Serial and regional assessment of the right ventricular molecular and functional response to pressure-loading.

BACKGROUND: Right ventricular(RV) function determines outcomes in RV pressure-loading. A better understanding of the time-course and regional distribution of RV remodeling may help optimize targets and timing for therapeutic intervention. We sought to characterize RV remodeling between zero and 6-weeks after initiation of RV pressure-loading. METHODS AND RESULTS: Thirty-six rats were randomized to either sham surgery or to pulmonary artery banding(PAB). After echocardiography and conductance catheter studies, groups of rats were euthanized at 1-week, 3-weeks and 6-weeks after sham surgery, or induction of RV pressure-loading, for RV histological, RNA and molecular analysis. A vigorous inflammatory response characterized by increased RV inflammatory cytokines, chemokines and macrophage markers was observed at 1-week following PAB. Metabolic changes, TGF-ß1 canonical signaling, collagenous fibrosis deposition and apoptosis were already significantly increased by 1-week after PAB. Genes marking fibroblast activation were upregulated at 1-week but not 6-week post-PAB surgery. Mitochondrial dysfunction as evidenced by increased PDK activity and decreased PDH phosphorylation significantly at 6-week post PAB. These processes preceded the development of overt myocardial hypertrophy and impaired echo parameters of systolic and diastolic function which occurred significantly from 3-weeks after PAB. CONCLUSION: RV myocardial inflammation, metabolic shift, metabolic gene transcription and pro-fibrotic signaling occur early after initiation of pressure-loading when RV pressures are only moderately elevated, before the development of overt myocardial hypertrophy and dysfunction, suggesting that adaptive hypertrophy and maladaptive remodeling occur simultaneously. These results suggest that therapeutic intervention to reduce adverse RV remodeling may be needed earlier and at lower thresholds than currently employed.

Diastolic dysfunction: assessment and implications on the single ventricle circulation.

PURPOSE OF REVIEW: Patients with a functionally single ventricle (SV) are palliated with a series of procedures leading to a Fontan circulation. Over the life span, a substantial proportion of SV patients develop heart failure that can arise from circulatory or ventricular failure. Diastolic dysfunction (DD) is an important determinant of adverse outcomes in SV patients. However, assessment and categorization of DD in the SV remains elusive. We review recent literature and developments in assessment of DD in the SV and its relation to clinical outcomes. RECENT FINDINGS: DD is prevalent in the SV and associated with worse outcomes. Occult DD can be exposed with provocative testing by exercise or preload challenge during catheterization. Likewise, sensitivity to detect DD may be increased via assessment of atrial function and strain imaging. Recent studies revisiting previous concepts such as incoordinate diastolic wall motion show that these are associated with SV end-diastolic pressures and post-Fontan recovery, yielding accessible DD assessment. Emerging technologies such as ultrafast ultrasound (UFUS) can provide noninvasive assessment of myocardial stiffness, inefficient diastolic flow patterns and intraventricular pressure gradients, thereby yielding new tools and insights into diastolic myocardial and hemodynamic properties. SUMMARY: Characterizing DD in the SV continues to have substantial limitations, necessitating synthesis of multiple parameters into an overall assessment, accounting for their change over time, and in the context of the patient's clinical status. New and emerging techniques may help advance DD assessment and the ability to track response to treatment of new targets.

Impact of Right Ventricular Pressure Overload on Myocardial Stiffness Assessed by Natural Wave Imaging.

