Atorvastatin for Anthracycline-Associated Cardiac Dysfunction: The STOP-CA Randomized Clinical Trial.

Importance: Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use. Objective: To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction. Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022. Interventions: Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months. Main Outcomes and Measures: The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months. Results: Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups. Conclusions and Relevance: Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use. Trial Registration: ClinicalTrials.gov Identifier: NCT02943590.

Abnormal Mechanics Relate to Myocardial Fibrosis and Ventricular Arrhythmias in Patients With Mitral Valve Prolapse.

BACKGROUND: The relation between ventricular arrhythmia and fibrosis in mitral valve prolapse (MVP) is reported, but underlying valve-induced mechanisms remain unknown. We evaluated the association between abnormal MVP-related mechanics and myocardial fibrosis, and their association with arrhythmia. METHODS: We studied 113 patients with MVP with both echocardiogram and gadolinium cardiac magnetic resonance imaging for myocardial fibrosis. Two-dimensional and speckle-tracking echocardiography evaluated mitral regurgitation, superior leaflet and papillary muscle displacement with associated exaggerated basal myocardial systolic curling, and myocardial longitudinal strain. Follow-up assessed arrhythmic events (nonsustained or sustained ventricular tachycardia or ventricular fibrillation). RESULTS: Myocardial fibrosis was observed in 43 patients with MVP, predominantly in the basal-midventricular inferior-lateral wall and papillary muscles. Patients with MVP with fibrosis had greater mitral regurgitation, prolapse, and superior papillary muscle displacement with basal curling and more impaired inferior-posterior basal strain than those without fibrosis (P<0.001). An abnormal strain pattern with distinct peaks pre-end-systole and post-end-systole in inferior-lateral wall was frequent in patients with fibrosis (81 versus 26%, P<0.001) but absent in patients without MVP with basal inferior-lateral wall fibrosis (n=20). During median follow-up of 1008 days, 36 of 87 patients with MVP with >6-month follow-up developed ventricular arrhythmias associated (univariable) with fibrosis, greater prolapse, mitral annular disjunction, and double-peak strain. In multivariable analysis, double-peak strain showed incremental risk of arrhythmia over fibrosis. CONCLUSIONS: Basal inferior-posterior myocardial fibrosis in MVP is associated with abnormal MVP-related myocardial mechanics, which are potentially associated with ventricular arrhythmia. These associations suggest pathophysiological links between MVP-related mechanical abnormalities and myocardial fibrosis, which also may relate to ventricular arrhythmia and offer potential imaging markers of increased arrhythmic risk.

Evaluation of left atrial function and mechanical dispersion in breast cancer patients after chemotherapy.

BACKGROUND: Left atrial (LA) function and mechanical dispersion changes in breast cancer patients treated with chemotherapy remain unclear. HYPOTHESIS: LA function and LA mechanical dispersion in breast cancer patients would be impaired after chemotherapy. METHODS: This single-center retrospective study included 91 consecutive breast cancer patients treated with chemotherapy and 30 controls. Patients were examined by echocardiography three times at intervals. Conventional parameters, left ventricular strain, LA strain, and LA mechanical dispersion were evaluated and compared. RESULTS: LA strain during reservoir phase (LASr), conduit phase (LAScd), and contraction phase (LASct) all decreased markedly after chemotherapy and were lower than those of the controls (all p < .01). The standard deviation of time to peak positive strain during LA reservoir phase corrected by R-R interval (LA SD-TPSr) was significantly increased after chemotherapy and was higher than that of the controls (p < .001). The change of LA function was expressed as Δ. Multivariate linear regression analyses showed that LAVIp (0.399, 95% confidence interval [CI]: 0.610, 1.756, p = .000) was independently associated with ΔLASr, LAPEF (-0.325, 95% CI: -45.123, -10.676, p = .002) and age (0.227, 95% CI: 0.021, 0.350, p = .027) were independently associated with ΔLAScd, and LAVImax (0.341, 95% CI: 0.192, 0.723, p = .001) was independently associated with ΔLASct. LAVImax (0.505, 95% CI: 0.000, 0.001, p = .039) and mitral E (-0.256, 95% CI: 0.000, 0.000, p = .024）were independently associated with ΔLA SD-TPSr. CONCLUSIONS: Mechanical function of LA declined after chemotherapy in breast cancer patients. With the decrease of LA mechanical function, LA mechanical dispersion assessed by two-dimensional speckle-tracking echocardiography increased significantly, and its clinical value needs to be further studied.

Specific Considerations for Sonographers When Performing Echocardiography during the 2019 Novel Coronavirus Outbreak: Supplement to the American Society of Echocardiography Statement.

Sonographers need to be familiar with and prepared to implement strategies for reducing the risk of exposure to and transmission of the COVID-19 virus. Strategies to employ can be grouped into three broad categories: (1) whom to scan, (2) where to scan, and (3) how to scan. Whom to scan addresses sonographer strategies for determining essential and emergent scan status. Where to scan addresses sonographer practice strategies for selecting equipment, use of rooms, portable examinations, and training personnel. How to scan addresses the topics of scanning techniques (tailored protocols, right-handed scanning, use of barrier devices) and equipment cleaning and disinfecting.

