Distinguishing heart failure with reduced ejection fraction from heart failure with preserved ejection fraction: A phenomics approach

被引:2
作者
van Essen, Bart J. [1 ]
Tharshana, Ganash N. [2 ,3 ]
Ouwerkerk, Wouter [4 ,5 ]
Yeo, Poh Suan Daniel [6 ]
Sim, David [5 ]
Jaufeerally, Fazlur [7 ,8 ]
Ong, Hean Yee [9 ]
Ling, Lieng Hsi [10 ]
Soon, Dinna Kar Nee [9 ]
Lee, Shao Guang Sheldon [10 ]
Leong, Gerard [11 ]
Loh, Seet Yoong [6 ]
San Tan, Ru [5 ]
Ramachandra, Chrishan J. [5 ,11 ]
Hausenloy, Derek J. [5 ,11 ,12 ,13 ,14 ]
Liew, Oi Wai [10 ]
Chong, Jenny [10 ]
Voors, Adriaan A. [1 ]
Lam, Carolyn S. P. [1 ,5 ,7 ]
Richards, A. Mark [9 ,15 ]
Tromp, Jasper [2 ,3 ,7 ,16 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands
[2] Saw Swee Hock Sch Publ Hlth, Singapore, Singapore
[3] Natl Univ Hlth Syst, Singapore, Singapore
[4] Univ Amsterdam, Amsterdam UMC, Amsterdam Infect & Immun Inst, Dept Dermatol, Amsterdam, Netherlands
[5] Natl Heart Res Inst Singapore, Natl Heart Ctr, Singapore, Singapore
[6] Tan Tock Seng Hosp, Singapore, Singapore
[7] Duke NUS Med Sch, Singapore, Singapore
[8] Singapore Gen Hosp, Dept Med, Singapore, Singapore
[9] Khoo Teck Puat Hosp, Singapore, Singapore
[10] Natl Univ Singapore, Natl Univ Heart Ctr Singapore, Cardiovasc Res Inst Singapore, Singapore, Singapore
[11] Changi Gen Hosp, Singapore, Singapore
[12] Duke Natl Univ, Cardiovasc & Metab Disorders Program, Singapore Med Sch, Singapore, Singapore
[13] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore, Singapore
[14] UCL, Hatter Cardiovasc Inst, London, England
[15] Univ Otago, Christchurch Heart Inst, Dunedin, New Zealand
[16] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, 12 Sci Dr 2, 10-01, Singapore 117549, Singapore
关键词
Heart failure; Biomarkers; NONCARDIAC COMORBIDITIES; DYSFUNCTION; GUIDELINES; DIAGNOSIS; MIDRANGE; TRIAL; ESC;
D O I
10.1002/ejhf.3156
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aim Pathophysiological differences between patients with heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction (EF) remain unclear. Therefore we used a phenomics approach, integrating selected proteomics data with patient characteristics and cardiac structural and functional parameters, to get insight into differential pathophysiological mechanisms and identify potential treatment targets. Methods and results We report data from a representative subcohort of the prospective Singapore Heart Failure Outcomes and Phenotypes (SHOP), including patients with HFrEF (EF <40%, n = 217), HFpEF (EF >= 50%, n = 213), and age- and sex-matched controls without HF (n = 216). We measured 92 biomarkers using a proximity extension assay and assessed cardiac structure and function in all participants using echocardiography. We used multi-block projection to latent structure analysis to integrate clinical, echocardiographic, and biomarker variables. Candidate biomarker targets were cross-referenced with small-molecule and drug databases. The total cohort had a median age of 65 years (interquartile range 60-71), and 50% were women. Protein profiles strongly discriminated patients with HFrEF (area under the curve [AUC] = 0.89) and HFpEF (AUC = 0.94) from controls. Phenomics analyses identified unique druggable inflammatory markers in HFpEF from the tumour necrosis factor receptor superfamily (TNFRSF), which were positively associated with hypertension, diabetes, and increased posterior and relative wall thickness. In HFrEF, interleukin (IL)-8 and IL-6 were possible targets related to lower EF and worsening renal function. Conclusion We identified pathophysiological mechanisms related to increased cardiac wall thickness parameters and potentially druggable inflammatory markers from the TNFRSF in HFpEF.
引用
收藏
页码:841 / 850
页数:10
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