Right Ventricular End-systolic Volume Research Articles

An Explainable Machine Learning Approach Reveals Prognostic Significance of Right Ventricular Dysfunction in Nonischemic Cardiomyopathy

ObjectivesThe authors implemented an explainable machine learning (ML) model to gain insight into the association between cardiac magnetic resonance markers and adverse outcomes of cardiovascular hospitalization and all-cause death (composite endpoint) in patients with nonischemic dilated cardiomyopathy (NICM). BackgroundRisk stratification of patients with NICM remains challenging. An explainable ML model has the potential to provide insight into the contributions of different risk markers in the prediction model. MethodsAn explainable ML model based on extreme gradient boosting (XGBoost) machines was developed using cardiac magnetic resonance and clinical parameters. The study cohorts consist of patients with NICM from 2 academic medical centers: Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women’s Hospital (BWH), with 328 and 214 patients, respectively. XGBoost was trained on 70% of patients from the BIDMC cohort and evaluated based on the other 30% as internal validation. The model was externally validated using the BWH cohort. To investigate the contribution of different features in our risk prediction model, we used Shapley additive explanations (SHAP) analysis. ResultsDuring a mean follow-up duration of 40 months, 34 patients from BIDMC and 33 patients from BWH experienced the composite endpoint. The area under the curve for predicting the composite endpoint was 0.71 for the internal BIDMC validation and 0.69 for the BWH cohort. SHAP analysis identified parameters associated with right ventricular (RV) dysfunction and remodeling as primary markers of adverse outcomes. High risk thresholds were identified by SHAP analysis and thus provided thresholds for top predictive continuous clinical variables. ConclusionsAn explainable ML-based risk prediction model has the potential to identify patients with NICM at risk for cardiovascular hospitalization and all-cause death. RV ejection fraction, end-systolic and end-diastolic volumes (as indicators of RV dysfunction and remodeling) were determined to be major risk markers.

4D flow cardiovascular magnetic resonance recovery profiles following pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension

BackgroundFour-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) allows comprehensive assessment of pulmonary artery (PA) flow dynamics. Few studies have characterized longitudinal changes in pulmonary flow dynamics and right ventricular (RV) recovery following a pulmonary endarterectomy (PEA) for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This can provide novel insights of RV and PA dynamics during recovery. We investigated the longitudinal trajectory of 4D flow metrics following a PEA including velocity, vorticity, helicity, and PA vessel wall stiffness.MethodsTwenty patients with CTEPH underwent pre-PEA and > 6 months post-PEA CMR imaging including 4D flow CMR; right heart catheter measurements were performed in 18 of these patients. We developed a semi-automated pipeline to extract integrated 4D flow-derived main, left, and right PA (MPA, LPA, RPA) volumes, velocity flow profiles, and secondary flow profiles. We focused on secondary flow metrics of vorticity, volume fraction of positive helicity (clockwise rotation), and the helical flow index (HFI) that measures helicity intensity.ResultsMean PA pressures (mPAP), total pulmonary resistance (TPR), and normalized RV end-systolic volume (RVESV) decreased significantly post-PEA (P < 0.002). 4D flow-derived PA volumes decreased (P < 0.001) and stiffness, velocity, and vorticity increased (P < 0.01) post-PEA. Longitudinal improvements from pre- to post-PEA in mPAP were associated with longitudinal decreases in MPA area (r = 0.68, P = 0.002). Longitudinal improvements in TPR were associated with longitudinal increases in the maximum RPA HFI (r=-0.85, P < 0.001). Longitudinal improvements in RVESV were associated with longitudinal decreases in MPA fraction of positive helicity (r = 0.75, P = 0.003) and minimum MPA HFI (r=-0.72, P = 0.005).ConclusionWe developed a semi-automated pipeline for analyzing 4D flow metrics of vessel stiffness and flow profiles. PEA was associated with changes in 4D flow metrics of PA flow profiles and vessel stiffness. Longitudinal analysis revealed that PA helicity was associated with pulmonary remodeling and RV reverse remodeling following a PEA.

Cardiovascular magnetic resonance imaging characteristics in patients with methamphetamine-associated cardiomyopathy

BackgroundMethamphetamine-associated cardiomyopathy (MA-CMP) is an increasingly recognised aetiology of cardiomyopathy. Cardiovascular magnetic resonance (CMR) is a specialised cardiac imaging modality commonly used in assessment of cardiomyopathy. We aimed to identify specific CMR features associated with MA-CMP.MethodsA retrospective cohort study of CMR scans was performed in a single centre between January 2015 and December 2020. Thirty patients with MA-CMP who had undergone CMR were identified. MA-CMP was defined as those with a history of significant methamphetamine use hospitalised with acute decompensated heart failure (other causes of cardiomyopathy excluded). A retrospective analysis of index admission CMRs was performed. All studies were performed on a 1.5 T CMR scanner.ResultsThe mean age of MA-CMP patients was 43.7 ± 7.5 years, and 86.7% were male. The mean left ventricular (LV) volume obtained in this cohort was consistent with severe LV dilatation (LV end-diastolic volume (334 ± 99 ml); LV end-systolic volume: 269 ± 98 ml), whilst the right ventricular (RV) volume indicated moderate-to-severe dilatation (RV end-diastolic volume: 272 ± 91 ml; RV end-systolic volume: 173 ± 82 ml). Mean LV ejection fraction (20.9 ± 9.2%) indicated severe LV dysfunction, with moderate-to-severe RV dysfunction also detected (RV ejection fraction: 29.4 ± 13.4%). 22 patients (73.3%) had myocardial late gadolinium enhancement (LGE), of which 59.1% were located in the mid-wall, with all of these involving the interventricular septum. 22.7% displayed localised regions of sub-endocardial LGE in a variety of locations, and 18.2% had transmural regions of LGE that were located in the inferior and inferolateral segments. 6 patients (20%) had intracardiac thrombus (4 LV, 2 both LV and RV).ConclusionMA-CMP was associated with severe biventricular dilatation and dysfunction, with a high prevalence of intraventricular thrombus. This cohort study highlights that MA-CMP patients have a high prevalence of CMR findings.

