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.

Hypertrophic obstructive cardiomyopathy with left ventricle outflow tract chordae insertion: Surgery or alcohol septal ablation? A case report.

Anomalous insertion of chordae is a rare disease that could be associated with hypertrophic obstructive cardiomyopathy (HOCM), but clinical and echocardiographic diagnoses tend to be delayed. Alcohol septal ablation has emerged as an alternative to surgical myomectomy in HOCM. When a patient showed an anomalous insertion of chordae, physicians generally opt for surgery and not alcohol septal ablation. In this report, we present the case of a lady, with symptomatic HOCM associated with a chord inserted on the left ventricular outflow tract. We succeeded to relieve obstruction by alcohol septal ablation without the need for surgery.

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.

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.

Fatal falls from great height in Sousse (Tunisia): Study of 141 medicolegal autopsy cases.

INTRODUCTION: Falls from great heights constitute a violent trauma that can lead to death. This represents a suspicious death, leading to initiate legal proceedings with in particular the practice of an autopsy. AIMS: to determine the features of victims of falls from height and relations between medico-legal form of the death, the height of the fall and the nature of traumatic injuries Methods: A retrospective study about 141 cases of death after fall from great height. Data were collected at the Legal Medicine Department of the Farhat Hached University Hospital in Sousse (Tunisia) over a period of 14 years from 2007 to 2020. RESULTS: The average age of the victims was 37±12.8 years with a sex ratio of 6.05. Half of them were day laborers. The majority had no history of psychiatric illness (91.5%). The majority of victims (41.8%) fell from a height of 3 to 6 meters. Regarding injuries, rib fractures (52.4) were predominant, especially on the right side followed by skull fractures (31.2%). A significant difference in the prevalence of rib cage lesions in the groups over 9 meters in height (p<0.05) was found. The lesions of the lower limbs were proportional to the increase in the height of the fall. Deaths were accidental in 80.8% and suicides in 13.5%. CONCLUSION: In cases of high falls, a forensic autopsy is essential to make a complete evaluation of the injuries, to search a correlation between severity of injuries and height of the fall and finally to orientate towards the medico legal form of the fall.

[Advantages of simulation-based training in improving skills of beginners in interventional cardiology procedures: a Tunisian cross-sectional study]. / Apport de la simulation dans l'apprentissage de la cardiologie interventionnelle chez les débutants: étude tunisienne transversale.

Introduction: simulator training in interventional cardiology (ST) is an educational tool that is rapidly spreading worldwide. The purpose of this study was to evaluate the advantages of ST in improving skills of beginners in interventional cardiology procedures, through a short training cycle. Methods: we conducted a before-and-after quasi-experimental evaluative study in the simulation center of the Faculty of Medicine in Sfax. We involved cardiology residents at the beginning of their training in interventional cardiology. All the participants attended a 4-hour training course on a Cathi®, high-fidelity simulator, after giving their consent. The primary endpoint was a significant improvement in performance and competence scores before and after the course. The secondary endpoint was the reduction in irradiation time and the time of the procedure. Results: thirteen learners participated in our study. The performance score improved by a median of 216.12% (ISQ = 285%). This improvement was significantly greater for learners who had never had access to the catheterisation room. The performance score ranged from a median of 31 (ISQ=40.5) to a median of 120 (ISQ=19.7), (p=0.001). The competence score for coronary angiography improved significantly, from a median of 16 (ISQ=18) to a median of 70 (ISQ=6), (p=0.001). The competence score for angioplasty improved significantly from a median of 10 (ISQ=17) to a median of 50 (ISQ=13.7), p=0.001. Procedure time of coronary angiography and angioplasty were significantly shortened from 12 min (ISQ=2) to 7 min (ISQ=1) after the simulation cycle (p=0.001), and from a median of 19 min to a median of 17 min after simulation, p=0.002. Conclusion: despite a short-time simulation training, our pilot study demonstrates a significant improvement in the learners´ skills and performance, as well as a reduction in the time taken to carry out procedures and irradiation. This could eventually increase the number of procedures carried out daily in our cathlab and limit radiation exposure of staff and patients, while ensuring that the learners receive adequate training.

Design and Rationale of the National Tunisian Registry of Percutaneous Coronary Intervention: Protocol for a Prospective Multicenter Observational Study.

