Abstract
BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is increasingly recognized as an important clinical entity. Preclinical studies have shown differences in the pathophysiology between HFpEF and HF with reduced ejection fraction (HFrEF). Therefore, we hypothesized that a systematic metabolomic analysis would reveal a novel metabolomic fingerprint of HFpEF that will help understand its pathophysiology and assist in establishing new biomarkers for its diagnosis.Methods and ResultsAmbulatory patients with clinical diagnosis of HFpEF (n = 24), HFrEF (n = 20), and age-matched non-HF controls (n = 38) were selected for metabolomic analysis as part of the Alberta HEART (Heart Failure Etiology and Analysis Research Team) project. 181 serum metabolites were quantified by LC-MS/MS and 1H-NMR spectroscopy. Compared to non-HF control, HFpEF patients demonstrated higher serum concentrations of acylcarnitines, carnitine, creatinine, betaine, and amino acids; and lower levels of phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins. Medium and long-chain acylcarnitines and ketone bodies were higher in HFpEF than HFrEF patients. Using logistic regression, two panels of metabolites were identified that can separate HFpEF patients from both non-HF controls and HFrEF patients with area under the receiver operating characteristic (ROC) curves of 0.942 and 0.981, respectively.ConclusionsThe metabolomics approach employed in this study identified a unique metabolomic fingerprint of HFpEF that is distinct from that of HFrEF. This metabolomic fingerprint has been utilized to identify two novel panels of metabolites that can separate HFpEF patients from both non-HF controls and HFrEF patients.Clinical Trial RegistrationClinicalTrials.gov NCT02052804
Highlights
Heart failure (HF) affects more than 5 million people in North America, with approximately 825,000 incident cases per year in the United States alone [1]
Ambulatory patients with clinical diagnosis of HFpEF (n = 24), HF with reduced ejection fraction (HFrEF) (n = 20), and agematched non-HF controls (n = 38) were selected for metabolomic analysis as part of the Alberta HEART (Heart Failure Etiology and Analysis Research Team) project. 181 serum metabolites were quantified by LC-MS/MS and 1H-NMR spectroscopy
Medium and long-chain acylcarnitines and ketone bodies were higher in HFpEF than HFrEF patients
Summary
Heart failure (HF) affects more than 5 million people in North America, with approximately 825,000 incident cases per year in the United States alone [1]. Despite the advent of several new medications, devices and multidisciplinary clinics to manage HF, the prognosis of HF remains poor, with an estimated survival rate of 50% within 5 years after initial HF diagnosis [1]. During the initial clinical work-up for patients with confirmed or suspected HF, patients are classified via ejection fraction (EF) into one of two groups: a) HF with reduced ejection fraction (HFrEF) or b) HF with preserved ejection fraction (HFpEF). HFpEF is becoming increasingly recognized as a distinct clinical entity and accounts for 30–40% of all HF cases [3, 4]. Patients with HFpEF have a similar one-year mortality as patients with HFrEF [6]. Heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly recognized as an important clinical entity. Preclinical studies have shown differences in the pathophysiology between HFpEF and HF with reduced ejection fraction (HFrEF). We hypothesized that a systematic metabolomic analysis would reveal a novel metabolomic fingerprint of HFpEF that will help understand its pathophysiology and assist in establishing new biomarkers for its diagnosis
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