Right-left ventricular shape variations in tetralogy of Fallot: associations with pulmonary regurgitation

Background Relationships between right ventricular (RV) and left ventricular (LV) shape and function may be useful in determining optimal timing for pulmonary valve replacement in patients with repaired tetralogy of Fallot (rTOF). However, these are multivariate and difficult to quantify. We aimed to quantify variations in biventricular shape associated with pulmonary regurgitant volume (PRV) in rTOF using a biventricular atlas. Methods In this cross-sectional retrospective study, a biventricular shape model was customized to cardiovascular magnetic resonance (CMR) images from 88 rTOF patients (median age 16, inter-quartile range 11.8–24.3 years). Morphometric scores quantifying biventricular shape at end-diastole and end-systole were computed using principal component analysis. Multivariate linear regression was used to quantify biventricular shape associations with PRV, corrected for age, sex, height, and weight. Regional associations were confirmed by univariate correlations with distances and angles computed from the models, as well as global systolic strains computed from changes in arc length from end-diastole to end-systole. Results PRV was significantly associated with 5 biventricular morphometric scores, independent of covariates, and accounted for 12.3% of total shape variation (p < 0.05). Increasing PRV was associated with RV dilation and basal bulging, in conjunction with decreased LV septal-lateral dimension (LV flattening) and systolic septal motion towards the RV (all p < 0.05). Increased global RV radial, longitudinal, circumferential and LV radial systolic strains were significantly associated with increased PRV (all p < 0.05). Conclusion A biventricular atlas of rTOF patients quantified multivariate relationships between left–right ventricular morphometry and wall motion with pulmonary regurgitation. Regional RV dilation, LV reduction, LV septal-lateral flattening and increased RV strain were all associated with increased pulmonary regurgitant volume. Morphometric scores provide simple metrics linking mechanisms for structural and functional alteration with important clinical indices.

Comparison of mitral regurgitation severity assessments based on magnetic resonance imaging and echocardiography in patients with hypertrophic cardiomyopathy

Mitral regurgitation (MR), which is one of the factors responsible for heart failure symptoms and the development of atrial fibrillation, is an important feature of hypertrophic cardiomyopathy (HCM), and its presence affects which treatment options are chosen. Although cardiac magnetic resonance imaging (MRI) is considered the reference standard for assessing the regurgitant volume (RV) and fraction (RF), echocardiography is the most common method for assessing MR severity. Accordingly, the aim of this study was to compare the results of echocardiography and cardiac MRI for assessing MR severity in a cohort of patients with HCM. MR severity was assessed in 53 patients using cardiac MRI by determining the mitral RV (MRV) and mitral RF (MRF). The results were graded according to thresholds recommended in current guidelines. MR severity assessed by echocardiography was graded by integrating indices of severity. Greater than mild MR, as assessed using echocardiography, was present in 22 patients (41.5%) with HCM and in none of the control patients (p = 0.001). In all, 31 patients (58.5%) had no more than mild MR. When MR severity was assessed using different methods, either moderate (kappa = 0.44, 95% confidence interval = 0.21–0.67), poor or no agreement was found between MRI-derived and echocardiography-derived grades. HCM patients with echocardiography-derived moderate and severe MR had similar median MRVs and MRFs (p = 0.59 and p = 0.11, respectively). In HCM patients, cardiac MRI and echocardiography were at most in modest agreement in assessing MR severity. Importantly, echocardiography-derived moderate and severe MR were not distinguishable by either MRV or MRF.

