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.

Atrial flutter ablation by femoral approach in a woman with azygos continuation of an interrupted inferior vena cava and dual chamber pacemaker.

This report describes a case of isthmus-dependent atrial flutter ablation by the femoral approach in a 54-year-old woman with a previously unknown absence of the inferior vena cava (IVC) and dual chamber pacemaker. Despite looping of the catheters, ablation and termination of atrial flutter were performed successfully without function alteration of the pacemaker leads.  This is the first report of an inferior-to-superior approach for ablation of atrial flutter in the absence of the perihepatic IVC with the presence of chronic indwelling leads in the area targeted for radiofrequency.

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.

Successful pregnancies after transvenous cardiac resynchronization therapy in a woman with congenitally corrected transposition of the great arteries.

Congenitally corrected transposition of the great arteries is a rare heart defect that can be associated with systemic ventricular dysfunction and conduction disturbances. The use of cardiac resynchronization therapy in patients with congenital heart disease is not fully established, and achievement of successful pregnancies after implantation of transvenous, biventricular system has never been described, and which resulted in a significant clinical improvement. We describe a 33-year-old female with congenitally corrected transposition of the great arteries, who achieved six pregnancies and successful vaginal deliveries. The two last pregnancies were achieved after cardiac resynchronization therapy for systemic ventricular dysfunction and complete heart block. A congenital cardiac disease has been identified in only one offspring.

Right ventricular myxoma obstructing the right ventricular outflow tract: a case report.

INTRODUCTION: Primary cardiac tumors are uncommon during infancy and childhood. Myxomas originating from the right ventricle are even less common in pediatric patients. CASE PRESENTATION: Here we describe a case of an 11-year-old Tunisian boy who was referred for syncope. Transthoracic echocardiography revealed a large mobile mass attached to his right ventricle, obstructing his right ventricular outflow tract. Complete surgical excision of the mass with preservation of the pulmonary valve was performed. The diagnosis of myxoma was histologically confirmed. CONCLUSION: Cardiac myxomas located in the right ventricular outflow tract are rare and can present unusual diagnostic and therapeutic challenges.

Association between haptoglobin 2-2 genotype and coronary artery disease and its severity in a tunisian population.

Haptoglobin (Hp) polymorphism generates three common human genotypes (Hp1-1, Hp2-1, and Hp2-2), having functional differences, related to the risk of development of cardiovascular diseases. These functions are a consequence of hemoglobin binding that leads to the synthesis of an antioxidant like ferritin. We explored the association of Hp polymorphism with significant coronary stenosis (SCS) and its severity within 400 Tunisian patients, using genotyping, biochemical parameters, and the Gensini score. After adjustments for age and gender, Hp2-2 was associated with the highest ferritin but the lowest Hp concentrations. After adjustments for confounding parameters, the OR of SCS associated with Hp2-2 was 1.74 (95% CI 1.18-2.58; p = 0.005). This effect was enhanced within diabetics (OR 1.90, 95% CI 1.11-3.24; p = 0.018), obese subjects (OR 1.98, 95% CI 1.10-4.86; p = 0.034), and smokers (OR 4.17, 95% CI 1.54-1.29; p = 0.005). The Hp2-2 genotype is associated with an increase in SCS especially in diabetics, the obese, and smokers.

Association of three polymorphisms of scavenger receptor class BI gene (exon8, exon1, intron5) with coronary stenosis in a coronary Tunisian population.

