Right Ventricular Insertion Point Research Articles

Deep phenotyping the right ventricle to establish translational MRI biomarkers for characterization of adaptive and maladaptive states in pulmonary hypertension

Deep phenotyping the right ventricle (RV) is essential for understanding the mechanisms of adaptive and maladaptive RV responses to pulmonary hypertension (PH). In this study, feature selection coupled with machine learning classification/ranking of specific cardiac magnetic resonance imaging (MRI) features from cine-MRI, flow-sensitized, and extracellular-volume techniques were used to assess RV remodelling in monocrotaline (MCT) and Sugen hypoxia (SuHx) PH rats. Early physiological changes associated with RV adaptation were detected along with prediction of RV maladaptive outcomes. Key adaptation features included haemodynamic alterations of pulmonary blood flow ejection and wave reflection, mild RV dilatation, progressive RV hypertrophy with subtle extracellular volume growth of RV wall. A dominant component of maladaptation was the extracellular matrix increase at RV insertion points and septum, observations compatible with histopathologic and RNA-sequencing results. The upregulation of mammalian target of rapamycin (mTOR) paralleled by AMP-activated protein kinase (AMPK) deactivation was seen at 4-week MCT and 8-week SuHx, along with reduced sarcoplasmic/endoplasmic reticulum Ca2+ATPase (SERCA2) expression, strongly associated with the RV systolic malfunction seen at this stage in vivo. The here established MRI features can serve as potential imaging biomarkers to evaluate PH treatment efficacy in preclinical studies and build up translational markers for the PH clinic.

Volume-pressure loop hemodynamic characterization of pulmonary hypertension

Abstract Background Pulmonary hypertension (PH) includes a wide spectrum of pathologies with different pathological bases and a variety of clinical scenarios in which right ventricular (RV)-pulmonary artery (PA) coupling has relevant prognostic implications. Currently, diagnosis and hemodynamic severity of PH is typically based on mean pulmonary arterial pressure (mPAP), pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance (PVR). However, this conception does not take into consideration the evolution of these parameters throughout the cardiac cycle. We hypothesized that not only the magnitude but also the dynamics over time plays an important role in RV adaptation to pressure overload (i.e., constant fixed resistances throughout the cycle will have a different impact than a fluctuating resistances). Purpose To assess PA hemodynamic patterns throughout the cardiac cycle and their association with RV remodelling, by combining right heart catheterization (RHC) and cardiac magnetic resonance imaging (CMR) data. Methods 66 patients with PH (38 women, aged 63.59±14.70years, BMI 28.49±6.21 kg.m2) who underwent RHC in the supine position with a 7.5-FrSwan-Ganz catheter under fluoroscopic guidance (37 precapillary, 17 combined pre-postcapillary, 12 isolated postcapillary PH) and CMR with flow-encoded phase-contrast sequence were included. Pressure and flow tracings at the level of the main PA were integrated to obtain volume-pressure loops throughout the cardiac cycle. The resulting patterns based on morphology (Image 1) and slope (Pattern 1 mean slope 16,11% vs Pattern 2 mean slope 10,37%) were analysed and classified into 2 groups: Pattern 1 and Pattern 2. RV end-systolic (iRVESV) and end-diastolic volumes (iRVEDV), RV ejection fraction, RV mass and presence of late gadolinium enhancement (LGE) at the RV insertion points were compared between groups using parametric and non-parametric tests. Results Patients with Pattern 1 showed significantly higher mPAP (46.03±11.62 vs. 35.77±8.10 mmHg) and iPVR (746.22±584.54 vs 319.56±306.21 dynes.s.cm-5.m2) and lower PCWP (11.8±7.6 vs 17.7±7.2 mmHg). Precapillary PH patients more frequently presented a Pattern 1 (n=27; 77.1% vs 10; 32.3%). In addition, patients with Pattern 1 had higher RV volumes (iRVEDV= 105.45±34.62 ml/m2 vs 84.22±35.0 ml/m2, p=0,002; iRVESV 65.05±27.59 ml/m2 vs 44.63±25.09 ml/m2, p=0,001), poorer RV function (RVEF 39.81±11.33% vs 48.96±10.90%; p=0,001), larger RV mass (27.95±9.46 vs 23,44±7.46 g/m2, p=0,045) and smaller left atrial size (24.18±11.47 vs 34.06±19.15 cm2, p<0,001) than patients with Pattern 2. The quantification of LGE was also higher in Pattern 1 as compared with Pattern 2 (5.4±2.4% vs 3.0±2.3%, p<0.001). Conclusion Volume-pressure loops at the level of the main PA may differentiate patterns of PA hemodynamic fluctuations that have different impact on RV performance regardless the PH severity within the wide spectrum of PH.Volume-pressure loop patterns

Subclinical myocardial fibrosis is almost ubiquitous in the hearts of older British persons: 'MyoFit46' cardiovascular sub-study of the NSHD

