Salem Kachboura

Consanguinity, endogamy, and genetic disorders in Tunisia

Consanguinity refers to marriages between individuals who share at least one common ancestor. In clinical genetics, a consanguineous marriage is defined as a union between two individuals who are related as second cousins or closer, with the inbreeding coefficient (F) equal or higher than 0.0156 (Bittles2001). However, reports on consanguinity rates may sometimes include marriages between third cousins or more distantly related individuals (Hamamy2011). It is estimate that more than 690 million people in the world are consan- guineous (Bittles and Black 2010 ). Middle East, Northern Africa, and South Asia are regions that have historically and culturally had a high rate of consanguineous unions (Al- Awadi et al. 1985; Al-Gazali et al.1997; Jaber et al.1997;Bittles et al.2002; Bener and Alali2006). Recent studieshave shown that 20 % to 50 % of marriages in Arab countries are between relatives (Tadmouri et al. 2009;Bittles2011; Hamamy et al.2011). The rate was 68 % inEgypt (Mokhtar and Abdel-Fattah2001), 51-58 % in Jordan

Cardiac hydatid cyst revealed by ventricular tachycardia

Hydatid disease is a human parasitic infestation caused by the larval stage of Echinococcus Granulosus. The liver and the lungs are the most common locations. Cardiac involvement is rare and accounts for 0.5-2% of all hydatid disease. We report an unusual presentation of cardiac hydatid cyst revealed by ventricular tachycardia in a patient with a history of cerebral hydatid cyst.

Cardiac resynchronization therapy allows the optimization of medical treatment in heart failure patients

AIM Cardiac resynchronization therapy (CRT) is recommended for selected patients with advanced heart failure (HF) despite optimal medical treatment. However, the doses of pharmaceuticals in this population are often limited by adverse effects. We compared the drug regimens of 21 patients before and 6 months after they underwent the implantation CRT systems. METHODS We studied 17 men and four women (mean age=63.4 ± 11 years) presenting in New York Heart Association HF classes III-IV, and with a left ventricular ejection fraction (LVEF) ≤ 35% and cardiac dyssynchrony, who underwent implantation of CRT systems. RESULTS At baseline, 52% of patients were treated with β-adrenergic blockers (β-B), though in optimal doses in only 19%. The introduction of (β-B) was complicated by cardiogenic shock in three patients. At baseline, all patients were treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB), of whom 76% received optimal doses. After 6 months of CRT, β-B were administered to 76% of patients, in optimaklon ACE or ARB but 75% of them were receiving maximal doses. After 6 months of CRT, β blockers have been introduced in 72% of patients and maximal doses have been achieved in 60% of them. Maximal doses of ACE or ARB were reached in 95% of the study population. We noticed that systolic blood pressure was higher after implantation. There was also a significant improvement in functional status and left ventricular ejection fraction compared to baseline. CONCLUSION CRT is an efficacious adjunctive device therapy to standard medical therapy for patients with heart failure and cardiac dyssynchrony. Its benefits are in addition to those afforded by standard pharmacological therapy. Achieving maximal doses of medical treatment and the possibility of introducing β blockers after CRT prove that CRT and pharmacological treatment are complementary strategies and should not be considered as competitive.

Does Ramadan fasting affect the intensity of acenocoumarol‐induced anticoagulant effect?

