Clinically Inapparent Right Heart Dysfunction is Associated with Reduced Myofilament Force Development in Coronary Artery Disease

Abstract Background: Right ventricular dysfunction after CABG is associated with poor peri- and postoperative outcomes. We hypothesized that inapparent RV dysfunction in these patients is already associated with pathological changes at the level of myofilaments in concert with altered biomarkers of myocardial remodeling and endothelial dysfunction.Methods: From 08/2016 to 02/2018, 218 patients scheduled for CABG were divided into two groups (TAPSE ≥20mm, n=178;TAPSE<20mm,n=40). Baseline serum samples for biomarkers (Galectin,TGFß1,N Acyl-SDMA, Arginine, ADMA and Pentraxin-3), clinical laboratory and transthoracic echocardiographic parameters were evaluated. To examine the myocardial apparatus of the right ventricle intraoperative right auricular tissue was harvested for stepwise skinned fiber force measurements.Results: Patients with TAPSE <20mm had a higher incidence of DM (55vs34%,p=0.018), preoperative AFib (43vs16%,p=0.000), reduced GFR (67±18vs77±24 ml/min/1.73m2,p=0.013), larger LA area (22±6vs20±5cm2,p=0.005) and reduced LVEF (50vs55 %,p=0.008). Furthermore, higher serum ADMA (0.70±0.13vs0.65±0.15µmol/l, p=0.046) and higher serum Pentraxin-3 levels (3371±1068vs2681±1353pg/dl,p=0.004) were observed in these Patients. Skinned fibre force measurements showed significant lower values at almost every step of calcium concentration (pCa 4.52 to pCa 5.5,p<0.01 and pCa 5.75 to 6.0,p< 0.05). Multivariable analysis revealed DM (OR 2.53 CI1.12-5.73, Euro Score II (OR1.34 CI 1.02-1.78), preoperative AF (OR4.86 CI2.06-11.47), GFR (OR7.72 CI 1.87-31.96), albumin (OR1.56 CI 0.52-2.60), Pentraxin-3 (OR19.68 CI14.13-25.24), depressed LVEF (OR8.61 CI 6.37-10.86), lower force values: (pCa 5.4; OR2.34 CI 0.40-4.29 and pCa 5.2; OR2.00 CI 0.39-3.60) as predictors for clinical inapparent right heart dysfunction. Conclusions: These preliminary data showed that inapparent right heart dysfunction in CAD is already associated with reduced force development of the contractile apparatus.