Assessment of left ventricular mechanics in right ventricular overload using in silico rat models

Abstract Background To preserve cardiac function in overload conditions, the RV adapts by developing muscular hypertrophy through progressive tissue remodelling. This process may lead to a vicious cycle with detrimental effects on RV diastolic and systolic function, as seen in pulmonary arterial hypertension (PAH) patients [1]. However, how RV overload affects LV function and remodelling remains an open question [2]. Computational models of cardiac physiology offer an opportunity for investigating mechanisms difficult or impossible to analyse otherwise due to the existence of overlapping factors and technical limitations. Aim This study aims to assess the acute effects of RV overload and increased myocardial passive stiffness on the LV mechanical properties in an anatomically-based computational model of healthy rat heart. Methods A computational simulation pipeline of cardiac mechanics based on the Holzapfel-Ogden model has been implemented using MR images from a healthy rat. Whereas LV function was modelled realistically using catheter measurements conducted on the same subject than the MR imaging, RV function was based on representative literature values for healthy and PAH rats with RV overload. The following cases were defined (Fig. 1): CTRL, with normal RV function; PAH1, with 30% increase in RV ESV (end-systolic volume) and 15% increase in RV ESP (end-systolic pressure) in comparison to CTRL; and PAH2, with 60% increase in RV ESV and 30% increase in RV ESP compared to CTRL. The cardiac cycle was simulated for all cases whilst fitting the experimentally measured LV pressure and volume values from a healthy rat, which allowed quantifying the effects of RV overload on LV function. Results The increase of average circumferential strain in the LV correlated with the degree of RV overload simulated (CTRL: −8.7%, PAH1: −8.9%, PAH2: −9.2%), whilst average radial (CTRL: 35.2%, PAH1: 34.8%, PAH2: 30.3%) and longitudinal strains decreased (CTRL: −7.7%, PAH1: −7.4%, PAH2: −6.6%), as seen in Fig.2. However, regional differences in strain were significant: under RV overload conditions, circumferential strain increased in the septum (−3.5% difference in PAH2 vs. CTRL) but lower values were observed in the lateral wall (+1.7% difference in PAH2 vs. CTRL). Cardiac function of case PAH2 was simulated also with increased myocardial passive stiffness (2.67 kPa instead of 1.34 kPa) which presented a mild strain increase in the mid LV ventricle in comparison to PAH2 with normal stiffness (circumferential strain: −0.8%, radial strain: +0.5%, longitudinal strain: −0.2%). Conclusion Our study provides mechanistic evidence on how RV overload and increased passive myocardial stiffness causes a redistribution of strain and fibre stress in the LV, which may play a significant role in LV remodelling and function. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): K.G. Jebsen Center for Cardiac Research Figure 1. Pressure – volume loopsFigure 2. Mean mid-LV strains

Age- and Sex-Specific Characteristics of Right Ventricular Compacted and Non-compacted Myocardium by Cardiac Magnetic Resonance.

The age and sex-specific characteristics of right ventricular compacted (RV-CMi) and RV-trabeculated myocardial mass (RV-TMi) and the determinants of RV myocardium are less well-studied; however, in different conditions, these might provide additional diagnostic information. We aimed to describe the age- and sex-specific characteristics of RV-CMi, RV-TMi, and RV volumetric and functional parameters and investigate the determinants of RV myocardial mass with cardiac magnetic resonance (CMR). Two hundred healthy Caucasian volunteers free of known cardiovascular or systemic diseases were prospectively enrolled in this study. Four different age groups were established with equal numbers of males and females: Group A (n = 50, 20-29 years, mean age: 24.3 ± 3.2 years), Group B (n = 50, 30-39 years, mean age: 33.6 ± 2.6 years), Group C (n = 50, 40-49 years, mean age: 44.7 ± 2.7 years), and Group D (n = 50, ≥50 years, mean age: 55.1 ± 3.9 years). Left ventricular (LV) and RV volumetric, functional, CMi, and TMi values were measured with a threshold-based post-processing CMR method. The volumetric parameters, RV-CMi, and RV-TMi values were larger, and the ejection fraction (EF) was lower in males. The RV-CMi did not correlate with age in either of the sexes, while the RV-TMi decreased with age in females but remained stable in males. The RV-TMi and RV-CMi correlated positively with RV volumetric parameters, the LV-CMi, the LV-TMi, and each other in both sexes. LV-TMi, LV-CMi, RV end-systolic volume, and sex were independent predictors of RV-TMi. Understanding the characteristics of RV-trabeculated and RV-compacted myocardium might have additive value in diagnosing different conditions with RV hypertrophy or hypertrabeculation.

