Right Ventricular End-diastolic Volume Research Articles

Abstract 12930: Plasma Proteome Distinguishes Adaptive and Maladaptive Signaling in Repaired Tetralogy of Fallot

Introduction: Patients who have undergone tetralogy of Fallot (TOF) repair are subject to chronic volume and/or pressure overload, leading to a 40% probability of right ventricular (RV) failure by the third decade of life. We sought to identify a plasma proteome profile of the systemic response to right heart stress to better understand the mechanisms of RV failure and identify novel RV remodeling biomarkers. Methods: Patients with repaired TOF were recruited at the time of standard of care cardiac MRI (CMR) (N=14), and blood samples were collected. Plasma proteomics was assessed using data independent acquisition mass spectrometry. Proteins that were significantly affected between groups were identified and used for pathway enrichment analysis. Results: Patients underwent primary TOF repair at median 2.9m (IQR 0.8, 4.1) and CMR at median 16yrs (IQR 15, 18). Patients were grouped based on median indexed RV end diastolic volume (RVEDVi). Group 1: median RVEDVi 146ml/m 2 (IQR 139, 164) (N=9); Group 2: median RVEDVi 114ml/m 2 (IQR 104, 130) (N=5); p<0.001. RV ejection fraction was equal between groups (mean 56% vs. 55%; p=0.68). Forty-one proteins were significantly differentially abundant: 19 enriched in Group 1 and 22 enriched in Group 2 (Fig 1; p<0.05). Adaptive signaling in Group 1 was characterized by upregulation of proteins involved in antioxidant mechanisms (SOD1, TXN, PRDX1&2), calcium handling (S100A6, CALM1), and proteostasis (UBB, HSPA8). Maladaptive signaling was characterized by upregulation of glycolytic pathways (MDH1, PGK1) and heme protein oxidation (ALAD) and downregulation of proteins to counter acute stress (complements, ORM1&2). Conclusion: Patients with repaired TOF and moderate-severe RV dilation have a distinct maladaptive plasma proteomic profile independent of ejection fraction. These data suggest that profiling the circulating plasma proteome may be used to monitor disease progression prior to the onset of clinical heart failure.

Abstract 10990: The Prognostic Significance of Right Ventricular Dilation Assessed by Cardiac Magnetic Resonance Imaging in Heart Failure With Reduced Ejection Fraction

Background: Quantitative volumetric assessment of the right ventricle (RV) can significantly enhance risk stratification in heart failure (HF), especially with the increasing availability of cardiac MRI (CMR). The prognostic value of RV dilation measured by RV end diastolic volume indexed to body surface area (RVEDVi) is not yet well established. In this analysis, we investigate the prognostic significance of RVEDVi measured by CMR in a stable HF cohort. Methods: We conducted a retrospective analysis on the DERIVATE registry, a large cohort of stable HF patients who underwent baseline CMR and echocardiography assessment. We used the cut-off value 90ml/m 2 as the upper limit of normal for CMR-derived RVEDVi. The primary outcome was all-cause mortality (ACM), while the secondary outcome was a composite of ACM and/or heart failure hospitalization (HFH). A Cox proportional hazard model was used to evaluate the association with outcomes. Results: 2,447 patients with HF and reduced ejection fraction (HFrEF) were included, with a median follow-up time of 959 days (IQR: 560-1590). Mean LVEF was 34.0 ± 10.8, mean age was 59.8 ± 14.0 years and 42% were females. Mean RVEDVi was 75.0 ± 29.4 ml/m 2 and 23.2% had an RVEDVi >90 ml/m 2 . Elevated RVEDVi (>90 ml/m 2 ) was significantly associated with an increased risk for ACM (aHR= 1.40, 95% CI [1.17-1.67] p =0.01) and the composite of ACM/HFH (aHR= 1.40, 95% CI [1.03-1.90] p = 0.03). Conclusion: In a large cohort of HFrEF undergoing baseline CMR, elevated RVEDVi was associated with an increased risk of ACM and ACM and/or HFH, independent of LV systolic function.

Abstract 11710: Sex Differences in Right Ventricular Flow Dynamics and Kinetic Energy in Healthy Volunteers

