Phenotyping progression of secondary mitral regurgitation in chronic systolic heart failure

Abstract

BackgroundSecondary mitral regurgitation (sMR) drives adverse cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF). Progression in severity over time contributes to a transition towards more advanced HF stages. Early identification of patients at risk for sMR progression remains challenging. We therefore sought to assess a broad spectrum of neurohumoral biomarkers in patients with HFrEF to explore their ability to predict progression of sMR.MethodsA total of 249 HFrEF patients were enrolled. Biomarkers encompassing key neurohumoral pathways in heart failure were sampled at baseline, and sMR progression was assessed over 3 years of follow‐up.ResultsOf 191 patients with nonsevere sMR at baseline, 18% showed progressive sMR within three years after study enrolment. Progression of sMR was associated with higher levels of MR‐proADM (adj.OR 2.25, 95% CI 1.29‐3.93; P = .004), MR‐proANP (adj.OR 1.84, 95% CI 1.14‐3.00; P = .012), copeptin (adj.OR 1.66, 95% CI 1.04‐2.67; P = .035) and CT‐pro‐ET1 (adj.OR 1.68, 95% CI 1.06‐2.68; P = .027) but not with NT‐proBNP (P = .54).ConclusionIncreased plasma levels of neurohumoral cardiac biomarkers are predictors of sMR progression in patients with HFrEF and add easily available incremental prognostic information for risk stratification. Importantly, NT‐proBNP was not useful to predict progressive sMR in the present analysis. On the contrary, MR‐proANP, primarily produced in the atria, copeptin partly triggered by intra‐cardiac and intra‐arterial pressures and MR‐proADM, a marker of forward failure and peripheral released vasoactive CT‐proET1, increase based on a progressive loading burden by sMR and may thus serve as better predictors of sMR progression.

Systematic Evaluation of Systemic Right Ventricular Function

“…Progressive volume overload in a failing ventricle increases diastolic wall stress and stimulates an up-regulation of systemic and local neurohumoral activation. Thus, neurohormones are commonly measured as a marker of disease progression in patients with systolic left ventricular failure [19]. In the current study, NT-proBNP levels correlated both with the volumetric function parameter CMR-EF and with the longitudinal function parameter TAPSE.…”

An Integrated Imaging and Circulating Biomarker Approach for Secondary Tricuspid Regurgitation

“…Accordingly, our data show a strong correlation between the level of natriuretic peptides and echocardiographic parameters for cardiac chamber dimensions. MR-proANP has already been shown to be related to the size of the left atrium and ventricle in the context of secondary mitral regurgitation (sMR) [ 11 , 12 ], reflecting morphologic maladaptation as a result of valvular regurgitation on the atrial and ventricular myocardium [ 29 ]. In addition, in the presence of sTR as in our study, MR-proANP displayed the strongest correlation with atrial diameters of both sides, while NT-proBNP correlated best with diameters of the right and left atrium and ventricle.…”

“…Interestingly, while MR-proADM infers prognostic impact for progressive mitral regurgitation [ 11 ], it was not able to predict severe sTR. The correlation with cardiac index and systemic vascular resistance was more pronounced than with pulmonary resistance parameters in our study.…”

“…In HFrEF, volume overload of the dysfunctional ventricles and the vascular system induces wall stress, thereby promoting local and systemic neurohumoral activation, leading to further remodeling at a molecular and morphologic level. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) are released in response to an alteration in transmural pressure of the myocardium and have been associated with volume overload in heart failure and valvular regurgitation [ 11 , 12 , 13 ]. C-terminal pro-endothelin-1 (CT-pro-ET1) reflects the activity of Endothelin-1, which has previously been reported as a marker for venous congestion and increased pulmonary pressures [ 14 , 15 , 16 ].…”

“…Copeptin, a peptide derived from the precursor of vasopressin, has been associated with increased mortality in advanced heart failure patients [ 17 , 18 ]. Finally, mid-regional pro-adrenomedullin (MR-proADM) is a peptide reflecting the actions of adrenomedullin, a potent vasodilator that has been associated with heart failure and progressive mitral regurgitation [ 11 , 19 , 20 ]. These neurohumoral biomarkers therefore illustrate the hemodynamic state from a cardiac perspective as well as from a systemic vascular point of view.…”