BACKGROUND: Right ventricular (RV) hemodynamic performance determines the prognosis of patients with RV pressure overload. Using ultrafast ultrasound, natural wave velocity (NWV) induced by cardiac valve closure was proposed as a new surrogate to quantify myocardial stiffness. OBJECTIVES: This study aimed to assess RV NWV in rodent models and children with RV pressure overload vs control subjects and to correlate NWV with RV hemodynamic parameters. METHODS: Six-week-old rats were randomized to pulmonary artery banding (n = 6), Sugen hypoxia-induced pulmonary arterial hypertension (n = 7), or sham (n = 6) groups. They underwent natural wave imaging, echocardiography, and hemodynamic assessment at baseline and 6 weeks postoperatively. The authors analyzed NWV after tricuspid and after pulmonary valve closure (TVC and PVC, respectively). Conductance catheters were used to generate pressure-volume loops. In parallel, the authors prospectively recruited 14 children (7 RV pressure overload; 7 age-matched control subjects) and compared RV NWV with echocardiographic and invasive hemodynamic parameters. RESULTS: NWV significantly increased in RV pressure overload rat models (4.99 ± 0.27 m/s after TVC and 5.03 ± 0.32 m/s after PVC in pulmonary artery banding at 6 weeks; 4.89 ± 0.26 m/s after TVC and 4.84 ± 0.30 m/s after PVC in Sugen hypoxia at 6 weeks) compared with control subjects (2.83 ± 0.15 m/s after TVC and 2.72 ± 0.34 m/s after PVC). NWV after TVC correlated with both systolic and diastolic parameters including RV dP/dtmax (r = 0.75; P < 0.005) and RV Ees (r = 0.81; P < 0.005). NWV after PVC correlated with both diastolic and systolic parameters and notably with RV end-diastolic pressure (r = 0.65; P < 0.01). In children, NWV after both right valves closure in RV pressure overload were higher than in healthy volunteers (P < 0.01). NWV after PVC correlated with RV E/E' (r = 0.81; P = 0.008) and with RV chamber stiffness (r = 0.97; P = 0.03). CONCLUSIONS: Both RV early-systolic and early-diastolic myocardial stiffness show significant increase in response to pressure overload. Based on physiology and our observations, early-systolic myocardial stiffness may reflect contractility, whereas early-diastolic myocardial stiffness might be indicative of diastolic function.

Inhibition of MRTF-A Ameliorates Pathological Remodeling of the Pressure-loaded Right Ventricle.

Right ventricular (RV) fibrosis is associated with RV dysfunction in a variety of RV pressure-loading conditions where RV mechanical stress is increased, but the underlying mechanisms driving RV fibrosis are incompletely understood. In pulmonary and cardiovascular diseases characterized by elevated mechanical stress and transforming growth factor - beta-1 (TGF-ß1) signaling, myocardin-related transcription factor A (MRTF-A) is a mechanosensitive protein critical to driving myofibroblast transition and fibrosis. Here we investigated whether MRTF-A inhibition improves RV pro-fibrotic remodeling and function in response to a pulmonary artery banding (PAB) model of RV pressure-loading. Rats were assigned into either 1) sham or 2) PAB groups. MRTF-A inhibitor CCG-1423 was administered daily at 0.75mg/kg in a subset of PAB animals. Echocardiography and pressure-volume hemodynamics were obtained at a terminal experiment 6-weeks later. RV myocardial samples were analyzed for fibrosis, cardiomyocyte hypertrophy, and pro-fibrotic signaling. MRTF-A inhibition slightly reduced systolic dysfunction in PAB rats reflected by increased lateral tricuspid annulus peak systolic velocity, while diastolic function parameters were not significantly improved. RV remodeling was attenuated in PAB rats with MRTF-A inhibition, displaying reduced fibrosis. This was accompanied with a reduction in PAB-induced upregulation of yes-associated protein (YAP) and its paralog transcriptional co-activator with PDZ-binding motif (TAZ). We also confirmed using a second-generation MRTF-A inhibitor CCG-203971 that MRTF-A is critical in driving RV fibroblast expression of TAZ and markers of myofibroblast transition in response to TGF-ß1 stress and RhoA activation. These studies identify RhoA, MRTF-A, and YAP/TAZ as interconnected regulators of pro-fibrotic signaling in RV pressure-loading, and as potential targets to improve RV pro-fibrotic remodeling.

Biventricular responses to exercise and their relation to cardiorespiratory fitness in pediatric pulmonary hypertension.