Introduction: Accurate right ventricular (RV) flow and function is crucial for optimal cardiovascular health. However, research on RV flow and function has lagged behind that for the left ventricle. Whole-heart 4D flow cardiovascular magnetic resonance (CMR) uniquely quantifies simultaneous multi-directional phasic blood flow and kinetic energy (KE). Gender differences in these parameters have not been well studied and may contribute to the predilection for developing certain cardiovascular diseases among females. This study aims to compare RV flow and KE parameters in healthy female and male subjects. Methods: Healthy subjects from 2 centers (n=163) were prospectively recruited to undergo 4D flow CMR. RV flow components —direct flow, retained inflow, delayed ejection flow and residual volume —and KE (KE=1/2·ρ blood · V voxel · v 2 where ρ blood is blood density 1.06 g/cm 3 ; V voxel , voxel volume; and v , velocity) were calculated. All KE parameters were indexed to RV end-diastolic volume (KEi EDV ) and expressed in μJ/ml. KEi EDV parameters at physiologically relevant epochs (global [entire cycle], systole, diastole) and cardiac cycle time points (peak systole, peak E-wave, peak A-wave) were extracted from a time-resolved KEi EDV curve. Results: Compared to males (n=95, mean age 44 years old), females (n=68, mean age 42 years old) had higher RV ejection fraction but smaller RV volumes; higher RV direct flow (38 vs 34%, P=0.007) and delayed ejection flow (17 vs 15%, P=0.043) and lower RV residual volume (27 vs 33%, P=0.001). Females had higher global KEi EDV (8.9 vs 7.5μJ/ml, P=0.005), diastolic KEi EDV (6.7 vs 5.6μJ/ml, P<0.001), peak E-wave KEi EDV (14.4 vs 11.9μJ/ml, P<0.001) and E-wave/A-wave ratio (1.68 vs 1.30, P=0.028) than males. No differences were observed for RV retained inflow, RV peak systolic, average systolic and peak A-wave KEi EDV between gender. Conclusion: Females have higher RV direct flow and lower RV residual volume, higher preload-adjusted RV global, average diastolic, peak E-wave and E-wave/A-wave ratio KEi EDV , compared to males by 4D flow cardiovascular magnetic resonance imaging. These parameters that related to right heart efficiency may lead to further understanding of the sex-based predispositions to right heart disease.

Computational modelling of multi-temporal ventricular-vascular interactions during the progression of pulmonary arterial hypertension.

A computational framework is developed to consider the concurrent growth and remodelling (G&R) processes occurring in the large pulmonary artery (PA) and right ventricle (RV), as well as ventricular-vascular interactions during the progression of pulmonary arterial hypertension (PAH). This computational framework couples the RV and the proximal PA in a closed-loop circulatory system that operates in a short timescale of a cardiac cycle, and evolves over a long timescale due to G&R processes in the PA and RV. The framework predicts changes in haemodynamics (e.g. 68.2% increase in mean PA pressure), RV geometry (e.g. 38% increase in RV end-diastolic volume) and PA tissue microstructure (e.g. 90% increase in collagen mass) that are consistent with clinical and experimental measurements of PAH. The framework also predicts that a reduction in RV contractility is associated with long-term RV chamber dilation, a common biomarker observed in the late-stage PAH. Sensitivity analyses on the G&R rate constants show that large PA stiffening (both short and long term) is affected by RV remodelling more than the reverse. This framework can serve as a foundation for the future development of a more predictive and comprehensive cardiovascular G&R model with realistic heart and vascular geometries.

Impact of percutaneous mitral valve clipping on right ventricular functions

Abstract Background Percutaneous mitral valve clipping (PMVC) is being used successfully in the management of severe functional mitral regurgitation (MR) in patients with high surgical risk. However, the impact of (PMVC) on right ventricular volumes and functions is not clear. Aim The aim of the present study was to assess the impact of (PMVC) (on both short and intermediate terms) on right ventricular (RV) volumes and functions using trans-thoracic echocardiography. Methods The study population included 37 patients with severe (MR), and congestive heart failurewho wereat high surgical risk. The mean age was 61±14 years, 9 (24.3%)were males. (PMVC) was successfully done for all patients.All had clinical and echocardiographic follow up at 6 and 12-months post (PMVC). Results MR showed significant improvement after (PMVC). MRwas less than grade II in 29 (78%)of patients at 6 months and persisted at 12 months (P=0.0001). Similarly, tricuspid regurgitation (TR) showed marked improvement. Severe (TR) was seen in 29 patients (78%) before), but decreased to 7 patients (18.9%) after (PMVC) (P=0.004). Left ventricular ejection fraction (LVEF) improved from 32.63±13.35% at base line to 36.31±13.28% at 6 months (P=0.003). This was maintained at 12 months (35.38±91%) Table 1 shows the changes in RV end diastolic volume (RVDV); RV end systolic volume (RVSV) RV ejection fraction (RVEF), Tricuspid annulus plane systolic excursion (TAPSE), RV longitudinal systolic function by tissue Doppler imaging (TDI) as well as peak systolic pulmonary artery pressure (PASP). Conclusion (PMVC) induced a significant reverse remodeling of RV by decreasing both (RVDV) and (RVSV). Moreover, it improved longitudinal RV systolic function as well as (RVEF). This was maintained up to one year follow up. Funding Acknowledgement Type of funding sources: None.

3D-echocardiography for evaluation of the right ventricle in patients with repaired Tetralogy of Fallot: a comparison study with cardiac magnetic resonance

