Analysis of heart rhythm disturbances in fetuses

Analýza mechanismu vzniku poruch srdečního rytmu u plodů V.Tomek Abstrakt Úvod: Předmětem disertační práce je sledování srdečního selhání u plodů s poruchou srdečního rytmu. Cílem je analýza mechanismů, podílejících se na vzniku arytmie, posouzení vlivu podání farmakologických látek na průběh fetálně zjištěné dysrytmie a sledování pozdních důsledků prenatálních arytmií. Arytmie jsou prenatálně málo časté, ale mohou vést k srdečnímu selhání, hydropsu a bez správně vedené léčby k úmrtí plodu. Metodika: Změřili jsme mechanický atrioventrikulární interval u lidských plodů pomocí Dopplerovské echokardiografie a vytvořili normy pro různé gestační stáří a srdeční frekvenci. Výsledky jsme srovnali s plody matek s pozitivním nálezem cirkulujících autoprotilátek anti-SSARo/SSB La. Podíleli jsme se na multicentrické mezinárodní retrospektivní studii 175 plodů s diagnózou atrioventrikulární blokády s cílem analyzovat vliv léčby na osud plodů. Srovnali jsme výsledky 2 léčebných protokolů (digoxin vs. flecainide) u plodů se supraventrikulární tachykardií (SVT) s cílem určení optimální léčby Významnost srdečního selhání u plodů s kompletní AV blokádou a SVT byla hodnocena na základě měření frakce zkrácení levé komory, přítomnosti výpotků event. hydropsu plodu, kardiothorakálního indexu a dle celkového parametru tzv. Skóre...Analysis of heart rhythm distrubances V.Tomek Abstract Objective: The dissertation was focused on prenatal cardiology. Prenatal cardiology is a relatively young field, which is focused on diagnosis and treatment of fetal heart. In the thesis, I focused on the issue of cardiac arrhythmias: pathophysiology, diagnosis and therapeutic management of prenatally heart rhythm disturbances. The most frequent type of prenatal arrhythmias are fetal isolated complete atrioventricular (AV) block and supraventricular tachycardia (SVT). Although these rhythm heart disorders are relatively rare, but can lead to heart failure and are important causes of fetal mortality. Methods: We performed measurement of mechanical atrioventricular conduction time intervals in human foetuses assessed by Doppler echocardiography and provided reference values. We compared reference values with foetuses of mothers with anti-SSA Ro/SSB La autoantibodies, being in risk of isolated congenital heart block development. We collaborated in a multinational, multicenter retrospective study of 175 fetuses diagnosed with AV block (2000 -2007) to analyse the influence of the treatment. We compared 2 treatment protocols (Prague and London) to find out the optimal treatment strategy of fetuses with supraventricular tachycardia. The severity of heart...Units out of CUMimofakultní pracoviště2. lékařská fakultaSecond Faculty of Medicin

Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy

Congenital heart disease is the most common type of birth defect, accounting for one-third of all congenital anomalies. Using whole-exome sequencing of 2718 patients with congenital heart disease and a search in GeneMatcher, we identified 30 patients from 21 unrelated families of different ancestries with biallelic phospholipase D1 (PLD1) variants who presented predominantly with congenital cardiac valve defects. We also associated recessive PLD1 variants with isolated neonatal cardiomyopathy. Furthermore, we established that p.I668F is a founder variant among Ashkenazi Jews (allele frequency of ~2%) and describe the phenotypic spectrum of PLD1-associated congenital heart defects. PLD1 missense variants were overrepresented in regions of the protein critical for catalytic activity, and, correspondingly, we observed a strong reduction in enzymatic activity for most of the mutant proteins in an enzymatic assay. Finally, we demonstrate that PLD1 inhibition decreased endothelial-mesenchymal transition, an established pivotal early step in valvulogenesis. In conclusion, our study provides a more detailed understanding of disease mechanisms and phenotypic expression associated with PLD1 loss of function

Analysis of heart rhythm disturbances in fetuses

Analysis of heart rhythm distrubances V.Tomek Abstract Objective: The dissertation was focused on prenatal cardiology. Prenatal cardiology is a relatively young field, which is focused on diagnosis and treatment of fetal heart. In the thesis, I focused on the issue of cardiac arrhythmias: pathophysiology, diagnosis and therapeutic management of prenatally heart rhythm disturbances. The most frequent type of prenatal arrhythmias are fetal isolated complete atrioventricular (AV) block and supraventricular tachycardia (SVT). Although these rhythm heart disorders are relatively rare, but can lead to heart failure and are important causes of fetal mortality. Methods: We performed measurement of mechanical atrioventricular conduction time intervals in human foetuses assessed by Doppler echocardiography and provided reference values. We compared reference values with foetuses of mothers with anti-SSA Ro/SSB La autoantibodies, being in risk of isolated congenital heart block development. We collaborated in a multinational, multicenter retrospective study of 175 fetuses diagnosed with AV block (2000 -2007) to analyse the influence of the treatment. We compared 2 treatment protocols (Prague and London) to find out the optimal treatment strategy of fetuses with supraventricular tachycardia. The severity of heart..

Long‐Term Results of Congenital Aortic Stenosis Treatment in the Era of Percutaneous Balloon Valvuloplasty: Up to 33 Years Follow‐Up

Background The goal of this study was to evaluate long‐term results of percutaneous balloon valvuloplasty (BVPL) used exclusively for initial management of congenital aortic stenosis in children. Methods and Results A total of 409 consecutive pediatric patients (134 newborns, 275 older patients) who underwent BVPL as initial treatment of aortic stenosis in a single nationwide pediatric center were subjected to a retrospective follow‐up study. The resulting follow‐up time reached a median of 18.5 (interquartile range, 12.2–25.1) years. Successful BVPL was defined by residual Doppler gradient <70/40 (systolic/mean) mm Hg. The primary end point was death; secondary end points included any valve reintervention, balloon revalvuloplasty, any aortic valve surgery, and aortic valve replacement, respectively. BVPL effectively reduced the peak and mean gradient both immediately and at the latest follow‐up (P<0.001). There was significant procedure‐related progression of aortic insufficiency (P<0.001). Higher aortic annulus z score was predictive for severe aortic regurgitation (P<0.05) and lower z score for insufficient gradient reduction (P<0.05). The actuarial probability of survival/survival free from any valve reintervention was 89.9%/59.9%, 85.9%/35.2%, and 82.0%/26.7% at 10, 20, and 30 years after first BVPL, respectively. Left ventricular dysfunction or arterial duct dependency as the indication for BVPL was predictive of both worse survival and survival free from any reintervention (P<0.001). Lower aortic annulus z score and lower balloon‐to‐annulus ratio were predictive of a need for revalvuloplasty (P<0.001). Conclusions Percutaneous BVPL provides good initial palliation. In patients with hypoplastic annuli and left ventricular or mitral valve comorbidity, the results are less favorable