Direct Planimetry of Left Ventricular Outflow Tract Area by Simultaneous Biplane Imaging: Challenging the Need for a Circular Assumption of the Left Ventricular Outflow Tract in the Assessment of Aortic Stenosis.

BACKGROUND: Evaluation of aortic stenosis (AS) requires calculation of aortic valve area (AVA), which relies on the assumption of a circular-shaped left ventricular outflow tract (LVOT). However, the LVOT is often elliptical, and the circular assumption underestimates the true LVOT area (LVOTA). Biplane imaging using transthoracic echocardiography allows direct planimetry of LVOTA. The aim of this study was to assess the feasibility of obtaining LVOTA using this technique and its impact on the discordance between AVA and gradient criteria in AS grading. METHODS: We prospectively studied 134 patients (median age, 80 years; interquartile range, 73-87 years; 39% women) with AS, including 82 (61%) with severe AS and 52 (39%) with mild or moderate AS. LVOTA was traced using direct planimetry (LVOTAbiplane) and compared with LVOTA calculated using the circular assumption (LVOTAcirc). In a subset of patients who underwent cardiac computed tomography, direct planimetry of LVOTA was used as a reference standard. RESULTS: LVOTAbiplane was significantly larger than LVOTAcirc (4.20 cm2 [interquartile range, 3.66-4.90 cm2] vs 3.73 cm2 [interquartile range, 3.14-4.15 cm2], P < .001). Among 30 patients who underwent cardiac computed tomography, LVOTAbiplane had better agreement with LVOTA by direct planimetry than LVOTAcirc (mean bias, -0.45 ± 0.63 vs -1.02 ± 0.63 cm2; P < .0001). Of 82 patients with severe AS (AVA ≤ 1 cm2 using LVOTAcirc), 40 (49%) had discordant mean gradient (<40 mm Hg). By using LVOTAbiplane, patients with discordant AVA and mean gradient decreased from 49% to 27% (P = .004), and 29% of patients with severe AS were reclassified with moderate AS, with the highest percentage of reclassification in the group with low-gradient AS with preserved left ventricular ejection fraction. CONCLUSIONS: Direct planimetry using biplane imaging avoids the inherent underestimation of LVOTA using the circular assumption. LVOTA obtained by biplane planimetry can lead to better concordance between AVA and mean gradient and classification of AS severity.

Assessment of Tricuspid Annular Motion by Speckle Tracking in Anesthetized Patients Using Transesophageal Echocardiography.

BACKGROUND: The perioperative assessment of right ventricular (RV) function remains a challenge. Tricuspid annular plane systolic excursion (TAPSE) using M-mode is a widely used measure of RV function. However, accurate alignment of the ultrasound beam with the direction of annular movement can be difficult with transesophageal echocardiography (TEE) to measure TAPSE, precluding effective use of M-mode to measure annular excursion. Tracking of specular reflectors in the myocardium may provide an angle-independent method to assess annular motion with TEE. We hypothesized that TEE speckle tracking of the lateral tricuspid annular motion represents a comparable measurement to the well-validated M-mode TAPSE on transthoracic echocardiogram (TTE), and may be considered as a reasonable alternative to TAPSE. METHODS: This is a prospective, observational cohort study. We included all patients, who were in sinus rhythm, with a preoperative TTE within 3 months of scheduled cardiac surgery that required intraoperative TEE. Tissue motion annular displacements (TMAD) of the lateral (L), septal (S), and midpoint (M) tricuspid annulus were measured (QLAB Cardiac Motion Quantification; Philips Medical, Andover, MA) after induction of general anesthesia. This was compared to the preoperative M-mode TAPSE on TTE. RESULTS: Seventy-two consecutive patients who met eligibility requirements were enrolled from September to November 2016. Twelve were excluded due to poor image quality, allowing TMAD to be analyzed in 60 patients. TMAD was analyzed offline and TMAD analysis was able to track tricuspid annular motion in all patients. The mean TMAD (L), TMAD (S), and TMAD (M) were 17.4 ± 5.2, 10.2 ± 4.8, and 14.2 ± 4.8 mm, respectively. TMAD (L) showed close correlation with M-mode TAPSE on TTE (r = 0.87, 95% confidence interval, 0.79-0.92; P < .01). All patients with a preoperative TAPSE <17 mm had a TMAD (L) <17 mm, while 71% of those with a TAPSE ≥ 17 mm had a TMAD (L) ≥ 17 mm. There was strong positive correlation between TMAD (L) and intraoperative RV fractional area change (r = 0.86, 95% confidence interval, 0.77-0.91; P < .01). Reproducibility analysis of TMAD within and across observers showed excellent correlation. CONCLUSIONS: TMAD is a quick and angle-independent method to quantitatively assess RV longitudinal function by TEE. It correlates strongly with M-mode TAPSE on TTE. Because TMAD and TAPSE were not simultaneously measured in this study, their correlation is subject to differences in loading conditions, general anesthesia, and changes in the disease process. TMAD may be easily applied in routine clinical settings and its role in the perioperative environment deserves to be further explored.

