Table 4.
Clinical evidence on the link between HFpEF and cardiac fibrosis
| Patient population | Fibrosis marker | Finding | References |
|---|---|---|---|
| Hypertensives | Serum markers of collagen turnover (MMP2, CITP, PIIINP) | In a population of hypertensive subjects, markers of collagen turnover (circulating levels of MMP2, CITP, PIIINP) identified patients with diastolic dysfunction and HFpEF. | 502 |
| Heart failure (HFpEF and HFrEF) | Histology | In a heart failure population, histologically assessed fibrosis was comparable in HFpEF and HFrEF groups. | 503 |
| Heart failure (HFpEF and HFrEF) | Circulating biomarkers of fibrosis, CMR | HFpEF patients had elevated plasma biomarkers of inflammation and fibrosis (including TN-C, MMP3, 7 8 and GDF15) in comparison to controls. Biomarker levels were associated with CMR-assessed fibrosis (extracellular volume, ECV). However, indicators of inflammation and fibrosis were comparable between HFrEF and HFpEF patients. | 504 |
| HFpEF | CMR-assessed ECV | On the basis of ECV assessment, two subpopulations of HFpEF patients could be identified. Patients with higher ECV had a higher stiffness constant, whereas those with lower ECV had evidence of prolonged active LV relaxation. | 505 |
| HFpEF | Histology | HFpEF patients exhibited varying levels of fibrosis. Myocardial stiffness increased acutely following manoeuvres associated with transient elevations in systolic blood pressure (such as handgrip). This increase correlated with the levels of myocardial collagen deposition. | 506 |
| HFpEF with and without diabetes | Circulating biomarkers of ECM remodelling. | HFpEF patients with diabetes had increased plasma biomarkers of inflammation (IL-8 and TNFR1) and fibrosis (MMP7, TIMP1), in comparison to non-diabetic HFpEF patients. | 507 |
| HFpEF | CMR-assessed ECV | In HFpEF patients, CMR-assessed LV fibrosis was associated with impaired diastolic function. | 508 |
| HFpEF and patients at risk for HFpEF | CMR-assessed ECV | Similar levels of CMR-assessed myocardial fibrosis were present in patients with HFpEF and those ‘at risk’ for HFpEF (based on elevated B-type natriuretic peptide (BNP) levels). Thus, fibrosis may precede development of HFpEF. | 509 |
| Patients dying with HFpEF or conditions unrelated to heart failure | Histology | In an autopsy study, HFpEF subjects had more severe left ventricular fibrosis and capillary rarefaction than age-matched controls with non-cardiac death and no heart failure. The HFpEF group also had more severe coronary artery disease (CAD), and a higher prevalence of hypertension and diabetes that may account for the increased fibrosis. However, myocardial fibrosis was comparable in HFpEF patients with and without CAD. | 510 |