Paszkowska Agata, Piekutowska-Abramczuk Dorota, Ciara Elżbieta, Mirecka-Rola Alicja, Brzezinska Monika, Wicher Dorota, Kostrzewa Grażyna, Sarnecki Jędrzej, Ziółkowska Lidia
Department of Cardiology, The Children's Memorial Health Institute, 04-730 Warsaw, Poland.
Department of Medical Genetics, The Children's Memorial Health Institute, 04-730 Warsaw, Poland.
Genes (Basel). 2022 Mar 8;13(3):477. doi: 10.3390/genes13030477.
Left ventricular noncompaction (LVNC) is a genetically and phenotypically heterogeneous cardiomyopathy in which myocardium consists of two, distinct compacted and noncompacted layers, and prominent ventricular trabeculations and deep intertrabecular recesses are present. LVNC is associated with an increased risk of heart failure, atrial and ventricular arrhythmias and thromboembolic events. Familial forms of primary sinus bradycardia have been attributed to alterations in . There are very few reports about the association between and LVNC. The aim of our study was to characterize the clinical phenotype of families with LVNC and sinus bradycardia caused by pathogenic variants of the gene.
From March 2008 to July 2021, we enrolled six patients from four families with diagnosed isolated LVNC based on the clinical presentation, family history and echocardiographic and cardiovascular magnetic resonance (CMR) evidence of LVNC. Next generation sequencing (NGS) analysis was undertaken for the evaluation of the molecular basis of the disease in each family.
A total of six children (median age 11 years) were recruited and followed prospectively for the median of 12 years. All six patients were diagnosed with LVNC by echocardiography, and five participants additionally by CMR. The presence of late gadolinium enhancement (LGE) was found in three children. Sinus bradycardia and dilation of the ascending aorta occurred in five studied patients. In four patients from three families, the molecular studies demonstrated the presence of rare heterozygous variants.
(1) The molecular variants influence the presence of a complex LVNC phenotype, sinus bradycardia and dilation of the ascending aorta. (2) The alteration may be associated with the early presentation of clinical symptoms and the severe course of the disease. (3) It is particularly important to assess myocardial fibrosis not only within the ventricles, but also in the atria in patients with LVNC and sinus bradycardia.
左心室心肌致密化不全（LVNC）是一种具有遗传和表型异质性的心肌病，其心肌由两层不同的致密层和非致密层组成，存在明显的心室小梁和深陷的小梁间隐窝。LVNC与心力衰竭、房性和室性心律失常以及血栓栓塞事件的风险增加相关。原发性窦性心动过缓的家族形式归因于……的改变。关于……与LVNC之间关联的报道非常少。我们研究的目的是描述由……基因的致病变异引起的LVNC和窦性心动过缓家族的临床表型。
从2008年3月至2021年7月，我们根据临床表现、家族史以及LVNC的超声心动图和心血管磁共振（CMR）证据，招募了来自四个家庭的六名被诊断为孤立性LVNC的患者。对每个家庭进行下一代测序（NGS）分析以评估疾病的分子基础。
共招募了六名儿童（中位年龄11岁），并对他们进行了中位时间为12年的前瞻性随访。所有六名患者均通过超声心动图诊断为LVNC，另外五名参与者通过CMR诊断。在三名儿童中发现了延迟钆增强（LGE）。五名研究患者出现窦性心动过缓和升主动脉扩张。在来自三个家庭的四名患者中，分子研究表明存在罕见的杂合……变异。
（1）……分子变异影响复杂的LVNC表型、窦性心动过缓和升主动脉扩张的存在。（2）……改变可能与临床症状的早期出现和疾病的严重病程相关。（3）对于LVNC和窦性心动过缓患者，不仅评估心室内的心肌纤维化，而且评估心房内的心肌纤维化尤为重要。