BACKGROUND: The potential role of scavenger receptor class BI (gene name SCARB1) in the regulation of lipoproteins metabolism and atherosclerosis has attracted considerable interest. We tested the relationship of SCARB1 polymorphisms with significant coronary stenosis (SCS) and lipid profile in a coronary Tunisian population. METHODS: Three SCARB1 polymorphisms (exon8 (C/T), exon1 (G/A), intron5 (C/T)) were studied in 316 Tunisian patients undergoing coronary angiography. SCS was defined as a luminal narrowing of ≥ 50% in at least one major coronary artery. Lipid profile was measured. Genotyping was performed using PCR-RFLP. RESULTS: Individuals with TT genotypes of exon8 were associated with higher concentrations of plasma HDL-C and ApoAI in the group without SCS. Carriers of T allele of exon8 were associated with 41% lower risk of SCS. This protective effect seemed to be particularly significant in women, nondiabetics and nonsmokers. Subjects homozygous for the variant allele of intron5 were significantly associated with an increased risk of SCS, particularly in smokers. AA genotype of exon1 was associated with an increased risk of SCS in diabetics and in patients with metabolic syndrome. The (CAT) haplotype was associated with increase in the risk of SCS compared to the wild haplotype and had a 4-fold greater risk of SCS than patients with haplotype (TGC) which seems to be the most protective against SCS. CONCLUSION: Carriers of T allele of exon8 in SCARB1 seemed to increase HDL-C and ApoAI concentrations and reduce the risk of SCS. The intron5, exon1 and (CAT) haplotype seemed to have an atherogenic effect.

Six lipoprotein lipase gene polymorphisms, lipid profile and coronary stenosis in a Tunisian population.

Lipoprotein lipase (LPL) is the rate-limiting enzyme in the hydrolysis of triglyceride-rich lipoprotein particles (Chylomicrons and very-low-density lipoprotein). LPL polymorphisms' effects on lipids and coronary artery disease are controversial among studies and populations. Our aim was to study the association between six polymorphisms, haplotypes and significant coronary stenosis (SCS), disease severity and lipid parameters in Tunisian patients. LPL PvuII, 93 T/G, 188 G/E, HindIII, N291S and D9N polymorphisms were analyzed in 316 patients who underwent coronary angiography. Assessment of coronary angiograms identified SCS as the presence of stenosis >50 % in at least one major coronary artery. The stenosis severity was determined by using Gensini score and vessels number. A significant association of SCS with TT of the HindIII polymorphism was showed (odds ratio (OR): 2.84, 95 % CI, 1.19-7.40, p = 0.017) and TG (OR: 1.77, 95 % CI, 1.99-2.82, p = 0.033). The mutated HindIII genotype was significantly associated with increased TG and ApoB/ApoA-I ratio and with decreased HDL-C. Haplotype analysis showed that OR of SCS associated with the CTGTAG haplotype was 2.12 (95 % CI 1.05-4.25, p = 0.032) and with CGGGAA was 0.71 (95 % CI 0.26-1.95, p = 0.022) compared to the CTGTAA. Significant difference in Gensini score was observed among HindIII genotype and haplotypes. A significant association between the mutated genotype of HindIII polymorphism and decreased HDL-C level and increased ApoB/ApoA-I ratio and TG level was showed. Our results suggest that HindIII and D9N polymorphisms and CTGTAG haplotype seem to be considered as marker of predisposition to coronary stenosis. In another hand, HindIII and haplotypes were related to stenosis severity.

Acute left ventricular dysfunction secondary to right ventricular septal pacing in a woman with initial preserved contractility: a case report.

INTRODUCTION: Right ventricular apical pacing-related heart failure is reported in some patients after long-term pacing. The exact mechanism is not yet clear but may be related to left ventricular dyssynchrony induced by right ventricular apical pacing. Right ventricular septal pacing is thought to deteriorate left ventricular function less frequently because of a more normal left ventricular activation pattern. CASE PRESENTATION: We report the case of a 55-year-old Tunisian woman with preserved ventricular function, implanted with a dual-chamber pacemaker for complete atrioventricular block. Right ventricular septal pacing induced a major ventricular dyssynchrony, severe left ventricular ejection fraction deterioration and symptoms of congestive heart failure. Upgrading to a biventricular device was associated with a decrease in the symptoms and the ventricular dyssynchrony, and an increase of left ventricular ejection fraction. CONCLUSION: Right ventricular septal pacing can induce reversible left ventricular dysfunction and heart failure secondary to left ventricular dyssynchrony. This complication remains an unpredictable complication of right ventricular septal pacing.

