Genophenotypic correlates and long-term outcome prognosticators of left ventricular non-compaction in children

Wei‐Chieh Tseng; Shuenn‐Nan Chiu; Wen‐Pin Chen; Ni‐Chung Lee; Mei‐Hwan Wu

doi:10.1016/j.jfma.2024.09.032

September 26, 2024Journal of the Formosan Medical AssociationOpen Access

Genophenotypic correlates and long-term outcome prognosticators of left ventricular non-compaction in children

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Why the study?

Outcomes, clinical prognosticators, and genetic profiles of pediatric left ventricular non-compaction required further investigation.

Structured PICO

P

Population

33 pediatric patients (<18 years old) diagnosed with left ventricular non-compaction (LVNC), median age 0.33 years, 57.6% male.

O

Outcome

Composite outcome including death, heart transplant, and left ventricular assist device implantationcomposite

In pediatric LVNC, baseline NT-proBNP and lack of its improvement, along with specific genetic variants, are strong predictors of poor long-term outcomes including death or need for advanced heart failure therapies.

Implication

Outcomes in this small pediatric LVNC cohort are hypothesis-generating; larger prospective studies needed to validate prognosticators.

Abstract

To investigate the outcomes, clinical prognosticators, and genetic profiles of pediatric left ventricular non-compaction (LVNC). All subjects were <18 years old, diagnosed with LVNC between January 2008 and December 2020. Whole-exome sequencing was undertaken. The primary endpoint was composite outcome, including death, heart transplant, and left ventricular assist device implantation. Thirty-three patients were enrolled, males predominating (57.6%). Median age at diagnosis was 0.33 (0.1–7.2) years. Family history was documented in four (12.1%). Five (15.2%) had sustained arrhythmias. Mean follow-up period was 9.5 years, and 5- and 10-year event-free survival were 84.8% and 66.9%, respectively. Seven died of heart failure, four received heart transplants, and one required left ventricular assist device placement. Log of baseline NT-proBNP (adjusted odds ratio [aOR] = 4.4, p = 0.012) and lack of improvement in NT-proBNP (aOR = 41.2, p = 0.033) impacted the primary outcome most significantly. Eighteen out of 25 genetic testing (72%) revealed chromosomal anomalies, or pathogenic or likely pathogenic variants. Three genetic variants ( PLEKHM2 p.G419R , RYR2 p.V2571A , and SCN5A p.M1676I ) were significantly associated with the primary outcome (p = 1.52 × 10 −6 ). Pediatric LVNC is a rare disorder with variable genetic underpinnings. Baseline NT-proBNP values and lack of improvement in NT-proBNP levels were important predictors of poor long-term outcomes. Pathogenic genetic variants or chromosomal anomalies are not unusual.