Biomarker sST2 in Adults with Transposition of the Great Arteries Palliated by Mustard Procedure: A Five-Year Follow-up.

The Mustard procedure was an early cardiac surgery for transposition of the great arteries (TGA). Despite being successful, it has been associated with long-term arrhythmias and heart failure. A key factor complicating management in adults with congenital heart disease (CHD) is the deficiency of biomarkers predicting outcome. Soluble suppression of tumorogenicity-2 (sST2) is secreted by cardiomyocytes in response to mechanical strain and fibrosis. We hypothesized that adults with a Mustard procedure would have higher levels of sST2 than healthy individuals, and this would correlate with clinical outcome. We performed a single-center study in patients managed during childhood with a Mustard procedure versus age-matched controls. Clinical and demographic data were collected and biomarkers (sST2, cTnI, BNP, lipid panel, insulin, and glucose) were obtained. There were 18 patients (12 male) in the Mustard cohort and 18 patients (6 male) in the control group (22-49 years, mean of 35.8 vs. mean 32.6 years, respectively, p = ns). Nine Mustard subjects were NYHA class II, and 9 subjects were class III. The control group was asymptomatic. sST2 in the Mustard group was elevated in 56% vs. 17% in controls (p = 0.035). Of the Mustard subjects with elevated sST2, 60% had elevated cTnI and BNP, and 90% had low HDL. Over five years, the Mustard patients with elevated sST2 values had greater medication use, arrhythmias, hospitalizations, and ablation/pacer implantations than Mustard subjects with normal sST2. Mustard subjects with elevated sST2 had other biomarker abnormalities and clinically worse outcomes. Thus, sST2 may add a predictive value to cardiac-related morbidity and mortality.

Tricuspid leaflet kinematics after annular size reduction in ovine functional tricuspid regurgitation.

OBJECTIVE: Tricuspid annular size reduction with annuloplasty rings represents the foundation of surgical repair of functional tricuspid regurgitation. However, the precise effect of annular size reduction on leaflet motion and geometry remains unknown. METHODS: Ten sheep underwent surgical implantation of a pacemaker with an epicardial lead and were paced 200-240 beats/min to achieve biventricular dysfunction and functional tricuspid regurgitation. Subsequently, sonomicrometry crystals were implanted on the right ventricle, the tricuspid annulus, and on the belly of anterior, posterior, and septal tricuspid leaflets. Double-layer polypropylene suture was placed around the tricuspid annulus and externalized to a tourniquet. Simultaneous echocardiographic, hemodynamic, and sonomicrometry data were acquired with functional tricuspid regurgitation and during 5 consecutive annular reduction steps. Annular area, tenting height, and volume, together with each leaflet strain, radial length, and angles, were calculated from crystal coordinates. RESULTS: Rapid pacing reduced both left ventricle and right ventricle function and induced functional tricuspid regurgitation (0-3+) in all animals (from 0 ± 0 to 2.4 ± 0.7, P = .002), whereas tricuspid annulus diameter increased from 2.6 ± 0.3 cm to 3.3 ± 0.3 cm (P = .001). Tricuspid annular size reduction 1 to 5 resulted in 16% ± 7%, 37% ± 11%, 55% ± 11%, 66% ± 10%, and 76% ± 8% tricuspid annulus area reduction, respectively, and successively decreased tricuspid regurgitation. Tricuspid annular size reduction 2 to 5 induced anterior and posterior leaflet restricted motion and lower diastolic motion velocities. Tricuspid annular size reduction 5 perturbed septal leaflet range of motion but preserved its angle velocities. Tricuspid annular size reduction 3-5 generated compressive strains in all leaflets. CONCLUSIONS: Tricuspid annular area reduction of 55% perturbed anterior and posterior leaflet motion while maintaining normal septal leaflet movement. More extreme reduction triggered profound changes in anterior and posterior leaflet motion, suggesting that aggressive undersizing impairs leaflet kinematics.

Effect of variable annular reduction on functional tricuspid regurgitation and right ventricular dynamics in an ovine model of tachycardia-induced cardiomyopathy.