Despite exercise intolerance being predictive of outcomes in pulmonary arterial hypertension (PAH), its underlying cardiac mechanisms are not well described. The aim of the study was to explore the biventricular response to exercise and its associations with cardiorespiratory fitness in children with PAH. Participants underwent incremental cardiopulmonary exercise testing and simultaneous exercise echocardiography on a recumbent cycle ergometer. Linear mixed models were used to assess cardiac function variance and associations between cardiac and metabolic parameters during exercise. Eleven participants were included with a mean age of 13.4 ± 2.9 yr old. Right ventricle (RV) systolic pressure (RVsp) increased from a mean of 59 ± 25 mmHg at rest to 130 ± 40 mmHg at peak exercise (P < 0.001), whereas RV fractional area change (RV-FAC) and RV-free wall longitudinal strain (RVFW-Sl) worsened (35.2 vs. 27%, P = 0.09 and -16.6 vs. -14.6%, P = 0.1, respectively). At low- and moderate-intensity exercise, RVsp was positively associated with stroke volume and O2 pulse (P < 0.1). At high-intensity exercise, RV-FAC, RVFW-Sl, and left ventricular longitudinal strain were positively associated with oxygen uptake and O2 pulse (P < 0.1), whereas stroke volume decreased toward peak (P = 0.04). In children with PAH, the increase of pulmonary pressure alone does not limit peak exercise, but rather the concomitant reduced RV functional reserve, resulting in RV to pulmonary artery (RV-PA) uncoupling, worsening of interventricular interaction and LV dysfunction. A better mechanistic understanding of PAH exercise physiopathology can inform stress testing and cardiac rehabilitation in this population.NEW & NOTEWORTHY In children with pulmonary arterial hypertension, there is a marked increase in pulmonary artery pressure during physical activity, but this is not the underlying mechanism that limits exercise. Instead, right ventricle-to-pulmonary artery uncoupling occurs at the transition from moderate to high-intensity exercise and correlates with lower peak oxygen uptake. This highlights the more complex underlying pathological responses and the need for multiparametric assessment of cardiac function reserve in these patients when feasible.

Regulation of the RhoA exchange factor GEF-H1 by profibrotic stimuli through a positive feedback loop involving RhoA, MRTF, and Sp1.

RhoA and its effectors, the transcriptional coactivators myocardin-related transcription factor (MRTF) and serum response factor (SRF), control epithelial phenotype and are indispensable for profibrotic epithelial reprogramming during fibrogenesis. Context-dependent control of RhoA and fibrosis-associated changes in its regulators, however, remain incompletely characterized. We previously identified the guanine nucleotide exchange factor GEF-H1 as a central mediator of RhoA activation in renal tubular cells exposed to inflammatory or fibrotic stimuli. Here we found that GEF-H1 expression and phosphorylation were strongly elevated in two animal models of fibrosis. In the Unilateral Ureteral Obstruction mouse kidney fibrosis model, GEF-H1 was upregulated predominantly in the tubular compartment. GEF-H1 was also elevated and phosphorylated in a rat pulmonary artery banding (PAB) model of right ventricular fibrosis. Prolonged stimulation of LLC-PK1 tubular cells with tumor necrosis factor (TNF)-α or transforming growth factor (TGF)-ß1 increased GEF-H1 expression and activated a luciferase-coupled GEF-H1 promoter. Knockdown and overexpression studies revealed that these effects were mediated by RhoA, cytoskeleton remodeling, and MRTF, indicative of a positive feedback cycle. Indeed, silencing endogenous GEF-H1 attenuated activation of the GEF-H1 promoter. Of importance, inhibition of MRTF using CCG-1423 prevented GEF-H1 upregulation in both animal models. MRTF-dependent increase in GEF-H1 was prevented by inhibition of the transcription factor Sp1, and mutating putative Sp1 binding sites in the GEF-H1 promoter eliminated its MRTF-dependent activation. As the GEF-H1/RhoA axis is key for fibrogenesis, this novel MRTF/Sp1-dependent regulation of GEF-H1 abundance represents a potential target for reducing renal and cardiac fibrosis.NEW & NOTEWORTHY We show that expression of the RhoA regulator GEF-H1 is upregulated in tubular cells exposed to fibrogenic cytokines and in animal models of kidney and heart fibrosis. We identify a pathway wherein GEF-H1/RhoA-dependent MRTF activation through its noncanonical partner Sp1 upregulates GEF-H1. Our data reveal the existence of a positive feedback cycle that enhances Rho signaling through control of both GEF-H1 activation and expression. This feedback loop may play an important role in organ fibrosis.