Abstract Background Unprecedented numbers are now surviving to older age, but little is known about the burden or pattern of myocardial fibrosis in the asymptomatic elderly population. Previous 1.5 Tesla (T) cardiovascular magnetic resonance (CMR) studies found a prevalence of unexpected infarct-pattern late gadolinium enhancement (LGE) of 17-20% above 75 years but less is known about non-infarct pattern scar in this group. We investigated the prevalence, patterns, and clinical predictors of left ventricular (LV) scar in a large asymptomatic older age cohort. Methods CMR with a single 3T magnet was performed on participants all born in the same week in March 1946, as part of the longest running continued surveillance birth cohort: the National Survey of Health and Development. LV short-axis stack LGE imaging was performed using a free-breathing motion-corrected balanced steady-state free precession sequence with phase-sensitive inversion-recovery. Two blinded observers independently recorded the prevalence, extent, and pattern of LGE per participant. Logistic regression was used to study the association between clinicodemographic parameters and LGE. Results 460 participants were prospectively recruited of which 406 completed CMR with LGE imaging (77.8 ± 0.1 years, 44% male). 341 (84%) demonstrated LGE affecting a mean of 2.1±1.2 myocardial segments per participant (Figure 1). The commonest pattern of LGE was inferior right ventricular insertion point (RVIP), observed in 66.9%. Other patterns included (Figure 2): Linear mid-wall (19.6%) of which 38% were located in the inferior/lateral walls; subepicardial (12.1%); subendocardial infarct-pattern (8.8%); patchy/diffuse (1.6%); embolic LGE (0.6%). Sub-analysis was performed comparing those without significant unexpected fibrosis (LGE–) vs those with focal fibrosis (LGE+, excluding RVIP and those participants with a known history of prior myocardial infarction). LGE+ participants were more likely to be female (71.7% vs 49.1%, p<0.001) or diabetic (11.3% vs 5.1%, p=0.05), had a higher body surface area (BSA, 1.9 vs 1.8 m2, p<0.001), weight (80.1 vs 72.8 kg, p<0.001), LV indexed end systolic volume (24.2 vs 20.4 ml/m2, p=0.001) and LV indexed mass (59.2 vs 55.4 g/m2, p<0.001), and a lower LV ejection fraction (67.9 vs 71.8%, p<0.001) In multivariable logistic regression: BSA, LV indexed mass, LV ejection fraction and diabetic status were independently associated with LGE+ status (odds ratios [95% confidence intervals]: 9.4 [0.7–3.8]; 1.0 [0.01–0.05]; 0.9 [-0.08--0.02]; and 2.5 [0.03–1.7] respectively, p<0.05). Conclusion Advanced PSIR MOCO LGE imaging at 3T reveals that the majority (84%) of asymptomatic British persons above the age of 75 harbour unexpected ‘subclinical’ focal fibrosis, with a substantial proportion of these scars consistent with probable historical myocarditis events. Further work will now explore the life-course determinants of this scar burden in the older age human heart.

The Importance of Cardiac Magnetic Resonance in the Assessment Risk of Cardiac Arrhythmias in Patients with Arterial Hypertension.

Objectives: Arterial hypertension (AH) is one of the major risk factors for cardiovascular diseases. An association between untreated AH and arrhythmia is observed. Cardiac magnetic resonance (CMR) assesses myocardial fibrosis by detecting foci of late gadolinium enhancement (LGE). Clinical significance of LGE at the right ventricular insertion point (RVIP) is not fully established. This study aimed to assess the relationship between the presence of LGE at the RVIP determined by CMR and the incidence of arrhythmia in a group suffering from arterial hypertension. Methods: The study group consisted of 81 patients with AH (37 men and 44 women, age: 56.7 ± 7.1 years). All subjects underwent CMR and 24 h Holter ECG monitoring. Two subgroups were distinguished in the study group based on the criterion of the presence of LGE at the RVIP in CMR. The RVIP+ subgroup consisted of patients with LGE at the RVIP, while the RVIP- group consisted of patients without LGE at the RVIP. Results: The RVIP+ subgroup was characterized by higher maximum and minimum heart rates in 24 h Holter ECG recordings compared to the RVIP- subgroup (p < 0.05). The RVIP+ subgroup had a statistically significantly higher number of single premature supraventricular beats, supraventricular tachycardias, and single premature ventricular beats than the RVIP- subgroup (p < 0.05). Regression analysis documented that a longer duration of AH (counted from diagnosis) as well as the occurrence of LGE at the RVIP (assessed by CMR) are independent risk factors for arrhythmia (p < 0.05). Conclusions: Due to the possibility of detecting LGE at the RVIP, CMR may be a useful diagnostic method in estimating the risk of arrhythmias in the group of patients with AH.

THE IMPORTANCE OF CARDIAC MAGNETIC RESONANCE IMAGING IN THE ASSESSMENT OF THE RISK OF CARDIAC ARRHYTHMIAS IN PATIENTS WITH ARTERIAL HYPERTENSION

Objective: Arterial hypertension leads to organ changes, including left ventricular hypertrophy. The increased mass of left ventricle increases the risk of cardiac arrhythmias, which enhances the risk of sudden cardiac death. Cardiac magnetic resonance imaging (CMRI) can identify the presence of myocardial fibrosis by assessing late gadolinium enhancement (LGE). The aim of the study was to assess the relationship between the presence of late gadolinium enhancement at the right ventricular insertion point (RVIP) determined by CMRI and the occurrence of cardiac arrhythmias in patients with arterial hypertension. Design and method: 30 patients with essential hypertension were qualified for the study, 18 men and 12 women, the average age of the subjects was 55.5 ± 12.4 years. All subjects underwent cardiac magnetic resonance imaging and 24-hour Holter ECG monitoring. Based on the presence of LGE at the right ventricular insertion point, assessed by CMRI, the subjects were divided into two subgroups. The first subgroup consisted of subjects with LGE at the right ventricular insertion point (RVIP + subgroup), while the second subgroup consisted of subjects without LGE at the right ventricular insertion point (RVIP - subgroup). Results: Subjects with LGE at the right ventricular insertion point were characterized by higher maximum and minimum heart rates in 24-hour Holter ECG recordings compared to subjects without LGE at the right ventricular insertion point (p &lt; 0.05). In subjects with LGE at the right ventricular insertion point, Holter ECG evaluation revealed a statistically significantly higher number of single premature supraventricular beats, single premature ventricular beats and supraventricular tachycardias compared to subjects without LGE at the right ventricular insertion point (p &lt; 0.05). The regression analysis performed showed that a longer time from the diagnosis of hypertension and the occurrence of LGE at the right ventricular insertion point assessed using CMRI are independent risk factors for cardiac arrhythmias (p &lt; 0.05). Conclusions: Cardiac magnetic resonance imaging by identifying of late gadolinium enhancement at the right ventricular insertion point may be a useful diagnostic method in assessing the risk of cardiac arrhythmias in a group of patients with arterial hypertension.

