among these patients (12 mg/l vs 5 mg/l, p < 10.4). Patients having a CRP > or = 3 mg/l have a higher risk of developing complications (66% vs 13%, p = 0.002). Elevation of CRP predicted poor outcome of intrahospital evolution with a sensitivity of 86%, a specificity 68%, a positive and negative predictive values of 66% and 86%. The CRP in our preliminary study is an independent risk factor of early outcome of unstable angina. In association with clinical scores and other cardiac markers will lead to a better identification of high risk patients.

[Hydatid pulmonary embolism]. / Embolie pulmonaire hydatique.

Hydatid pulmonary embolism is an uncommon condition resulting from the rupture of hydatid heart cyst or the opening of a visceral hydatid cyst often in the liver into the venous circulation. We report a case of 60 years old woman, admitted to hospital for acute heart pulmonale due to fistulization of an hepatic hydatid cyst into the inferior vena cava.