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

<p>Abstract</p> <p>Introduction</p> <p>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.</p> <p>Case presentation</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Case Report - Cardiomyopathie hypertrophique néonatale de diagnostic étiologique difficile

La cardiomyopathie hypertrophique n&#233;onatale est une entit&#233; rare, h&#233;t&#233;rog&#232;ne regroupant plusieurs formes cliniques et donc de diagnostic &#233;tiologique difficile. Nous rapportons l&#8217;observation d&#8217;un nouveau n&#233; issu d&#8217;une grossesse g&#233;mellaire, ayant pr&#233;sent&#233; &#224; la naissance un tableau d&#8217;insuffisance cardiaque, l&#8217;&#233;chocardiographie avait conclut &#224; une cardiomyopathie hypertrophique obstructive. Le bilan &#233;tiologique &#233;tait n&#233;gatif notamment une m&#232;re non diab&#233;tique. L&#8217;&#233;volution &#233;tait favorable avec r&#233;gression de l&#8217;hypertrophie 2 semaines apr&#232;s la naissance. L&#8217;&#233;tiologie finalement sugg&#233;r&#233;e &#233;tait une cardiomyopathie secondaire &#224; l&#8217;injection ant&#233;natale de cortico&#239;des dans le but d&#8217;acc&#233;l&#233;rer la maturation pulmonaire. L&#8217;&#233;tablissement par les soci&#233;t&#233;s savantes d&#8217;un consensus de bilan &#233;tiologique minimal standard selon une chronologie bien d&#233;termin&#233;e serait d&#8217;un grand apport dans la prise en charge de cette anomalie

Targeted next generation sequencing screening of Lynch syndrome in Tunisian population

A high colorectal cancer (CRC) incidence is observed in Tunisia, with a relatively high proportion of patients developing CRC before the age of 40. While this suggests a genetic susceptibility, only a few Tunisian Lynch Syndrome families have been described. In this study we aimed to identify the underlying genetic cause in 32 patients with early onset CRC and/or a positive family history. Of twenty-four patients' tumor or biopsies could be analyzed with immunohistochemical staining to detect loss of expression of one of the MMR proteins. Ten tumors showed loss of expression, of which one tumor was from a patient where a germline pathogenic MSH2 variant was detected previously with Sanger sequencing. Next generation sequencing of the MMR, POLE and POLD1 genes was performed in leukocyte and tumor DNA of the remaining nine patients, as well as in two patients with MMR-proficient tumors, but with severe family history. In six of 11 patients a germline variant was detected in MLH1 (n=5) or MSH2 (n=1). Two of six patients were from the same family and both were found to carry a novel in-frame MLH1 deletion, predicted to affect MLH1 function. All MLH1 variant carriers had loss of heterozygosity with retention of the variant in the tumors, while a somatic pathogenic variant was detected in the patient with the germline MSH2 variant.Molecular tumour pathology - and tumour geneticsMTG2 - Moleculaire genetica van gastrointestinale tumore

Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice

Autosomal dominant hypophosphatemic rickets (ADHR) is unique among the disorders involving Fibroblast growth factor 23 (FGF23) because individuals with R176Q/W and R179Q/W mutations in the FGF23 176RXXR179/S180 proteolytic cleavage motif can cycle from unaffected status to delayed onset of disease. This onset may occur in physiological states associated with iron deficiency, including puberty and pregnancy. To test the role of iron status in development of the ADHR phenotype, WT and R176Q-Fgf23 knock-in (ADHR) mice were placed on control or low-iron diets. Both the WT and ADHR mice receiving low-iron diet had significantly elevated bone Fgf23 mRNA. WT mice on a low-iron diet maintained normal serum intact Fgf23 and phosphate metabolism, with elevated serum C-terminal Fgf23 fragments. In contrast, the ADHR mice on the low-iron diet had elevated intact and C-terminal Fgf23 with hypophosphatemic osteomalacia. We used in vitro iron chelation to isolate the effects of iron deficiency on Fgf23 expression. We found that iron chelation in vitro resulted in a significant increase in Fgf23 mRNA that was dependent upon Mapk. Thus, unlike other syndromes of elevated FGF23, our findings support the concept that late-onset ADHR is the product of gene–environment interactions whereby the combined presence of an Fgf23-stabilizing mutation and iron deficiency can lead to ADHR