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.

Sulodexide Significantly Improves Endothelial Dysfunction and Alleviates Chest Pain and Palpitations in Patients With Long-COVID-19: Insights From TUN-EndCOV Study.

Objective: Non-respiratory long-coronavirus disease 2019 (COVID-19) symptoms are mainly related to a long-lasting endothelial dysfunction and microcirculation impairment. We hypothesized that Sulodexide, a purified glycosaminoglycan mixture with a beneficial endothelial effect in arterial and venous peripheral diseases, may be effective in a subset of patients with long COVID-19. Approach and Results: We conducted a multicenter prospective quasi-experimental study. A total of 290 patients from the TUN-EndCOV study with long-COVID-19 symptoms and endothelial dysfunction were included. The endothelial function was clinically assessed using a post-occlusive reactive hyperemia protocol with finger thermal monitoring device. Endothelial quality index (EQI) was assessed at inclusion and at 21 days later. The study population was assigned to a sulodexide group (144 patients) or a no-medical treatment group (146 patients). Clinical characteristics were similar at inclusion in the two groups. Fatigue, shortness of breath, and chest pain were the most common symptoms, respectively, 54.5, 53.8, and 28.3%. At 21 days, the sulodexide group improved significantly better than the no-medical treatment group in chest pain (83.7 vs. 43.6%, p < 10-3), palpitations (85.2 vs. 52.9%, p = 0.009), and endothelial function [median delta-EQI 0.66 (0.6) vs. 0.18 (0.3); p < 10-3]. Endothelial function improvement was significantly correlated with chest pain and palpitations recovery (AUC, i.e., area under the curve = 0.66, CI [0.57- 0.75], p = 0.001 and AUC = 0.60, CI [0.51- 0.69], p = 0.03, respectively). Conclusion: Sulodexide significantly improves long-lasting post-COVID-19 endothelial dysfunction and alleviates chest pain and palpitations.

Long COVID 19 Syndrome: Is It Related to Microcirculation and Endothelial Dysfunction? Insights From TUN-EndCOV Study.

The COVID-19 disease is a multisystem disease due in part to the vascular endothelium injury. Lasting effects and long-term sequelae could persist after the infection and may be due to persistent endothelial dysfunction. Our study focused on the evaluation of endothelial quality index (EQI) by finger thermal monitoring with E4 diagnosis Polymath in a large cohort of long COVID-19 patients to determine whether long-covid 19 symptoms are associated with endothelial dysfunction. This is a cross-sectional multicenter observational study with prospective recruitment of patients. A total of 798 patients were included in this study. A total of 618 patients (77.4%) had long COVID-19 symptoms. The mean EQI was 2.02 ± 0.99 IC95% [1.95-2.08]. A total of 397 (49.7%) patients had impaired EQI. Fatigue, chest pain, and neuro-cognitive difficulties were significantly associated with endothelium dysfunction with an EQI <2 after adjustment for age, sex, diabetes, hypertension, dyslipidemia, coronary heart disease, and the severity of acute COVID-19 infection. In multivariate analysis, endothelial dysfunction (EQI <2), female gender, and severe clinical status at acute COVID-19 infection with a need for oxygen supplementation were independent risk factors of long COVID-19 syndrome. Long COVID-19 symptoms, specifically non-respiratory symptoms, are due to persistent endothelial dysfunction. These findings allow for better care of patients with long COVID-19 symptoms.

Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population.

Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the -786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects. A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and -786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR. There was significant linkage disequilibrium between the three NOS3 polymorphisms (p<0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not -786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24-15.41; p=0.021, dominant model OR: 1.66, 95%CI: 1.14-2.42); p=0.007, and recessive model OR: 3.85, 95%CI: 1.10-13.47; p=0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR=12.05, p=0.010) was a risk factor of MI after controlling for classical risk factors. These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients.

Association between endothelial nitric oxide gene intron 4a4b VNTR polymorphism and plasma homocysteine concentrations in Tunisian male patients with myocardial infarction.

