Early Detection of Genetic Cardiomyopathies in Relatives | 129 INTRODUCTION It is recommended to screen relatives of patients with genetic cardiomyopathies, as they are at risk of developing a similar disease as the index patient.1–3 If a (likely-)pathogenic genetic variant has been identified in the index patient, targeted genetic testing can be performed to identify relatives who carry the same variant and are therefore at high risk of developing the disease.4 However, management of these relatives is complicated as they often have no symptoms nor detectable cardiovascular abnormalities at presentation. In addition, penetrance is often incomplete, which implies that not all carriers of the (likely-)pathogenic variant will eventually develop the disease.3,5–7 It is important to identify the relatives who are at highest risk to develop the disease, as they may potentially benefit from early therapeutic intervention to prevent detrimental adverse events such as sudden cardiac death. To identify these relatives in an early stage, sensitive diagnostic tools that reveal the earliest signs of disease meet an important clinical need. Cardiac imaging has a major role in genetic cardiomyopathies.8–10 It contributes not only to the diagnostic criteria of these cardiomyopathies, but also has important prognostic value. Unfortunately, conventional imaging modalities often lack sensitivity to detect early disease in relatives without overt disease expression.11 This can be attributed to the fact that imaging parameters and their cut-off values are typically derived from affected individuals and therefore represent more established disease. Most relatives at early stages of disease fall in the grey zone or are even classified as normal when conventional imaging parameters are used. Over the last decade, deformation imaging has emerged as more sensitive compared to conventional imaging for quantification of cardiac function.12–14 This allows quantification of global and regional myocardial deformation and may reveal subtle changes in the early stages of many cardiac diseases.13,14 Echocardiographic two-dimensional (2D) speckle tracking is the most commonly used tool for myocardial deformation imaging, and has been standardized for all cardiac chambers: the left and right ventricles (LV/RV), and the left and right atria (LA/ RA).15,16 Echocardiographic speckle tracking is particularly attractive for routine clinical use because of its non-invasive nature, wide availability and low cost compared to other imaging modalities. Furthermore, speckle tracking derived indices have superior inter- and intraobserver reproducibility compared to conventional functional measurements.17 Deformation imaging has unequivocal diagnostic and prognostic value in patients with established genetic cardiomyopathies.18–21 Multiple studies suggest that it may also identify subtle mechanical alterations in the relatives of patients. However, deformation imaging has not been broadly implemented in the routine clinical screening of relatives. We conducted a systematic literature search on the use of echocardiographic deformation imaging in the screening of relatives, with the goals of evaluating the current evidence, identifying knowledge gaps, and determining future directions. 7
RkJQdWJsaXNoZXIy MTk4NDMw