Cardiac magnetic resonance imaging in patients with Beh\xe7et's disease

BackgroundBehçet’s disease (BD) is a multisystemic vasculitis that may affect the heart. However, the incidence and nature of cardiac involvement in BD have not been clearly documented yet. The aim of this study was to delineate the cardiac magnetic resonance imaging (MRI) appearances of cardiac involvement in BD patients.MethodsThis cross-sectional observational study was carried out 30 BD patients without known cardiac disease. Patients were subjected to history taking, physical examination, echocardiography and cardiac MRI.ResultsAt least one abnormality on cardiac MRI was observed in 20/30 patients (66.67%). Myocardial oedema was observed in 3 patients (10%) and late gadolinium enhancement in 1 patient (3.3%). Pericardial effusion was found in 3 patients (10.0%), global hypokinesia in 6 patients (20.0%) and intra-cardiac thrombosis in only 1 patient (3.3%). Pulmonary artery was dilated in 4 patients (13.3%). Left ventricular (LV) and right ventricular (RV) end diastolic volume were altered in 4 patients (13.3%) and 7 patients (23.3%) respectively. LV and RV end systolic volume were abnormal in 7 patients (23.3%) and 5 patients (16.7%) respectively. There was aortic valve regurge in 2 patients (6.7%), tricuspid valve regurge in 9 patients (30%), and mitral valve regurge in 9 patients (30%). Dilated left main coronary artery was found in 2 patients (6.7%) and arrhythmogenic right ventricular dysplasia in only one patient 1 patient (3.3%). On logistic regression analysis, BD activity index score was a significant predictor of cardiac abnormalities.ConclusionBD may cause cardiac abnormalities without clinical manifestations and cardiac MRI may represent a tool for early detection of these subtle abnormalities. Higher BD activity index scores are strongly linked to cardiac problems.

Echocardiographic assessment of right ventricular volume in repaired tetralogy of Fallot: a novel approach to an older technique.

In repaired tetralogy of Fallot (rTOF), right ventricular (RV) enlargement leads to poor outcomes. However, evaluating the RV has limitations; cardiac magnetic resonance (CMR) and 3D echocardiography have barriers including cost and accessibility. Traditional echocardiography is limited given the complex geometry and anterior location of the RV. We propose a novel echocardiographic evaluation of RV volume using 2 separate views. This is a retrospective study of rTOF patients with echocardiogram, CMR, and exercise tests. By echocardiogram, we collected RV length in parasternal long axis (PLAX), area in 4-chamber (4C) view, and measurements per standard guidelines. RV end-diastolic and end-systolic volume (RVEDV and RVESV) were calculated as 5/9 (4C area * PLAX length). Forty-five patients with 66 sets of CMR, echocardiogram, and exercise tests were included (mean age 13.3 ± 3.2years). The echocardiographic RVEDV and RVESV showed strong correlation with CMR parameters (r = 0.81 and 0.72; p≤ 0.0001), and moderate correlation with peak oxygen pulse (0.63 and 0.49; p≤0.0001). Guideline measurements had no significant correlation. Echocardiographic RVEDV and RVESV were higher in those requiring subsequent pulmonary valve replacement. Indexed echocardiographic RVEDV of 93ml/m2 had 92% sensitivity and 50% specificity (area under curve 0.75 (p = 0.001)) in predicting CMR RV/LV EDV ratio > 2, which is an early indicator for pulmonary valve replacement. This novel technique correlates strongly with CMR, better than traditional parameters. While echocardiogram will not replace CMR, this method would be useful in predicting the RV volume, progression of dilation, and timing of CMR.

Outcome and right ventricle remodelling after valve replacement for pulmonic stenosis

BackgroundComplications and need for reinterventions are frequent in patients with pulmonary valve stenosis (PVS). Pulmonary regurgitation is common, but no data are available on outcome after pulmonary valve replacement (PVR).MethodsWe...

Right heart exercise-training-adaptation and remodelling in endurance athletes

Long-term sports training leads to myocardial adaptations, with remodelling of the heart chambers. However, while myocardial adaptations of the left heart are well described, remodelling of the right heart and its impact on the development of arrhythmias is still debated. To conduct a systematic review on right ventricle (RV) and right atrium (RA) structural and functional changes in athletes who participate in long-term endurance training. Systematic review. A systematic literature search was conducted. All the articles reporting right heart echocardiographic (ECHO) and cardiac magnetic resonance (CMR) parameters evaluated in endurance athletes and sedentary subjects were considered eligible. A multivariate analysis was conducted to investigate whether age, sex, body surface area (BSA), intensity of training are associated with RV ECHO, CMR parameters and RA ECHO parameters. A positive association between age and right atrium area (RAA) (P = 0.01) was found. This is a negative association to RV E/A (P = 0.004), and RV end diastolic diameter (RVED) longitudinal (P = 0.01). A positive association between BSA and RVED middle (P = 0.001), as well between BSA and RAA (P = 0.05) was found, along with a negative association with RV E/A (P = 0.002). A positive association between intensity of training and RV end systolic area (RVESA) (P = 0.03), RV end diastolic volume indexed (RVEDVI) (P = 0.01), RV end systolic volume indexed (RVESVI) (P = 0.01) was found, along with a negative association with ejection fraction (EF %) (P = 0.01). Endurance athletes demonstrated an association between RV remodelling and age, BSA and intensity of training.

Abstract 12362: Association Between GP130 Signaling, Microtubule Regulation, and RV Function in Porcine RV Pressure Overload

Introduction: Pulmonary arterial hypertension (PAH) is a rare but lethal disease, which results in rightventricle (RV) failure. Unfortunately, there are no available therapies to directly combat RV failure and improvesurvival in PAH. We previously showed antagonism of the GP130 signaling pathway prevents microtubuleremodeling and enhances RV function in rat PAH. However, rodent models does not always recapitulatehuman physiology, which may limit translatability of our finding. Therefore, we examined the relationshipsbetween GP130 activation, microtubule regulation, t-tubule structure, and RV function in porcine RV pressureoverload. Methods: Pulmonary artery banding (PAB) was performed on old Yorskhire piglets and animals wereevaluated 4 weeks after. Immunoblots of RV extracts were probed with GP130, STAT3, phosphorylatedSTAT3, α-tubulin, β-tubulin, and detyrosinated α-tubulin primary antibodies to quantify GP130 activation andmicrotubule remodeling respectively. T-tubule architecture was examined using confocal microscopy. Finally,cardiac MRI quantified RV structure and function. Results: PAB pigs exhibited induction of GP130 signaling with higher levels of GP130, STAT3, andpSTAT3. Additionally, there was evidence of microtubule remodeling with elevated expression of α-, β-, anddetyrosinated α-tubulin. Confocal microscopy revealed t-tubule derangements in PAB pigs. Cardiac MRIshowed PAB pigs had significantly increased RV end systolic volume, reduced RV ejection fraction, andimpaired RV-pulmonary artery coupling. Finally, GP130 and tubulin expression levels were inverselyassociated with RV ejection fraction and RV-pulmonary artery coupling. Conclusion: Increased expression of GP130 and tubulin is associated with lower RV ejection fraction andworse RV-PA coupling. Future studies are needed to determine if GP130 antagonism enhances RV function inporcine RV pressure overload.

