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Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
Published on: February 13, 2021
Biomarker profiles in heart failure with preserved vs. reduced ejection fraction: results from the DIAST-CHF study
Abass Eidizadeh1, Moritz Schnelle1,2, Andreas Leha2,3
1Institute for Clinical Chemistry/Interdisciplinary UMG Laboratory, University Medical Center Göttingen, Göttingen, Germany.
Insights
This study identified novel protein biomarkers and signaling pathways in heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). These findings offer new diagnostic and therapeutic strategies for chronic heart failure patients.
Area of Science:
- Cardiology
- Proteomics
- Biochemistry
Background:
- Chronic heart failure (HF) is a leading global cause of mortality.
- Heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) are distinct clinical entities with differing pathophysiologies and treatment responses.
Purpose of the Study:
- To utilize a broad proteomic approach to identify novel pathobiochemical signaling pathways and biomarkers differentiating HFpEF and HFrEF.
- To compare proteomic profiles of HFpEF and HFrEF patients against healthy controls.
Main Methods:
- Plasma samples from 127 patients with HFpEF or HFrEF and 40 healthy controls were analyzed using a proteomic approach.
- 180 biomarkers were examined, with significant differences in protein expression compared to controls identified.
Main Results:
- 35 proteins showed significant differential expression in both HF groups versus controls.
- Unique protein signatures were identified for HFpEF (29 proteins) and HFrEF (33 proteins).
- Trefoil factor 3 (TFF3) and contactin-1 were identified as novel HF biomarkers, with TFF3 also predicting cardiovascular events in HFpEF. Serine protease 27 was found to be reduced in HFpEF, suggesting a therapeutic target. Network analyses highlighted distinct pathway roles in HFpEF (e.g., platelet-derived growth factor subunit A) and HFrEF (e.g., perlecan).
Conclusions:
- The identified proteins and signaling pathways provide novel avenues for therapeutic and diagnostic advancements in chronic heart failure management.
- Specific pathways related to metabolic processes, cellular stress, and iron metabolism are crucial in HFrEF, while HFpEF involves oxygen stress, hemostasis, and cell proliferation pathways.
Aims:
Chronic heart failure (HF) is a common disease and one of the leading causes of death worldwide. Heart failure with preserved ejection fraction (HFpEF) and with reduced ejection fraction (HFrEF) are different diseases with distinct as well as comparable pathophysiologies and diverse responses to therapeutic agents. We aimed to identify possible pathobiochemical signalling pathways and biomarkers in HFpEF and HFrEF by using a broad proteomic approach.
Methods And Results:
A total of 180 biomarkers in the plasma of a representative subgroup (71 years old) of HFpEF (70% female) with a left ventricular ejection fraction (LVEF) ≥ 50% and HFrEF (18% female) with an LVEF ≤ 40% patients (n = 127) from the Prevalence and Clinical Course of Diastolic Dysfunction and Diastolic Heart Failure (DIAST-CHF) trial were examined and compared with a healthy control group (n = 40; 48% female). We were able to identify 35 proteins that were expressed significantly different in both HF groups compared with the control group. We determine 29 unique proteins expressed in HFpEF and 33 unique proteins in HFrEF. Significantly up-regulated trefoil factor 3 (TFF3) and down-regulated contactin-1 could be identified as previously unknown biomarkers for HF. However, TFF3 is also a predictive factor for the occurrence of a cardiovascular event in HFpEF patients. In HFpEF, serine protease 27 was found at reduced levels for the first time, which could offer a new therapeutic target. Additionally, network analyses showed a special role of platelet-derived growth factor subunit A, Dickkopf-related protein 1, and tumour necrosis factor receptor superfamily member 6 in HFpEF patients, whereas perlecan and junctional adhesion molecule A stood out in the HFrEF group. Overall, signalling pathways of metabolic processes, cellular stress, and iron metabolism seemed to be important for HFrEF, whereas for HFpEF, oxygen stress, haemostasis, cell renewal, cell migration, and cell proliferation are in the foreground.
Conclusions:
The identified proteins and signalling pathways offer new therapeutic and diagnostic approaches for patients with chronic HF.
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