Review Article

Biomarkers of Inflammation in Left Ventricular Diastolic Dysfunction

Table 1

Novel inflammatory biomarkers for diagnosis and/or prognosis in LVDD and HFpEF.

BiomarkerAuthorsClinical studyPopulation ()Diagnosis biomarkerPrognosis biomarker

Single marker
CRPSciarretta et al. [95]128Correlated with LVMI and
Koller et al. [96]LURIC study459HR: 1.32 (95% CI 1.08–1.62), CV mortality at 5 years
Sinning et al. [97]GHS study5000AUC 0.66 (95% CI: 0.61–0.71)HR: 1.5 (95% CI: 1.3–1.7)
DuBrock et al. [98]RELAX study214Higher levels in LVDD
IL-6Haugen et al. [62]72Higher levels in LVDD, 1-year mortality
Mocan et al. [14]72AUC 0.73 (95% CI: 0.61–0.83)
Kloch et al. [99]EPOGH study303Correlated with ()
IL-8Collier et al. [57]275Higher values in HFpEF hypertensive patients
Phelan et al. [100]41Higher levels with greater LVMI and LAVI
TNF-αSciarretta et al. [95]128Correlated with LVMI and
Dunlay et al. [69]Olmsted County study486HR: 2.10 (95% CI: 1.30–3.38)
Pentraxin-3Matsubara et al. [71]82OR: 1.49 (95% CI: 1.11-1.98)
MCP-1Ding et al. [75]Guangdong Coronary Artery Disease Cohort1411HR: 1.5-2.11
C-index +12,6%
Galectin-3Shah et al. [101]PRIDE study115Correlated with ()
De Boer et al. [78]COACH study592HR: 1.97 (1.62–2.42), better for HFpEF than for HFrEF
Edelmann et al. [102]Aldo-DHF trial422HR: 3.319 (95% CI: 1.214-9.07), all-cause death or hospitalization at 6 or 12 months
Soluble ST2Bartunek et al. [103]163ST2 mARN higher in LVDD, correlated with LVEDP
Shah et al. [104]134Correlated with amplitude
Manzano-Fernández et al. [105]447Cut-off 0.35 ng/mL
HR: 3.26 (95% CI: 1.50–7.05), prediction of 1-year mortality
Shah et al. [106]387HR: 2.85 (95% CI: 2.04–3.99), prediction of 1-year mortality
Santhanakrishnan et al. [93]SHOP study151Cut-off 26.47 ng/mL, AUC 0.662 (95% CI: 0.554–0.770)
Se 70%, Sp 48% for HFpEF
Wang et al. [107]Cut-off 13.5 ng/mL
OR: 11.7 (95% CI: 2.9-47.4) for HFpEF
Anand et al. [108]VAL-HEFT study1650
Cox logHR: 0.048 (0.031-0.065), 1-year mortality
Sinning et al. [97]GHS study5000AUC 0.62 (95% CI: 0.56–0.67)HR: 1.4 (95% CI: 1.2–1.6)
Farcas et al. [82]76OR: 2.43 (95% CI: 1.32-7.24) at baseline predicts the CV events for 1 year
Farcas et al. [81]88Cut-off 28.14 ng/mL (Se 94.4%, Sp 69.1%) for LVDD
Cut-off 14 04 ng/mL (Se 82.1%, Sp 53.8%) for LVH
AUC: 0.732 (95% CI: 0.613–0.850)
Najjar et al. [109]193HR: 6.62 (95% CI: 1.04–42.28) for mortality or rehospitalization
GDF-15Stahrenberg et al. [92]1935Cut-off 1.16 ng/mL, AUC 0.891 (95% CI: 0.850-0.932)
Santhanakrishnan et al. [93]SHOP study151Cut-off 879 pg/mL (Se 92%, Sp 84%)
Cut-off 1120 pg/mL (Sp 92%, Se 82%)
Sinning et al. [97]GHS study5000AUC 0.79 (95% CI: 0.75–0.83)HR: 1.7 (95% CI: 1.6–1.9)
Chan et al. [94]SHOP study488HR: 1.68 (95% CI: 1.15–2.45) CV events at 6 months
MyBP-CJeong et al. [50]Higher values in HFpEF than in HFrEF ( vs. )
Tong et al. [49]158Prestress cut-off 127 ng/mL, HR: 8.1 (95% CI: 1.09-60.09)
Poststress cut-off 214 ng/mL, HR: 4.77 (95% CI: 1.75-12.98)

Multimarker score
CRP+GDF-15+sST2/NT-proBNP and GDF-15/NT-proBNPSinning et al. [97]GHS study5000Discrimination between HFpEF and HFrEF
NT-proBNP+GDF-15Stahrenberg et al. [92]1935AUC 0.942 (0.912-0.972)
+ (Se 56.6%, Sp 98.9%)
Chan et al. [94]488AUC: 0.891 (95% CI: 0.850-0.932) for GDF-15HR: 1.68 (95% CI: 1.15–2.45), risk for composite outcome (mortality and rehospitalization)

AUC: area under the curve; CI: confidence interval; CRP: C reactive protein; CV: cardiovascular; EPOGH: European Project on Genes in Hypertension; GDF-15: growth differentiation factor 15; GHS: Gothenburg Heart Study; IL: interleukin; HFrEF: heart failure with reduced ejection fraction; HFpEF: heart failure with preserved ejection fraction; HR: hazard ratio; LAVI: left atrial volume index; LVDD: left ventricular diastolic dysfunction; LVED: left ventricular end-diastolic pressure; LVMI: left ventricular mass index; MCP-1: monocyte chemoattractant protein 1; MyBP-C: myosin-binding protein C; NT-proBNP: N-terminal probrain natriuretic peptide; OR: odds ratio; PRIDE: Pro-BNP Investigation of Dyspnea in the Emergency Department; RELAX: Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure; SHOP: Singapore Heart Failure Outcomes and Phenotypes; TNF-α: tumor necrosis factor alpha; sST2: soluble ST2; VAL-HEFT: Valsartan Heart Failure Trial.