Guidelines for Performing a Comprehensive Pediatric Transthoracic Echocardiogram: Recommendations From the American Society of Echocardiography.

Echocardiography is a fundamental component of pediatric cardiology, and appropriate indications have been established for its use in the setting of suspected, congenital, or acquired heart disease in children. Since the publication of guidelines for pediatric transthoracic echocardiography in 2006 and 2010, advances in knowledge and technology have expanded the scope of practice beyond the use of traditional modalities such as two-dimensional, M-mode, and Doppler echocardiography to evaluate the cardiac segmental structures and their function. Adjunct modalities such as contrast, three-dimensional, and speckle-tracking echocardiography are now used routinely at many pediatric centers. Guidelines and recommendations for the use of traditional and newer adjunct modalities in children are described in detail in this document. In addition, suggested protocols related to standard operations, infection control, sedation, and quality assurance and improvement are included to provide an organizational structure for centers performing pediatric transthoracic echocardiograms.

Adverse remodelling in tetralogy of Fallot: From risk factors to imaging analysis and future perspectives.

Although contemporary outcomes of initial surgical repair of tetralogy of Fallot (TOF) are excellent, the survival of adult patients remains significantly lower than that of the normal population due to the high incidence of heart failure, ventricular arrhythmias, and sudden cardiac death. The underlying mechanisms are only partially understood but involve an adverse biventricular response, so-called remodelling, to key stressors such as right ventricular (RV) pressure-and/or volume-overload, myocardial fibrosis, and electro-mechanical dyssynchrony. In this review, we explore risk factors and mechanisms of biventricular remodelling, from histological to electro-mechanical aspects, and the role of imaging in their assessment. We discuss unsolved challenges and future directions to better understand and treat the long-term sequelae of this complex congenital heart disease.

Left ventricular remodelling in rheumatic heart disease - trends over time and implications for follow-up in childhood.

BACKGROUND: Rheumatic heart disease (RHD) is the most common form of acquired heart disease worldwide. In RHD, volume loading from mitral regurgitation leads to left ventricular (LV) dilatation, increased wall stress, and ultimately LV dysfunction. Improved understanding of LV dynamics may contribute to refined timing of intervention. We aimed to characterize and compare left ventricular remodelling between rheumatic heart disease (RHD) severity groups by way of serial echocardiographic assessment of volumes and function in children. METHODS: Children with RHD referred to Perth Children's Hospital (formally Princess Margaret Hospital) (1987-2020) were reviewed. Patients with longitudinal pre-operative echocardiograms at diagnosis, approximately 12 months and at most recent follow-up, were included and stratified into RHD severity groups. Left ventricular (LV) echocardiographic parameters were assessed. Adjusted linear mixed effect models were used to compare interval changes. RESULTS: 146 patients (median age 10 years, IQR 6-14 years) with available longitudinal echocardiograms were analysed. Eighty-five (58.2%) patients had mild, 33 (22.6%) moderate and 28 (19.2%) severe RHD at diagnosis. Mean duration of follow-up was 4.6 years from the initial diagnosis. Severe RHD patients had significantly increased end-systolic volumes (ESV) and end-diastolic volumes (EDV) compared to mild/moderate groups at diagnosis (severe versus mild EDV mean difference 27.05 ml/m2, p < 0.001, severe versus moderate EDV mean difference 14.95 ml/m2, p = 0.006). Mild and moderate groups experienced no significant progression of changes in volume measures. In severe RHD, LV dilatation worsened over time. All groups had preserved cardiac function. CONCLUSIONS: In mild and moderate RHD, the lack of progression of valvular regurgitation and ventricular dimensions suggest a stable longer-term course. Significant LV remodelling occurred at baseline in severe RHD with progression of LV dilatation over time. LV function was preserved across all groups. Our findings may guide clinicians in deciding the frequency and timing of follow-up and may be of clinical utility during further reiterations of the Australia and New Zealand RHD Guidelines.

Diastolic myocardial mechanics and their relation to ventricular filling pressures and postoperative course in functionally single ventricles.

