Non-familial cardiomyopathies in Lebanon: exome sequencing results for five idiopathic cases.

BACKGROUND: Cardiomyopathies affect more than 0.5% of the general population. They are associated with high risk of sudden cardiac death, which can result from either heart failure or electrical abnormalities. Although different mechanisms underlie the various types of cardiomyopathies, a principal pathology is common to all and is usually at the level of the cardiac muscle. With a relatively high incidence rate in most countries, and a subsequent major health burden on both the families and governments, cardiomyopathies are gaining more attention by researchers and pharmaceutical companies as well as health government bodies. In Lebanon, there is no official data about the spectrum of the diseases in terms of their respective prevalence, clinical, or genetic profiles. METHODS: We used exome sequencing to unravel the genetic basis of idiopathic cases of cardiomyopathies in Lebanon, a relatively small country with high rates of consanguineous marriages. RESULTS: Five cases were diagnosed with different forms of cardiomyopathies, and exome sequencing revealed the presence of already documented or novel mutations in known genes in three cases: LMNA for an Emery Dreifuss Muscular Dystrophy case, PKP2 for an arrhythmogenic right ventricle dysplasia case, and MYPN for a dilated cardiomyopathy case. Interestingly two brothers with hypertrophic cardiomyopathy have a novel missense variation in NPR1, the gene encoding the natriuretic peptides receptor type I, not reported previously to be causing cardiomyopathies. CONCLUSION: Our results unravel novel mutations in known genes implicated in cardiomyopathies in Lebanon. Changes in clinical management however, require genetic profiling of a larger cohort of patients.

Propafenone hepatotoxicity: report of a new case and review of the literature.

Propafenone is a class Ic antiarrhythmic drug. It is a beta-adrenergic blocker that causes bradycardia and bronchospasm. It is metabolized primarily in the liver. Its bioavailability and plasma concentration differ among patients under long-term therapy. They are genetically determined by the hepatic cytochrome P-450 2D6. Hepatic toxicity is highly uncommon. To date, only eight patients were reported in the reviewed world literature. In this article, one new case will be reported emphasizing the importance of medication history taking in patients presenting with new-onset liver enzymes abnormalities.

Plasma myeloperoxidase concentration predicts the presence and severity of coronary disease in patients with chest pain and negative troponin-T.

BACKGROUND: A non-negligible proportion of patients with chest pain with negative cardiac troponin may harbor a disrupted coronary plaque. A marker of plaque rupture upstream from myocardial necrosis may help identify high-risk patients among this patient population. The purpose of this study was to investigate the correlation of plasma myeloperoxidase (MPO) concentration and angiographic coronary disease among patients with suspected troponin-negative coronary syndromes. PATIENTS AND METHODS: Patients presenting with chest pain and negative cardiac troponin-T concentration and undergoing coronary angiography were enrolled in our study. Plasma MPO concentration was measured using a single blood sample collected prior to cardiac catheterization. The primary angiographic endpoint was the presence of at least one coronary stenosis causing a 70% or more diameter reduction; secondary endpoints were number of diseased vessels, presence of coronary thrombus, and lesion ulceration. The main clinical endpoint was coronary revascularization. RESULTS: Three hundred and eighty-nine patients were enrolled. Presence of coronary stenosis causing a 70% or more diameter reduction increased with increasing quartiles of myeloperoxidase concentration (P<0.0001), as did the presence of coronary thrombus (P<0.0001) and plaque ulceration (P<0.0001). The need for percutaneous coronary revascularization also increased with increasing quartiles of systemic myeloperoxidase levels (P<0.0001). Coronary surgical revascularization did not differ among myeloperoxidase quartiles. CONCLUSION: Among patients with chest pain without troponin elevation, a single measurement of plasma MPO concentration can help identify patients with a higher risk of having significant coronary stenoses and high-risk angiographic features.

Cardiac sarcoidosis responding to monotherapy with infliximab.

Cardiac involvement is a rare and potentially life-threatening complication of sarcoidosis. We report the case of a young previously healthy woman who presented with complete atrioventricular heart block. Further evaluation revealed non-caseating granulomas in the hilar and mediastinal regions. A pacemaker was inserted, and she was treated with four doses of infliximab after she refused treatment with steroids. Rapid resolution of the pulmonary lymph nodes was documented and repeated interrogations of the pacemaker 1 year after her last infliximab infusion documented that she was in sinus rhythm. Infliximab may be considered as an alternative first-line therapy in sarcoidosis with serious organ involvement.

Characteristics of inflammatory bowel disease with onset during the first year of life.

BACKGROUND: Inflammatory bowel disease (IBD) is recognized in young children, however, only rare data on onset and evolution are available in children younger than 1 year. In the present clinical study, we aimed to analyze characteristics and clinical course of children with very early onset IBD. We were particularly interested in the relationship between bacterial infections and the use of antibiotics before the onset of IBD. PATIENTS AND METHODS: The IBD database of Necker-Enfants-Malades-Hospital was screened for patients with IBD with disease onset during the first year of life and a follow-up of at least 2.5 years. Ten patients were identified during the period 1996-2002. RESULTS: All patients presented with rectal bleeding and had colonic involvement. Four patients had definitive diagnosis of Crohn disease; ulcerative or indeterminate colitis was seen in 2 and 4 children, respectively. Five of the patients had a positive history of neonatal or early-onset bacterial infection with use of antibiotics before onset of IBD, 4 patients were still breastfed and 3 just weaned when GI symptoms started. Seven patients had a severe onset of disease requiring bowel rest, parenteral nutrition and steroid medication, followed by azathioprine or cyclosporine medication. Surgery was necessary in 3 of 10 patients. Disease relapses were frequent and observed in 8 of 10 children. DISCUSSION: Very early onset IBD may reflect a subgroup of patients characterized by a particular sensitivity to modifications of the intestinal flora. Neonatal IBD was most often severe in presentation and evolution.