Quantitative Profiling of Serum Carnitines Facilitates the Etiology Diagnosis and Prognosis Prediction in Heart Failure

Background: The perturbation of fatty acid metabolism in heart failure (HF) has been a critical issue. It is unclear whether the amounts of circulating carnitines will benefit primary etiology diagnosis and prognostic prediction in HF. This study was designed to assess the diagnostic and prognostic values of serum carnitine profiles between ischemic and non-ischemic derived heart failure. Methods: HF patients (non-ischemic dilated cardiomyopathy: DCM-HF, n = 98; ischemic heart disease: IHD-HF, n = 63) and control individuals (n = 48) were enrolled consecutively. The serum carnitines were quantitatively measured using the UHPLC-MS/MS method. All patients underwent a median follow-up of 28.3 months. Multivariate Cox regression analysis was performed during the prognosis evaluation. Results: Amongst 25 carnitines measured, all of them were increased in HF patients, and 20 acylcarnitines were associated with HF diagnosis independently. Seven acylcarnitines were confirmed to increase the probability of DCM diagnosis independently. The addition of isobutyryl-L-carnitine and stearoyl-L-carnitine to conventional clinical factors significantly improved the area under the receiver operating characteristic curve (ROC) from 0.771 to 0.832 (p = 0.023) for DCM-HF diagnosis (calibration test for the composite model: Hosmer-Lemeshow & chi;(2) = 7.376, p = 0.497 > 0.05). Using a multivariate COX survival analysis adjusted with clinical factors simultaneously, oleoyl L-carnitine >300 nmol/L (HR = 2.364, 95% CI = 1.122-4.976, p = 0.024) and isovaleryl-L-carnitine <100 nmol/L (HR = 2.108, 95% CI = 1.091-4.074, p = 0.026) increased the prediction of all-cause mortality independently, while linoleoyl-L-carnitine >420 nmol/L, succinyl carnitine >60 nmol/L and isovaleryl-L-carnitine <100 nmol/L increased the risk of HF rehospitalization independently. Conclusions: Serum carnitines could not only serve as diagnostic and predictive biomarkers in HF but also benefit the identification of HF primary etiology and prognosis.

Automated summary

This study measured serum carnitine levels in heart failure patients and found that all 25 carnitines were increased in these patients, with 20 being independently associated with heart failure diagnosis. In non-ischemic dilated cardiomyopathy patients, seven carnitines were identified to independently increase the diagnostic probability. Adding isobutyryl-L-carnitine and stearoyl-L-carnitine to clinical factors improved the accuracy of DCM-HF diagnosis. Certain carnitine levels were found to independently predict the risk of death and rehospitalization in heart failure patients. Therefore, serum carnitines can serve as diagnostic, prognostic, and etiological biomarkers in heart failure.