Heart Failure

Heart Failure (HF) is a complex clinical syndrome leading to the inability of the heart to pump adequate amounts of blood. HF remains a major cause for morbidity and mortality, causing tremendous economic burden worldwide. Despite improvements in the management of HF, its prevalence is still rising. This was achieved in urine samples using capillary electrophoresis online coupled to mass spectrometry (CE-MS).

Heart failure with reserved ejection fraction (HFrEF)
A diagnostic classifier for the discrimination between individuals with asymptomatic and symptomatic HFrEF and controls was established. The classifier called HFrEF103 comprised 103 urinary peptides. The signature panel showed a 93.4% sensitivity and a 92.9 % specificity1. Additionally, HFrEF was also diagnosed despite the presence of chronic kidney diseases (CKD). For this purpose, a classifier was developed for the discrimination between HFrEF patients with CKD and controls.  The signature panel showed an 84% sensitivity and a 91 % specificity2.

 
Figure 1: Polypeptide patterns distinguishing patients with heart failure with reduced ejection fraction (HFrEF) from controls. This figure shows the comparison of two classifiers developed for the diagnosis of HFrEF. The classifiers included: HFrEF103 composed of 103 urinary peptides and HFrEF79 composed of 79 urinary peptides. The performance of HFrEF103 was better with an area under the curve, AUC= 0.9721.

 
Figure 2: Polypeptide patterns distinguishing heart failure with reduced ejection fraction (HFrEF) patients with CKD from controls. This figure shows the compiled data sets of HFrEF patients with CKD samples (upper right panel) and control subjects (upper left panel) of the training set. Normalized molecular weight is plotted against normalized migration time. The mean signal intensity is given in 3D-depiction. The lower panel depicts 107 indicative polypeptides defining the specific pattern for HFrEF with CKD (lower right panel) and controls (lower left panel)2.

 

Heart failure with preserved ejection fraction (HFpEF)
Novel diagnostic methods to detect preclinical or asmptomatic HFpEF and improve its management are indispensable. A diagnostic classifier for the discrimination between asymptomatic HFpEF and controls was developed. The classifier called HF1 including 85 urinary peptides was able to discriminate between asymptomatic HFpEF patients and controls with an area under the curve, AUC= 0.843.

 
Figure 3: Polypeptide patterns distinguishing heart failure with asymptomatic preserved ejection fraction (HFpEF) patients from controls. This figure shows the compiled data sets of HFpEF patients (upper left panel) and control subjects (upper right panel) of the training set. Normalized molecular weight is plotted against normalized migration time. The mean signal intensity is given in 3D-depiction. The lower panel depicts 85 indicative polypeptides defining the specific pattern for asymptomatic HFpEF (lower left panel) and controls (lower right panel)3.
Furthermore, a classifier predicting the progression from preclinical or asymptomatic systolic and diastolic dysfunction respectively to symptomatic HFrEF and HFpEF was established from a large cohort. The discriminatory prognostic performance reached an area under the curve, AUC= 0.759 superior than the current clinical gold-standard blood peptide biomarker N-terminal pro B-type natriuretic peptide (NT-proBNP)4.

 

 
Figure 4: Polypeptide patterns distinguishing between patients with preclinical or asymptomatic systolic and diastolic dysfunction respectively to heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). This figure shows the comparison of the polypeptide classifier (LVHF) with the current state-of-the-art  N-terminal pro B-type natriuretic peptide (NT-proBNP). The performance of LVHFP was significantly better than NT-proBNP with AUC= 0.7594.

 

REFERENCES
1. Rossing K et al. PLoS ONE. 2016; 11(6): e0157167.
2. Farmakis D et al. Eur. J. Heart. Fail. 2016 ; 18 :822-829
3. Kuznetsova T et al. Eur. Heart. J. 2013 ; 33 :2342-2350
4. Zhang ZY et al. Manuscript in submission