Many studies have shown that hyperhomocysteinemia may be an independent risk factor for coronary artery disease. However, not all prospective studies support an association between elevated plasma homocysteine levels and coronary artery disease. Nitric oxide (NO) plays a relevant role in various events during atherogenesis, and in vitro data suggest that NO may modulate total homocysteine (tHcy) concentrations, whereas polymorphisms of the endothelial nitric oxide (NOS3) gene have been reported to be related to an increased risk of myocardial infarction (MI) and hyperhomocysteinemia, but the results have been controversial. We hypothesized that the NOS3 synthase 4a4b VNTR polymorphism is a determinant of tHcy concentrations and tested this in 310 patients with MI and 250 controls. The NOS3 gene intron 4a4b VNTR polymorphism was analyzed by polymerase chain reaction analysis. There was no significant difference in the homocysteine levels between patients with MI and controls. The frequencies of the NOS34b4b, 4b4a, and 4a4a genotypes in the MI group were significantly different from those in the control group. In patients with MI, plasma tHcy concentrations were significantly different among the NOS3 genotypes (13.5±4.5, 18.5±3.9, and 20.4±2.1 µmol/L for 4b4b, 4a4b, and 4a4a genotypes, respectively; P<.001). However, no significant difference was observed for tHcy concentrations in the control group. In conclusion, the NOS34a4b gene polymorphism (presence of 4a allele) is associated with MI and influences plasma tHcy concentrations in patients with MI in the Tunisian male population.

Polymorphisms in the CC-chemokine receptor-2 (CCR2) and -5 (CCR5) genes and risk of myocardial infarction among Tunisian male patients.

OBJECTIVES: The aim of the present study was to investigate the association between CCR2-Val64Ile and CCR5-Δ32 variants and the estimation of haplotypes with MI in a sample of the Tunisian population. DESIGN AND METHODS: A total of 290 unrelated MI patients and 282 healthy controls were studied. The CCR2-Val64Ile and CCR5-Δ32 variants were analyzed by PCR-RFLP. RESULTS: Subjects carrying at least one copy of the CCR5-deletion allele were significantly more common in the control group, suggesting an atheroprotective effect (adjusted OR=0.44, 95% CI=0.28-0.72, p=0.001). Haplotype analysis showed that MI patients had significantly less 64Val-Del haplotype (9.9% vs. 21.3%, OR=0.30, 95% CI=0.21-0.43, p<0.001) and 64Ile-Ins haplotype (12.3% vs. 16.7%, OR=0.58, 95% CI=0.42-0.80, p<0.001). CONCLUSION: A protective effect of the CCR5-Δ32 polymorphism against MI in the Tunisian population was found.

Association of a DNA polymorphism of the apolipoprotein AI-CIII-AIV gene cluster with myocardial infarction in a Tunisian population.

BACKGROUND: Apolipoproteins AI-CIII-AIV play important roles in the metabolism of triglycerides and high-density lipoprotein cholesterol. However, whether genetic variations in the ApoAI-CIII-AIV gene cluster are associated with the risk of myocardial infarction (MI) remains uncertain. In the present study, we examined a possible association of the ApoCIII SacI polymorphism in the ApoAI-CIII-AIV gene cluster with lipid parameters and MI in a sample of the Tunisian population. METHODS: A total of 326 Tunisian patients with MI and 361 controls were included in the study. Genotypes were determined by polymerase chain reaction--restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: A significant difference in genotype distribution and allele frequency was observed between patients and controls. At the multivariate analysis after adjustment for traditional vascular risk factors, the ApoCIII SacI polymorphism was significantly associated with MI, according to co-dominant and dominant models (co-dominant model odds ratio [OR]: 1.53, 95% confidence interval [CI]: 1.0-2.35, p=0.04; dominant model OR: 2.02, 95% CI: 1.11-3.67, p=0.02). The MI patient group showed a significant higher frequency of the S2 allele compared to the controls (10.2% vs. 6.5%; OR: 1.64, 95% CI: 1.10-2.47, p=0.01). There was no statistically significant association between ApoAI-CIII-AIV cluster gene polymorphism and lipid, lipoprotein, and apolipoprotein levels in both MI patients and controls. CONCLUSION: In the current study, a significant association between the ApoCIII SacI polymorphism (presence of S2 allele) and MI in the Tunisian population was found.

