Measuring circulating cardiac fibrosis markers in patients treated for heart failure
Expert opinion
Congestive heart failure (CHF) is a progressive chronic disease that gradually impairs the pumping and contracting power of heart muscle fibers. Often referred to as “heart failure,” CHF specifically designates the stage in which fluid accumulates around the heart and slowly triggers inefficient pumping. The most effective therapeutic approach to treat patients suffering from CHF typically includes a combination of diuretics, digoxin, and a vasodilator. Sometimes, however, long-term tri-therapy prescription is not enough to ensure symptomatic benefits and may ultimately compromise the patient’s chances for survival.
CHF is considered “refractory” when CHF symptoms occur while the patient is at rest, or if CFH continues to worsen even under triple-drug therapy. Most refractory CHF patients need hemodynamic monitoring and treatment in intensive care units. Peritoneal dialysis (PD) is used to complement drug treatment for the clinical management of these patients.
This serious and invasive technique does not always yield effective results, which depend greatly on a patient’s clinical profile. There is a need to find a way to easily monitor its impact at the clinic and in heart function recovery, notably by assessing cardiac collagen remodeling and myocardial fibrosis.
In this article, Margarita Kunin conducted a prospective clinical study on a population of refractory CHF patients treated with PD. She measured three circulating cardiac fibrosis markers: procollagen type III C-Peptide (PIIINP), matrix metalloproteinase II (MMP-2), and tissue inhibitor of metalloproteinases I (TIMP-1). She was able to easily correlate the decrease of MMP-2 and TIMP-1 in patients treated with PD.
Interestingly, circulating PIIINP showed either a decrease or an increase in patients treated with PD. Those two patterns of change for PIIINP levels were found to be linked with the specificities of the clinical subgroups. Combined with MMP-2 and TIMP-1 decrease, patients with higher baseline median PIIINP showed a higher survival rate.
Lung, liver, kidney, and now heart… data is increasingly showing the role of PIIINP for monitoring fibrosis. Undoubtedly, PIIINP still has some
Abstract
Background: Cardiac collagen remodeling is important in the progression of heart failure. Estimation of cardiac collagen turnover by serum levels of serological markers is used for monitoring cardiac tissue repair and fibrosis. Peritoneal dialysis (PD) is used for the long-term management of refractory congestive heart failure (CHF). In this study, we investigated the effect of PD treatment on circulating fibrosis markers levels in patients with refractory CHF and fluid overload. Methods: Twenty-five patients with refractory CHF treated with PD were prospectively enrolled in the study. Circulating fibrosis markers procollagen type III C-peptide (PIIINP), matrix metalloproteinase 2 (MMP-2), and tissue inhibitor of metalloproteinases I (TIMP-1) levels were checked at baseline and after three and six months of treatment. Results: The clinical benefit of PD manifested by improved NYHA functional class and reduced hospitalization rate. Serum brain natriuretic peptide (BNP) levels decreased significantly during the treatment. Serum MMP-2 and TIMP-1 decreased significantly on PD. Circulating PIIINP showed two patterns of change, either decreased or increased following PD treatment. Patients in whom circulating PIIINP decreased had significantly lower baseline serum albumin, lower baseline mean arterial blood pressure, higher serum CRP, and a less significant improvement in hospitalization rate compared to the patients in whom circulating PIIINP increased. Patients in whom all three markers decreased demonstrated a trend to longer survival compared to patients whose markers increased or did not change. Conclusion: In refractory CHF patients PD treatment was associated with a reduction in circulating fibrosis markers.