Normal CMR Bi-Atrial and Biventricular Reference Values in Sickle Cell Disease Patients without Heart Damage

Background. Cardiac function indices in patients with hemoglobinopathies are different from those in healthy population, mainly due to chronic anemia. Normal reference values specific for SCD patients are not available by CMR.Aim. We aimed to define the normal cut-off value in SCD patients for bi-atrial and biventricular cardiac magnetic resonance (CMR) parameters.Methods. We considered forty-eight adult SCD patients with no known risk factors or cardiac disease, normal electrocardiogram, no macroscopic myocardial fibrosis, and all cardiac segments with T2*≥20 ms, consecutively enrolled in the MIOT network (Myocardial iron overload in thalassemia). SCD patients were compared with ninety-six healthy controls and 96 thalassemia major (TM) patients without cardiac damage, both matched for age and gender. Nine pediatric SCD patients were also analysed in comparison with 9 TM patients and 9 healthy subjects matched for age and gender. Cine images were acquired to quantify biventricular function parameters: LV and RV end-diastolic volume (EDV), end-systolic volume (ESV) and stroke volume (SV) were normalized for body surface area (EDVI, ESVI, SVI), as well as biventricular mass and atrial areas. Myocardial iron overload was assessed by segmental T2* technique. Late gadolinium enhancement (LGE) images were acquired for evaluation of macroscopic myocardial fibrosis.Results. In all three groups males showed higher biventricular volumes and mass indexes than females. SCD male patients had significantly higher LVEDVI (p<0.0001), LVESVI (p=0.010), LVSVI (p=0.003), cardiac index (p=0.002), LV and RV mass index (p=0.008 and p=0.001, respectively) and left and right atrial areas (p<0.001 and p=0.011) than healthy subjects. No significant differences were found in RVEDVI, EVESVI and biventricular EF. Compared to healthy volunteers, females with SCD showed a larger LVEDVI (p=0.020), LVSVI (p=0.039), RV mass index (p=0.002) and left atrial area (p=0.008).SCD and TM patients showed comparable values of bi-atrial and biventricular volumes and function. When compared to TM, SCD patients showed a larger LV (p<0.001) and RV mass index (p=0.001) in male group and a larger RV mass index (p=0.001) in female group. Table 1 shows the cut-offs for bi-atrial and biventricular MR parameters for adult SCD patients by gender.No significant differences in MR parameters were found among the pediatric groups.Conclusions. Normal reference ranges of bi-atrial and biventricular MR parameters for adult males and females SCD patients were established. The use of these reference values will prevent possible misdiagnosis of cardiomyopathy in patients with SCD. [Display omitted] DisclosuresPepe: Chiesi Farmaceutici S.p.A: Other: no profit support; Bayer S.p.A.: Other: no profit support. Quarta: Sanofi - Genzyme: Membership on an entity's Board of Directors or advisory committees, Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Speaker at conferences; Blue Bird Bio: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Celgene: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; Speaker at conferences; Takeda: Other: collaboration relationships for Advisory boards, Webinar events, editorial projects; speaker at conferences; Bristol Meyer Squibb: Membership on an entity's Board of Directors or advisory committees, Other: Speaker at conferences. Maggio: Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

A Pilot Project to Identify Simple Echocardiographic Tools as an Alternative to Cardiac Magnetic Resonance Imaging to Predict a Reduced Right Ventricular Ejection Fraction in Patients with Repaired Tetralogy of Fallot

Background: Right ventricular (RV) dysfunction is an important predictor of adverse events after tetralogy of Fallot (TOF) repair. A study comparing echocardiography with cardiac magnetic resonance (CMR) might provide simple tools for their serial inexpensive assessment. Methods: Echocardiographic RV functional parameters including fractional area change (FAC), rate of pressure rise (dP/dt), free wall strain, myocardial performance index (MPI), tricuspid annular plane systolic excursion (TAPSE), and tissue Doppler S' velocity in patients with repaired TOF were correlated with CMR-derived ejection fraction (EF) using receiver operator characteristic (ROC) curves. Bland–Altman plots analyzed agreement between the RV end-diastolic volumes (EDVs), end-systolic volumes (ESVs), and EF derived from three-dimensional echocardiography (3DE) and CMR. Results: Eighteen patients were included. The echocardiographic parameters that showed a good positive correlation with CMR-derived EF were FAC (r = 0.851, P = 0.001), dP/dt (r = 0.730, P = 0.001), and free wall strain (r = −0.660, P = 0.003). ROC curve analysis provided a cutoff value for FAC (&lt;36.6), dP/dt (&lt;370 mmHg/s), free wall strain (&lt;−18.5) and MPI (&gt;0.565) to predict EF &lt;45%. TAPSE and S' velocity had poor correlation. Correlation was strong between 3DE and CMR-derived EDV (r = 0.938, P &lt;0.001), ESV (r = 0.936, P &lt;0.001) and EF (r = 0.916, P &lt;0.001). 3DE underestimated volumes compared to CMR with a mean bias of − 31.78 ± 18.8 ml for EDV and −17.28 ± 11.6 ml for ESV, but EF was not affected (mean bias − 1% ± 3.7%). Conclusions: RV free wall strain, FAC and dP/dt were simple tools with good accuracy to predict RV EF &lt;45% in patients with repaired TOF. TAPSE and S' velocity assessed basal longitudinal function without considering the dysfunctional outflow tract and showed poor correlation. EF assessment by 3DE was a good alternative to CMR. Underestimation of volumes by 3DE might restrict its use in timing surgery.