Diastolic dysfunction affects clinical outcomes in patients with a functionally single ventricle (FSV). The objective of this work is to study the association of ventricular mechanics and interventricular dependence on diastolic parameters and early post-Fontan outcomes. Sixty-one patients with FSV underwent echocardiography, cardiac catheterization, and magnetic resonance imaging on the same day before or after the Fontan procedure. Echocardiographic diastolic parameters, ventricular mass, and incoordinate wall motion, defined by the number of dyskinetic segments or by the lateral wall delay, were determined and studied for relationships with invasively measured hemodynamics and early postoperative Fontan course. In subjects with a sizable secondary ventricle, incoordinate motion was additionally analyzed at the left- and right-sided ventricular free walls. Resting ventricular end-diastolic pressure (VEDP) was ≤10 mmHg in most subjects. Individual echocardiographic parameters of the diastolic flow and tissue velocities did not correlate with VEDP, other hemodynamics, or post-Fontan clinical course. Incoordinate wall motion in the dominant and in the sizeable secondary ventricle, defined by the lateral wall delay or by the number of dyskinetic segments, was the only echo parameter that correlated, albeit weakly, with VEDP (r = 0.247, P = 0.040), oxygen saturation (r = -0.417, P = 0.001), pulmonary vascular resistance and flow (Qp) (r = -0.303, P = 0.011), Fontan fenestration flow (r = 0.512, P = 0.009), and duration of endotracheal intubation (r = 0.292, P = 0.022). When the nondominant (secondary) ventricle was accounted for in the analysis of incoordinate wall motion, these associations strengthened. The degree of incoordinate ventricular wall motion in diastole was associated with VEDP and postoperative Fontan course in FSV. Analysis of incoordinate wall motion of the dominant and sizeable secondary ventricle may be warranted and should be included in the assessment of the FSV after the Fontan procedure.NEW & NOTEWORTHY Diastolic dysfunction affects outcomes in patients with functionally single ventricles (FSVs) but is difficult to assess. We found that incoordinate wall motion was the only echo parameter that correlated with FSV end-diastolic pressure, oxygen saturation, pulmonary vascular resistance and flow, and duration of endotracheal intubation. Analysis of incoordinate wall motion in the nondominant (secondary) ventricle strengthened these associations. Analyzing incoordinate wall motion should be included in the assessment of the FSV after the Fontan procedure.

Electromechanical Dyssynchrony Is Associated With Right Ventricular Remodeling and Dysfunction Independently of Pulmonary Regurgitation Late After Tetralogy of Fallot Repair.

BACKGROUND: The aim of this study was to investigate the relationship among right ventricular (RV) dilatation, dysfunction, and electromechanical dyssynchrony (EMD) in patients with repaired tetralogy of Fallot (rTOF). METHODS: Data from a prospective rTOF registry of subjects with moderate or greater pulmonary regurgitation (PR) and contemporary imaging were analyzed. Electrocardiograms and echocardiograms were analyzed for EMD (prolonged QRS duration [QRSd], echocardiographic septal flash, and mechanical delay) and mechanical dispersion. The relationship among these, RV measurements on cardiac magnetic resonance, exercise capacity, and incident arrhythmia or death was analyzed with adjustment for PR. RESULTS: In total, 271 patients with rTOF (42% women; median age, 32 years; interquartile range [IQR], 23-34 years) were included. Patients had moderate to severe PR (median PR fraction, 38%; IQR, 30%-47%), moderate to severe RV enlargement (median RV end-diastolic volume index, 161 mL/m2; IQR, 138-186 mL/m2) and mild RV systolic dysfunction (median RV ejection fraction [RVEF], 44%; IQR, 38%-48%). Eleven patients (4%) experienced ventricular arrhythmia or death. Presence of EMD was associated with larger RV size (RV end-diastolic volume index and RV end-systolic volume index, P = .006 and P < .001, respectively) and lower RVEF (P < .001). A sharp inflection in the relation among QRSd, RV size, and RVEF was observed when QRSd exceeded 150 msec (3.1% decrease in RVEF for every 20-msec increase in QRSd between 160 and 200 msec). Similar inflection points were observed for the mechanical delay between the RV basal-lateral and midseptal segments. The mechanical delay was higher in patients with vs without incident atrial arrhythmia (371 vs 276 msec, P = .014). CONCLUSIONS: In adults with rTOF, EMD is independently associated with larger RV size, lower RVEF, and incident atrial arrhythmias.