Abstract Background Patients with repaired Tetralogy of Fallot (ToF) need periodic instrumental assessments, due to complications they can meet during lifetime. Right ventricle (RV) dilation and dysfunction are some examples that explain why those patients regularly undergo Cardiac Magnetic Resonance (CMR), currently the gold standard method to detect these complications. Purpose 3D-echocardiography is an emerging tool to study RV, but there is little data supporting its use in congenital heart diseases. This study aimed at evaluating its accuracy in assessing RV dimensions and systolic function in ToF patients, in comparison to CMR. Methods 34 patients were prospectively enrolled after CMR performance. They all underwent standard 2D-echocardiography and Multi-Beat-ECG-triggered 3D Full-Volume acquisition. RV End Diastolic Volume (RV-EDV), End Systolic Volume and Ejection Fraction (RV-EF) were defined both in 3D-echocardiography and CMR. Results Post-hoc analysis of 3D images was performed through a vendor-independent software in 30 patients, resulting in a feasibility of 88%. A Bland-Altman analysis was performed, showing that 3D-echocardiography underestimates the RV-EDV/BSA of −27.39 mL/m2 on average (CI 95%: −29.46; −25.31, SD: 5.68 mL/m2), compared to CMR, as expected. However, when compared to normality reference, 3D-echocardiography identified RV dilatation with a significant correlation to CMR (V=0.66, p<0.001). Moreover, ROC curves showed that 3D-echo-RV-EDV/BSA is the echocardiographic measure that best correlates to CMR in detecting RV dilatation (AUC 1, CI 95%: 1.00; 1.00), followed by RVOT diameter in PLAX (AUC 0.89, CI 95%: 0.69; 0.99). Youden analysis suggested 77 mL/m2 (Se 95%, Sp 100%; J 0,95) as optimal limit to define RV dilatation in 3D-echocardiography. Regarding the RV-EF, the Bland-Altman analysis showed that 3D-echocardiography overestimates the RV-EF by 1,97% on average (CI 95%: 0.01; 3.95, SD: 5.43), compared to CMR. Secondly, accuracy of different echocardiographic parameters (both 2D and 3D) in detecting a RV systolic impairment was analyzed: ROC curves showed that RV-EF in 3D echocardiography is the measurement that best correlates to CMR in detecting RV dysfunction (AUC 0.92, CI 95%: 0.79–1.00), followed by Fractional Area Change (FAC) (AUC 0.78, CI 95%: 0.60; 0.96). Tricuspid Annular Plane Systolic Excursion (TAPSE) and tricuspid valve annular motion velocities in systole (S'-TDI), instead, showed very poor correlation. Conclusions 3D-echocardiography showed good agreement with CMR in defining RV dimensions and systolic function in ToF patients, even more than the bidimensional measurements cardiologists are used to. This could lead to a wider use of this tool in daily clinical practice, involving a reduction in the execution of the numerous CMR patients usually undergo. Moreover, it could be a valid instrument in patients with contraindication to CMR. Funding Acknowledgement Type of funding sources: None.

Right ventricular quantification using 3D echocardiography: a comparison with CMR

Abstract Background Volumetric and functional right ventricular (RV) indices such as ejection fraction (EF) and global strains are known independent predictors of adverse cardiovascular events. While cardiac magnetic resonance (CMR) imaging remains the reference standard for volume quantification, echocardiography is more accessible and allows for rapid ventricular assessment. Compared to conventional 2D echocardiography, 3D echocardiography (3DE) enables full volume acquisitions and the ability to circumvent geometric assumptions. Given the complexity of RV geometry and sensitivity to image plane positioning, this advantage offers the potential to obtain more accurate diagnostic measurements. Purpose Tools for RV analysis in 3DE have been less extensively studied compared to those for the left ventricle (LV). We sought to quantify discrepancies in RV indices derived from 3DE and CMR. Methods Transthoracic real-time 3DE and cine CMR imaging were performed in 20 prospectively recruited participants (12 patients with acquired cardiac disease and 8 healthy controls), <1 hour apart. Dynamic 3D biventricular models were constructed semi-automatically from CMR by identifying fiducial landmarks, correcting in-plane breath-hold mis-registrations, and interactively fitting contours to the endocardial and epicardial borders on long- and short-axis slices. For 3DE, right ventricular endocardial models were created by fitting contours on 2D image planes resampled from the 3D volume at end-diastole and end-systole, which were subsequently tracked over one cardiac cycle (Figure 1). RV indices including end-diastolic volume (EDV), end-systolic volume (ESV), EF, global longitudinal strain (GLS), and global circumferential strain (GCS) were calculated from the 3DE- and CMR-derived 3D geometric models and compared. Paired-sample t-tests were performed to identify statistically significant differences (where P<0.05), and intraclass correlation coefficients (ICC) for absolute agreement were computed to assess the reliability for each measurement. Results Differences (mean ± SD) in RV indices between 3DE and CMR, with corresponding ICCs are presented in Table 1. Statistically significant differences in RV EDV, ESV, EF, and GLS were observed, with 3DE consistently underestimating volumes and overestimating function when compared to CMR. Although a statistically significant difference in RV GCS was not observed, a low ICC score indicated poor reliability. Conclusions Volume underestimation in RV indices between 3DE and CMR were found to be larger than those previously reported for the LV, which is likely due to the increased geometric complexity and surface area to volume ratio for the RV. Moreover, 3DE tends to overestimate RV function in terms of EF and GLS, which may impact treatment pathways if used in a clinical setting. Recognising systematic differences between modalities reinforces the need to further develop 3DE technologies for more accurate RV quantification. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Health Research Council (HRC) of New Zealand;National Heart Foundation (NHF) of New Zealand

Right ventricular reverse remodeling after mitral valve transcatheter edge-to-edge repair