BACKGROUND: Coronary artery diseases remain the leading cause of death in the world. The management of this condition has improved remarkably in the recent years owing to the development of new technical tools and multicentric registries. OBJECTIVE: The aim of this study is to investigate the in-hospital and 1-year clinical outcomes of patients treated with percutaneous coronary intervention (PCI) in Tunisia. METHODS: We will conduct a prospective multicentric observational study with patients older than 18 years who underwent PCI between January 31, 2020 and June 30, 2020. The primary end point is the occurrence of a major adverse cardiovascular event, defined as cardiovascular death, myocardial infarction, cerebrovascular accident, or target vessel revascularization with either repeat PCI or coronary artery bypass grafting (CABG). The secondary end points are procedural success rate, stent thrombosis, and the rate of redo PCI/CABG for in-stent restenosis. RESULTS: In this study, the demographic profile and the general risk profile of Tunisian patients who underwent PCI and their end points will be analyzed. The complexity level of the procedures and the left main occlusion, bifurcation occlusion, and chronic total occlusion PCI will be analyzed, and immediate as well as long-term results will be determined. The National Tunisian Registry of PCI (NATURE-PCI) will be the first national multicentric registry of angioplasty in Africa. For this study, the institutional ethical committee approval was obtained (0223/2020). This trial consists of 97 cardiologists and 2498 patients who have undergone PCI with a 1-year follow-up period. Twenty-eight catheterization laboratories from both public (15 laboratories) and private (13 laboratories) sectors will enroll patients after receiving informed consent. Of the 2498 patients, 1897 (75.9%) are managed in the public sector and 601 (24.1%) are managed in the private sector. The COVID-19 pandemic started in Tunisia in March 2020; 719 patients (31.9%) were included before the COVID-19 pandemic and 1779 (60.1%) during the pandemic. The inclusion of patients has been finished, and we expect to publish the results by the end of 2022. CONCLUSIONS: This study would add data and provide a valuable opportunity for real-world clinical epidemiology and practice in the field of interventional cardiology in Tunisia with insights into the uptake of PCI in this limited-income region. TRIAL REGISTRATION: Clinicaltrials.gov NCT04219761; https://clinicaltrials.gov/ct2/show/NCT04219761. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/24595.

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.

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.

Angioplasty of Anomalous Coronaries Arising from the Opposite Sinus with an Interarterial Course, is it Safe?

BACKGROUND: The coronary artery with an interarterial course CAIAC is the most threatening coronary anomaly, especially if it concerns the left coronary. Percutaneous coronary intervention PCI is scarcely described given its low prevalence and lack of long-term outcome data. Therefore, we assessed through this case series the feasibility and safety of PCI in this population. METHODS: This is an observational multicentric study including patients with CAIAC arising from the opposite sinus of Valsalva. The primary endpoints were immediate angiographic success and target lesion revascularization. RESULTS: During the period of the study, we performed 27235 PCI in six Cath labs, 26 procedures concerning abnormal coronaries including 12 with CAIAC. The median age was 57 years extremes: 43-78 with male predominance 1:11. Anomalous coronary artery was Right coronary artery RCA in eight patients, Left main LM in three patients, and left anterior descending LAD in one patient. The stenosis was located in all cases in proximal segments beyond the inter-arterial course proximal LAD, the superior genius of the RCA, or the proximal segment of mid-RCA. Five patients showed slit-like ostium and all have an angle take-off <45° on CT scan. After a median follow-up of 24 months, four subjects presented target lesion revascularization TLR, all were initially treated with either a bare-metal stent or with balloons. CONCLUSIONS: PCI of patients with CAIAC is feasible and appears safe. The operator should carefully analyze the angiogram before PCI to choose the appropriate guiding catheter and should be acquainted with the different techniques for improving backup.

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.

Reperfusion strategy for patients with renal dysfunction presenting with STEMI: which is better in the North African context?

