Mitral valve prolapse morphofunctional features by cardiovascular magnetic resonance: more than just a valvular disease

Introduction Mitral valve (MV) prolapse (MVP) is a primary valvular abnormality. We hypothesized that additionally there are concomitant abnormalities of the left ventricle (LV) and MV apparatus in this entity even in the absence of significant mitral regurgitation (MR). Objective To characterize MV and LV anatomic and functional features in MVP with preserved LV ejection fraction, with and without significant MR, using cardiovascular magnetic resonance (CMR). Methods Consecutive MVP patients (n = 80, mean 52 years, 37% males) with preserved LV ejection fraction, and 44 controls (46 years, 52% males) by CMR were included, as well as 13 additional patients with “borderline” MVP. From cine images we quantified LV volumes, MV and LV anatomic measurements (including angle between diastolic and systolic annular planes, annular displacement, and basal inferolateral hypertrophy) and, using feature tracking, longitudinal and circumferential peak systolic strains. Results Significant MR was found in 46 (56%) MVP patients. Compared with controls, MVP patients had LV enlargement, basal inferolateral hypertrophy, higher posterior annular excursion, and reduced shortening of the papillary muscles. LV basal strains were significantly increased, particularly in several basal segments. These differences remained significant in patients without significant MR, and many persisted in “borderline” MVP. Conclusions In patients with MVP and preserved LV ejection fraction there is LV dilatation, basal inferolateral hypertrophy, exaggerated posterior annular displacement and increased basal deformation, even in the absence of significant MR or overt MVP. These findings suggest that MVP is a disease not only of the MV but also of the adjacent myocardium.

Semi-automated left ventricular endocardial detection versus hand-tracing in the measurement of left ventricular volumes and ejection fraction in daily clinical practice

Background The common method of assessing left ventricle (LV) volumes and ejection fraction (EF) is hand-tracing Biplane Simpson method. Alternatively, ultrasound vendors offer different semi-automated LV endocardial border detection software with anatomical intelligence to assess LV volumes and EF. By using speckle-tracking technique, this software tracks the LV endocardium throughout the cardiac cycle and computes the LV volumes in every image frame using the disk summation method from which a volume-curve is generated, and the EF is calculated using the maximum and minimum volumes obtained. Data on the performance of this method in comparison with the hand-tracing Biplane Simpson method in daily clinical practice is scarce. Purpose To determine the accuracy of LV volumes and EF using semi-automated LV endocardial detection tracing, and to compare the reproducibility of this method with the hand-tracing Biplane Simpson method, among operators with varying level of experience in echocardiography. Methods This was a single center retrospective observational study, conducted in year 2020. 127 patients, aged >18 years, who underwent clinically indicated transthoracic echocardiography were recruited. The echocardiographic images were analyzed independently in a blinded fashion by 3 operators – a sonographer, a fellow-in-training and a cardiologist specialized in echocardiography. The LV volumes and EF were first measured using hand-tracing Biplane Simpson method, then repeated using semi-automated tracing at a different time and the operator were blinded to the initial hand-tracing measurements. Results The mean age of patients was 50±16 years, 35.4% were male, mean body surface area was 1.62±0.18m2, 92.1% were in sinus rhythm, and 61.4% had good acoustic window. Table 1 shows the LV end-diastolic volume (EDV), end-systolic volume (ESV) and EF, measured using different method, by the 3 operators. There were excellent correlation and agreement between semi-automated tracing measurements and hand-tracing measurements of LV EDV (r=0.985, LOA [mean ± 1.96 SD] 16.9 ml, ICC 0.991), ESV (r=0.990, LOA 12.7 ml, ICC 0.994) and EF (r=0.962, LOA 7.43%, ICC 0.967) by experienced cardiologist. The limit of agreement (LOA) between cardiologist and sonographer for semi-automated tracing measurement of LV EDV, ESV and EF were 29.13 ml, 19.74 ml and 9.25% respectively, which was comparable with that of hand-tracing measurement. The agreement between cardiologist and fellow-in-training for semi-automated tracing measurement of LV volumes and EF was slightly better than hand-tracing method, with a LOA of 25.60 ml, 17.48 ml and 7.08%, for EDV, ESV and EF respectively (Table 2). Conclusion In daily clinical practice, measurement of LV volumes and EF using semi-automated LV endocardial tracing method is accurate and demonstrates comparable reproducibility with hand-tracing Biplane Simpson method among operators with different level of experience in echocardiography. FUNDunding Acknowledgement Type of funding sources: None.