Abstract Background Right ventricular dysfunction (RVD) is an important predictor for outcome in patients undergoing transcatheter mitral or tricuspid valve edge-to-edge repair (M/T-TEER). Due to the unique anatomy and contraction pattern of the RV, three-dimensional echocardiography (3DE) has emerged as a valuable tool in the assessment of RV function. While 3DE data showed RV reverse remodeling (RVRR) following T-TEER, respective data are absent in the setting of M-TEER. Purpose We sought to assess RVRR after M-TEER using 3DE comparing baseline and follow-up RV measurements. Methods Patients undergoing M-TEER treatment for relevant MR between August 2016 and February 2021 with eligible transthoracic 3DE of the RV at baseline and follow-up were included in the study. 3DE comprised RV end-diastolic and end-systolic volumes (RVEDV3D, RVESV3D), total RV stroke volume (RVSV3D) and RV ejection fraction (RVEF3D). Further, RV length (RVL3D) as well as RV basal (RVbase3D) and mid-ventricular diameters (RVmid3D) were derived from 3DE. RVRR was assessed as change in the respective 3DE parameters of RV dimensions between baseline and follow-up. Results A total of 66 patients (45.5% female; age 78.5±8.2 years; EuroScore II 4.6±3.6%) were included in the study. From baseline to latest available follow-up (median interval 364 days, interquartile range 180–728 days), a significant reduction of RVEDV3D and RVESV3D was observed (RVEDV3D 140.2±50.2 ml to 128.1±46.1 ml, p<0.01 and RVESV3D 93.1±37.8ml to 87.1±34.7ml, p=0.04). The decrease in 3D-derived linear RV dimensions primarily occurred in the septolateral direction, while RV length did not change significantly. The observed RVRR was associated with significant reduction of TR severity. Of note, patients with RVRR showed also left ventricular reverse remodeling (LVRR). Conclusion M-TEER is an effective treatment option for patients with MR which leads to LVRR and RVRR. Funding Acknowledgement Type of funding sources: None.

Right ventricular mechanics and its association with symptoms in transcatheter aortic valve replacement candidates: a three-dimensional echocardiography study

Abstract Aortic valve stenosis is one of the most prevalent valvular disease with significant clinical burden. While it is initially a disorder of the left ventricle (LV), long-term effects of the disease also affect the right ventricle (RV) as well. Nevertheless, data are scarce regarding the changes of RV mechanics and their association with symptomatic status of the patients. 3D echocardiography allows a more detailed assessment of the RV, which may unveil distinct changes of its morphology and function in this clinical setting. Accordingly, our aim was to examine LV and RV mechanics in TAVR candidate patients with severe aortic stenosis using three-dimensional (3D) echocardiography. Seventy patients (51% male, age: 80±6 years) were enrolled. Detailed medical history and symptomatic status were obtained. Beyond conventional transthoracic echocardiographic protocol, 3D loops were also acquired. We measured 3D LV and RV end-diastolic volume indexed to body surface area (EDVi), ejection fraction (EF) and global longitudinal (GLS) using dedicated software. Furthermore, we have determined 3D RV global longitudinal (RV GLS) and circumferential strain (RV GCS) using the ReVISION method. LV EF (r=0.28, p<0.05) and LV GLS (r=−0.26, p<0.05) significantly correlated with age, while RV EF (r=0.21, p=0.11), RV GLS (r=−0.17, p=0.19) and RV GCS (r=−0.07, p=0.61) did not show association with it. 41% (n=29) of the patient population mentioned angina or had syncope. Patients with these symptoms had comparable LV EDVi (73±23 vs. 69±25 mL/m2, p=0.47), LV EF (47±15 vs. 51±10%, p=0.14) and LV GLS (−13.6±4.8 vs. −14.8±2.6%, p=0.25) to those who did not mention these complaints. On the other hand, patients with angina or syncope in their medical history had significantly lower RV EDVi (58±13 vs. 70±23 mL/m2, p<0.05), while having significantly higher RV EF (46±10 vs. 52±7%, p<0.05). Moreover, symptomatic patients had significantly lower RV GCS (−15.7±5.6 vs. −19.6±5.3%, p<0.01), while RV GLS did not differ (−15.8±4.8 vs. −17.4±4.1%, p=0.17). Patients with severe aortic stenosis have marked changes in not only the LV, but the RV mechanics as well. While the symptomatic status does not seem to be associated with LV morphology and function, patients with angina or syncope had distinct changes in RV size and the contraction pattern of the chamber. Funding Acknowledgement Type of funding sources: None.

Prediction of response to cardiac resynchronization therapy using cardiac magnetic resonance imaging in non-ischemic dilated cardiomyopathy