Feasibility and Accuracy of a Fully Automated Right Ventricular Quantification Software With Three-Dimensional Echocardiography: Comparison With Cardiac Magnetic Resonance.

Background: A novel, fully automated right ventricular (RV) software for three-dimensional quantification of RV volumes and function was developed. The direct comparison of the software performance with cardiac magnetic resonance (CMR) was limited. Therefore, the aim of this study was to test the feasibility, accuracy, and reproducibility of a fully automated RV quantification software against CMR imaging as a reference.Methods: A total of 170 patients who underwent both CMR and three-dimensional echocardiography were enrolled. RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), and RV ejection fraction (RVEF) were obtained using fully automated three-dimensional RV quantification software and compared with a CMR reference. For inter-technical agreement, Spearman correlation and Bland–Altman analysis were used.Results: The fully automated RV quantification software was feasible in 149 patients. RVEDV and RVESV were underestimated, and RVEF was overestimated compared with CMR values. RV measurements obtained from the manual editing method correlated better with CMR values than that without manual editing (RVEDV, 0.924 vs. 0.794: RVESV, 0.955 vs. 0.854; RVEF, 0.941 vs. 0.781 respectively, all p < 0.0001) with less bias and narrower limit of agreement (LOA). The bias and LOA for RV volumes and EF using the automated software without and with manual editing were greater in patients with severely impaired RV function or low frame rate than those with normal and mild impaired RV function, or high frame rate. The fully automated RV three-dimensional measurements were highly reproducible.Conclusion: The novel fully automated RV software shows good feasibility and reproducibility, and the measurements had a high correlation with CMR values. These findings support the routine application of the novel 3D automated RV software in clinical practice.

Role of cardiac magnetic resonance in stratifying the prognosis of patients with pulmonary arterial hypertension

Abstract Background Pulmonary arterial hypertension (PAH) is a rare disease characterized by a complex remodeling of heart structures. Cardiac magnetic resonance (CMR) is the gold standard for a non-invasive evaluation of right ventricle (RV) volumes and mass. Purpose To define the relationship between clinical, functional, biochemical, haemodynamic and CMR parameters and survival in patients with PAH. Methods Consecutive patients with PAH referred to our centre underwent clinical, functional, brain natriuretic peptide (BNP) plasma levels, haemodynamic and CMR evaluation. All patients were treated according to current guidelines. Univariate Cox analysis for survival was performed. Parameters with a p-value &amp;lt;0.1 at the univariate analysis were included in the multivariate analysis. Results One hundred forty-seven patients with PAH (mean age 49±17 years, 69% female) were included in the study. Etiology of PAH was: idiopathic/heritable (49%), associated with connective tissue disease (19%), congenital heart disease (12%), portal hypertension/HIV infection (12%) and pulmonary veno-occlusive disease (8%). Thirty-six patients died during follow-up. Parameters significantly associated with mortality at the univariate analysis were age [Hazard Ratio (95% Confidence Interval): 1.043 (1.020–1.067); p&amp;lt;0.001], six-minute walk test (6MWT) [HR: 0.995 (0.993–0.998); p&amp;lt;0.001], WHO-functional class [HR: 2.489 (1.025–6.041); p=0.044], idiopathic-heritable-congenital heart disease aetiology [HR: 0.182 (0.085–0.389); p&amp;lt;0.001], connective tissue disease aetiology [HR: 2.274 (1.099–4.704); p=0.027], pulmonary veno-occlusive disease aetiology [HR: 5.864 (2.328–14.773); p&amp;lt;0.001], right atrial pressure [HR: 1.098 (1.032–1.169); p=0.003], pulmonary artery oxygen saturation [HR: 0.947 (0.921–0.975); p&amp;lt;0.001], BNP levels [HR: 2.214 (1.213–4.039); p=0.010], RV wall thickness [HR: 0.633 (0.399–1.006); p=0.053], RV end diastolic volume [HR: 1.012 (1.003–1.021); p=0.007], RV end systolic volume [HR: 1.014 (1.003–1.024); p=0.011]. Parameters independently associated with mortality at the multivariate analysis were age [HR: 1.035 (1.006–1.064); p=0.018], idiopathic-heritable-congenital heart disease aetiology [HR: 0.355 (0.146–0.860); p=0.022], pulmonary veno-occlusive disease aetiology [HR: 3.129 (1.071–9.143); p=0.037], pulmonary artery oxygen saturation [HR: 0.953 (0.919–0.989); p=0.011], RV wall thickness [HR: 0.527 (0.300–0.927); p=0.026], RV end systolic volume [HR: 1.016 (1.003–1.029); p=0.014]. Conclusion RV wall thickness and RV end-systolic volume are associated with prognosis in patients with PAH independently from clinical and haemodynamic characteristics. These parameters may be used in the overall risk stratification of PAH patients. Funding Acknowledgement Type of funding sources: None.