Each year, during the holy month of Ramadan, millions of healthy adult Muslims refrain from eating and drinking from dawn to dusk. Although fasting is not obligatory for the sick, many patients with stable diseases and taking oral medications are motivated to observe Ramadan fasting, including those treated with vitamin-K antagonists (VKAs) the main oral anticoagulants used to prevent and treat many thrombotic disorders. It is well known that the dose–response to VKA can be affected by various factors, such as diet (Cust odio das Dôres et al, 2007) and drug interactions (Ansell et al, 2008). During Ramadan, not only are eating patterns altered but also the amount and types of food. The daily medication schedule is also changed because of fasting. Thus, the relationship between dose and response to VKA may be affected during Ramadan. However, data on the effects of Ramadan fasting on VKA-anticoagulant activity are scarce. This study evaluated the effects of Ramadan fasting on International Normalized Ratio (INR) stability in patients treated with long-term acenocoumarol. A total of 67 patients (29 females, 38 males, mean age 60 11 4 years) were included in this prospective, open, single-centre study. Exclusion criteria were an INR <1 7 or >4 5 before Ramadan. To study the effect of fasting on INR stability, the INR of patients was assessed at three time-points: an initial visit at 3 d before Ramadan began (INR1), a second visit on the 15th day of Ramadan (INR2), and a third visit just before the end of Ramadan (INR3). INR3 was assessed only in those patients with an INR2 < 4 5. Asymptomatic AVK overdose was defined as INR >4 5. The INR values were determined by measuring the prothrombin time using a fully automated STA-R coagulation analyser (Diagnostica Stago, Asnier, France). All statistical analyses were performed using SPSS version 18.0 (SPSS Inc., Chicago, IL, USA). INRs values were compared with the non-parametric Wilcoxon test. A P-value of <0 05 was considered statistically significant. The INR increased acutely during the first 2 weeks of Ramadan for the majority of patients. Indeed, the mean INR2 value was significantly higher than that of INR1 (4 1 1 7 vs. 2 9 0 8; P < 0 0001, respectively) (Fig 1) and a mean variation of +46 5% (range: 35% to +256 4%) was observed between INR1 and INR2. Furthermore, 25 (37 3%) patients had an INR2 > 4 5. These patients were excluded from the second part of the study. A significant increase in the INR was also observed during the last 2 weeks of Ramadan (Fig 1). Indeed, the mean INR3 value recorded at the end of Ramadan was significantly higher than that of INR2 (3 4 0 88 vs. 2 9 0 6; P < 0 0001, respectively). However, only five (11 9%) patients reached an INR3 > 4 5. Baseline INR value and acenocoumarol daily dosage were significantly higher in patients with an INR >4 5 (n = 30) compared to those with an INR ≤4 5 (n = 37) (Table I). Multivariate analyses identified two independent predictors factors were associated with a high INR (INR>4 5) during Ramadan: baseline INR > 3 [odds ratio (OR) = 10 6; 95% confidence interval (CI) 2 49–27 02; P < 0 001] and acenocoumarol dosage ≥4 mg/d (OR = 4 15; 95% CI 1 14–15 09; P = 0 003). Five bleeding episodes were recorded (7 4%) during the whole study period. According to the Bleeding Academic Research Consortium (Mehran et al, 2011), one was classified as type 3c (intracranial haemorrhage) and four were classified as type 1 (two cases of bleeding gums, one of small bruising and one nosebleed). All of the bleeding events occurred in patients with an INR > 7. This pilot study showed that Ramadan fasting significantly affects the INR stability of patients treated for long-term with acenocoumarol. Indeed, about half (44 8%) of our patients reached a VKA overdose (INR >4 5) and bleeding complications occurred in 7 4% of the patients during the study period.

Clinical and Genetic Investigation of Atrial Septal Defect with Atrioventricular Conduction Defect in a Large Consanguineous Tunisian Family

BACKGROUND Atrial septal defect (ASD) is an autosomal dominant disease characterized by left-to-right shunting and increased right ventricular output. Approximately 5-10% of congenital heart diseases (CHD) are due to ASD, which is one of the most frequent CHD found in adults. The gene responsible for ASD was mapped to chromosome 5q35 encoding the transcription factor NKX2-5 that plays an important role for the regulation of septation during cardiac morphogenesis. METHODS A Tunisian family including four affected members was investigated. Individuals were genotyped using the polymorphic microsatellite markers D5S394 and D5S2069 overlapping the NKX2-5 gene. RESULTS We report here clinical and molecular investigation of a Tunisian consanguineous family with four affected members. Two presented with ASD associated with prolonged PR interval, whereas the other two presented only a prolonged PR interval. We also identified five asymptomatic individuals in the same family with ventricular preexcitation. Although the patients were products of a consanguineous marriage, no other abnormalities were observed in this family. Genotyping and linkage analysis showed exclusion of linkage between the gene responsible for ASD in this family and NKX2.5 gene. CONCLUSIONS Our results further confirm the genetic heterogeneity of ASD.

256: Ramadan fasting and high sensitive CRP in patients with stable coronary artery disease: a pilot study

Introduction Ramadan fasting is one of the five pillars observed by Muslim adults worldwide. Data on incidence of acute coronary syndrome during fasting Ramadan are scarce and conflicting. Inflammation plays a major role in atherothrombosis, and measurement of cardiac biomarkers such as High sensitive C-reactive protein (hs-CRP) may provide a strong independent predictor of future cardiac events. Aim of this study was to evaluate the effect of fasting during Ramadan on hs-CRP in patients with stable coronary artery disease (CAD). Patients and Methods it was a prospective pilot study among 27 patients with stable CAD (within the last 6 months) who were observed before and at the end of Ramadan fasting. Patients were recruited from outpatients department. Twenty one were males and 6 were females with a mean age of 59±8.2 years (52-75 y). Fifteen patients had hypertension, 10 were smokers and 7 were diabetics. Blood was analyzed at the first visit was a week before the onset of Ramadan and the second visit at the third week of Ramadan. The assay of hs-CRP was done with the collected sera by Demeditec Diagnostics Systems Laboratories (Germany). Results Six patients were excluded for the second visit due to various reasons (break voluntary of fasting in two cases, 4 patients with concurrent inflammatory disorders e.g. rheumatoid disease in 2 cases and intercurrent infections in two others). A total of 21 subjects were screened during this period. There was a significant reduction in hs-CRP during Ramadan compared before this period: 6.6±8.7 vs 3.8±5.5 (p Conclusion The practice of fasting during the month of Ramadan by the people with stable CAD might be cardio-protective as it resulted in the lowering of hs-CRP.