Abstract Background Cardiac resynchronization therapy (CRT) is a well-established therapy for symptomatic heart failure with reduced ejection fraction, but the response is different for individuals. Although many modalities have been conducted to predict CRT response, cardiac magnetic resonance (CMR) to predict CRT response has still insufficient usefulness. Purpose We determine whether the parameters including late gadolinium enhancement (LGE) identified in CMR could act as predictors of CRT response. Methods We retrospectively investigated 124 patients with non-ischemic dilated cardiomyopathy who underwent CMR before CRT implantation between Jan 2010 and July 2021 in a single center. CRT response was defined as a decrease in left ventricular end-systolic volume (LVESV) >15% on echocardiography after at least 3 months after CRT implantation. Results Among the study population (mean age 65.7±11.2 years, mean EF 25±6.5%, 50% of female), 85 (69%) patients were defined as CRT responder. The CRT responders had more left bundle branch block (LBBB) compared with non-responders [79 (92.9%) vs. 23 (59.0%), p<0.001], but there was a no difference of QRS duration (158.7 vs 165.0ms, p=0.054) between two groups. CMR analysis showed that there were no significant differences in the left ventricular (LV) chamber volume and LV ejection fraction between CRT-responder and non-responder. However, the right ventricular (RV) chamber volume was smaller (RV end-diastolic volume index, 86.3 vs 103.5 ml/m2, p=0.039; RV end-systolic volume index, 49.3 vs 68.5 ml/m2, p=0.013) and the RV ejection fraction (RVEF) was higher (46.9 vs 37.6%, p=0.002) in CRT-responders compared with non-responders. The LGE on CMR was more shown in non-responders than in CRT-responders [33 (84.6%) vs 45 (52.9%), p<0.001]. In CMR parameters, RV dysfunction (RVEF <45%) [Odds ratio (OR), 0.21 (0.05–0.93), p=0.045] and LGE [OR, 0.21 (0.05–0.58), p=0.01] were significantly associated with poor CRT response. Conclusions The presence of LGE and RV dysfunction on CMR were associated with poor CRT response in patients with non-ischemic dilated cardiomyopathy. Further investigation with CMR for pre-CRT patients is needed to support these results. Funding Acknowledgement Type of funding sources: None.

Ratio between left and right ventricular end-diastolic volumes and outcomes in patients with heart failure and preserved ejection fraction

Abstract Background Reference left and right ventricular (LV/RV) volumes normalized to age and gender have been published. However, the relative dilation of the LV compared to the RV in patients with heart failure (HF) symptoms and its prognostic association have not been evaluated. Purpose The present study investigated the relative dilation of the LV compared to the RV among patients with HF and preserved LV ejection fraction (HFpEF). We explored the association between LV/RV ratio (defined as the ratio between LV end-diastolic volume index [LVEDVi] and RV end-diastolic volume index [RVEDVi]) and outcomes. Methods Clinical and imaging data from consecutive ambulatory patients diagnosed with HFpEF between April 2011 and November 2021, and undergoing a cardiac magnetic resonance examination were retrieved. The endpoints were 1) all-cause death or first HF hospitalization, and 2) cardiovascular death or first HF hospitalization, 3) repeated HF hospitalizations. Results A total of 159 patients (median age 58 years [interquartile range 49–69], 64% men) were included. Median LVEF was 60% (54–70%), and the LV/RV ratio was 1.21 (1.07–1.40). Over a 3.5-year follow-up (1.5–5.0), all-cause death or first HF hospitalization occurred in 23 patients (15%) and cardiovascular death or first HF hospitalization in 22 (14%). Spline curve analysis showed a bimodal relationship between LV/RV and both outcomes, with a steep increase in risk <1.0 and ≥1.4 (Figure 1). Accordingly, patients with either LV/RV <1.0 or ≥1.4 had a much shorter survival free from both endpoints than patients with LV/RV 1.0–1.3 (Figure 2). An LV/RV <1 was associated with a higher risk of all-cause death or first HF hospitalization (hazard ratio [HR] 5.95, 95% confidence interval [CI] 1.67–21.28; p=0.006) and a higher risk of cardiovascular death or first HF hospitalization (HR 5.68, 95% CI 1.58–20.35; p=0.008). Furthermore, an LV/RV ≥1.4 was associated with a higher risk of all-cause death or first HF hospitalization (HR 4.10, 95% CI 1.58–10.61; p=0.004) and a higher risk of cardiovascular death or first HF hospitalization (HR 3.71, 95% CI 1.41–9.79; p=0.008). Nine patients (6%) had more than 1 HF hospitalization. The crude incidence of HF hospitalizations was much higher in patients with an LV/RV <1.0 (16.6 per 100 patient/years) or ≥1.4 (10.29 per 100 patient/years) than in those with LV/RV 1–1.3 (1.88 per 100 patient/years). Multivariable binomial negative regression showed significant association between LV/RV and recurrent HF hospitalizations after adjustment by age, gender and New York Heart Association class: LV/RV <1.0 vs. 1.0–1.3, incidence rate ratio 9.0 per 100 patient/years (4.1–19.6), p<0.001; LV/RV ≥1.4 vs. 1.0–1.3, incidence rate ratio 5.3 per 100 patient/years (1.5–8.4), p=0.009. Conclusions Among patients with HFpEF, an RVEDVi larger than the LVEDVi, or an LVEDVi ≥40% larger than the RVEDVi were significantly associated with worse outcomes. Funding Acknowledgement Type of funding sources: None.

Accuracy of new transthoracic 3D echocardiographic automated algorithm for right ventricle quantification in children with congenital heart disease