Right ventricular fibrosis in adults with uncorrected secundum atrial septal defect and pulmonary hypertension: a cardiovascular magnetic resonance study with late gadolinium enhancement, native T1 and extracellular volume.

Right ventricular (RV) fibrosis represents both adaptive and maladaptive responses to the overloaded RV condition. Its role in pulmonary hypertension (PH) associated with secundum atrial septal defect (ASD), which is the most common adult congenital heart disease (CHD), remains poorly understood. We enrolled 65 participants aged ≥18 years old with uncorrected secundum ASD who had undergone clinically indicated right heart catheterization (RHC), divided into the non-PH group (n = 7), PH group (n = 42), and Eisenmenger syndrome (ES) group (n = 16). We conducted cardiovascular magnetic resonance (CMR) studies with late gadolinium enhancement (LGE) imaging, native T1 mapping, and extracellular volume (ECV) measurement to evaluate the extent and clinical correlates of RV fibrosis. LGE was present in 94% of the population and 86% of the non-PH group, mostly located at the right ventricular insertion point (RVIP) regions. LGE in the septal and inferior RV region was predominantly observed in the ES group compared to the other groups (p = 0.031 and p < 0.001, respectively). The mean LGE scores in the ES and PH groups were significantly higher than those in the non-PH group (3.38 ± 0.96 vs. 2.74 ± 1.04 vs. 1.57 ± 0.79; p = 0.001). The ES and PH groups had significantly higher degrees of interstitial RV fibrosis compared to those in the non-PH group, indicated by native T1 (1,199.9 ± 68.9 ms vs. 1,131.4 ± 47.8 ms vs. 1,105.4 ± 44.0 ms; p < 0.001) and ECV (43.6 ± 6.6% vs. 39.5 ± 4.9% vs. 39.4 ± 5.8%; p = 0.037). Additionally, native T1 significantly correlated with pulmonary vascular resistance (r = 0.708, p < 0.001), RV ejection fraction (r = -0.468, p < 0.001) and peripheral oxygen saturation (r = -0.410, p = 0.001). In patients with uncorrected secundum ASD, RV fibrosis may occur before the development of PH and progressively intensify alongside the progression of PH severity. A higher degree of RV fibrosis, derived from CMR imaging, correlates with worse hemodynamics, RV dysfunction, and poorer clinical conditions.

Subendocardial Involvement as an Underrecognized LGE Subtype Related to Adverse Outcomes in Hypertrophic Cardiomyopathy

BackgroundLate gadolinium enhancement (LGE) has been established as an independent predictor for adverse outcomes in hypertrophic cardiomyopathy (HCM). However, the prevalence and clinical significance of some LGE subtypes have not been well demonstrated. ObjectivesIn this study, the authors sought to investigate the prognostic value of subendocardium-involved LGE pattern and location of right ventricle insertion points (RVIPs) with LGE in HCM patients. MethodsIn this single-center retrospective study, 497 consecutive HCM patients with LGE confirmed by cardiac magnetic resonance (CMR) were included. Subendocardium-involved LGE was defined as LGE involving subendocardium not corresponding to a coronary vascular distribution. Subjects with ischemic heart disease that would contribute to subendocardial LGE were excluded. Endpoints included a composite of heart failure–related events, arrhythmic events, and stroke. ResultsOf the 497 patients, subendocardium-involved LGE and RVIP LGE were observed in 184 (37.0%) and 414 (83.3%), respectively. Extensive LGE (≥15% of left ventricular mass) was detected in 135 patients. During a median follow-up of 57.9 months, 66 patients (13.3%) experienced composite endpoints. Patients with extensive LGE had a significantly higher annual incidence of adverse events (5.1% vs 1.9% per year; P < 0.001). However, spline analysis showed that the association between LGE extent and HRs for adverse outcomes tended to be nonlinear. The risk of composite endpoint increased with percentage increase in LGE extent in patients with extensive LGE, whereas a similar trend was not observed in patients with nonextensive LGE (<15%). In patients with extensive LGE, LGE extent significantly correlated with composite endpoints (HR: 1.05; P = 0.03) after adjusting for left ventricular ejection fraction <50%, atrial fibrillation, and nonsustained ventricular tachycardia, whereas in patients with nonextensive LGE, subendocardium-involved LGE rather than LGE extent was independently associated with adverse outcomes (HR: 2.12; P = 0.03). RVIP LGE was not significantly associated with poor outcomes. ConclusionsIn HCM patients with nonextensive LGE, the presence of subendocardium-involved LGE rather than LGE extent is associated with unfavorable outcomes. Given that the prognostic value of extensive LGE has been broadly recognized, subendocardial involvement as an underrecognized LGE pattern shows the potential to improve risk stratification in HCM patients with nonextensive LGE.

