51 Plasma MMP-3: A Novel Indicator of Left Ventricle Remodelling and Adverse Outcomes in Patients with Acute Heart Failure

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Abstract

Purpose

Changes in the intercellular matrix have previously been found to be important in left ventricle (LV) remodelling in chronic heart failure (HF). We investigated whether plasma matrix metalloproteinase (MMP) 3 and 9 were associated with adverse clinical outcomes in acute HF.

Methods

In a prospective cohort study pre-discharge plasma MMP-3 and 9 levels were measured in 400 consecutive patients presenting to hospital with acute HF. LV ejection fraction (LVEF) was assessed by echocardiography. The clinical endpoints were death and death or HF readmission at 1 year.

Results

By 1 year 103 patients had died and 173 patients had died or been readmitted with HF. MMP-3 was significantly greater in males (p < 0.001), those with hypertension (p < 0.01) and with a past history of chronic HF (p = 0.01) and chronic kidney disease (CKD) (p < 0.001). MMP-3 was significantly correlated with age (p < 0.001) while being inversely correlated with eGFR (p < 0.001) and heart rate (p < 0.008). MMP-3 was significantly greater in patients with a LVEF < 40% compared with those with EF > 40% (p = 0.017). MMP-3 levels were significantly greater in the 108 patients who died compared to those who did not [median = 29.7 [19. to 41.1] vs. 18.9 [11.8 to 30.7] pg/ml, p < 0.001) as well as in those with the combined endpoint compared to those without (26.1 [16.7 to 36.4] vs. 17.9 [11.4 to 31.3] pg/ml, p < 0.001). In Kaplan-Meier analysis, patients with above median MMP-3 levels were significantly more likely to experience the endpoint (p < 0.001) compared to those who did not.

Results

Discharge MMP-9 levels were significantly inversely correlated with age (p = 0.003) but had no relationship with LVEF. MMP-9 levels were significantly lower in patients who died (p < 0.007) and in those with the combined outcome of death or HF readmission (p < 0.001). In Kaplan-Meier analysis, patients with below median MMP-9 levels were significantly more likely to experience the endpoint (p = 0.007) compared to those who did not.

Results

The AUC of MMP-3 combined with NTproBNP was significantly greater than NTproBNP alone (p = 0.044) for outcome death but not death or HF readmission (p = 0.092) while the AUC of MMP-9 combined with NTproBNP was significantly greater than NTproBNP alone for the combined endpoint (p = 0.027) but not death alone (p = 0.085)

Conclusion

Increased MMP-3 but decreased MMP-9 levels are associated with worse prognosis after admission with acute HF. MMP-3 added prognostic value to NTproBNP for prediction of death while MMP-9 added prognostic value to NTproBNP for prediction of death or HF readmission at 1 year.

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