OBJECTIVE: To investigate the effect of variable tricuspid annular reduction (TAR) on functional tricuspid regurgitation (FTR) and right ventricular (RV) dynamics in ovine tachycardia-induced cardiomyopathy. METHODS: Nine adult sheep underwent implantation of a pacemaker with an epicardial lead and were paced at 200 to 240 bpm until the development of biventricular dysfunction and functional TR was noted. During reoperation on cardiopulmonary bypass, 6 sonomicrometry crystals were placed around the tricuspid annulus (TA) and 14 were placed on the RV epicardium. Annuloplasty suture was placed around the TA and externalized to an epicardial tourniquet. After weaning from cardiopulmonary bypass, echocardiographic, hemodynamic, and sonomicrometry data were acquired at baseline and during 5 progressive TARs achieved with suture cinching. TA area and RV free wall strains and function were calculated from crystal coordinates. RESULTS: After pacing, changes in left ventricular (LV) ejection fraction and RV fractional area decreased significantly. Mean TA diameter increased from 25.1 ± 2.9 mm to 31.5 ± 3.3 mm (P = .005), and median TR (range, 0-3+) increased from 0 (0) to 3 (2) (P = .004). Progressive suture cinching reduced the TA area by 18 ± 6%, 38 ± 11%, 56 ± 10%, 67 ± 9%, and 76 ± 8%. Only aggressive annular reductions (67% and 76%) decreased TR significantly, but these were associated with deterioration of RV function and strain. A moderate annular reduction of 56% led to a substantial reduction of TR with little deleterious effect on regional RV function. CONCLUSIONS: A moderate TAR of approximately 50% may be most advantageous for correction of functional TR and simultaneous maintenance of regional RV performance. Additional subvalvular interventions may be needed to achieve complete valvular competence.

Tricuspid Valve Anterior Leaflet Strains in Ovine Functional Tricuspid Regurgitation.

Functional tricuspid regurgitation (FTR) is thought to arise due to annular dilation and alteration of right ventricular (RV) geometry in the presence of normal leaflets, yet mitral leaflets have been shown to remodel significantly in functional mitral regurgitation. We set out to evaluate tricuspid valve anterior leaflet deformations in ovine FTR. Eleven animals (FTR group) underwent implantation of a pacemaker with high rate pacing to induce biventricular dysfunction and at least moderate TR. Subsequently, both FTR (n = 11) and Control (n = 12) animals underwent implantation of 6 sonomicrometry crystals around the tricuspid annulus, 4 on the anterior leaflet, and 14 on RV epicardium. Tricuspid valve geometry and anterior leaflet strains were calculated from crystal coordinates. Left ventricular ejection fraction and RV fractional area change were significantly lower in FTR animals versus Control. Tricuspid annular area, septo-lateral diameter, RV pressures were all significantly greater in the FTR group. Mean TR grade (+0-3) was 0.7 ± 0.5 in Control and 2.4 ± 0.5 in FTR (P = < 0.001). The anterior leaflet area and length increased significantly. Global radial leaflet strain was significantly lower in FTR mostly driven by decreased free edge leaflet strain. Global circumferential anterior leaflet strain was also significantly lower in FTR with more remarkable reduction in the belly region. Rapid ventricular pacing in sheep resulted in a clinically pertinent model of RV and annular dilation with FTR and leaflet enlargement. Both circumferential and radial anterior leaflet strains were significantly reduced with FTR. Functional TR may be associated with alteration of leaflet mechanical properties.

Conformation and Aggregation of Human Serum Albumin in the Presence of Green Tea Polyphenol (EGCg) and/or Palmitic Acid.

Polyphenols such as epigallocatechin gallate (EGCg) may have roles in preventing some chronic diseases when they are ingested as components of plant-based foods and beverages. Human serum albumin (HSA) is a multi-domain protein that binds various ligands and aids in their transport, distribution, and metabolism in the circulatory system. In the present study, the HSA-EGCg interaction in the absence or presence of fatty acid has been investigated. Förster resonance energy transfer (FRET) was used to determine inter- and intra-domain distances in the protein with and without EGCg and palmitic acid (PA). By labeling Cys-34 with 7-(diethyl amino)-4-methylcoumarin 3-maleimide (CPM), the distance between Trp-214 at domain IIA and CPM-Cys-34 at domain IA could be established. A small amount of PA decreased the distance, while a large amount increased the distance up to 5.4 Å. EGCg increased the inter-domain distance in HSA and HSA-PA up to 2.8 and 7.6 Å, respectively. We concluded that PA affects protein conformation more significantly compared to EGCg. Circular dichroism (CD) established that EGCg affects protein secondary structure more significantly than PA. PA had little effect on the α-helix content of HSA, while EGCg decreased the α-helix content in a dose-dependent fashion. Moreover, EGCg decreased α-helix content in HSA and HSA-PA to the same level. Dynamic light scattering (DLS) data revealed that both PA and EGCg increased HSA aggregation. EGCg increased HSA aggregation more significantly and promoted formation of aggregates that were more heterogenous. Any of these effects could impact the ability of serum albumin to transport and stabilize ligands including EGCg and other polyphenols.