68Ga-FAPI PET/CT for molecular assessment of fibroblast activation in right heart in pulmonary arterial hypertension: a single-center, pilot study

BackgroundPositron emission tomography (PET) imaging with radiolabeled fibroblasts activation protein inhibitor (FAPI) provides the opportunity to directly visualize fibrosis. This study aimed to investigate the feasibility of 68Ga-FAPI PET imaging in assessing right ventricular (RV) fibrotic remodeling and the relationship between FAPI uptake with parameters of pulmonary hemodynamics and cardiac function in pulmonary arterial hypertension (PAH) patients. MethodsIn this pilot study, sixteen PAH patients were enrolled to participate in cardiac 68Ga-FAPI PET/CT imaging. All patients underwent right heart catheterization and echocardiography for assessment of pulmonary hemodynamics and cardiac function within seven days. Cardiac FAPI uptake was visually assessed and quantified as maximum standardized uptake value (SUVmax). ResultsTwelve PAH patients exhibited FAPI uptake in RV free wall and insertion point. The overall activity of FAPI accumulated in the RV free wall (SUVmax: 2.5 ± 1.8, P < 0.001) and insertion point (SUVmax:2.5 ± 1.7, P < 0.001) was significantly upregulated compared to left ventricle (SUVmax:1.5 ± 0.5). Patients with tricuspid annular plane systolic excursion (TAPSE) < 17 mm presented significantly higher uptake than those with TAPSE ≥ 17 mm in both RV free wall (SUVmax: 3.4 ± 1.9 vs 1.7 ± 1.1, P = 0.010) and insertion point (SUVmax: 3.4 ± 1.9 vs 1.6 ± 0.7, P = 0.028), indicating RV uptake of FAPI was associated with RV dysfunction. There was significant positive correlation between cardiac FAPI uptake and total pulmonary resistance and the level of N-terminal pro b-type natriuretic peptide. Conclusions68Ga-FAPI PET/CT imaging is feasible to directly visualize fibrotic remodeling of RV in patients with PAH.

Cardiac structure discontinuities revealed by ex-vivo microstructural characterization. A focus on the basal inferoseptal left ventricle region

BackgroundWhile the microstructure of the left ventricle (LV) has been largely described, only a few studies investigated the right ventricular insertion point (RVIP). It was accepted that the aggregate cardiomyocytes organization was much more complex due to the intersection of the ventricular cavities but a precise structural characterization in the human heart was lacking even if clinical phenotypes related to right ventricular wall stress or arrhythmia were observed in this region. MethodsMRI-derived anatomical imaging (150 µm3) and diffusion tensor imaging (600 µm3) were performed in large mammalian whole hearts (human: N = 5, sheep: N = 5). Fractional anisotropy, aggregate cardiomyocytes orientations and tractography were compared within both species. Aggregate cardiomyocytes orientation on one ex-vivo sheep whole heart was then computed using structure tensor imaging (STI) from 21 µm isotropic acquisition acquired with micro computed tomography (MicroCT) imaging. Macroscopic and histological examination were performed. Lastly, experimental cardiomyocytes orientation distribution was then compared to the usual rule-based model using electrophysiological (EP) modeling. Electrical activity was modeled with the monodomain formulation. ResultsThe RVIP at the level of the inferior ventricular septum presented a unique arrangement of aggregate cardiomyocytes. An abrupt, mid-myocardial change in cardiomyocytes orientation was observed, delimiting a triangle-shaped region, present in both sheep and human hearts. FA's histogram distribution (mean ± std: 0.29 ± 0.06) of the identified region as well as the main dimension (22.2 mm ± 5.6 mm) was found homogeneous across samples and species. Averaged volume is 0.34 cm3 ± 0.15 cm3. Both local activation time (LAT) and morphology of pseudo-ECGs were strongly impacted with delayed LAT and change in peak-to-peak amplitude in the simulated wedge model. ConclusionThe study was the first to describe the 3D cardiomyocytes architecture of the basal inferoseptal left ventricle region in human hearts and identify the presence of a well-organized aggregate cardiomyocytes arrangement and cardiac structural discontinuities. The results might offer a better appreciation of clinical phenotypes like RVIP-late gadolinium enhancement or uncommon idiopathic ventricular arrhythmias (VA) originating from this region.

The discrepancy between FDG uptake and myocardial fibrosis in patients with pulmonary arterial hypertension – PET/MRI study

