Table 1.
Novel inflammatory biomarkers for diagnosis and/or prognosis in LVDD and HFpEF.
| Biomarker | Authors | Clinical study | Population (n) | Diagnosis biomarker | Prognosis biomarker |
|---|---|---|---|---|---|
| Single marker | |||||
| CRP | Sciarretta et al. [95] | 128 | Correlated with LVMI and E/E′ | ||
| Koller et al. [96] | LURIC study | 459 | HR: 1.32 (95% CI 1.08–1.62), CV mortality at 5 years | ||
| Sinning et al. [97] | GHS study | 5000 | AUC 0.66 (95% CI: 0.61–0.71) | HR: 1.5 (95% CI: 1.3–1.7) | |
| DuBrock et al. [98] | RELAX study | 214 | Higher levels in LVDD | ||
| IL-6 | Haugen et al. [62] | 72 | Higher levels in LVDD | Cut − off value > 10 ng/L, 1-year mortality | |
| Mocan et al. [14] | 72 | AUC 0.73 (95% CI: 0.61–0.83) | |||
| Kloch et al. [99] | EPOGH study | 303 | Correlated with E′ (r = 0.039) | ||
| IL-8 | Collier et al. [57] | 275 | Higher values in HFpEF hypertensive patients | ||
| Phelan et al. [100] | 41 | Higher levels with greater LVMI and LAVI | |||
| TNF-α | Sciarretta et al. [95] | 128 | Correlated with LVMI and E/E′ | ||
| Dunlay et al. [69] | Olmsted County study | 486 | HR: 2.10 (95% CI: 1.30–3.38) | ||
| Pentraxin-3 | Matsubara et al. [71] | 82 | OR: 1.49 (95% CI: 1.11-1.98) | ||
| MCP-1 | Ding et al. [75] | Guangdong Coronary Artery Disease Cohort | 1411 | HR: 1.5-2.11 C-index +12,6% |
|
| Galectin-3 | Shah et al. [101] | PRIDE study | 115 | Correlated with E/E′ (r = 0.035) | |
| De Boer et al. [78] | COACH study | 592 | HR: 1.97 (1.62–2.42), better for HFpEF than for HFrEF | ||
| Edelmann et al. [102] | Aldo-DHF trial | 422 | HR: 3.319 (95% CI: 1.214-9.07), all-cause death or hospitalization at 6 or 12 months | ||
| Soluble ST2 | Bartunek et al. [103] | 163 | ST2 mARN higher in LVDD, correlated with LVEDP | ||
| Shah et al. [104] | 134 | Correlated with E amplitude | |||
| Manzano-Fernández et al. [105] | 447 | Cut-off 0.35 ng/mL HR: 3.26 (95% CI: 1.50–7.05), prediction of 1-year mortality |
|||
| Shah et al. [106] | 387 | HR: 2.85 (95% CI: 2.04–3.99), prediction of 1-year mortality | |||
| Santhanakrishnan et al. [93] | SHOP study | 151 | Cut-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 study | 1650 | Cut − off sST2 ≤ 33.2 ng/mL Cox logHR: 0.048 (0.031-0.065), 1-year mortality |
||
| Sinning et al. [97] | GHS study | 5000 | AUC 0.62 (95% CI: 0.56–0.67) | HR: 1.4 (95% CI: 1.2–1.6) | |
| Farcas et al. [82] | 76 | OR: 2.43 (95% CI: 1.32-7.24) at baseline predicts the CV events for 1 year | |||
| Farcas et al. [81] | 88 | Cut-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] | 193 | HR: 6.62 (95% CI: 1.04–42.28) for mortality or rehospitalization | |||
| GDF-15 | Stahrenberg et al. [92] | 1935 | Cut-off 1.16 ng/mL, AUC 0.891 (95% CI: 0.850-0.932) | ||
| Santhanakrishnan et al. [93] | SHOP study | 151 | Cut-off 879 pg/mL (Se 92%, Sp 84%) Cut-off 1120 pg/mL (Sp 92%, Se 82%) |
||
| Sinning et al. [97] | GHS study | 5000 | AUC 0.79 (95% CI: 0.75–0.83) | HR: 1.7 (95% CI: 1.6–1.9) | |
| Chan et al. [94] | SHOP study | 488 | HR: 1.68 (95% CI: 1.15–2.45) CV events at 6 months | ||
| MyBP-C | Jeong et al. [50] | Higher values in HFpEF than in HFrEF (4.02 ± 1.4 vs. 2.01 ± 0.61) | |||
| Tong et al. [49] | 158 | Prestress 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-proBNP | Sinning et al. [97] | GHS study | 5000 | Discrimination between HFpEF and HFrEF | |
| NT-proBNP+GDF-15 | Stahrenberg et al. [92] | 1935 | AUC 0.942 (0.912-0.972) GDF − 15 ≥ 1.16 ng/mL + NT − proBNP ≥ 200.7 ng/L (Se 56.6%, Sp 98.9%) |
||
| Chan et al. [94] | 488 | AUC: 0.891 (95% CI: 0.850-0.932) for GDF-15 | HR: 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.