Multimodality Imaging of Right Heart Function: JACC Scientific Statement.

Right ventricular (RV) size and function assessed by multimodality imaging are associated with outcomes in a variety of cardiovascular diseases. Understanding RV anatomy and physiology is essential in appreciating the strengths and weaknesses of current imaging methods and gives these measurements greater context. The adaptation of the right ventricle to different types and severity of stress, particularly over time, is specific to the cardiovascular disease process. Multimodality imaging parameters, which determine outcomes, reflect the ability to image the initial and longitudinal RV response to stress. This paper will review the standard and novel imaging methods for assessing RV function and the impact of these parameters on outcomes in specific disease states.

Longitudinal Changes in Ventricular Mechanics in Adolescents After the Fontan Operation.

BACKGROUND: Ventricular dysfunction is a significant clinical challenge in the long-term follow-up of patients with single-ventricle (SV) physiology. Ventricular function and myocardial mechanics can be studied using speckle-tracking echocardiography, which provides information on myocardial deformation. Limited information is available on serial changes in SV myocardial mechanics after the Fontan operation. The aim of this study was to describe serial changes in myocardial mechanics in children after the Fontan operation and the relationship of these changes with myocardial fibrosis markers as obtained by cardiac magnetic resonance and exercise performance parameters. METHODS: The authors hypothesized that ventricular mechanics decline in patients with SVs over time and are associated with increased myocardial fibrosis and reduced exercise performance. A single-center retrospective cohort study including adolescents after the Fontan operation was conducted. Ventricular strain and torsion were assessed using speckle-tracking echocardiography. Cardiac magnetic resonance and cardiopulmonary exercise testing data closest to the latest echocardiographic examinations were performed. The most recent follow-up echocardiographic and cardiac magnetic resonance data were compared with those from sex- and age-matched control subjects and with individual patients' early post-Fontan data. RESULTS: Fifty patients with SVs (31 left ventricle, 13 right ventricle [RV], and six codominant) were included. Median time at follow-up echocardiography from the time of Fontan was 12.8 years (interquartile range [IQR], 10.6 to 16.6 years). Compared with early post-Fontan echocardiography, follow-up assessment showed reduced global longitudinal strain (-17.5% [IQR, -14.5% to -19.5%] vs -19.8% [IQR, -16.0% to -21.7%], P = .01], circumferential strain (-15.7% [IQR, -11.4% to -18.7%] vs -18.9% [IQR, -15.2% to -25.0%], P = .009), and torsion (1.28°/cm [IQR, 0.51°/cm to 1.74°/cm] vs 1.72°/cm [IQR, 0.92°/cm to 2.34°/cm], P = .02), with decreased apical rotation but no significant change in basal rotation. Single RVs had lower torsion compared with single left ventricles (1.04°/cm [IQR, 0.12°/cm to 2.20°/cm] vs 1.25°/cm [IQR, 0.25°/cm to 2.51°/cm], P = .01). T1 values were higher in patients with SV compared with control subjects (1,009 ± 36 vs 958 ± 40 msec, P = .004) and in those with single RVs compared with single left ventricles (1,023 ± 19 vs 1,006 ± 17 msec, P = .02). T1 was correlated with circumferential strain (r = 0.59, P = .04) and inversely correlated with O2 saturation (r = -0.67, P < .001) and torsion (r = -0.71, P = .02). Peak oxygen consumption was correlated with torsion (r = 0.52, P = .001) and untwist rates (r = 0.23, P = .03). CONCLUSIONS: After the Fontan procedures, there is a progressive decrease in myocardial deformation parameters. The progressive decrease in SV torsion is related to a decrease in apical rotation, which is more pronounced in single RVs. Decreased torsion is associated with increased markers of myocardial fibrosis and lower maximal exercise capacity. Torsional mechanics may be an important parameter to monitor after Fontan palliation, but further prognostic information is required.

