Galectin-3: A Link between Myocardial and Arterial Stiffening in Patients with Acute Decompensated Heart Failure?

Abstract

BackgroundHeart failure is accompanied by abnormalities in ventricular-vascular interaction due to increased myocardial and arterial stiffness. Galectin-3 is a recently discovered biomarker that plays an important role in myocardial and vascular fibrosis and heart failure progression.ObjectivesThe aim of this study was to determine whether galectin-3 is correlated with arterial stiffening markers and impaired ventricular-arterial coupling in decompensated heart failure patients.MethodsA total of 79 inpatients with acute decompensated heart failure were evaluated. Serum galectin-3 was determined at baseline, and during admission, transthoracic echocardiography and measurements of vascular indices by Doppler ultrasonography were performed.ResultsElevated pulse wave velocity and low arterial carotid distensibility are associated with heart failure in patients with preserved ejection fraction (p = 0.04, p = 0.009). Pulse wave velocity, carotid distensibility and Young’s modulus did not correlate with serum galectin-3 levels. Conversely, raised galectin-3 levels correlated with an increased ventricular-arterial coupling ratio (Ea/Elv) p = 0.047, OR = 1.9, 95% CI (1.0‑3.6). Increased galectin-3 levels were associated with lower rates of left ventricular pressure rise in early systole (dp/dt) (p=0.018) and raised pulmonary artery pressure (p = 0.046). High galectin-3 levels (p = 0.038, HR = 3.07) and arterial pulmonary pressure (p = 0.007, HR = 1.06) were found to be independent risk factors for all-cause mortality and readmissions.ConclusionsThis study showed no significant correlation between serum galectin-3 levels and arterial stiffening markers. Instead, high galectin-3 levels predicted impaired ventricular-arterial coupling. Galectin-3 may be predictive of raised pulmonary artery pressures. Elevated galectin-3 levels correlate with severe systolic dysfunction and together with pulmonary hypertension are independent markers of outcome.

Galectin-3 as a novel biotarget in cardiovascular alterations associated to development of severe aortic stenosis

“…These results suggest that Gal-3 may contribute toward adverse cardiovascular effects in part through an effect on aortic stiffness. In line with these findings, it has been shown that Gal-3 also contributes to ventricular-vascular uncoupling in HF patients 57 .…”

The role of ventricular–arterial coupling in cardiac disease and heart failure: assessment, clinical implications and therapeutic interventions. A consensus document of the European Society of Cardiology Working Group on Aorta & Peripheral Vascular Diseases, European Association of Cardiovascular Imaging, and Heart Failure Association

“…Wave reflection assessment by wave separation analysis is based on the principle that reflected waves add to forward pressure and subtract from forward flow distorting the linear relationship between the increase in pressure and the increase in flow that is seen in early systole when the pulsatile pressure–flow relation is governed by aortic root Zc ( Figure E and G ). Several lines of evidence support the importance of late systolic load from wave reflections as a determinant of maladaptive LV remodelling, diastolic and systolic dysfunction, and HF risk ( Table ) …”

“…Degradation is the task of matrix metalloproteinases. In the presence of disease or with aging, extracellular matrix synthesis gradually predominates, setting the stage for accelerated fibrosis . High galectin‐3 levels, a marker of myocardial and vascular fibrosis, predicted impaired VAC …”

Beneficial Effects of Galectin-3 Blockade in Vascular and Aortic Valve Alterations in an Experimental Pressure Overload Model

“…The authors suggest that Gal-3 may contribute toward adverse cardiovascular effects in-part through an effect on aortic stiffness, effects which cannot be attributed to generalized inflammation. Moreover, Gal-3 contributes to ventricular-vascular uncoupling in HF patients [ 25 ]. In line with these findings, Gal-3 blockade improved vascular remodeling in PO animals, diminishing vascular hypertrophy, fibrosis, and inflammation.…”