[Late stent thrombosis in a young patient who had ulcerative colitis]. / Thrombose Tardive de Stent chez un sujet de 35 ans porteur d'une Rectocolite Hémorragique.

BACKGROUND: Arterial and venous thrombosis are well recognized systemic complications of inflammatory bowel disease predominantly in patients with crohn's colitis and in those with ulcerative colitis (UC). Aim : report a new case. CASE: We describe the case of a 35 years old man presenting previously an anterior infarct with a tighten stenosis in the middle part of the left anterior descending artery (LAD). The stenosis was treated percutaneously with a bare stent deployment. During an acute exacerbation of UC, the patient developed an acute coronary syndrome with ST elevation secondary to a late stent thrombosis, needing a primary coronary angioplasty. Following course is favorable. CONCLUSION: Based on this case, we'll discuss the relationship between UC and thrombosis, and therapeutic considerations inherent to thrombotic and bleeding risks.

[Immediate and 12-month outcomes of an interventional reperfusion strategy in acute ST elevation myocardial infarction. Report of 208 successive patients]. / Pronostics immédiat et à 12 mois après une stratégie de revascularisation interventionnelle a la phase aigue d'un infarctus du myocarde avec sus décalage ST a propos de 208 patients consécutifs.

BACKGROUND: Percutaneous coronary intervention (PCI) has been proven to be the gold standard of reperfusion therapies in acute ST-elevation myocardial infarction (STEMI) in the western world. Highly trained teams and good logistical management of cathlabs may be limiting factors in developing countries and data about outcomes following PCI in such areas is scarce. AIM: The objectives of this study were to describe the procedural and clinical outcomes of patients undergoing PCI for STEMI at a university hospital in Tunisia and make a comparison with outcomes from the West. METHODS: We conducted a retrospective cohort study at a tertiary care university hospital in Tunis, Tunisia. A total of 208 consecutive patients undergoing PCI between January 2005 and June 2007 were reviewed. Univariate, multivariate and Kaplan meier analyses were constructed. The primary outcome was mortality: in-hospital, 30 days, and 12 months later. RESULTS: Cardiovascular risk factors were mainly smoking (63%) and diabetes (35.1%). The mean patient's TIMI score was 3.8+0.2 (10% were in cardiogenic shok). Procedural success was 75.5%. In-hospital, 30 days and 12-month mortality were respectively 5.3%, 6.7% and 8.2%, comparing favorably with TIMI's score predicted mortality and the published registries from developed countries. Multivariate predictors of in-hospital death included age >70 years, mutivessel disease and PCI failure. Multivariate predictors of 12-month death were killip score >2 at admission (odds ratio = 2.1) and PCI failure (odds ratio = 2.9). CONCLUSION: We conclude that, despite the logistical difficulties, excellent outcomes for acute interventional reperfusion strategy in STEMI can be achieved in a developing country, possibly similar to those seen in the West. There is a strong need for making the practice of PCI in STEMI more widespread in developing regions.

[Assessment of endothelial function reliably predicts the existence and the severity of coronary disease]. / L'étude de la fonction endothéliale permet de prédire l'existence et la sévérité de la maladie coronaire.

