RESUMEN
Whole-exome sequencing (WES) is a powerful and comprehensive tool for the genetic diagnosis of rare diseases, but few reports describe its timely application and clinical impact on infantile cardiomyopathies (CM). We conducted a retrospective analysis of patients with infantile CMs who had trio (proband and parents)-WES to determine whether results contributed to clinical management in urgent and non-urgent settings. Twenty-nine out of 42 enrolled patients (69.0%) received a definitive molecular diagnosis. The mean time-to-diagnosis was 9.7 days in urgent settings, and 17 out of 24 patients (70.8%) obtained an etiological classification. In non-urgent settings, the mean time-to-diagnosis was 225 days, and 12 out of 18 patients (66.7%) had a molecular diagnosis. In 37 out of 42 patients (88.1%), the genetic findings contributed to clinical management, including heart transplantation, palliative care, or medical treatment, independent of the patient's critical condition. All 29 patients and families with a definitive diagnosis received specific counseling about recurrence risk, and in seven (24.1%) cases, the result facilitated diagnosis in parents or siblings. In conclusion, genetic diagnosis significantly contributes to patients' clinical and family management, and trio-WES should be performed promptly to be an essential part of care in infantile cardiomyopathy, maximizing its clinical utility.
RESUMEN
BACKGROUND: In pediatric age echocardiographic evaluation of left ventricular systolic function is usually based on indexes obtained by measurements at the endocardial level. In the presence of ventricular hypertrophy this may lead to an overestimation of systolic function. The aim of this study was to assess the developmental changes of left ventricular systolic mechanics measured at the endocardial and midwall levels. METHODS: In 239 normal subjects divided into six age groups we measured left ventricular end-diastolic volume, mass and mass/volume ratio, fractional shortening, and rate-corrected mean velocity of circumferential shortening at the endocardial and midwall levels. Endocardial meridional end-systolic stress and midwall circumferential end-systolic stress were considered as indexes of afterload. Relations of extent and velocity of fiber shortening to afterload at the endocardial and midwall levels were used to assess left ventricular contractility. RESULTS: Blood pressure, left ventricular afterload, volume and mass increased, whereas the mass/volume ratio remained stable during growth. Fractional shortening and mean velocity of circumferential shortening at the endocardial level decreased and showed an inverse relation to afterload. Midwall fractional shortening and rate-corrected mean velocity of circumferential shortening were lower during the first months and did not change during the first year of life. CONCLUSIONS: Left ventricular volume and mass increase with age, mass/volume ratio remains almost constant while afterload increases. Endocardial systolic function indexes are higher in the first period of life, due to low afterload and increased mass/volume ratio. In the first months of life the left ventricular myocardium shows a greater sensitivity to changes in afterload and a reduced contractility measured at the midwall level.