Abstract Background Inflammatory processes play an important role in pulmonary arterial hypertension (PAH) pathophysiology. We previously confirmed that in case of right ventricle (RV) failure, changes of cytokines' levels are correlated with myocardial metabolic and hemodynamic alterations observed in PET/MRI hybrid imaging. Presence of late gadolinium enhancement (LGE) in RV insertion points (RVIPs) has been found in majority of PAH patients and is often recognized as evidence of myocardial fibrosis due to RV pressure overload. As qualitative and/or quantitative assessments of LGE may vary due to natural PAH progression or specific therapy, we hypothesized that simple presence of LGE at RVIPs is not unequivocal to fibrotic tissue (without metabolic activity). Purpose To check the relationship between LGE mass and 18F-fluorodexyglucose uptake in RV insertion points in PAH patients using PET/MRI hybrid imaging. Methods Twenty-eight clinically stable PAH patients (49.9±15.9 years) had simultaneous PET/MRI scans during baseline and follow up (FU) visits, Figure. 18F-fluorodexyglucose (FDG) was used as a tracer and its cardiac uptake was presented as a maximum standardized uptake value (SUV) for RV insertion points (SUV in RVIPS). Septal delayed enhancement mass was quantified in RVIPs and presented as LGE mass. Occurrences of clinical end-points (CEP, defined as death or clinical deterioration) were assessed during 24 months observation. Results LGE was found in RVIPs of all PAH patients. Mean LGE mass was 6.32±4.41 g and mean SUV in RVIPS was 7.28±5.36. Follow up values were 8.01±7.75g (p=0.4) and 5.80±3.16 (p=0.16), respectively. We observed significant correlation between baseline SUV in RVIPS and mean pulmonary pressure, mPAP (r=0.49, p=0.04) but no correlation was found between LGE mass and SUV in RVIPS (in both baseline and FU scans). Between baseline and follow up visits, 16 patients had CEP and needed PAH therapy escalation. CEP+ group of PAH patients presented higher baseline LGE mass (7.53±4.75 vs 3.92±2.21, p=0.04) and SUV in RVIPS (7.27±5.42 vs 6.01±4.52, p=0.4). In all CEP patients who initiated prostacycline therapy and survived (n=8, 50%), SUV in RVIPS decreased in FU PET scans together with an increase in LGE mass in MRI. At FU visits we also observed significant improvement of MRI-derived RV ejection fraction (45.1±9.6% to 52.4±12.9%, p=0.01), and mPAP (50.5±18.3 to 42.8±18.6 mmHg, p=0.03). Conclusions Effective PAH therapy have an impact on both LGE mass and FDG uptake in cardiac local tissue changes. Since there was no correlation between LGE mass and FDG uptake RV insertion points, the question arises what the cause of these LGE changes is. Increased fibrosis should cause diminished local glucose metabolism. This phenomenon opens new questions concerning pathophysiology processes in RVIPs and requires confirmation on bigger PAH population. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Center for Science in Poland

Late gadolinium enhancement patterns in severe symptomatic high-gradient aortic stenosis

Abstract Background Left ventricular (LV) remodeling in patients with severe aortic valve stenosis (AS) is a complex process that goes beyond hypertrophic response and may involve reparative/replacement fibrosis. Currently, cardiac magnetic resonance (CMR) is the gold-standard imaging technique for detecting focal myocardial fibrosis through late gadolinium enhancement (LGE). However, myocardial fibrosis prevalence and distribution is quite variable among series. Our goal was to assess LGE prevalence and distribution pattern in severe symptomatic high-gradient AS. Methodology Single-center prospective cohort of 132 patients with severe symptomatic high-gradient AS (mean age 73±11 years; 48% male, mean valvular transaortic gradient 60±20 mmHg; mean aortic valve area 0.7±0.2 cm2/m2; mean LV ejection fraction by 2D echocardiogram 58±9%), all with normal flow (except one) undergoing surgical aortic valve replacement. Those with previous history of acute myocardial infarction, ischemic cardiomyopathy or other cardiomyopathy were excluded. All patients performed 1.5T CMR assessment with LV myocardium tissue characterization prior to surgery. Segmental LGE presence was assessed by two independent operators and classified according to the AHA 16 segment model, using 5-standard deviations from remote myocardium as the signal intensity cut-off for LGE identification and quantification. Results Overall, 96 patients (74%) had non-ischemic LGE (median LGE mass 3.2 g [IQR 0.2–8.3] g; median percentage of LGE myocardial mass 2.5% [IQR 0.1–6.1]%); 22 patients [17%] with exclusively junctional LGE); in one patient an incidental ischemic scar (subendocardial distribution) was identified. No cases of subepicardial distribution were found. Intramyocardial LGE was most frequently observed in basal and mid-anterior and inferior interventricular septum – see Figure 1. In these segments, LGE was most often junctional at right-ventricular insertion points (54%), followed by mid-wall LGE (32%) or both sites involvement (14%). Conclusion LGE is frequent in symptomatic high-gradient AS patients with preserved left ventricular ejection fraction, most often presenting as junctional enhancement in basal/mid-anterior and inferior interventricular septum. Future studies may address whether distinct LGE patterns may impact patient prognosis. Funding Acknowledgement Type of funding sources: None.

Myocardial extracellular volume quantification by cardiac CT in pulmonary hypertension: Comparison with cardiac MRI

PurposeMyocardial extracellular volume (ECV) measured by cardiac magnetic resonance imaging (MRI) has been suggested as a marker of disease severity in pulmonary hypertension (PH). However, consistency between ECVs quantified by computed tomography (CT) and MRI has not been sufficiently investigated in (PH). We investigated the utility of CT-ECV in PH, using MRI-ECV as a reference standard. MethodWe evaluated 20 patients with known or suspected PH who underwent dual-energy CT, cardiac MRI, and right heart catheterization. We used Pearson correlation analysis to investigate correlations between CT-ECV and MRI-ECV. We also assessed correlations between ECV and mean pulmonary artery pressure (mPAP). ResultsCT-ECV showed a very strong correlation with MRI-ECV at the anterior (r = 0.83) and posterior right ventricular insertion points (RVIPs) (r = 0.84). CT-ECV and MRI-ECV were strongly correlated in the septum and left ventricular free wall (r = 0.79–0.73) but weakly correlated in the right ventricular free wall (r = 0.26). CT-ECV showed a strong correlation with mPAP in the anterior RVIP (r = 0.64) and a moderate correlation in the posterior RVIP and septum (r = 0.50–0.42). Compared with CT-ECV, MRI-ECV had a higher correlation with mPAP; however, the difference was not significant (anterior RVIP, r = 0.72 [MRI-ECV] vs. 0.64 [CT-ECV], p = 0.663; posterior RVIP, r = 0.67 vs. 0.50, p = 0.446). ConclusionDual-energy CT can quantify myocardial ECV and yield results comparable to those obtained using cardiac MRI. CT-ECV in the anterior RVIP could be a noninvasive surrogate marker of disease severity in PH.