Prognostic value of diastolic function parameters in significant aortic regurgitation. The role of the left atrial strain

Background The management of patients with asymptomatic significant aortic regurgitation (sAR) is often challenging and appropriate timing of aortic valve surgery remains controversial. There are no strong indicators to recommend early surgery in patients with sAR, however delaying the time for the intervention could bring potential negative consequences, such as the risk of permanent left ventricular (LV) dysfunction. The prognostic value of diastolic parameters has been demonstrated in several cardiac diseases. In particular, left atrial (LA) function has been shown to be an important determinant of morbimortality. Purpose The purpose of this study was to analyze the prognostic significance of diastolic function parameters, included LA strain, in asymptomatic patients with sAR and to evaluate whether these parameters could help to identify patients at high risk of adverse events that could benefit from early cardiac surgery. Methods From February 2013 to November 2019 consecutive asymptomatic patients with chronic sAR evaluated in the Heart Valve Clinic with a comprehensive transthoracic echocardiogram (TTE) were included. Combined clinical endpoint included hospital admission due to heart failure, cardiovascular mortality, or indication for aortic valve surgery. Results A total of 126 patients were included. During a mean follow up of 33±19 month, 25 (19.8%) patients reached the combined end-point. In a sub-group of 57 patients with TTE performed in the Philips stations, LA auto-strain analysis was obtained (figure 1). Univariate analysis showed that LV volumes, LVEF, E wave, E/e' ratio, LA volume and LA reservoir strain (LASr) were significant predictors of events, whereas LA diameter, and LV diastolic diameters were not. Multivariate model 1 that tested all echocardiographic variables statistically significant in the univariate model showed that the LVEDV and E/e' ratio, were significant predictors of events. In the subgroup of patients with LA auto-strain analyzed, a second multivariable model was built, including the previous significant variables for the first model (LVEDV and E/e' ratio), as well as the LA volume and LASr. It showed that LVEDV and LASr were the most significant predictors of cardiovascular events (figure 2). Conclusions In this population of asymptomatic patients with sAR and normal LV systolic function, baseline diastolic parameters were prognostic markers of cardiovascular events; among them, LA reservoir strain played a strong independent predictor role. In addition, our results also showed that LV volumes had greater prognostic value that LV diameters in patients with asymptomatic sAR. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Sex differences in left ventricular remodeling in patients with severe aortic valve stenosis

Background Women with severe aortic valve stenosis (AS) have better long-term outcomes after transcatheter aortic valve implantation (TAVI) but worse survival after surgical aortic valve replacement compared to men. Whether this is related to sex differences in left ventricular (LV) remodeling is unknown. Purpose To examine sex differences in LV remodeling and outcomes in patients with severe AS undergoing TAVI. Methods Patients with severe AS who underwent TAVI between 2007 and 2018 with a pre-procedural multidetector row computed tomography (MDCT) scan were included. LV volumes, mass and function were analyzed with MDCT. Patients were classified into 4 LV remodeling patterns based on LV mass index and LV mass-to-volume ratio: 1) normal geometry, 2) concentric remodeling, 3) concentric hypertrophy and 4) eccentric hypertrophy. The primary endpoint was all-cause mortality after TAVI. Results A total of 289 patients (age 80±6 years, 54% male) were included. Women showed smaller LV volumes and mass compared to men. Concentric hypertrophy (50%) was the most frequent pattern of LV remodeling followed by eccentric hypertrophy (33%), normal geometry (13%) and concentric remodeling (4%). Concentric remodeling was more frequently observed in men compared to women (91% vs. 9% respectively, p=0.011). However, no sex differences were observed in the remaining LV remodeling patterns (Figure 1). During a median follow-up of 3.8 (IQR 2.2–5.1) years after TAVI, 87 patients died. Women demonstrated better outcome after TAVI compared to men (log-rank χ2=4.29, p=0.038). The survival benefit of women over men was mainly present among patients with concentric hypertrophy (log-rank χ2=4.91, p=0.027, Figure 2). Conclusion LV concentric and eccentric hypertrophy are similarly observed in men and women with severe AS. Women demonstrated better outcome after TAVI as compared to men, particularly among those with LV concentric hypertrophy. However, the outcome benefit of females after TAVI seems not to be related to sex-differences in LV remodeling. FUNDunding Acknowledgement Type of funding sources: None. Distribution of sex in LV remodeling All-cause mortality after TAVI