The use of 2-D speckle tracking echocardiography in differentiating healthy adolescent athletes with right ventricular outflow tract dilation from patients with arrhythmogenic cardiomyopathy.

AIMS: Echocardiographic assessment of adolescent athletes for arrhythmogenic cardiomyopathy (ACM) can be challenging owing to right ventricular (RV) exercise-related remodelling, particularly RV outflow tract (RVOT) dilation. The aim of this study is to evaluate the role of RV 2-D speckle tracking echocardiography (STE) in comparing healthy adolescent athletes with and without RVOT dilation to patients with ACM. METHODS AND RESULTS: A total of 391 adolescent athletes, mean age 14.5 ± 1.7 years, evaluated at three sports academies between 2014 and 2019 were included, and compared to previously reported ACM patients (n = 38 definite and n = 39 borderline). Peak systolic RV free wall (RVFW-Sl), global and segmental strain (Sl), and corresponding strain rates (SRl) were calculated. The participants meeting the major modified Task Force Criteria (mTFC) for RVOT dilation were defined as mTFC+ (n = 58, 14.8%), and the rest as mTFC- (n = 333, 85.2%). Mean RVFW-Sl was -27.6 ± 3.4% overall, -28.2 ± 4.1% in the mTFC+ group and - 27.5 ± 3.3% in the mTFC- group. mTFC+ athletes had normal RV-FW-Sl when compared to definite (-29% vs -19%, p < 0.001) and borderline ACM (-29% vs -21%, p < 0.001) cohorts. In addition, all mean global and regional Sl and SRl values were no worse in the mTFC+ group compared to the mTFC- (p values range < 0.0001 to 0.1, inferiority margin of 2% and 0.1 s-1 respectively). CONCLUSIONS: In athletes with RVOT dilation meeting the major mTFC, STE evaluation of the RV can demostrate normal function and differentiate physiological remodelling from pathological changes found in ACM, improving screening in grey-area cases.

Right Ventricular Electromechanical Dyssynchrony and Its Relation to Right Ventricular Remodeling, Dysfunction, and Exercise Capacity in Ebstein Anomaly.

BACKGROUND: Abnormal atrioventricular and intraventricular electrical conduction and dysfunction of the functional right ventricle (fRV) are common in Ebstein anomaly (EA). However, fRV mechanical dyssynchrony and its relation to fRV function are poorly characterized. We evaluated fRV mechanical dyssynchrony in EA patients in relation to fRV remodeling, dysfunction, and exercise intolerance. METHODS: We retrospectively analyzed data from nonoperated EA patients and age-matched controls who underwent echocardiography, cardiovascular magnetic resonance imaging, and cardiopulmonary exercise testing to quantify right ventricular (RV) remodeling, dysfunction, and exercise capacity. The relation of these to fRV dyssynchrony was retrospectively investigated. Right ventricular mechanical dyssynchrony was defined by early fRV septal activation (right-sided septal flash), RV lateral wall prestretch/late contraction, postsystolic shortening, and intra-RV delay using two-dimensional strain echocardiography. The SD of time to peak shortening among the fRV segments was calculated as a parameter of mechanical dispersion. RESULTS: Thirty-five EA patients (10 of whom were <18 years of age) and 35 age-matched controls were studied. Ebstein anomaly patients had worse RV function and increased intra-RV dyssynchrony versus controls. Nineteen of 35 (54%) EA patients had early septal activation with simultaneous stretch and consequent late activation and postsystolic shortening of RV lateral segments. Intra-fRV mechanical delay correlated with fRV end-diastolic volume index (r = 0.43, P < .05) and fRV end-systolic volume index (r = 0.63, P < .001). The fRV ejection fraction was lower in EA with versus without right-sided septal flash (44.9 ± 11.0 vs 54.2 ± 8.2, P = .012). The fRV mechanical dispersion correlated with the percentage of predicted peak VO2 (r = -0.35, P < .05). CONCLUSIONS: In EA, fRV mechanical dyssynchrony is associated with fRV remodeling, dysfunction, and impaired exercise capacity. Mechanical dyssynchrony as a therapeutic target in selected EA patients warrants further study.