BACKGROUND: Endothelial dysfunction has been proven to be a cornerstone of atherosclerosis occurrence, development and progression. However, its use in clinical practice is still unclearly defined. AIM: To prospectively assess how accurately endothelial function assessment predicts the existence and the extensiveness of significant coronary artery disease. METHODS: Fifty adults (37 men and 13 women, mean age of 59.9 +/- 12.6 years) were randomly included among candidates for a coronary angiography. They previously underwent endothelial function assessment by the Flow-mediated dilation technique (FMD) according to ACC guidelines. The FMD% was expressed as maximal percent change in brachial artery diameter from baseline and the test was considered positive when FMD% was below 5%. RESULTS: Endothelial function impairment has been diagnosed in 36 patients and at least one significant coronary artery stenosis (>50%) in 38 patients. Endothelial dysfunction predicted significant coronary stenosis with a sensibility and a specificity of 89.5% and 83% respectively; positive predictive and negative predictive values were 94.4% and 71.4% respectively. Statistical correlation has been found between FMD% and the number of significantly diseased coronary vessels (rs = -0.44; p = 0.001). An FMD% less than 8% reliably predicted all multivessel coronary-diseased patients. In multivariate analysis, endothelial dysfunction was the only independent predictive factor of coronary disease (p = 0.02). CONCLUSION: Endothelial dysfunction has been proven to be highly correlated to the existence of significant coronary stenosis at coronary angiography (PPV = -94.4%). The severity of endothelial dysfunction assessed by the FMD% has also been significantly correlated to the extensiveness of coronary disease.

Radial access for concomitant coronary, subclavian and renal artery angioplasty: one case report.

BACKGROUND: Concomitant coronary and peripheral angioplasty is a more frequently reported situation. Patient's outcome is significantly conditioned by access site complications especially in femoral and brachial approaches. The radial artery access is a safe and a well established alternative in coronary interventions and could be suitable for many peripheral angioplasty cases, thanks to devices enhancement. AIM: Report a new case. CASE DESCRIPTION: We report the case of a 56-year-old woman with multivessel coronary artery disease, significant left subclavian (SCA) and bilateral renal arteries stenoses. Because of a severe resistant hypertension and prior to scheduled coronary bypass surgery a triple angioplasty of left renal artery, SCA, and left anterior descending (LAD) was attempted. Stenting of the three sites was successful in the same procedure through the left radial artery route. CONCLUSION: Radial artery access in peripheral, combined and complex percutaneous transluminal angioplasty seems to be suitable and safe. However, prospective clinical trials are still lacking.

Coronary angiogram video compression adapted to medical imaging applications.

H.264/AVC coder has proven to use the most advanced video compression, but, at the cost of high computational complexity. On the other hand, analysis of coronary x-ray images reveals large areas containing no diagnostically important information. In this paper, we propose to exploit the energy characteristics in slice equal size regions to determine the active zones in coronary x-ray sequences to be encoded as normal using the H.264 coding system. The other regions, are compressed using conventional low complex approaches. Experimental results have shown that this procedure reduces the coder computing time of about 20% while attaining the same compression performance. A clinical subjective assessment by three expert physicians in interventional cardiology leads to a compression ratio of about 30:1 which insures both a diagnosis adequacy and a sufficient compression in regards to storage and transmission requirements.

[Short coupled variant of torsade de pointes: our experience and review of the literature]. / La torsade de pointes a couplage court: notre expérience et revue de la littérature.

We present three cases of short-coupled variant of torsade de pointes with review of the literature. These women presented with syncope or presyncope due to torsade de pointes initiated by a short-coupled premature ventricular beat and without evidence of prolonged QT. There were no electrolyte disturbances in all cases, no apparent structural heart disease in two cases and a mild interventricular septum hypertrophy in the other case. One patient took spiramycin and metronidazole and another was taking pheniramin and lincomycin without any evidence of cause to effect relationship. One patient responded to verapamil but died suddendly after 44 months of follow-up. The two others recieved implantable cardioverter-defibrillators and verapamil per os. They still alive 46 and 54 months later. Short-coupled variant of torsade de pointes have a high incidence of sudden death, so it is very important for physicians to identify and treat it promptly. Long-term verapamil treatement is effective but still insufficient and patients should be considered for implantable cardioverter-defibrillator therapy.