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BACKGROUND: Cardiac rotational parameters in primary symptomatic left ventricular noncompaction (LVNC) with preserved left ventricular ejection fraction (LVEF) are not well understood. We aimed to analyze cardiac rotation measured with cardiac magnetic resonance feature-tracking (CMR-FT) and speckle-tracking echocardiography (Echo-ST) in LVNC morphology subjects with preserved LVEF and different genotypes and healthy controls. METHODS: Our retrospective study included 54 LVNC subjects with preserved LVEF and 54 control individuals. We evaluated functional and rotational parameters with CMR in the total study population and with echocardiography in 39 LVNC and 40 C individuals. All LVNC subjects were genotyped with a 174-gene next-generation sequencing panel and grouped into the subgroups: benign (B), variant of uncertain significance (VUS), and pathogenic (P). RESULTS: In comparison with controls, LVNC subjects had reduced apical rotational degree (p = 0.004) and one-third had negative apical rotation. While the degree of apical rotation was comparable between the three genetic subgroups, they differed significantly in the direction of apical rotation (p<0.001). In contrast to control and B groups, all four studied cardiac rotational patterns were identified in the P and VUS subgroups, namely normal rotation, positive and negative rigid body rotation, and reverse rotation. When the CMR-FT and Echo-ST methods were compared, the direction and pattern of cardiac rotation had moderate to good association (p<0.001) whereas the rotational degrees showed no reasonable correlation or agreement. CONCLUSION: While measuring cardiac rotation using both CMR-FT and Echo-ST methods, subclinical mechanical differences were identified in subjects with LVNC phenotype and preserved LVEF, especially in cases with genetic involvement.

Asunto(s)

Ecocardiografía , Imagen Multimodal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Ecocardiografía/métodos , Estudios Retrospectivos , Rotación , Imagen Multimodal/métodos , Adulto , Volumen Sistólico , Función Ventricular Izquierda/fisiología , Imagen por Resonancia Magnética/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Anciano , Estudios de Casos y Controles , No Compactación Aislada del Miocardio Ventricular/diagnóstico por imagen , No Compactación Aislada del Miocardio Ventricular/genética , No Compactación Aislada del Miocardio Ventricular/fisiopatología

RESUMEN

Introduction: The genotype of symptomatic left ventricular noncompaction phenotype (LVNC) subjects with preserved left ventricular ejection fraction (LVEF) and its effect on clinical presentation are less well studied. We aimed to characterize the genetic, cardiac magnetic resonance (CMR) and clinical background, and genotype-phenotype relationship in LVNC with preserved LVEF. Methods: We included 54 symptomatic LVNC individuals (LVEF: 65 ± 5%) whose samples were analyzed with a 174-gene next-generation sequencing panel and 54 control (C) subjects. The results were evaluated using the criteria of the American College of Medical Genetics and Genomics. Medical data suggesting a higher risk of cardiovascular complications were considered "red flags". Results: Of the LVNC population, 24% carried pathogenic or likely pathogenic (P) mutations; 56% carried variants of uncertain significance (VUS); and 20% were free from cardiomyopathy-related mutations. Regarding the CMR parameters, the LVNC and C groups differed significantly, while the three genetic subgroups were comparable. We found a significant relationship between red flags and genotype; furthermore, the number of red flags in a single subject differed significantly among the genetic subgroups (p = 0.002) and correlated with the genotype (r = 0.457, p = 0.01). In 6 out of 7 LVNC subjects diagnosed in childhood, P or VUS mutations were found. Discussion: The large number of P mutations and the association between red flags and genotype underline the importance of genetic-assisted risk stratification in symptomatic LVNC with preserved LVEF.

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OBJECTIVE: Next-generation sequencing is increasingly utilized worldwide as a research and diagnostic tool and is anticipated to be implemented into everyday clinical practice. Since Central-Eastern European attitude toward genetic testing, especially broad genetic testing, is not well known, we performed a survey on this issue among Hungarian participants. METHODS: A self-administered questionnaire was distributed among patients and patient relatives at our neurogenetic outpatient clinic. Members of the general population were also recruited via public media. We used chi-square testing and binary logistic regression to examine factors influencing attitude. RESULTS: We identified a mixed attitude toward genetic testing. Access to physician consultation positively influenced attitude. A higher self-determined genetic familiarity score associated with higher perceived genetic influence score, which in turn associated with greater willingness to participate in genetic testing. Medical professionals constituted a skeptical group. CONCLUSIONS: We think that given the controversies and complexities of the next-generation sequencing field, the optimal clinical translation of NGS data should be performed in institutions which have the unique capability to provide interprofessional health education, transformative biomedical research, and crucial patient care. With optimization of the clinical translational process, improvement of genetic literacy may increase patient engagement and empowerment. RELEVANCE OF THE ARTICLE FOR PREDICTIVE PREVENTIVE AND PERSONALIZED MEDICINE: The paper highlights that in countries with relatively low-genetic literacy, a special strategy is needed to enhance the implementation of personalized medicine.