Abstract P414: Systems Genetics Analysis Reveals Significant Eqtls Associated With Echocardiography Parameters In Genetic Reference Population Of Bxd Strains.

Background: Causal and modifier genes, genetic background and environment underlie clinical heterogeneity in cardiomyopathy (CM). The BXD recombinant inbred (RI) family represents a murine genetic reference population (GRP) that are descendants from crosses between C57BL/6J (B6) and DBA/2J (D2) mice. The parental D2 mouse is a natural model of hypertrophic CM (HCM). The study aimed to dissect genetic architecture of cardiac traits in BXD GRP using systems genetics analysis. Methods: Echocardiography was performed in 88 strains of male (M) and female (F) BXDs (N>5/sex) at 4-5 months of age. Cardiac traits were then associated with heart transcriptome, and expression quantitative trait loci ( eQTL) mapping was performed. Results: More than 2-fold variance in ejection fraction (EF%), fractional shortening (FS%), left ventricular (LV) volumes at end-systole and end-diastole (Vol;s and Vol;d), internal dimensions (ID;s and ID;d), posterior wall (PW), and interventricular septum (IVS) thickness was found among BXDs. Traits seen in dilated CM (DCM) patients such as reduced EF%, FS%, and LVPW and increased Vol;s and ID;s are found in BXD78 (M, F), BXD32, 111, and 68 (F) strains. Strains D2, BXD90 and 155 (M, F), BXD44 and 65 (M), and BXD113, 16, 77 (F) had significantly greater LV mass, LVPW and IVS thickness compared to sex-matched controls, suggestive for traits seen in HCM patients. A 6.4 Mb QTL (peak LRS=18.50) was identified on chromosome (Chr) 8 to be significantly associated with ID;s, ID;d, Vol;s and Vol;d among male BXDs. eQTL mapping for each of 131 genes on Chr8 QTL identified 6 genes ( Coq9 , Ndrg4 , Crnde, Irx3, Rpgrip1l, and Rbl2 ) being cis -regulated and Ndrg, Slc6a2 and Ces1d being significantly (p < 0.05) correlated with LV volumes. In female BXDs, a significant QTL on Chr7 (40.2 Mb) with 9 genes that significantly correlated with LVPW;d was identified. A suggestive 92.6 Mb QTL on Chr3 with Snapin , Tpm3 , and Wars2 correlated with EF% and FS% (p < 0.05). Conclusions: Our study found cardiomyopathy-associated traits are segregated among BXD family and these traits vary among BXD lines. Multiple associated QTLs demonstrate that the BXD family is suitable to map gene variants and identify genetic factors and modifiers that influence cardiomyopathy phenotypes.