Computational analysis of quantitative echocardiographic assessments of functional mitral regurgitation: Proximal Isovelocity Surface Area (PISA) methods

While proximal isovelocity surface area (PISA) method is one of the most common echocardiographic methods for quantitative mitral regurgitation (MR) assessment, accurate MR quantification remains challenging. This study examined the theoretical background of PISA, performed virtual echocardiography on computer models of functional MR, and quantified different sources of errors in PISA. For regurgitant flow rate measurement, the conventional 2D hemispherical PISA caused significant underestimation due to underestimation of PISA area, the multiplane 2D hemiellipsoidal and hemicylindrical PISA provided improved accuracy with better assumptions on PISA contour shape. With the direct capture of PISA area, the 3D-PISA was found to be the most accurate. However, it should be noted that PISA method is subject to systematic underestimation due to the Doppler angle effect, and systematic overestimation due to the “flow direction angle” between the regurgitant flow direction and the PISA contour normal direction. For regurgitant volume quantification, integrated PISA, when performed properly, was able to capture the dynamic MR and therefore was more accurate than peak PISA. In specific, integrated PISA using the sum of regurgitant flow rates is recommended.ObjectivesThe aim of this study was to evaluate the accuracy of different proximal isovelocity surface area (PISA) methods, examine their theoretical background, and quantify multiple sources of error in functional mitral regurgitation (MR) assessment.BackgroundWhile PISA method is one of the most common echocardiographic methods for MR severity assessment, it is associated with multiple sources of errors, and accurate MR quantification remains challenging.MethodsFive functional MR (FMR) computer models were created, validated and treated as phantom models. The phantom models have fully resolved and detailed flow fields in the left atrium (LA), left ventricle (LV) and cross the mitral valve, from which the reference values of mitral regurgitant flow rate and regurgitant volume can be obtained. The virtual PISA measurements (i.e., 3D and 2D PISA) were performed on the phantom models assuming optimal echo probe angulation and positioning. The results of different PISA methods were compared with the reference values.ResultsFor regurgitant flow rate measurements, compared to the reference values, excellent correlations were observed for 3D-PISA (R = 0.97, bias -24.4 ± 55.5 ml/s), followed by multiplane 2D hemicylindrical (HC)-PISA (R = 0.88, bias -24.1 ± 85.4 ml/s) and hemiellipsoidal (HE)-PISA (R = 0.91, bias -55.7 ± 96.6 ml/s), while weaker correlations were observed for single plane 2D hemispherical (HS)-PISA with large underestimation (PLAX view: R = 0.71, bias -77.6 ± 124.5 ml/s; A2Ch view: R = 0.69, bias -52.0 ± 122.0 ml/s; A4Ch view: R = 0.82, bias -65.5 ± 107.3 ml/s). For regurgitant volume (RV) quantification, integrated PISA presented improved accuracy over peak PISA for all PISA methods. For 3D-PISA, the bias in RV improved from -12.7 ± 7.8 ml (peak PISA) to -2.1 ± 5.3 ml (integrated PISA).ConclusionsIn FMR, conventional single plane 2D HS-PISA significantly underestimated MR, multiplane 2D PISA (HE-PISA and HC-PISA) improved the accuracy, and 3D-PISA is the most accurate. To better capture the dynamic feature of MR, integrated PISA using the sum of regurgitant flow rates is recommended.

Disproportionate mitral regurgitation: new entity or reflection of measurment errors?