Assessment of left ventricular mechanics in right ventricular overload using in silico rat models

Abstract Background To preserve cardiac function in overload conditions, the RV adapts by developing muscular hypertrophy through progressive tissue remodelling. This process may lead to a vicious cycle with detrimental effects on RV diastolic and systolic function, as seen in pulmonary arterial hypertension (PAH) patients [1]. However, how RV overload affects LV function and remodelling remains an open question [2]. Computational models of cardiac physiology offer an opportunity for investigating mechanisms difficult or impossible to analyse otherwise due to the existence of overlapping factors and technical limitations. Aim This study aims to assess the acute effects of RV overload and increased myocardial passive stiffness on the LV mechanical properties in an anatomically-based computational model of healthy rat heart. Methods A computational simulation pipeline of cardiac mechanics based on the Holzapfel-Ogden model has been implemented using MR images from a healthy rat. Whereas LV function was modelled realistically using catheter measurements conducted on the same subject than the MR imaging, RV function was based on representative literature values for healthy and PAH rats with RV overload. The following cases were defined (Fig. 1): CTRL, with normal RV function; PAH1, with 30% increase in RV ESV (end-systolic volume) and 15% increase in RV ESP (end-systolic pressure) in comparison to CTRL; and PAH2, with 60% increase in RV ESV and 30% increase in RV ESP compared to CTRL. The cardiac cycle was simulated for all cases whilst fitting the experimentally measured LV pressure and volume values from a healthy rat, which allowed quantifying the effects of RV overload on LV function. Results The increase of average circumferential strain in the LV correlated with the degree of RV overload simulated (CTRL: −8.7%, PAH1: −8.9%, PAH2: −9.2%), whilst average radial (CTRL: 35.2%, PAH1: 34.8%, PAH2: 30.3%) and longitudinal strains decreased (CTRL: −7.7%, PAH1: −7.4%, PAH2: −6.6%), as seen in Fig.2. However, regional differences in strain were significant: under RV overload conditions, circumferential strain increased in the septum (−3.5% difference in PAH2 vs. CTRL) but lower values were observed in the lateral wall (+1.7% difference in PAH2 vs. CTRL). Cardiac function of case PAH2 was simulated also with increased myocardial passive stiffness (2.67 kPa instead of 1.34 kPa) which presented a mild strain increase in the mid LV ventricle in comparison to PAH2 with normal stiffness (circumferential strain: −0.8%, radial strain: +0.5%, longitudinal strain: −0.2%). Conclusion Our study provides mechanistic evidence on how RV overload and increased passive myocardial stiffness causes a redistribution of strain and fibre stress in the LV, which may play a significant role in LV remodelling and function. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): K.G. Jebsen Center for Cardiac Research Figure 1. Pressure – volume loopsFigure 2. Mean mid-LV strains

Value of echocardiography using knowledge-based reconstruction in determining right ventricular volumes in pulmonary sarcoidosis: comparison with cardiac magnetic resonance imaging

Abstract Background Right ventricular (RV) dysfunction in sarcoidosis is associated with adverse outcomes. Assessment of RV function by conventional transthoracic echocardiography (TTE) is challenging due to the complex RV geometry. Knowledge-based reconstruction (KBR) combines TTE measurements with three-dimensional coordinates to determine RV volumes. Purpose The aim of this study was to investigate the accuracy of TTE-KBR compared to the gold standard cardiac magnetic resonance imaging (CMR) in determining RV dimensions in pulmonary sarcoidosis. Methods Pulmonary sarcoidosis patients prospectively received same-day TTE and TTE-KBR. If performed, CMR within three months after TTE-KBR was used as reference standard. Outcome parameters included RV end-diastolic volume (RVEDV), end-systolic volume (RVESV), stroke volume (RVSV) and ejection fraction (RVEF). Results 282 patients underwent same day TTE and TTE-KBR. In total, 122 patients received a CMR within 90 days of TTE and were included. TTE-KBR measured RVEDV and RVESV showed strong correlation with CMR measurements (R=0.73, R=0.76), while RVSV and RVEF correlated weakly (R=0.46, R=0.46). Bland-Altman analyses (mean bias ±95% limits of agreement), showed good agreement for RVEDV (ΔRVEDVKBR-CMR, 5.67±55.4mL), while RVESV, RVSV and RVEF showed poor agreement (ΔRVESVKBR-CMR, 21.6±34.1mL; ΔRVSVKBR-CMR, −16.1±42.9mL; ΔRVEFKBR-CMR, −12.9±16.4%). Image quality, time to CMR and learning curve showed no impact. Conclusions TTE-KBR is convenient and shows good agreement with CMR for RVEDV. However, there is poor agreement for RVESV, RVSV and RVEF. The use of TTE-KBR does not seem to provide additional value in the determination of RV dimensions in pulmonary sarcoidosis patients. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): ZonMW (The Netherlands Organisation for Health Research and Development) Figure 1. Correlation plotsFigure 2. Bland-Altman plots

Changes in cMRI parameters following a switch to riociguat from phosphodiesterase type 5 inhibitors (PDE5i) in patients with pulmonary arterial hypertension: a REPLACE substudy

