NKX2-5 variants screening in patients with atrial septal defect in Indonesia

Background: NKX2-5 variant in atrial septal defect patients has been reported. However, it is not yet been described in the Southeast Asian population. Here, we screened the NKX2-5 variants in patients with atrial septal defect (ASD) in the Indonesian population. Method: We recruited 97 patients with ASD for genetic screening of the NKX2-5 variant using Sanger sequencing. Results: We identified three variants of NKX2-5: NM004387.4:c.63A>G at exon 1, NM004387.4:c.413G>A, and NM004387.4:c.561G>C at exon 2. The first variant is commonly found (85.6) and benign. The last two variants are heterozygous at the same locus. These variants are rare (3.1) and novel. Interestingly, these variants were discovered in familial atrial septal defects with a spectrum of arrhythmia and severe pulmonary hypertension. Conclusion: Our study is the first report of the NKX2-5 variant in ASD patients in the Southeast Asian population, including a novel heterozygous variant: NM004387.4:c.413G>A and NM004387.4:c.561G>C. These variants might contribute to familial ASD risk with arrhythmia and severe pulmonary hypertension. Functional studies are necessary to prove our findings. © 2022, The Author(s)

Usefulness of Combining NT-proBNP Level and Right Atrial Diameter for Simple and Early Noninvasive Detection of Pulmonary Hypertension Among Adult Patients with Atrial Septal Defect

Background: Atrial septal defect developed pulmonary hypertension (ASD-PH) at first diagnosis due to late presentation are common in Indonesia. Transthoracic echocardiogram (TTE) is a common tool to detect ASD-PH, before proceeding to invasive procedure. The NT-proBNP measurement to screen ASD-PH is not yet considered the standard approach, especially in limited resource conditions. The objective of this study is to assess the value of NT-proBNP, along with simple TTE parameter, to screen PH among adults with ASD. Methods: This was a cross-sectional study. The subjects were adult ASD-PH patients from the COHARD-PH registry (n=357). Right heart catheterization (RHC) was performed to diagnose PH. Blood sample was withdrawn during RHC for NT-proBNP measurement. The TTE was performed as standard procedure and its regular parameters were assessed, along with NT-proBNP, to detect PH. Results: Two parameters significantly predicted PH, namely NT-proBNP and right atrial (RA) diameter. The cut-off of NT-proBNP to detect PH was ≥140 pg/mL. The cut-off of RA diameter to detect PH was ≥46.0 mm. The combined values of NT-proBNP level ≥140 pg/mL and RA diameter ≥46.0 mm yielded 46.6 sensitivity, 91.8 specificity, 54.3 accuracy, 96.5 positive predictive value and 26.2 negative predictive value to detect PH, which were better than single value. Conclusion: NT-proBNP level ≥140 pg/mL represented PH in adult ASD patients. The NT-proBNP level ≥140 pg/mL and RA diameter ≥46.0 mm had a pre-test probability measures to triage patients needing more invasive procedure and also to determine when and if to start the PH-specific treatment. © 2022, Indonesian Society of Internal Medicine. All rights reserved