Funding Acknowledgements Type of funding sources: None. Background The results of recent studies of transcatheter mitral valve repair proposed a new conceptual framework that categorized mitral regurgitation (MR) into proportionate (propMR) or disproportionate (dispropMR) according to the relationship between effective regurgitant orifice area (EROA) and left ventricular (LV) end-diastolic volume (EDV). Purpose To determine the prevalence of dispropMR in consecutive heart failure patients with reduced ejection fraction (HFrEF) undergoing clinically indicated echocardiography over one year period and to examine characteristics of this new entity. Methods We retrospectively identified 179 patients(age:69 ± 12 years, male:132[74%]) with HFrEF who were classified more than mild MR by performing echocardiographer. Following parameters of MR severity were analysed: regurgitant volume(PISA-based regurgitant volume[RVol-PISA] and RVol calculated by the difference of total LV stroke volume by LV planimetry and Doppler-estimated effective LV stroke volume[RVol-SV]), PISA-based EROA and regurgitant fraction (RF). Grading of MR severity based on RVol was performed (mild:&lt;30 ml, mild-moderate:30-44ml, moderate-severe:45-59 ml, severe:≥60 ml). The distinction between propMR and dispropMR was determined by using a proportionality scheme by Grayburn, considering ratio EROA/LVEDV. DispropMR was identified by the ratio greater than 0.14, while the others were classified as propMR. Results In our cohort, 49(27.4%)patients had dispropMR. Both MR groups were comparable in age and gender. DispropMR group had significantly smaller LV dimensions(LV end-diastolic diameter:59 ± 9mm vs. 65 ± 8mm,p &lt; 0.001; LVEDV:164 ± 54ml vs. 222 ± 60ml,p &lt; 0.001) and higher EF(41 ± 11% vs. 34 ± 9%, p &lt; 0.001). Higher proportion of primary MR was noted in dispropMR group(15[31%] vs. 4[3.3%] patients, p &lt; 0.001). Significant differences were observed in PISA-based quantification of MR between both groups (p &lt; 0.001, for all), whereas RVol-SV was comparable(p = 0.667;Figure A). Discrepant grading in MR severity between RVol-PISA and RVol-SV methods was observed(p &lt; 0.001), with significant high discordance in dispropMR(p &lt; 0.001) and no significant differences in propMR(p = 0.187;Figure B). Additionally, difference in RVol assessed by PISA method and SV method were more prominent in dispropMR (RVol difference: dispropMR:27 ml[17-46] vs. propMR:13 ml[-4 to 24],p &lt; 0.001). MR severity would be reclassified in a substantial proportion of dispropMR when considering RVol-SV. Conclusion Our results suggest that dispropMR may be found in roughly one fourth of echocardiographic studies in patients with HFrEF. DispropMR patients have less extensive LV remodelling and more severe MR based on PISA parameters compared to propMR. However, inconsistencies between parameters of MR severity in dispropMR might suggest echocardiographic limitations of quantitative grading of the MR severity or/and LV volume assessment rather than a new pathophysiological concept of disproportionate MR. Abstract Figure A, B

Cardiac magnetic resonance and B-natriuretic peptide: prognostic value in patients with asymptomatic chronic aortic regurgitation

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by Ministry of Health of the Czech Republic 17-28265A. Background Indication for surgical treatment in asymptomatic patients with severe aortic regurgitation (AR) is curretly based on 2-dimensional echocardiography derived left ventricle (LV) diameter and ejection fraction. Suboptimal sensitivity of this quideline-directed approach may lead to late intervention in a substantial number of patients. Purpose We aimed to develop a new prognostic stratification scheme based on novel imaging and biochemical markers of heart failure. Methods Consecutive patients with chronic severe AR not indicated for surgery per the current guidelines were enrolled into prospective multi-center study. Baseline examination consisted of B-natriuretic peptide (BNP); comprehensive echocardiography (ECHO) including 3-dimensional (3D) vena contracta area (VCA); comprehensive cardiac magnetic resonance (CMR) including regurgitant volume and fraction measurement, and extracellular volume (ECV); all imaging data were analysed in core lab. The perioperative myocardial biopsy from basal septum was performed in all surgically treated patients for histological myocardial fibrosis quantification by Picrosirius Red staining. Patient follow-up was every 6 months. The endpoint was a disease progression (indication for surgery per the current guidelines). Results In total, 132 patients were enrolled between 2015 and 2019, the endpoint occurred in 39 patients during a median follow-up of 1217 days. Baseline clinical data did not differ between patients with endpoint (surgical group) and stable patients (medical group). Baseline BNP levels were higher in the surgical group (57 vs. 20, P &lt; 0.01). Most baseline ECHO parameters did not differ, only 3D VCA, mitral inflow E-wave and flow reversal velocity in the descending aorta were significantly different between two groups (33 vs. 25 mm2, 61 vs 68 cm/s, 21 vs. 19 cm/s with P = 0.012, P = 0.019, P = 0.001). Both CMR-derived end-systolic and end-diastolic LV volumes were significantly different (all P &lt; 0.01); the LV ejection fraction was similar (61 vs. 61%, P = 0.83). The ECV was similar in both groups (24.2 vs. 24%, P = 0.69) and correlated well with histologically validated diffuse myocardial fibrosis (15%). CMR-derived regurgitant volume and fraction were significantly higher in the surgical group (58 vs. 36 ml, P &lt; 0.01 and 45 vs. 33%, P &lt; 0.01). Based on our results, we developed a multi-factorial scoring system combining the independent predictors of disease progression (specificity 79%, sensitivity 74%). Conclusion Baseline CMR-derived LV volumes, CMR-derived regurgitant fraction, and BNP levels can predict disease progression in asymptomatic patients with chronic severe aortic regurgitation. The novel multi-factorial scoring system might identify candidates of early surgical treatment but this hypothesis will require prospective clinical testing. Abstract Figure. Cardiac magnetic resonance imaging