Management of many congenital heart diseases (CHD) depends on right ventricle (RV) assessment for which cardiac magnetic resonance (CMR) remains the gold standard. The objective of this study was to assess feasibility and reproducibility of a new semi-automated algorithm to quantify RV (4D auto RVQ) from 3D transthoracic echocardiography (3D TTE) in a pediatric population, and to compare measurements with those obtained from CMR. In all, 90 infants were prospectively included (age 7.5 years, 3–18). Fifteen healthy infants and 75 patients with CHD (30 repaired TOF, 25 ASD, 8 dilated pulmonary valve stenosis, 7 tricuspid regurgitation, 3 APVR, and 2 repaired TAC). All patients underwent 2D and 3D TTE (Vivid E95, GE Healthcare). RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV ejection volume (RVEV) and RV ejection fraction (RVEF) were analyzed by 4D auto RVQ and compared with measurements from 18 patients who underwent CMR exams for the follow up of their cardiopathy. 4D auto RVQ was feasible in 87 infants (96.7%). In 3 patients 4D auto RVQ was unable to detect RV contouring due to inadequate image quality. Manual contour adjustment was necessary in 81 cases (80%). Mean time of analysis including the time of manual adjustment was 62 seconds. RV was enlarged in 65 of 75 patients with CHD (mean 95 ml/m 2 , 62–165 ml/m 2 ). Good correlation for RVEDV, RVESV, RVEV and RVEF was found between 4D auto RVQ and CMR (r = 0.89–0.99, all P < 0.0001). 4D auto RVQ underestimated RVEDV/BSA of 8 ml/m 2 and RVEF by 6%, and overestimated RVESV/BSA of 9 ml/m 2 . Intraobserver and interobserver variability were low (4.7% and 8.9% respectively) ( Fig. 1 ). 4D auto RVQ is a promising tool for assessment of RV volume and function in children. Such simple and non-invasive exam could reduce the practice of CMR imaging during the follow up of children with CHD.

Three-Dimensional Echocardiography Right Ventricular Volumes and Ejection Fraction Reference Values in Children: A North American Multicentre Study.

Three-dimensional echocardiography (3DE) evaluation of right ventricular (RV) volumes and ejection fraction (EF) is increasingly used for clinical serial assessments and management in children. This study aims to generate sex-specific reference values and z-score equations for RV volumetric parameters, independent of age and body size indices, derived from multiple populations across North America. We prospectively recruited 455 healthy children (ages 0 to 18 years) from 5 centres. 3DE of the RV were acquired using various vendors with analyses performed offline using vendor-independent software. 3DE datasets with all walls of the RV endocardium visible were included. We reported data on RV EF, and generated z scores for end-systolic volumes (ESV), end-diastolic volumes (EDV) and stroke volume (SV). Differences between the sexes were explored. Of 455 3DE datasets, 312 (68%) met imaging criteria for analysis. Median age was 10.1 years (interquartile ratio [IQR]: 5.6, 14.0) with 17% being younger than 3 years of age. The mean and standard deviation for RV EDV, ESV, and SV for male and female patients were reported. We provided a downloadable z-score calculator with height and weight as independent variables to facilitate clinical utility. Although statistically significant differences between male and female RVEF was present (female 52.9 ± 3.9% vs male 51.6 ± 3.5%, P= 0.006), after adjusting for age, height, and weight, the magnitude of difference was clinically insignificant. Sex-specific reference values for pediatric RV volumes and EF, and z-score equations were derived from children 3DE datasets across 5 centres in North America.

Comparison of Cadmium Zinc Telluride ECG-gated SPECT equilibrium radionuclide angiocardiography to magnetic resonance imaging to measure right ventricular volumes and ejection fraction in patients with cardiomyopathy

AimsThe objective of this study was to determine the accuracy of right ventricular function (RVF) assessed by Cadmium Zinc Telluride ECG-gated SPECT equilibrium radionuclide angiocardiography (CZT-ERNA). Methods and resultsTwenty-one consecutive patients with cardiomyopathy (aged 54 ± 19 years; 62% male) were included. RV ejection fraction (EF) and volumes were analyzed by CZT-ERNA and compared with values obtained by cardiac magnetic resonance imaging (CMR). Mean values were not different between CZT-ERNA and MRI for RVEF (48.1 ± 10.4% vs 50.8 ± 10.0%; P = .23). Significant correlations (P < .0001) were observed between CZT-ERNA and MRI for RVEF, RV end-diastolic volume, and end-systolic volume (r = 0.81, r = 0.93, and r = 0.96, respectively). Bland–Altman analysis showed a mean difference (bias) between CZT-ERNA and MRI for RVEF of -2.69% (95% CI − 5.35 to − 0.42) with good agreement between the 2 techniques (limits of agreement, −14.3 to 8.99). Intraobserver and interobserver reproducibility of RVF measured by CZT-ERNA was high. ConclusionCZT-ERNA provides accurate, reproducible assessment of RVF and appears as a good alternative to cardiac magnetic resonance for the evaluation of the magnitude of RVF in patients with cardiomyopathy.

Abnormal flow conduction through pulmonary arteries is associated with right ventricular volume and function in patients with repaired tetralogy of Fallot: does flow quality affect afterload?