Abstract 12567: Reduced Myocardial Strain is Associated With Myocardial Inflammation and Fibrosis on Cardiovascular Magnetic Resonance Imaging in Collegiate Athletes Recovering From SARS-CoV-2 Infection

Introduction: Myocarditis is an important cause of sudden cardiac death in competitive athletes. There have been reports of myocardial inflammation on cardiovascular magnetic resonance (CMR) in athlete and non-athlete populations after SARS-CoV-2 infection; however, their clinical and functional significance is not known. We sought to investigate the relationship between left ventricular (LV) strain and other CMR markers suggestive of myocardial inflammation or fibrosis. Hypothesis: Reduced myocardial strain is associated with the presence of CMR abnormalities suggestive of inflammation, fibrosis, or necrosis in athletes recovering from SARS-CoV-2 infection. Methods: Collegiate athletes (N = 123) underwent a comprehensive CMR exam including strain encoded (SENC) imaging. We analyzed LV global longitudinal strain (GLS) across five groups defined by the presence or absence of late gadolinium enhancement (LGE), and T1 or T2 abnormalities. Myocarditis diagnosis on CMR required both abnormal T1 or LGE, and abnormal T2, in the same LV segment. Results: We enrolled 11 COVID negative control athletes (Group 1). Among COVID positive athletes, 42 had no abnormalities on CMR (Group 2), 31 had isolated right ventricular insertion point (RVIP) LGE (Group 3), 28 had LGE beyond RVIP (Group 4), and 11 athletes had myocarditis (Group 5). GLS was significantly lower in Groups 3, 4, and 5 compared with negative controls (p&lt;0.05, Figure 1). There was a deterioration in GLS as CMR abnormalities progressed from control athletes to those with LGE and myocarditis. There was no significant difference in LV ejection fraction between the 5 groups. Conclusions: In conclusion, SARS-CoV-2 infection in collegiate athletes leads to subtle abnormalities in cardiac function detected by GLS that correlate with abnormal mapping and LGE suggestive of myocardial inflammation and fibrosis. The clinical significance of these abnormalities remains to be determined.

Atrioventricular plane displacement and regional contribution to stroke volume to predict outcome in pulmonary arterial hypertension

Abstract Background Patients with pulmonary arterial hypertension (PAH) exhibit high mortality, partially related to right heart failure. Right ventricular (RV) volumes and ejection fraction (EF) can be measured accurately with cardiac magnetic resonance (CMR), but EF is a crude measure of cardiac function. Additional methods for risk assessment and prognosis are of value. Stroke volume (SV) is generated by longitudinal, lateral and septal myocardial contraction. Longitudinal contribution to SV (SVlong%) generated from the atrioventricular displacement (AVPD) is the major contributor to SV in both the left ventricle (LV) and RV. AVPD in both sides and LVSVlong% are lower in patients with PAH compared to controls. However, it is unknown if altered AVPD or regional contributions to SV are prognostic in patients with PAH. The aim of this study was therefore to evaluate if AVPD, longitudinal, lateral or septal contribution to LVSV and RVSV are associated with death or lung transplantation in patients with PAH. Purpose To evaluate if biventricular AVPD, and regional contributions to SV are associated with outcome in patients with PAH. Methods Seventy-one patients with PAH and 20 sex and age-matched healthy controls underwent CMR. Endocardial and epicardial borders and RV insertion points were defined in end diastole and end systole in cine short-axis stacks to compute biventricular volumes, SVlat% and SVsept%. Eight atrioventricular points were defined in end diastole and end systole in 2-, 3- and 4-chamber cine long-axis views, for computation of AVPD and SVlong%. Cut-off values for survival analysis were defined as above or below mean ± 2 standard deviations from the healthy controls. Outcome was defined as death or lung-transplantation. Results Median follow-up time was 3.6 [IQR 3.7] years. AVPD, SVlong%, SVlat% in both ventricles and SVsept% were altered in PAH compared to controls. Transplantation-free survival was lower with values below cut-off for LV-AVPD (hazard ratio (HR)=2.1, 95% CI: 1.2–3.9, p=0.02) and RV-AVPD (HR=9.8, 95% CI: 4.6–21.1, p=0.005) (fig 1). In cox regression analysis, decreased LV-AVPD and RV-AVPD inferred lower transplantation-free survival (LV: HR=1.16 per mm decrease, p=0.007; RV: HR=1.11 per mm decrease, p=0.01) (table 1). LVEF, RVEF, LV-SVlong%, RV-SVlong%, LV-SVlat%, RV-SVlat% or SVsept% did not affect outcome (table 1). Conclusions Decreased left and right AVDP were associated with decreased transplantation-free survival in patients with PAH. There were no associations between ejection fraction, longitudinal, lateral or septal contribution to stroke volume. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Skåne University Hospital, Region of Skåne Southern Healthcare Region of Sweden

Prognostic value of late gadolinium enhancement mass index in patients with pulmonary arterial hypertension