Regurgitant volume to left ventricular end-diastolic volume ratio: another step to risk stratification in patients with secondary mitral regurgitation?

Funding Acknowledgements Type of funding sources: None. Background Quantitative evaluation of secondary mitral valve regurgitation (MR) remains an important yet challenging step in the evaluation of this entity. Its severity can be underestimated when using the proximal isovelocity surface area (PISA) method, which does not take left ventricular (LV) volume into account. Normalizing mitral regurgitant volume (Rvol) for the LV end-diastolic volume (EDV) might overcome this key limitation. This study aimed to investigate the prognostic implication of Rvol/EDV ratio in patients with secondary MR. Methods Patients with at least mild secondary MR and reduced left ventricular ejection fraction (&lt;50%) under optimal guidelines-directed medical therapy were retrospectively identified at a single-center. The cohort was divided into terciles according to the RVol/EDV ratio. The primary endpoint was all-cause mortality. Results A total of 572 patients (median age 70 years; 76% male) were included. Median LVEF was 35% (IQR 28-40) and LVEDV was 169 ml (IQR 132-215). Median measures of secondary MR were EROA 14 mm2 (IQR 8-22) and RegVol 23 ml (12-34). During a median follow-up of 3.8 years (interquartile range 1.8 to 6.2 years) there were 254 deaths (44%). The unadjusted mortality incidence increases across terciles distribution. Patients at the 2nd and 3rd terciles of the RVol/EDV ratio showed significantly higher mortality when compared to those at the 1st one (baseline reference) (figure 1). After multivariable analysis, terciles of the Rvol/EDV ratio remained independently associated with increased all-cause mortality (considering the 1st tercile as the reference; adjusted HR for the 2nd tercile 1.46 [95% CI 1.05- 2.02] p = 0.023; adjusted HR for 3rd tercile 1.56 [95% CI 1.09 – 2.22], p = 0.015). Conclusion In patients with secondary MR, Rvol/EDV ratio is independently associated with all-cause mortality. However, the appropriate cut-off to determine any kind of clinical decision remains to be determined. Abstract Figure.

Long-term outcome after transcatheter mitral annuloplasty for secondary mitral regurgitation