Impact of Ventricular Geometric Characteristics on Myocardial Stiffness Assessment Using Shear-Wave Velocity in Healthy Children and Young Adults.

BACKGROUND: Diastolic myocardial stiffness (MS) can serve as a key diagnostic parameter for congenital or acquired heart diseases. Using shear modulus and shear-wave velocity (SWV), shear-wave elastography (SWE) is an emerging ultrasound-based technique that can allow noninvasive assessment of MS. However, MS extrinsic parameters such as left ventricular geometric characteristics could affect shear-wave propagation. The aims of this study were to determine a range of normal values of MS using SWE in age groups of healthy children and young adults and to explore the impact of left ventricular geometric characteristics on SWE. METHODS: Sixty healthy volunteers were recruited in the study and divided into 2 groups: neonates (0-1 months old, n = 15) and >1 month old (1 month to 45 years of age, n = 45). SWE was performed using the Verasonics Vantage systems with a phased-array ultrasound probe. The anteroseptal basal segment was assessed in two views. SWE was electrocardiographically triggered during the end-diastolic phase. Conventional echocardiography was performed to assess ventricular function and anatomy. Results are presented as stiffness values along with mean velocity measurements and SDs. Simple and multivariate linear regression analyses were performed. RESULTS: For neonates, mean MS was 1.87 ± 0.79 kPa (range, 0.59-2.91 kPa; mean SWV, 1.37 ± 0.57 m/sec), with high variability and no correlation with age (P = .239). For this age group, no statistically significant correlation was found between MS and any demographic or echocardiographic parameters (P > .05). For the >1 month old group, a mean MS value of 1.67 ± 0.53 kPa was observed (range, 0.6-3 kPa; mean SWV, 1.29 ± 0.49 m/sec) for healthy volunteers. When paired for age, no sex-related difference was observed (P = .55). In univariate linear regression analysis, age (r = 0.83, P < .01), diastolic interventricular septal thickness (r = 0.72, P < .01), and left ventricular end-diastolic diameter (r = 0.67, P < .01) were the parameters with the highest correlation coefficients with MS. In a multiple linear regression analysis incorporating these three parameters as cofounding factors, age was the only statistically significant parameters (r = 0.81, P = .02). CONCLUSION: Diastolic MS increases linearly in children and young adults. Diastolic MS correlates more robustly with age than with myocardial and left ventricular geometric characteristics. However, the geometry affects SWV, implying the need to determine well-established boundaries in future studies for the clinical application of SWE.

Growth of unrepaired hypoplastic proximal aortic arch and reintervention rate after aortic coarctation repair.

BACKGROUND: Treatment of tubular hypoplasia of the aortic arch (THAA) associated with aortic coarctation (CoA) remains controversial. We aimed to evaluate growth of unrepaired hypoplastic proximal aortic arches (PAAs) after surgical repair for CoA. METHODS: Preoperative and follow-up echocardiographic images of 139 patients who underwent CoA repairs from 2005 to 2012 were reviewed. THAA was defined as PAA z-score <-3 and non-THAA group z-score ≥-3. Reintervention rates due to aortic obstruction were assessed using competing risk models and diameters of the aorta were compared with Mann-Whitney U tests. RESULTS: Fifty patients (36%) had THAA and 89 (64%) had non-THAA. The survival rate was 94% at 10 years. The overall reintervention rate at 10 years was 9% in the THAA group and 16% in the non-THAA group (P = .54). The catheter reintervention rate at ten years was 2% in the THAA group and 16% in the non-THAA group (P = .031). The surgical reintervention rate at ten years was 7% in the THAA group and 0% in the non-THAA group (P = .016). All 4 patients who required surgical reintervention were in the THAA group and 3 patients with PAA obstruction had preoperative PAA z-scores -3.6, -4.2, and -4.3. Follow-up echocardiograms showed PAA catch-up growth in the THAA group compared with the non-THAA group (preoperative z-score of -3.6 vs -2.3, and at 7 years of -1.1 vs -1.2; P < .001). CONCLUSIONS: Unrepaired PAA hypoplasia grows after CoA repair. Reintervention rates were comparable between groups but those with THAA had higher surgical reintervention rates.