PurposeDysfunction of the right ventricle (RV) is an important determinant of survival in patients with pulmonary arterial hypertension (PAH). The presence of late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR) at RV insertion points (RVIPs) has been found in majority of PAH patients and was associated with parameters of RV dysfunction. We hypothesize, that more detailed quantification of LGE may provide additional prognostic information. Material and methodsTwenty-eight stable PAH patients (mean age 49.9 ​± ​15.9 years) and 12 healthy subjects (control group, 44.8 ​± ​13.5 years) were enrolled into the study. Septal LGE mass was quantified at the RVIPs and subsequently indexed by subject’s body surface area. Mean follow-up time of this study was 16.6 ​± ​7.5 months and the clinical end-point (CEP) was defined as death or clinical deterioration. ResultsMedian LGE mass index (LGEMI) at the RVIPs was 2.75 ​g/m2 [1.41–4.85]. We observed statistically significant correlations between LGEMI and hemodynamic parameters obtained from right heart catheterization – mPAP (r ​= ​0.61, p ​= ​0.001); PVR (r ​= ​0.52, p ​= ​0.007) and from CMR – RVEF (r ​= ​−0.54, p ​= ​0.005); RV global longitudinal strain (r ​= ​0.42, p ​= ​0.03). Patients who had CEP (n ​= ​16) had a significantly higher LGEMI (4.49 [2.75–6.17] vs 1.67 [0.74–2.7], p ​= ​0.01); univariate Cox analysis confirmed prognostic value of LGEMI. Furthermore, PAH patients with LGEMI higher than median had worse prognosis in Kaplan-Meier analysis (log-rank test, p ​= ​0.0006). ConclusionsThe body surface indexed mass of LGE at RV septal insertion points are suggestive of RV hemodynamic dysfunction and could be a useful non-invasive marker of PAH prognosis.

Clinical importance of late gadolinium enhancement at right ventricular insertion points in otherwise normal hearts.

Late gadolinium enhancement (LGE) has an established prognostic value in otherwise normal hearts, when detected with a subepicardial or intramyocardial pattern; nevertheless, the clinical relevance of isolated right ventricular insertion point (RVIP) LGE is yet to be defined. From a retrospectively identified cohort of 2000 consecutive patients undergoing CMR, we selected 420 patients according to study's inclusion and exclusion criteria (270 males, mean age 38 ± 17years) with apparently normal hearts: besides 36 patients with non-ischemic pattern LGE (other-LGE group), we found isolated RVIP-LGE in 44 patients and absence of LGE (no-LGE group) in 340 patients. Clinical follow-up was performed for a median of approximately 6years. Primary composite endpoint included cardiac death, resuscitated cardiac arrest, and appropriate implantable cardiac defibrillator shock. Prevalence of cardiac events was significantly lower in RVIP-LGE than in the other-LGE group (p = 0.006). Kaplan Meier curve analysis demonstrated no significant differences between patients with RVIP-LGE and no-LGE for the primary endpoint. On contrast, patients with other-LGE had worse prognosis than those with RVIP-LGE or no-LGE (p < 0.0001). RVIP-LGE in subjects without additional evidence of cardiac damage does not convey worse prognosis when compared to subjects without LGE and it should not be considered a marker of disease. Its diagnostic and prognostic significance is to be considered irrelevant.

Prevalence and pattern of cardiovascular magnetic resonance late gadolinium enhancement in highly trained endurance athletes

BackgroundIntensive endurance exercise may induce a broad spectrum of right ventricular (RV) adaptation/remodelling patterns. Late gadolinium enhancement (LGE) has also been described in cardiovascular magnetic resonance (CMR) of some endurance athletes and its clinical meaning remains controversial. Our aim was to characterize the features of contrast CMR and the observed patterns of the LGE distribution in a cohort of highly trained endurance athletes.MethodsNinety-three highly trained endurance athletes (> 12 h training/week at least during the last 5 years; 36 ± 6 years old; 53% male) and 72 age and gender-matched controls underwent a resting contrast CMR. In a subgroup of 28 athletes, T1 mapping was also performed.ResultsHigh endurance training load was associated with larger bi-ventricular and bi-atrial sizes and a slight reduction of biventricular ejection fraction, as compared to controls in both genders (p < 0.05). Focal LGE was significantly more prevalent in athletes than in healthy subjects (37.6% vs 2.8%; p < 0.001), with a typical pattern in the RV insertion points. In T1 mapping, those athletes who had focal LGE had higher extracellular volume (ECV) at the remote myocardium than those without (27 ± 2.2% vs 25.2 ± 2.1%; p < 0.05).ConclusionsHighly trained endurance athletes showed a ten-fold increase in the prevalence of focal LGE as compared to control subjects, always confined to the hinge points. Additionally, those athletes with focal LGE demonstrated globally higher myocardial ECV values. This matrix remodelling and potential presence of myocardial fibrosis may be another feature of the athlete’s heart, of which the clinical and prognostic significance remains to be determined.

P5258Native T1 time of right ventricular insertion points by CMR: relation with invasive hemodynamics and outcome in HFPEF

Abstract Background Increased afterload to the right ventricle (RV) has been shown to induce myocardial fibrosis at the RV insertion points (RVIPs). Such changes can be discrete but potentially detected by cardiac magnetic resonance (CMR) T1-mapping. Whether RVIP fibrosis is associated with prognosis in heart failure with preserved ejection fraction (HFpEF) is unknown. Methods We prospectively investigated 167 consecutive HFpEF patients, a population frequently suffering from postcapillary pulmonary hypertension (PH), who underwent CMR including T1-mapping. 92,8% also underwent right heart catheterization for hemodynamic assessment. Kaplan–Meier analysis, cox regression analysis and Spearman's rank order correlation were applied as statistical methods. The parameter with the strongest discriminative power of each group (clinical, hemodynamic and CMR) by receiver operating curve analysis was selected to the enter the multivariate cox model. Results Native T1 times were 995±73 ms at the anterior and 1040±90 ms at the inferior RVIP. By Spearman's rank order testing, RVIP T1 times were significantly correlated with pulmonary artery pressure (mean PAP, r=0.313 and 0.311 for anterior and inferior RVIP, respectively), pulmonary artery wedge pressure (r=0.301 and 0.251) and right atrial pressure (r=0.245 and 0.185; p for all&lt;0.05). During a mean follow-up of 43.2±22.6 months, 30 (18.0%) subjects died. By multivariable Cox regression, NTproBNP (Hazard ratio [HR] 2.105, 95% confidence interval [CI] 1.332–3.328; p=0.001), systolic PAP (HR 1.618, 95% CI 1.175–2.230; p=0.003), and native T1 time of the anterior RVIP (HR 1.659, 95% CI 1.125–2.445; p=0.011) were significantly associated with outcome. Also, by Kaplan-Meier analysis, T1 time at the anterior RVIP had a significant effect on survival (log-rank, p=0.002). Kaplan Meier Curve Conclusions Interstitial expansion of the anterior RVIP as detected by CMR T1-mapping reflects hemodynamic alterations, and is independently related with prognosis in HFpEF.

