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Higher Serum Lysophosphatidic Acids Predict Left Ventricular Reverse Remodeling in Pediatric Dilated Cardiomyopathy
Haichu Wen1, Hongzhao You1,2, Yulin Li1
1Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Insights
Lysophosphatidic acids (LysoPA) in serum can predict left ventricular reverse remodeling (LVRR) in pediatric dilated cardiomyopathy (PDCM). A LysoPA score combined with LVEDD z-score improves LVRR prediction, aiding prognosis and treatment monitoring.
Area of Science:
- Cardiology
- Metabolomics
- Pediatric Medicine
Background:
- Pediatric dilated cardiomyopathy (PDCM) has a variable prognosis, with left ventricular reverse remodeling (LVRR) indicating a favorable outcome.
- Lipid metabolism disturbances are linked to cardiac function changes, but their role in PDCM and LVRR is understudied.
Purpose of the Study:
- To investigate the association between lipidomics data and LVRR in pediatric patients with dilated cardiomyopathy.
- To identify specific lipid biomarkers for predicting LVRR and to develop a predictive risk score.
Main Methods:
- Utilized targeted lipidomics on 540 lipids from the prospective China-AOCC study (discovery and validation sets).
- Employed OPLS-DA and random forest analysis for candidate lipid screening.
- Developed a risk score based on significant lysophosphatidic acids (LysoPA) and assessed its predictive value in Cox regression models and AUC analysis.
Main Results:
- Four lysophosphatidic acids (LysoPA 16:0, 18:2, 18:1, 18:0) were significantly associated with LVRR after adjusting for clinical factors.
- A LysoPA score combining these four lipids improved the prediction of LVRR.
- The addition of the LysoPA score to the LVEDD z-score significantly increased the area under the curve (AUC) for LVRR prediction in both discovery and validation sets.
Conclusions:
- Serum LysoPA levels are predictive of LVRR in pediatric dilated cardiomyopathy patients.
- A combined LysoPA score and LVEDD z-score can enhance the prediction of LVRR, aiding in patient prognosis and monitoring therapeutic responses.
Abstract:
Background: The prognosis of pediatric dilated cardiomyopathy (PDCM) is highly variable, ranging from death to cardiac function recovery. Left ventricular reverse remodeling (LVRR) represents a favorable prognosis in PDCM. Disturbance of lipid metabolism is associated with the change of cardiac function, but no studies have examined lipidomics data and LVRR. Methods: Discovery analyses were based on 540 targeted lipids in an observational, prospective China-AOCC (An Integrative-Omics Study of Cardiomyopathy Patients for Diagnosis and Prognosis in China) study. The OPLS-DA and random forest (RF) analysis were used to screen the candidate lipids. Associations of the candidate lipids were examined in Cox proportional hazards regression models. Furthermore, we developed a risk score comprising the significant lipids, with each attributed a score of 1 when the concentration was above the median. All significant findings were replicated in a validation set of the China-AOCC study. Results: There were 59 patients in the discovery set and 24 patients in the validation set. LVRR was observed in 27 patients (32.5%). After adjusting for age, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic dimension (LVEDD) z-score, lysophosphatidic acids (LysoPA) 16:0, LysoPA 18:2, LysoPA 18:1, and LysoPA 18:0 were significantly associated with LVRR in the discovery set, and hazard ratios (HRs) were 2.793 (95% CI, 1.545-5.048), 2.812 (95% CI, 1.542-5.128), 2.831 (95% CI, 1.555-5.154), and 2.782 (95% CI, 1.548-5.002), respectively. We developed a LysoPA score comprising the four LysoPA. When the LysoPA score reached 4, LVRR was more likely to be observed in both sets. The AUC increased with the addition of the LysoPA score to the LVEDD z-score (from 0.693 to 0.875 in the discovery set, from 0.708 to 0.854 in the validation set) for prediction of LVRR. Conclusions: Serum LysoPA can predict LVRR in PDCM patients. When the LysoPA score was combined with the LVEDD z-score, it may help in ascertaining the prognosis and monitoring effects of anti-heart failure pharmacotherapy.