Abstract Background The REPLACE study investigated the effect of switching to riociguat (RIO) in patients with pulmonary arterial hypertension receiving PDE5i but still at intermediate risk. The centrally adjudicated composite primary endpoint was clinical improvement in the absence of clinical worsening, where clinical improvement was defined as meeting at least two of the following criteria: 6-minute walk distance (6MWD), increase by ≥10% or ≥30 m from baseline (BL) to Wk 24; World Health Organization functional class (WHO FC) I or II at Wk 24; or N-terminal prohormone of brain natriuretic peptide reduction of ≥30% from BL to Wk 24. Twice as many patients switching to RIO (45/111, 41%) met the primary endpoint compared with those remaining on PDE5i (23/113, 20%); odds ratio (OR): 2.78 (95% confidence interval [CI] 1.53–5.06); p=0.0007. Purpose Assess changes in right and left ventricular (RV; LV) function using cardiac magnetic resonance imaging (cMRI) in a subgroup of patients participating in REPLACE. Methods REPLACE was a randomised, open-label, 24-week, Phase 4 study (NCT02891850). Patients in WHO FC III, with 6MWD 165–440 m, were randomised to switch to RIO 2.5 mg–max tid or remain on PDE5i. Background endothelin receptor antagonist therapy was permitted in both arms. cMRI was performed on a subset of patients from the full analysis set as an exploratory substudy. The following parameters were measured at BL and Wk 24: RV and LV end-diastolic and end-systolic volumes (RVEDV; RVESV; LVEDV; LVESV), RV stroke volume and stroke volume index (RVSV; RVSVI), LV stroke volume (LVSV), RV ejection fraction (RVEF), and pericardial effusion. Results Twenty-seven patients participated in the cMRI substudy. This comprised 11/111 (10%) patients in the RIO arm (mean [standard deviation {SD}] 40.0 [12.4] years), and 16/113 (14%) patients (mean 44.5 [17.6] years) in the PDE5i arm. Like the main population, the treatment response in the cMRI subpopulation favoured RIO versus PDE5i (OR: 6.11 [95% CI 0.90–41.60]). From BL to Wk 24, RVEDV and RVESV decreased in the RIO treatment arm but increased in the PDE5i treatment arm (Table 1). Similar, but less pronounced, changes were observed for the left ventricle (LVESV, LVEDV). RVSV and RVEF levels were close to normal at BL and did not increase in either arm at Wk 24 (Table 1). Pericardial effusion, which was present in 5 patients in each group at BL, decreased in 1 patient in the RIO arm and no patients in the PDE5i arm. Conclusions Decreases in RVEDV and RVESV suggest improvements in cardiac function in the RIO arm compared with the PDE5i arm. Values for RVEF and RVSVI were close to normal at BL and did not change at Wk 24. Improvements in cMRI parameters were in line with the clinical improvement observed in patients switching to RIO in the overall population. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The REPLACE study was co-funded by Bayer AG (Berlin, Germany) and Merck Sharp &amp; Dohme Corp., a subsidiary of Merck &amp; Co., Inc. (Kenilworth, NJ, USA)

Prevalence and predictors of right ventricular dysfunction in cancer patients treated with cardiotoxic chemotherapy – a prospective cardiovascular magnetic resonance study

Abstract Background Right ventricular (RV) function has an established incremental prognostic value in cardiomyopathy. Studies on cancer therapeutics-related cardiac dysfunction (CTRCD) primarily focused on the left ventricle (LV), with conflicting results from small studies dedicated to RV dysfunction. Purpose We sought to investigate the influence of chemotherapy on RV function relative to LV function using serial cardiac magnetic resonance (CMR). Methods Patients were enrolled as part of Cardiotoxicity Prevention Research Initiative (CAPRI) Registry aimed at evaluating CMR-based markers for surveillance of CTRCD. Patients underwent non-contrast CMR imaging prior to initiation of anthracyclines and/or trastuzumab and serially every 3 months during the first year, then annually thereafter. We included patients who had a baseline and ≥1 follow-up scan and excluded those with baseline LV ejection fraction (EF)&amp;lt;50%, providing 320 patients completing 1,453 CMR studies. Cine images were analysed to calculate chamber volumes indexed to body surface area and EF. We defined LV CTRCD using CMR modality specific criteria of a drop in LV EF ≥5% from baseline to &amp;lt;57%; RV CTRCD as a drop ≥5% to &amp;lt;49% in females and &amp;lt;47% in males. We used linear mixed models to study the changes in ventricular volumes and EF with time. Results The majority of patients were females (80%), had breast cancer (68%) or lymphoma (32%), with a mean age of 52.7±13 years. Figure 1 shows temporal changes in mean ventricular volumes and function over the first year. Mean changes in RV function followed those of the LV, with the nadir of EF and maximum of volumes occurring at 6 months. Respective values for mean decrease in LV and RV EF at this time point versus baseline were 4.1 and 2.9% (p&amp;lt;0.001). Concomitant mean increase in indexed RV end-diastolic (ED) and end-systolic (ES) volumes were 1.6 and 2.7 ml/m2 (p=0.2 and &amp;lt;0.001). There was significant interaction of chemotherapy regimen with time for RV volumes (p=0.001 and 0.003), but not RV EF (p=0.7), with worst changes occurring with combined anthracyclines and trastuzumab. In all, 70 (22%) and 28 (9%) patients met criteria for LV and RV CTRCD, respectively. Among those who developed RV CTRCD, 10 had persistently normal LV function. Figure 2 shows the results of logistic regression to predict RV CTRCD. Significant univariable predictors included combined chemotherapy regimen and baseline LV and RV volumes and LV EF. Adjusting for age, sex, and chemotherapy regimen, baseline RV ED volume remained associated with RV CTRCD (odds ratio 1.6; p=0.005). Conclusion In this large study, RV volumes and function were similarly influenced by chemotherapy versus comparable LV-based measures. Using similar threshold criteria, the incidence of RV CTRCD was lower than for LV CTRCD; however, one third of those who develop RV CTRCD showed normal LV function. Future studies are warranted to study the prognostic influence of RV injury in cancer patients. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Alberta InnovatesGenome Alberta Figure 1. Temporal changes in LV &amp; RV functionFigure 2. Predictors of RV CTRCD

The prognostic value of cardiac magnetic resonance in assessment of right ventricular function after percutaneous balloon mitral valvuloplasty