ANÉVRYSME AORTIQUE D'ORIGINE SYPHILITIQUE : À propos d'un cas

: The incidence of tertiary syphilis has declined in recent years owing to the early recognition of the disease and use of antibiotics. As a result, syphilitic aortic aneurysms are rarely encountered nowadays. We report the case of a 65 years old man, who was admitted to our hospital in June 2004 for dyspnea, cough and chest discomfort. On physical examination, blood pressure was 130/80 mmHg with no significant laterality, pulse rate was 70 per minute and there was a decrease of breath sounds over the right lung. Laboratory findings revealed a slight elevation of the erythrocyte sedimentation rate. Serological studies for syphilis showed a positive venereal disease laboratory test (VDRL) at 1/32 and a positive Treponema pallidum hemagglutination test (TPHA) at 1/2560. The chest radiography showed a right para cardiac opacity measuring 16 x 12 cm. Fiber optic bronchoscopy showed an extrinsic compression of the right upper lobar bronchus. Gadolinium-enhanced magnetic resonance angiography and 16 multidetector-row spiral computed aortography showed a huge partially thrombosed saccular aneurysm of the ascending aorta measuring 132 mm in diameter. The circulating lumen measured 53 mm in its largest diameter. This aneurysm involved the innominate artery. There was no other arterial involvement. The patient was given a three week course of intravenous penicillin followed by a successful surgical procedure in September 2004 with ascending aortic replacement and innominate artery reimplantation. This case illustrates well a formerly common, but now extremely rare disease.

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

Left ventricular non-compaction and hypertrophic cardiomyopathy: two overlapping diseases or two manifestations of the same cardiomyopathy? Response to the letter concerning the article: “Left ventricular non-compaction associated with hypertrophic…

We thank Dr. Finsterer and Dr. Stollberger for their valuable comments on our paper [1]. First, we agree that both left ventricular non compaction (LVNC) and hypertrophic cardiomyopathy (HCM) can be associated with neuromuscular disorders [2]. Our patient did not report any symptoms suggestive of myopathy. He was also referred to a neurologist, who did not find any abnormality. Of note, creatine kinase serum level was normal. Second, LVNC and HCM have been accepted as distinct cardiomyopathies and classified as genetic cardiomyopathies by the American Heart Association [3]. We concur that since LVNC was reported to disappear and was even inducible in animal models, its genetic origin could be conflictual and debatable. Recently, Lorca et al. [4] studied three families with both LVNC and HCM diseases, with different common mutations in each family and autosomal dominant inheritance. Within one family, the investigators found the coexistence of both diseases in two patients, with a possible pathogenic candidate described: mutation of sarcomere cardiac b-myosin heavy chain gene (MYH7 L620P). In the two other families, the same mutation was described (MYBPC G263NX) with phenotype variability, and only one case associating both LVNC and HCM in each family [4]. Further genetic studies should be performed to try to answer to the following question: are HCM and LVNC two overlapping diseases or two different manifestations of the same cardiomyopathy spectrum? Unfortunately, we did not perform genetic analysis because the patient’s family refused it. Finally, regarding complications, our patient showed heart failure symptoms and signs with mildly impaired left ventricular ejection fraction, in addition to episodes of non-sustained ventricular tachycardia on 24-h Holter electrocardiography recording. According to sudden cardiac death score related to HCM, implantable cardiac defibrillator was indicated and thus implanted. Although the left atrium was dilated (area 27 cm2), no atrial fibrillation was found on 24-h Holter electrocardiogram recordings or on different telemetries; therefore, anti-coagulation was not indicated. To conclude, LVNC can be either primary (congenital) or secondary. When it is primary, LVNC genetic determination is close to that of HCM. Further genetic studies are needed to better elucidate this relationship and to better identify the pathogenic mutations.

Left ventricular non-compaction associated with hypertrophic cardiomyopathy in the same patient

Address for correspondence: Dr. Lobna Laaroussi, Université Tunis El Manar, Faculté de Médecine de Tunis, Service de Cardiologie Hopital Abderrahmen Mami, 2008 Ariana, Tunisia, e-mail: lobna_laroussi@hotmail.com Conflict of interest: none declared Kardiologia Polska Copyright