Takayasu arteritis with coronary aneurysms causing acute myocardial infarction in a young man.

Takayasu arteritis is an inflammatory condition that involves the large cardiac vessels, predominantly the aorta and its main branches. It typically affects young women (age, ≤40 yr), most often Asians and Latin Americans. Herein, we describe a rare manifestation of Takayasu arteritis in a 19-year-old black Tunisian man who presented with acute inferior myocardial infarction and complete atrioventricular block after occlusion from a giant aneurysm in the right coronary artery. The coronary artery disease was associated with aneurysmal dilations in the carotid, vertebral, and right renal arteries. Medical therapy improved Thrombolysis in Myocardial Infarction flow in the area of the giant aneurysm from grade 1 to grade 3. Upon the diagnosis of Takayasu arteritis, intravenous methylprednisolone and oral prednisone therapy was started. After 10 days of hospitalization, the patient was discharged on a medical regimen. Renovascular hypertension due to renal artery stenosis was suspected, so he underwent successful percutaneous transluminal angioplasty of the inferior segmental artery of the right renal artery. During 12 months of close postprocedural monitoring, he experienced lower blood pressure, no chest pain, and no cardiovascular complications.This association of conditions has not been previously reported. Besides presenting this very rare combination of findings, we discuss the differential diagnosis of Takayasu arteritis in our patient.

DDD versus VVIR pacing in patients, ages 70 and over, with complete heart block.

BACKGROUND: Dual-chamber pacing is believed to have an advantage over single-chamber ventricular pacing. The aim of the study was to determine whether elderly patients with implanted pacemaker for complete atrioventricular block gain significant benefit from dual-chamber (DDD) compared with single-chamber ventricular demand (VVIR). METHODS: The study was designed as a double-blind randomized two-period crossover study-each pacing mode was maintained for 3 months. Thirty patients (eight men, mean age 76.5 +/- 4.3 years) with implanted PM were submitted to a standard protocol, which included an interview, functional class assessment, quality of life (QoL) questionnaires, 6-minute walk test, and transthoracic echocardiographic examinations. QoL was measured by the SF-36. All these parameters were obtained on DDD mode pacing and VVIR mode pacing. Paired data were compared. RESULTS: QoL was significantly different between the two groups and showed the best values in DDD. Overall, no patient preferred VVIR mode, 18 preferred DDD mode, and 12 expressed no preference. No differences in mean walking distances were observed between patients with single-chamber and dual-chamber pacing. VVI pacing elicited marked decrease in left ventricle ejection fraction and significant enlargement of the left atrium. DDD pacing resulted in significant increase of the peak systolic velocities in lateral mitral annulus and septal mitral annulus. Early diastolic velocities on both sides of mitral annulus did not change. CONCLUSION: In active elderly patients with complete heart block, DDD pacing is associated with improved quality of life and systolic ventricular function compared with VVI pacing.

Chromatin mechanisms in genomic imprinting.

Mammalian imprinted genes are clustered in chromosomal domains. Their mono-allelic, parent-of-origin-specific expression is regulated by imprinting control regions (ICRs), which are essential sequence elements marked by DNA methylation on one of the two parental alleles. These methylation "imprints" are established during gametogenesis and, after fertilization, are somatically maintained throughout development. Nonhistone proteins and histone modifications contribute to this epigenetic process. The way ICRs mediate imprinted gene expression differs between domains. At some domains, for instance, ICRs produce long noncoding RNAs that mediate chromatin silencing. Lysine methylation on histone H3 is involved in this developmental process and is particularly important for imprinting in the placenta and brain. Together, the newly discovered chromatin mechanisms provide further clues for addressing imprinting-related pathologies in humans.