Impact of tricuspid annular size reduction on right ventricular function, geometry and strain.

OBJECTIVES: Restrictive tricuspid annuloplasty is a clinically accepted approach to treat functional tricuspid regurgitation. We set out to investigate the effect of varying degrees of tricuspid annular reduction on the right ventricular (RV) function, geometry and strain. METHODS: Eight, healthy sheep (45 ± 4 kg) had 6 sonomicrometry crystals implanted around the tricuspid annulus and 20 onto the epicardium of the right ventricle defining 3 free wall regions: basal, mid and lower. A polypropylene annuloplasty suture was placed around the tricuspid annulus and externalized to an epicardial tourniquet. Simultaneous echocardiographic, haemodynamic and sonomicrometry data were acquired at baseline and during 5 consecutive annular reduction steps (TAR 1-5) with successive (5-7 mm) suture cinching. RV free wall circumferential, longitudinal and areal cardiac and interventional strains, RV radius of curvature (ROC), cross-sectional area and tricuspid annular dimensions were calculated from 3-dimensional crystal coordinates. RESULTS: TAR 1-5 resulted in 19 ± 15%, 35 ± 15%, 51 ± 15%, 60 ± 15% and 68 ± 13% tricuspid annular area reduction, respectively. TAR 1 and 2 had minimal influence on the RV function, RV-ROC and strains. TAR 4 and 5 decreased RV-ROC in basal and mid-regions, but reduced the RV cross-sectional area change (from 19 ± 4% at baseline to 14 ± 3% and 13 ± 2%, respectively, P < 0.001) and circumferential and areal strains. TAR 3 significantly decreased free wall RV-ROC from 44.0 ± 1.5 to 42.6 ± 2.4 mm P < 0.001 at the RV base but maintained the regional ventricular function and strains. CONCLUSIONS: In healthy ovine hearts, a tricuspid annular area reduction of ∼50% provides optimal conditions for reducing RV-ROC while maintaining regional RV function and strain patterns.

Tricuspid Annular Geometry and Strain After Suture Annuloplasty in Acute Ovine Right Heart Failure.

BACKGROUND: Tricuspid valve repair using suture annuloplasty is thought to be more physiologic, but the effect of annular reduction on annular geometry and motion is unknown. We set out to investigate the effect of DeVega suture annuloplasty (DV) on tricuspid annular geometry and dynamics during acute right heart failure (RHF). METHODS: Ten adult sheep underwent implantation of sonomicrometry crystals around the tricuspid annulus and on the right ventricle; pressure transducers were placed in right ventricle, left ventricle, and right atrium. RHF was induced by a combination of 500 mL volume infusion, posterior descending artery occlusion, and pulmonary artery constriction. Hemodynamic, echocardiographic, and sonomicrometry data were acquired at baseline, with RHF, and after two progressive (8 to 10 mm) DV suture cinches (DV-1, DV-2) during RHF. Annular size, geometry, and dynamics were determined from crystal coordinates. RESULTS: Combination of volume infusion, ischemia, and pulmonary hypertension resulted in acute RHF and significant functional tricuspid regurgitation grade (0.5 ± 0.5 versus 2.7 ± 0.8, p < 0.001). Annular area increased with RHF from 700 ± 98 mm2 to 801 ± 128 mm2 (p < 0.001). DV-1 and DV-2 reduced annular area to 342 ± 88 mm2 and 180 ± 57 mm2 while reducing regurgitation grade to 1.2 ± 0.4 and 0.4 ± 0.5, respectively (all p < 0.001 versus RHF). Tricuspid annular area contraction was 12% ± 7%, 10% ± 6%, and 12% ± 6% for RHF, DV-1, and DV-2, respectively (p = 0.25) and annular height was 4.9 ± 2.0 mm, 5.6 ± 1.4 mm, and 5.5 ± 1.7 mm (p = 0.43). Mean transvalvular gradient was 1.3 ± 0.7 mm Hg and 2.0 ± 1.0 mm Hg with DV-1 and DV-2, respectively. CONCLUSIONS: During acute ovine RHF, DeVega annuloplasty successfully treated tricuspid regurgitation and preserved normal tricuspid annular dynamics and geometry. These data may lead to more physiologic tricuspid reparative techniques.