Flow through the proximal pulmonary arteries (PAs) of patients with repaired Tetralogy of Fallot (TOF) is known to be highly disordered and associated with significant regurgitation. The purpose of this study was to evaluate 4D-Flow MRI-derived viscous energy loss [Formula: see text])-as a result of non-efficient flow propagation, and relate this parameter to standard right ventricular (RV) size and function markers in patients with repaired TOF. Thirty-five patients with TOF and 14 controls underwent comprehensive 4D-Flow MRI evaluation for qualitative flow analysis and to calculate [Formula: see text] in the main and right pulmonary arteries. Sampled [Formula: see text] indices were correlated with the MRI-derived RV size and functional indices. All patients with TOF exhibited abnormal, supra-physiologic helical/vortical formations in the PAs. Patients with TOF had significantly increased peak systolic [Formula: see text] (8.0 vs 0.5 mW, p < 0.001), time-averaged [Formula: see text] (2.5 vs. 0.2 mW, p < 0.001), and peak systolic [Formula: see text] indexed to stroke volume (0.082 vs. 0.012 mW/mL, p < 0.001). [Formula: see text] indexed to stroke volume correlated with the RV end-diastolic volume (R = 0.68, p < 0.001), end-systolic volume (R = 0.62, p < 0.001), ejection fraction (R = -0.45, p = 0.002), and cardiac index (R = 0.45, p = 0.002). The mean estimated energy loss due to [Formula: see text] with regard to input RV mechanical power was 4.7%. This study demonstrates that patients with repaired TOF have highly abnormal flow conduction through the PAs which result into extensive viscous energy loss. This significant flow-mediated energy loss is associated with the RV volume and function, and might represent considerable loss of mechanical power generated by each cardiac cycle. Future studies are required to assess whether the abnormal flow conduction adds to the RV afterload and remodeling. • Abnormal flow patterns through proximal pulmonary arteries in patients with TOF are associated with excessive viscous energy loss. • Inefficient flow conduction is associated with the RV dilation and reduced function and might contribute to the RV adaptive remodeling.

Exercise-Induced Atrial Remodeling in Female Amateur Marathon Runners Assessed by Three-Dimensional and Speckle Tracking Echocardiography.

Endurance athletes have an increased risk of atrial remodeling and atrial arrhythmias. However, data regarding atrial adaptation to physical exercise in non-elite athletes are limited. Even less is known about atrial performance in women. We aimed to elucidate exercise-induced changes in atrial morphology and function in female amateur marathon runners using three-dimensional (3D) echocardiography and two-dimensional (2D) speckle tracking echocardiography (STE). The study group consisted of 27 female (40 ± 7 years) amateur athletes. Right (RA) and left atrial (LA) measures were assessed three times: 2–3 weeks before the marathon (stage 1), immediately after the run (stage 2), and 2 weeks after the competition (stage 3). Directly after the marathon, a remarkable RA dilatation, as assessed by RA maximal volume (RAVmax, 31.3 ± 6.8 vs. 35.0 ± 7.0 ml/m2; p = 0.008), with concomitant increase in RA contractile function [RA active emptying fraction (RA active EF), 27.7 ± 8.6 vs. 35.0 ± 12.1%; p = 0.014; RA peak atrial contraction strain (RA PACS) 13.8 ± 1.8 vs. 15.6 ± 2.5%; p = 0.016] was noticed. There were no significant changes in LA volumes between stages, while LA active EF (34.3 ± 6.4 vs. 39.4 ± 8.6%; p = 0.020), along with LA PACS (12.8 ± 2.1 vs. 14.9 ± 2.7%; p = 0.002), increased post race. After the race, an increase in right ventricular (RV) dimensions (RV end-diastolic volume index, 48.8 ± 11.0 vs. 60.0 ± 11.1 ml/m2; p = 0.001) and a decrease in RV function (RV ejection fraction, 54.9 ± 6.3 vs. 49.1 ± 6.3%; p = 0.006) were observed. The magnitude of post-race RV dilatation was correlated with peak RA longitudinal strain deterioration (r = −0.56, p = 0.032). The measured parameters did not differ between stages 1 and 3. In female amateur athletes, apart from RV enlargement and dysfunction, marathon running promotes transient biatrial remodeling, with more pronounced changes in the RA. Post-race RA dilatation and increment of the active contraction force of both atria are observed. However, RA reservoir function diminishes in those with post-race RV dilation.

Impact of reductive tricuspid ring annuloplasty on right ventricular size, geometry and strain in an ovine model of functional tricuspid regurgitation.

OBJECTIVESReductive ring annuloplasty of the tricuspid annulus represents the contemporary surgical approach to functional tricuspid regurgitation (FTR). We set out to investigate the influence of moderate reductive tricuspid ring annuloplasty on tricuspid regurgitation and right ventricular (RV) size, geometry and strain in an ovine model of chronic FTR.METHODSEight healthy Dorsett male sheep (62.8 + 2kg) underwent a left thoracotomy for placement and tightening of pulmonary artery band to at least double proximal pulmonary artery blood pressure. After 8 weeks of recovery, animals underwent sternotomy, epicardial echocardiography and sonomicrometry crystal implantation. Six crystals were placed around tricuspid annulus and 13 on RV free wall epicardium along 3 parallels defining 3 wall regions (basal, mid and lower) and 1 on the RV apex. All animals underwent beating heart implantation of 26 mm MC3 annuloplasty ring during a second cardiopulmonary bypass run after baseline data acquisition. Simultaneous haemodynamic, sonomicrometry and echocardiography data were acquired at Baseline and after reductive tricuspid ring annuloplasty.RESULTSImplantation of reductive ring annuloplasty resulted in 47 ± 7% annular area reduction (996 ± 152 mm vs 516 ± 52 mm2, P = 0.0002) and significantly decreased RV end-diastolic volume (185 ± 27 vs 165 ± 30 ml, P = 0.02). Tricuspid ring annuloplasty effectively reduced FTR grade (3.75 ± 0.6 vs 0.3 ± 0.5, P = 0.00004) and had little influence on RV function, cross-sectional area, radius of curvature or free wall regional strains.CONCLUSIONSIn adult sheep with 8 weeks of pulmonary artery banding and FTR, tricuspid annulus reduction of 47% with prosthetic ring annuloplasty effectively abolished FTR while maintaining regional RV function and strain patterns.