BACKGROUND: Patients with renal insufficiency experience worse prognosis after STEMI. The current guidelines do not clearly draw specific strategies for patients with renal dysfunction (RD). AIM: The aim of this study is to compare primary PCI (PPCI) and thrombolysis results as well as in-hospital mortality after successful reperfusion between the RD patients (RD+) and patients with normal renal function (RD-). METHODS: We retrospectively reviewed data for 1,388 patients admitted for STEMI between January 1995 and October 2011. Two groups were identified: PPCI (315 patients) and thrombolysis (379 patients). Ninety patients (13%) had RD defined by creatinine levels at admission > 130 micromol/l, they were equally treated by PPCI and thrombolysis. RESULTS: In the PPCI group, despite a similar pre-procedural TIMI flow (P = 0.82),TIMI III restoring was significantly lower in the RD+ group (78.6% vs. 91.8%, P = 0.013). Suboptimal result was also higher in the RD+ group (13.6% vs. 2.7%, P < 0.001), but ST regression after TIMI III achievement was similar in the 2 groups (P = 0.43), probably reflecting no microvascular damage. In the thrombolysis group, successful reperfusion was also significantly lower when RD exists (58% vs. 74%, P = 0.03). After successful reperfusion, RD+ patients experienced higher in-hospital mortality in the PPCI group (29% vs. 4.3%; P < 0.001), whereas mortality was similar in the thrombolysis group (3% vs. 0%, P = 0.42). CONCLUSION: RD reduces either PPCI or thrombolysis success, with no proven microvascular damage after PPCI. In-hospital prognosis, however, is worse in the RD group only after successful PPCI, but not after successful streptokinase thrombolysis.

Acute pericardial effusion following atrial fibrillation ablation: characteristics and relationship with arrhythmia recurrences.

BACKGROUND: Pericardial effusion (PE) can occur during or after atrial fibrillation (AF) ablation, and may induce atrial arrhythmia. AIM: To characterize the impact of PE on arrhythmia recurrences following AF ablation. METHODS: Patients referred for a first radiofrequency AF ablation were studied prospectively. Transthoracic echocardiography was performed before and 24h after the procedure. If PE was present, transthoracic echocardiography was repeated at 1 month to evaluate PE evolution. Early arrhythmia recurrences (EARs) were defined as any arrhythmia documented within 1 month of the procedure. RESULTS: PE was diagnosed in 18/81 patients (22%); and was present in significantly more patients with persistent versus paroxysmal AF (14/40 [35%] vs 4/41 [10%]; P=0.008). PEs were mild (mean 6 ± 3mm), mainly asymptomatic (89%), and none required pericardiocentesis. Early and late arrhythmia recurrences were present in 25/81 (31%) and 29/81 (36%), respectively. The incidence of PE was significantly higher among patients with EARs versus those without (12/25 [48%] vs 6/56 [11%]; P=0.0004). By multivariable analysis, PE and duration in AF were the two independent predictors of EARs. PE incidence was similar in patients with and without late arrhythmia recurrences. At 1 month, no patients had PE on transthoracic echocardiography. CONCLUSION: PE following radiofrequency AF ablation is frequent, particularly following persistent AF ablation. This effusion is generally mild, mainly asymptomatic, and independently associated with EARs.

Matrix metalloproteinase-1 and matrix metalloproteinase-12 gene polymorphisms and the outcome of coronary artery disease.

OBJECTIVES: In this study, we investigated the association between matrix metalloproteinase-1 (MMP-1) G-1607GG, MMP-12 A-82G and MMP-12 A1082G genotypes and haplotypes and the prognosis of coronary artery disease (CAD). METHODS: A total of 129 Tunisian patients with CAD were followed prospectively for a median of 2.5 years. Genotypes were determined by a PCR-based restriction fragment length polymorphism. Two endpoints were considered: restenosis and incidence of clinical vascular events (restenosis, myocardial infarction, stroke, cardiac death). RESULTS: Genotypes of MMP-1 G-1607GG, MMP-12 A-82G and MMP-12 A1082G were not associated with the incidence of restenosis or clinical events. Analysis of haplotypes consisting of alleles of MMP-1 G-1607GG and MMP-12 A1082G showed that the rate of clinical events was significantly higher in patients carrying the GG-A haplotype than those with other haplotypes (0.637 vs. 0.424, respectively, odds ratio=1.45; 95% confidence interval=1.04-2.04; P<0.05; P adjusted for multiple risk factors). However, after Bonferroni correction for multiple comparisons, this difference did not reach statistical significance (P=0.093), showing that there was a tendency for the association between the GG-A haplotype and future clinical events in patients with CAD. CONCLUSION: These findings showed a trend of the GG-A haplotype of MMP-1 G-1607GG/MMP-12 A1082G towards the prediction of future clinical events in patients with CAD and suggested a possible importance of these loci in the prediction of the prognosis of CAD. Studies with large sample size are warranted to better investigate this association, as MMP genotyping could aid in identifying patients who are likely to have unfavourable prognosis.

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.