P596Early markers of right ventricular involvement in experimental chronic postcapillary pulmonary hypertension

Abstract Background In chronic pulmonary hypertension (PH), the main cause of death is right ventricular (RV) failure. However, the onset of RV dysfunction varies significantly among patients. Early recognition of RV maladaptation would be highly relevant. Purpose To identify cardiac magnetic resonance (CMR)-derived parameters affected in early stages of PH before the development of RV dysfunction. Methods Experimental chronic PH was generated by pulmonary vein banding in 76 pigs whereas 14 animals underwent sham operation. Animals were followed-up monthly with right heart catheterization (RHC) and immediate CMR for a maximum of 9 months. CMR exams included a T1-mapping sequence to quantify equilibrium-extracellular volume (ECV) at the RV insertion points. Pairs of RHC and CMR examinations were compared among controls and PH with normal RV ejection fraction (RVEF≥55%) or reduced (REVF&lt;55%) using ANCOVA test with Bonferroni correction. All procedures followed the “Principles of laboratory animal care”. Results In the presence of PH confirmed by RHC and normal RVEF, the RV displays significant hypertrophy and increased myocardial native T1 and ECV, despite preserved ventricular dimensions and PA flow (Fig 1B). In advanced stages of the disease, RV-AP uncoupling and reduced PA pulsatility develop together with RV dilatation and failure (Fig 1C). CMR parameters in sham and PH animals Sham controls (n=25 evaluations) PH with normal RVEF (n=155 evaluations) PH with low RVEF (n=70) RVEF (%) 62±5 61±4 47±8# RVEDV (mL/m2) 73±18 83±17 111±29# RVESV (mL/m2) 28±8 32±8 61±25# RV mass (g/m2) 17±4 23±5* 30±11# PA area (cm2/m2) 5.5±1.2 6.3±1.6 8.7±2.2# Native T1 anterior RVIP (ms) 983±75 1043±78* 1055±90# ECV anterior RVIP (%) 27±5 31±6* 36±7# Native T1 inferior RVIP (ms) 959±68 1022±71* 1032±99# ECV inferior RVIP (%) 25±5 31±6* 36±7# PA pulsatility (%) 29±6 27±7 21±3# Ea/Emax 40±16 47±11 97±65# RVEDV: RV end-diastolic volume; RVESV: RV end-systolic volume; RVIP: RV insertion point. *p&lt;0.05 1 vs. 2; #1 vs. 3. NativeT1: control, PH-normal RV, RV dysf Conclusion RV hypertrophy and ECV expansion are early mechanisms in RV adaptation to postcapillary PH, whereas ventricular and PA dilatation, RV-PA uncoupling and reduced pulsatility appear in more advanced stages concurring with systolic dysfunction. Acknowledgement/Funding The CNIC is supported by the Ministerio de Ciencia, Innovaciόn y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence

Native T1 time of right ventricular insertion points by cardiac magnetic resonance: relation with invasive haemodynamics and outcome in heart failure with preserved ejection fraction

Increased afterload to the right ventricle (RV) has been shown to induce myocardial fibrosis at the RV insertion points (RVIPs). Such changes can be discrete but potentially detected by cardiac magnetic resonance (CMR) T1-mapping. Whether RVIP fibrosis is associated with prognosis in heart failure with preserved ejection fraction (HFpEF) is unknown. We prospectively investigated 167 consecutive HFpEF patients, a population frequently suffering from post-capillary pulmonary hypertension, who underwent CMR including T1-mapping. About 92.8% also underwent right heart catheterization for haemodynamic assessment.Native T1 times were 995 ± 73 ms at the anterior and 1040 ± 90 ms at the inferior RVIP. By Spearman's rank order testing, RVIP T1 times were significantly correlated with pulmonary artery pressure (mean PAP, r = 0.313 and 0.311 for anterior and inferior RVIP), pulmonary artery wedge pressure (r = 0.301 and 0.251) and right atrial pressure (r = 0.245 and 0.185; P for all <0.05). During a mean follow-up of 43.2 ± 22.6 months, 30 (18.0%) subjects died. By multivariable Cox regression, NTproBNP [Hazard ratio (HR) 2.105, 95% confidence interval (CI) 1.332-3.328; P = 0.001], systolic PAP (HR 1.618, 95% CI 1.175-2.230; P = 0.003), and native T1 time of the anterior RVIP (HR 1.659, 95% CI 1.125-2.445; P = 0.011) were significantly associated with outcome. Also, by Kaplan-Meier analysis, T1 times at the anterior RVIPs had a significant effect on survival (log-rank, P = 0.002). Interstitial expansion of the anterior RVIP as detected by CMR T1-mapping reflects haemodynamic alterations, and is independently related with prognosis in HFpEF.