Reliability of Cardiac Percussion Technique to Determine Left Ventricular Geometry in Comparison with Transthoracic Echocardiography

Background: Cardiac percussion (CP) is a bedside technique to evaluate cardiac borders and chamber size. Although advanced cardiac imaging has revolutionized the methods to detect cardiomegaly, art of CP remains the most convenient option, especially in emergent situations. Although transthoracic echocardiography (TTE) is considered the gold standard to determine left ventricular (LV) size, CP can estimate LV size with equal accuracy as TTE in appropriate clinical setting. The aim of this study was to investigate the correlation of LV size assessed by CP technique versus standard TTE, as well as cardiothoracic ratio (CTR) on chest roentgenography (CXR). Methods: This descriptive study was conducted on Telemetry units. Patients were positioned in supine position at Gatch angle of 30-45 degrees. Cardiac dullness was measured in cm by percussing from mid clavicular line towards gladiolus of sternal body. Subsequently, findings were correlated with TTE dimensions of left ventricular end-diastolic diameter (LVEDD). Results: In 200 patients, mean age was 63+15.8 years, with 51% females. The LV diameter (LVD) measured by CP technique was observed to be similar to LVEDD measured by TTE (Mean- 4.65+0.67 cm versus 4.69+0.76 cm, COV 7.6%). The BlandAltman comparison of CP technique and TTE measurements indicated significant differences in variances between the two measures (r=0.270, p=<0.001). The LVD measured by CXR did not show correlation with LVEDD (5.79+1.21 cm, COV 14.3%) with significant differences in the variances between the two measures (r=-0.475, p<0.001). The LV volumes measured by CP technique were observed to have correlation with LV volumes measured by TTE (COV 14.9%). Conclusion: CP technique is a convenient bedside method that can be utilized to assess LVD and volume. It is shown to have a precise correlation with LVEDD measured by TTE. The study emphasizes role of bedside estimation of LV size by using the art of physical examination.

Evaluation of systolic LV function and LV mechanics

Analysis of global and regional left ventricular (LV) function is the most frequent indication to perform echocardiography. While visual assessment based on 2D images is the basis for analysis of LV function, it may be supplemented by quantitative techniques to obtain parameters of global or regional function. 2D echocardiography tends to underestimate LV volumes compared to cardiac magnetic resonance (CMR), 3D echocardiography results in less volume underestimation and high accuracy in the analysis of ejection fraction. Visual analysis of regional function is limited by significant interobserver variability. Another approach to systolic LV function is the assessment of LV mechanics, typically by measuring global longitudinal deformation (strain) by speckle-tracking echocardiography. Alternatively, information on deformation can be obtained from CMR (currently, mostly by feature tracking). Deformation parameters detect early impairment of LV systolic function with higher sensitivity than ejection fraction. While echocardiography continues to be the first-choice modality for ejection fraction, CMR has become the gold standard for quantification of LV volumes and ejection fraction. Nuclear imaging should be applied to assess LV function only if simultaneous assessment of myocardial perfusion is requested.

Feasibility and Accuracy of the Automated Software for Dynamic Quantification of Left Ventricular and Atrial Volumes and Function in a Large Unselected Population

PurposeWe aimed to evaluate the feasibility and accuracy of machine learning based automated dynamic quantification of left ventricular (LV) and left atrial (LA) volumes in an unselected population.MethodsWe enrolled 600 unselected patients (12% in atrial fibrillation) clinically referred for transthoracic echocardiography (2DTTE), who also underwent 3D echocardiography (3DE) imaging. LV ejection fraction (EF), LV and LA volumes were obtained from 2D images; 3D images were analysed using Dynamic Heart Model (DHM) software resulting in LV and LA volume-time curves. A subgroup of 140 patients underwent also cardiac magnetic resonance (CMR) imaging. Average time of analysis, feasibility, and image quality were recorded and results were compared between 2DTTE, DHM and CMR.ResultsThe use of DHM was feasible in 529/600 cases (88%). When feasible, the boundary position was considered accurate in 335/522 patients (64%), while major (n=43) or minor (n=156) borders corrections were needed. The overall time required for DHM datasets was approximately 40 seconds, resulting in physiologically appearing LV and LA volume–time curves in all cases. As expected, DHM LV volumes were larger than 2D ones (end-diastolic volume: 173±64 vs 142±58 mL, respectively), while no differences were found for LV EF and LA volumes (EF: 55%±12 vs 56%±14; LA volume 89±36 vs 89±38 mL, respectively). The comparison between DHM and CMR values showed a high correlation for LV volumes (r=0.70 and r=0.82, p<0.001 for end-diastolic and end-systolic volume, respectively) and an excellent correlation for EF (r= 0.82, p<0.001) and LA volumes.ConclusionsThe DHM software is feasible, accurate and quick in a large series of unselected patients, including those with suboptimal 2D images or in atrial fibrillation.