Abstract Background Mitral stenosis (MS) results in right ventricular (RV) dysfunction secondary to chronic pulmonary hypertension. Poor outcomes have been reported in patients with persistent chronic RV dysfunction. Persistence RV dysfunction can affect the clinical improvement after percutaneous balloon mitral valvuloplasty (PBMV). Cardiac Magnetic Resonance (CMR) is emerged as a highly sensitive technique for assessment of RV function (RVF). Purpose To investigate RV function 3 months after PBMV using a variety of robust parameters associated with prognosis. Methods A prospective observational study was conducted in a tertiary University hospital included 31 patients with symptomatic uncomplicated MS with favorable morphology and having sinus rhythm who underwent PBMV. All patients were subjected to TTE and CMR examination 24 hours directly before and 3 months after PBMV for assessment of RV size and function. Results CMR showed reduced RV myocardial mass (36.1±6.1 vs 28.0±5.4g, P&amp;lt;0.001), RV end-diastolic volume (RV EDV) (123.5±31.3 vs 109.5±22.7 ml, P=0.03) and TR regurgitant fraction (19.6±8.6 vs 14.7±4.9%, P&amp;lt;0.001) On the other hand, there were increase in each of RV ejection fraction (60.0±10.4 vs 63.13±7.8%, P&amp;lt;0.001), RV stroke volume (SV) (50.2±15.1 vs 33.2±12.2 ml, P&amp;lt;0.001) and RV stroke index (44.2±7.7 vs 50.3±8.6 ml/beat/m2 &amp;lt;0.001). TTE showed improved systolic RV function parameters measured by fractional area change (42.1±7.8 vs 51.7±5.4%, P&amp;lt;0.00), Tei Index (0.6±0.1 vs 0.5±0.1, P&amp;lt;0.001) and TAPSE (22.2±3.3 vs 25.7±5.1 mm, P=0.04). Among RV diastolic parameters, there were an increase in TV-TDI E' (12.0±3.0 vs 14.0±2.0 cm/s, P&amp;lt;0.001), TV-TDI A' (13.0±3.0 vs 11.0±2.0 cm/s, P&amp;lt;0.001) and TV-TDI E'/A' (1.0±0.5 vs 1.3±0.3, P&amp;lt;0.001) with significantly decreased RV wall thickness (5.7±0.7 vs 4.3±0.8 mm P&amp;lt;0.001) 3 months after PBMV. Among patients who showing improved RV parameters by TTE, ten patients (32,3%) showed non improved RV end systolic volume, EDV, SV and stroke index by CMR. Conclusion Follow-up of RV function by TTE after PBMV yielded nearly similar results compared to CMR. However, CMR identified a subgroup of patient with persistent RV dysfunction 3 months after PBMV. That contributes to define the role of cardiac MRI in the evaluation of the prognosis in patients with MS. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Assiut University hospital and Al Orman Institute

Factors associated with the risk of heart failure progression in patients with non-compaction cardiomyopathy

Abstract Purpose To identify factors associated with the progression of chronic heart failure (CHF) to NYHA FC III, requiring hospitalization and to reveal high-risk pts. Methods The study included 156 pts with non-compaction cardiomyopathy (NCCM), who were prospectively observed in the RSPC “Cardiology”. The median follow-up was 36 months (6; 152). All pts underwent echocardiography (Echo), cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) and 24-hour Holter monitoring. The median age of the pts was 36 (26; 49) years, men predominated (57.4%). The diagnosis of NCCM was established on the basis of the following criteria: Echo – Jenni criteria, CMR – Petersen/Jaquier criteria. The end point of the study included progression of CHF from NYHA FC II to FC III, requiring hospitalization. Results At the initial examination, symptoms of CHF NYHA FC I were found in 56 (55.4%) pts, symptoms of CHF NYHA FC II – in 45 (44.6%) pts, systolic dysfunction was detected in 43% of pts. During the follow-up period, out of 156 pts, 55 (35.3%) had CHF symptoms that progressed to NYHA FC III and required hospitalization. As a result of the bivariate analysis, the following Echo characteristics were independent factors associated with a high risk of progression of CHF to NYHA FC III: LV EF &amp;lt;40% (HR 6.2; 95% CI 3.4–11.2); end-diastolic LV diameter &amp;gt;62 mm (HR 5.3; 95% CI 2.9–9.7); end-systolic LV diameter &amp;gt;56 mm (HR 6.6; 95% CI 3.8–11.7); end-diastolic LV volume &amp;gt;187 ml (HR 4.4; 95% CI 2.5–8); end-systolic LV volume &amp;gt;93 ml (HR 6.5; 95% CI 3.2–13). The risk of progression of CHF to NYHA FC III was 3.4 times higher in pts with right ventricular (RV) systolic dysfunction: with a decrease of RV fractional area change (FAC) &amp;lt;31% (HR 3.4; 95% CI 1.8–6.3) and 2.5 times higher with a decrease of tricuspid annular plane systolic excursion (TAPSE) (HR 2.5; 95% CI 1.3–4.5); 2.5 times higher in pts with initially increased anteroposterior RV diameter &amp;gt;28 (HR 2.5; 95% CI 1,4–4.5). According to the LGE-CMR data, the factors associated with the risk of progression of CHF to NYHA FC III were the following characteristics: an increase of BSA-indexed end-diastolic LV volume &amp;gt;145 ml/m2 (HR 6.7; 95% CI 3.4–13.3); BSA-indexed end-systolic LV volume &amp;gt;96 ml/m2 (HR 6.8; 95% CI 3.4–13.6); and an increase of RV end-systolic volume &amp;gt;145 ml (HR 5.0; 95% CI 2.3–11). The risk of CHF progression was 4.8 times higher in pts with baseline LV systolic dysfunction (LV EF &amp;lt;34%, HR 4.8; 95% CI 2.8–8.2); 2.7 times higher in pts with RV systolic dysfunction (LVEF &amp;lt;42%, HR 2.7; 95% CI 1.6–4.8). The NC/C ratio and the presence of myocardial replacement fibrosis according to LGE-CMR did not significantly affect the risk of progression of CHF. Conclusion The factors identified as a result of the study associated with the risk of progression of CHF based on biventricular assessment by cardiac imaging methods (Echo and LGE-CMR) can be used to reveal high-risk pts. Funding Acknowledgement Type of funding sources: None.