Inherited Hypertrabeculation? Genetic and Clinical Insights in Blood Relatives of Genetically Affected Left Ventricular Excessive Trabeculation Patients

Abstract

Genetically determined left ventricular excessive trabeculation (LVET) has a wide clinical spectrum ranging from asymptomatic subjects to severe heart failure with arrhythmias and thromboembolic events. Unlike other cardiomyopathies, the relatives of LVET patients never reach the spotlight of guidelines and clinical practice, although these family members can be often affected by these conditions. Thus, we aimed to investigate the relatives of LVET by multidimensional analysis, such as genetic testing, ECG and cardiac ultrasound (ECHO). We included 55 blood relatives from the family of 18 LVET patients (male = 27, age = 44 ± 20.8y), who underwent anamnesis registration. With Sanger sequencing, the relatives were classified into genetically positive (GEN-pos) and unaffected (GEN-neg) subgroups. In addition to regular ECG parameters, Sokolow-Lyon Index (SLI) values were calculated. 2D ECHO images were analysed with TomTec Arena, evaluating LV volumetric, functional (EF) and strain parameters. Individuals were categorized into JENNI-pos and JENNI-neg morphological subgroups according to the Jenni LVET ECHO criteria. Family history showed frequent involvement (arrhythmia 61%, stroke 56%, syncope 39%, sudden cardiac death 28%, implanted device 28%), as well as personal anamnesis (subjective symptoms 75%, arrhythmias 44%). ECG and ECHO parameters were within the normal range. In terms of genetics, 78% of families and 38% of relatives carried the index mutation. LV_SLI and QT duration were lower in the GEN-pos group; ECHO parameters were comparable in the subgroups. Morphologically, 33% of the relatives met Jenni-LVET criteria were genetically affected and showed lower LV_EF values. The frequently found genetic, morphological and clinical involvement may indicate the importance of screening and, if necessary, regular follow-up of relatives in the genetically affected LVET population.

Keywords: cardiology; cardiomyopathy screening; echocardiography; family health; genetics; left ventricular excessive trabeculation; noncompaction.

Figure 1

Screening model of study subjects. ECG: electrocardiogram, n: number of subjects.

Figure 2

Cardiac ultrasound images of the blood relatives with hypertrabeculation. (A): Four-chamber view; (B): Two-chamber view; (C): Three-chamber view; (D): End-systolic short-axis view of the left ventricle; apical third. The arrows represent the Jenni criterion, where the red line shows the noncompacted (NC) and the green line shows the compacted (C) layer diameter and the ratio of NC/C > 2.