Presence of contractile impairment appears crucial for structural remodeling in idiopathic left bundle-branch block

Background To differentiate effects of ventricular asynchrony from an underlying hypocontractile cardiomyopathy this study aimed to enhance the understanding of functional impairment and structural remodeling in idiopathic left bundle-branch block (LBBB). We hypothesize, that functional asynchrony with septal flash volume effects alone might not entirely explain the degree of functional impairment. Hence, we suggest the presence of a superimposed contractile cardiomyopathy. Methods In this retrospective study, 53 patients with idiopathic LBBB were identified and matched to controls with and without cardiovascular risk factors. Cardiovascular magnetic resonance (CMR) was used to evaluate cardiac function, volumes and myocardial fibrosis using native T1 mapping and late gadolinium enhancement (LGE). Septal flash volume was assessed by CMR volumetric measurements and allowed to stratify patients with systolic dysfunction solely due to isolated ventricular asynchrony or superimposed contractile impairment. Results Reduced systolic LV-function, increased LV-volumes and septal myocardial fibrosis were found in patients with idiopathic LBBB compared to healthy controls. LV-volumes increased and systolic LV-function declined with prolonged QRS duration. Fibrosis was typically located at the right ventricular insertion points. Subgroups with superimposed contractile impairment appeared with pronounced LV dilation and increased fibrotic remodeling compared to individuals with isolated ventricular asynchrony. Conclusions The presence of superimposed contractile impairment in idiopathic LBBB is crucial to identify patients with enhanced structural remodeling. This finding suggests an underlying cardiomyopathy. Future studies are needed to assess a possible prognostic impact of this entity and the development of heart failure. Trial registration: This study was retrospectively registered.

Implications of Atrial Fibrillation on the Mechanisms of Mitral Regurgitation and Response to MitraClip in the COAPT Trial

Background: Atrial fibrillation (AF), mitral regurgitation (MR), and left ventricular (LV) ejection fraction have a complex interplay. We evaluated the role of AF in patients with heart failure and moderate-to-severe or severe secondary MR enrolled in the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) and its impact on mechanisms and outcomes with the MitraClip. Methods: Patients in the COAPT trial were stratified by the presence (n=327) or absence (n=287) of a history of AF and by assignment to treatment group. Clinical, echocardiographic, and outcome measures were assessed. The primary outcome was the composite rate of death or heart failure hospitalization at 24 months. Results: Patients with history of AF were older and more often male. They had a higher LV ejection fraction, larger left atrial volumes and mitral valve orifice areas, smaller LV volumes, and similar MR severity. Patients with AF compared with those without a history of AF had a higher unadjusted (hazard ratio [HR], 1.32 [95% CI, 1.06–1.64], P =0.01) and adjusted (HR, 1.30 [1.03–1.64], P =0.03) 2-year rate of the primary outcome. Treatment with the MitraClip compared with guideline-directed medical therapy alone reduced death or heart failure hospitalization in both those with (HR, 0.61 [0.46–0.82]) and without (HR, 0.46 [0.33–0.66]) a history of AF ( P int =0.18). Treatment with the MitraClip was associated with a lower risk of stroke in patients with a history of AF (HR, 0.18 [0.04–0.86]) but not in those without a history of AF (HR, 1.64 [0.58–4.62]; P int =0.02). Conclusions: In the COAPT trial, patients with a history of AF had larger left atrial and mitral valve orifice areas with higher LV ejection fraction and smaller LV volumes, suggesting an atrial mechanism contribution to functional MR. Despite the worse prognosis of heart failure patients with a history of AF, MR reduction with the MitraClip still afforded substantial clinical benefits. Treatment with MitraClip was associated with a lower risk of stroke in patients with a history of AF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01626079.