Right ventricular volume-strain loops using 3D echocardiography-derived mesh models: proof-of-concept application on patients undergoing different types of open-heart surgery.

Right ventricular (RV) function can be quantified by right heart catheterization-derived pressure-volume loops. While this technique is invasive, echocardiography-based volume-strain loops (VSLs) potentially reflect a non-invasive alternative. In this study, an approach to generate VSLs from volume and multidimensional strain data of 3D echocardiography-derived RV mesh models is evaluated with regard to feasibility and reproducibility. In a retrospective cohort study design, 3D intraoperative transesophageal echocardiograms of twenty-three patients undergoing aortic valve surgery (AVS) and eighteen patients undergoing off-pump coronary artery bypass (OPCAB) grafting were available prior to sternotomy and after sternal closure. RV meshes were generated using 3D speckle-tracking. Custom-made software quantified the meshes' volumes, global longitudinal (RV-GLS) and global circumferential strain (RV-GCS) for VSL generation. Linear regression of systolic VSLs yielded slopes, intercepts and systolic areas. Polynomial regression of two orders was used to analyze systolic-diastolic coupling at 10% increments of the RV end-diastolic volume (RVEDV). Reproducibility was analyzed by fourfold double-measurements of four datasets. VSL calculation was feasible from all included 3D datasets. RV-GLS remained unaltered, but RV-GCS worsened in AVS [abs. diff. (∆) 3.9%, P<0.01] and OPCAB patients (∆4.5%, P<0.001). While RV-GCS systolic areas were markedly reduced at the end of AVS (∆268mL%, P<0.01) and OPCAB (∆185mL%, P<0.001), RV-GCS slopes did not change. Systolic-diastolic uncoupling was not observed, but in trend, decreased diastolic RV-GCS after AVS (P=0.06) and increased diastolic RV-GCS after OPCAB (P=0.06) were observed. Intraclass correlation coefficients (0.84-0.98) and coefficients of variation (6.4-11.8%) indicated good reproducibility. RV VSL generation using 3D echocardiography-derived mesh models is feasible. Longitudinal and circumferential strain vectors yield intrinsically different VSL indices. In future investigations, VSLs of multidimensional strains could provide further insight into periprocedural changes of RV mechanics.

QRS fragmentation versus QRS prolongation in predicting right ventricular enlargement and dysfunction in children and adults with repaired Tetralogy of Fallot

Patients with repaired Tetralogy of Fallot (rTOF) have risks of late life-threatening sequelae, including right ventricular (RV) dilation and failure, arrhythmias, and sudden death. QRS prolongation is a well-known ECG predictor of these outcomes but has poor sensitivity for mortality. Growing evidence demonstrates QRS fragmentation (fQRS) as a better prognostic marker for mortality in adults with rTOF, though the two markers have not been directly compared as correlates for CMR abnormalities. Additionally, fQRS has never been studied in pediatric TOF. This single institution retrospectively reviewed 138 CMRs in rTOF patients (median age 21.7 years) who had a corresponding 12-lead ECG within 1 year. fQRS was defined as ≥3 R-waves/notches in the R/S complex (>2 in right bundle branch block) in ≥2 contiguous leads. QRS prolongation was defined as QRS ≥160 ms. Nearly half (46%) the sample had fQRS (42.1% of pediatric subgroup), and 26% had QRS prolongation. Both markers were significantly associated with reduced RV ejection fraction (EF%) (p < 0.01) and larger RV end-diastolic volumes (p < 0.01). QRS prolongation alone predicted lower LV EF% (p = 0.02). Regression analyses showed both QRS prolongation (p < 0.01) and fQRS (p < 0.01) independently associated with reduced RV EF%; QRS prolongation alone predicted RV dilation (p < 0.01). We concluded that both QRS prolongation and fQRS are equivalent as significant markers of RV dysfunction in rTOF patients. QRS prolongation may be a better surrogate for RV dilation specifically. fQRS was frequently seen in children with rTOF and was significantly associated with similar late structural sequelae.

Genome-wide association analysis reveals insights into the genetic architecture of right ventricular structure and function.

Right ventricular (RV) structure and function influence the morbidity and mortality from coronary artery disease (CAD), dilated cardiomyopathy (DCM), pulmonary hypertension and heart failure. Little is known about the genetic basis of RV measurements. Here we perform genome-wide association analyses of four clinically relevant RV phenotypes (RV end-diastolic volume, RV end-systolic volume, RV stroke volume, RV ejection fraction) from cardiovascular magnetic resonance images, using a state-of-the-art deep learning algorithm in 29,506 UK Biobank participants. We identify 25 unique loci associated with at least one RV phenotype at P < 2.27 ×10-8, 17 of which are validated in a combined meta-analysis (n = 41,830). Several candidate genes overlap with Mendelian cardiomyopathy genes and are involved in cardiac muscle contraction and cellular adhesion. The RV polygenic risk scores (PRSs) are associated with DCM and CAD. The findings substantially advance our understanding of the genetic underpinning of RV measurements.