Funding Acknowledgements Type of funding sources: None. Background The long-term effects of transcatheter mitral valve annuloplasty (TMVA) for secondary mitral regurgitation is unknown. Purpose We studied the clinical outcome and the effects on left ventricular (LV) function and remodeling and on mitral regurgitation (MR) severity after TMVA using the Carillon annuloplasty device. Methods We analyzed 33 consecutive patients with symptomatic MR who were treated with TMVA at Leipzig University Hospital between 2012 and 2018. Echocardiography was performed before TMVA and at follow-up. MR severity was quantitatively assessed by regurgitant volume (calculated as LV total stroke volume – LV forward stroke volume) and regurgitant fraction (calculated as regurgitant volume / LV total stroke volume). Results Mean age was 80 ± 10 years, 19 patients were women. A Society of Thoracic Surgeons (STS) score of 8.1 ± 7.2% indicated high risk status for mitral valve surgery. In 26 patients, mitral regurgitation resulted from LV remodeling and LV dysfunction, 7 suffered from left atrial dilatation. LV ejection fraction at baseline was 38% (30-49%; median, interquartile range). During a mean follow-up time of 45 ± 20 months, 17 patients died, 2 patients withdraw consent, and 4 patients were lost. Of the remaining patients, 4 were hospitalized for decompensated heart failure, and 2 underwent additional transcatheter edge-to-edge mitral valve repair. At follow-up, NYHA functional class improved from 95% in class III/IV at baseline to 70% in class I/II with no patients in NYHA class IV (p &lt; 0.0001). Mitral regurgitant volume was reduced from 27mL (25-42mL) to 8mL (3-17mL) (p = 0.035) and regurgitant fraction from 43% (32-54%) to 11% (8-24%) (p = 0.020). LV end-diastolic volume index (92mL/m2 (71-107mL/m2) vs. 67mL/m2 (46-101mL/m2), p = 0.084) and end-systolic volumes index (51mL/m2 (44-69mL/m2) vs. 32mL/m2 (20-53mL/m2), p = 0.037) decreased. Thus, total stroke volume remained similar (38mL/m2 (33-43mL/m2) vs. 33mL/m2 (26-44mL/m2), p = 0.695) while LV ejection fraction increased (43% (31-49%) vs. 54% (46-57%), p = 0.032). Forward stroke volume, heart rate and forward cardiac output remained unchanged. Blood pressure was similar at baseline and at follow-up. Conclusion. Among high risk patients undergoing transcatheter mitral valve annuloplasty for symptomatic secondary MR, mortality was about 50% at 4 years. In the surviving patients, reduced MR severity was associated with fewer heart failure symptoms, reverse LV remodeling and improved LV function.

Abstract 15253: Significant Discrepancies in Quantification of Regurgitant Volume in Primary Mitral Regurgitation Observed on Multimodality Imaging: Is It Time for Reappraisal?

Introduction: Mitral valve regurgitation volume (RV) can be quantified using proximal isovelocity surface area (PISA) or stroke volume (SV). SV method incorporates mitral annulus (MA) diameter (assumed circular) on 2D transthoracic echo (2D TTE). However, MA area (MAA) can be precisely measured using 3D transesophageal echocardiographic (3DTEE) or computed tomography (CT). Hypothesis: We sought to compare RV obtained using a) PISA b) standard SV using MA diameter on 2D echo and c) modified SV using MAA on 3D TEE and d) MAA on CT. Methods: 37 patients (63±9 years, 81 % men) with severe primary mitral regurgitation (MR) undergoing surgery were prospectively recruited. RV was calculated using a) PISA b) standard SV method using MA diameter on 2D echo (0.785*diameter 2 MV *VTI MV -0.785*d 2 LVOT *VTI LVOT ) c) & d) modified SV methods where MAA (on 3D TEE and CT) were incorporated instead of MA diameter. Results: The mean MAA (cm 2 ) by 2DTTE, 3DTEE & CT were 10.7±3, 10.9 ±3 & 15.9 ±3. Mean RV (cc) by standard SV method, modified SV (3D TEE & CT) & PISA were 294±126, 276±82, 355±127 & 91±51, respectively. Correlations & agreements of SV-based RV are shown in Figure 1. RV was highest using CT-based MAA. The closest agreement was between 2D TTE & CT with a mean error (ME) of -61 cc. There was a large discrepancy in RV derived from PISA vs all SV methods, with a systemic overestimation using SV methods with root mean square errors (RMSE) ranging from 156 to 293 cc Figure 2. Conclusions: In severe MR,calculating RV using SV vs PISA yields vastly different values. The differences are exaggerated using modified SV method incorporating more accurate MAA on 3D TEE or CT. These techniques should not be interchanged to quantify MR.