Left Ventricular Global Longitudinal Strain in HER-2 + Breast Cancer Patients Treated with Anthracyclines and Trastuzumab Who Develop Cardiotoxicity Is Associated with Subsequent Recovery of Left Ventricular Ejection Fraction.

AIM: The combination of anthracyclines (AC) and trastuzumab (TRZ) is highly effective in patients with aggressive HER-2 + breast cancer, but has a significant risk of cardiotoxicity (CT). Trastuzumab-induced CT may be reversible. The aim of this study was to identify echocardiographic parameters associated with recovery of left ventricular ejection fraction (LVEF) in patients who developed CT after AC and TRZ treatment. METHODS AND RESULTS: Women with newly diagnosed breast cancer treated with AC followed by TRZ and monitored with serial echocardiograms were retrospectively studied. Left ventricular end-diastolic and systolic volumes, LVEF, and global longitudinal strain (GLS) were examined. Development and reversibility of CT were defined based on changes in LVEF according to the 2014 ASE/EACVI recommendations. Cox analysis was used to determine the association of echocardiographic variables with the subsequent development and reversibility of CT. Ninety-five patients underwent 5 echocardiograms or more in a 17-month (13-28 months) follow-up period. Nineteen patients (20%) developed CT. Left ventricular volumes, LVEF, and GLS measured after AC completion identified the subsequent development of CT. Of the 19 patients with CT, the LVEF partially or fully recovered in 13 (68%). GLS at the time of CT diagnosis was associated with subsequent recovery of LVEF (P = 0.004). CONCLUSION: In patients with breast cancer treated with AC and TRZ who develop CT, GLS at the time of CT diagnosis is associated with subsequent recovery of LVEF and may be useful for risk stratification and to guide treatment.

Leaflet area as a determinant of tricuspid regurgitation severity in patients with pulmonary hypertension.

BACKGROUND: Tricuspid regurgitation (TR) is a risk factor for mortality in pulmonary hypertension (PH). TR severity varies among patients with comparable degrees of PH and right ventricular remodeling. The contribution of leaflet adaptation to the pathophysiology of TR has yet to be examined. We hypothesized that tricuspid leaflet area (TLA) is increased in PH, and that the adequacy of this increase relative to right ventricular remodeling determines TR severity. METHODS AND RESULTS: A prospective cohort of 255 patients with PH from pre and postcapillary pathogeneses was assembled from 2 centers. Patients underwent a 3-dimensional echocardiogram focused on the tricuspid apparatus. TLA was measured with the Omni 4D software package. Compared with normal controls, patients with PH had a 2-fold increase in right ventricular volumes, 62% increase in annular area, and 49% increase in TLA. Those with severe TR demonstrated inadequate increase in TLA relative to the closure area, such that the ratio of TLA:closure area <1.78 was highly predictive of severe TR (odds ratio, 68.7; 95% confidence interval, 16.2-292.7). The median vena contracta width was 8.5 mm in the group with small TLA and large closure area as opposed to 4.8 mm in the group with large TLA and large closure area. CONCLUSIONS: TLA plays a significant role in determining which patients with PH develop severe functional TR. The ratio of TLA:closure area, reflecting the balance between leaflet adaptation versus annular dilation and tethering forces, is an indicator of TR severity that may identify which patients stand to benefit from leaflet augmentation during tricuspid valve repair.

Assessment of image quality in real time three-dimensional dobutamine stress echocardiography: an integrated 2D/3D approach.

BACKGROUND: Three-dimensional (3D) stress echocardiography is a relatively new technique offering the potential to acquire images of the entire left ventricle from 1 or 2 transducer positions in a time-efficient manner. Relative to two-dimensional (2D) imaging, the ability to quickly acquire full volume images during peak stress with 3D echocardiography can eliminate left ventricular (LV) foreshortening while reducing inter-operator variability. Our objectives were to (1) determine the practicality of a novel integrated 2D/3D stress protocol in incorporating 3D imaging into a standard 2D stress echocardiogram and (2) to determine whether the quality of imaging using the novel 2D/3D protocol was sufficient for interpretation. METHODS: Twenty-five patients referred for stress echocardiography underwent an integrated 2D/3D image acquisition protocol. LV segments were scored from 0 (absent or no clear endocardial visualization) to 3 (excellent/full visualization of endocardial border) with each modality. 2D segment quality scoring was compared with 3D. An integrated score was compared with either 2D or 3D imaging alone. RESULTS: Two-dimensional and 3D imaging were optimal for differing segments and the integrated protocol was superior to either modality alone. 3D imaging was superior in visualizing the anterior and anterolateral region of the base segments, compared to 2D imaging. 3D imaging was less useful for the base, the mid-inferior, and the inferoseptal segments, thus emphasizing the need to retain 2D imaging in stress echocardiography at this time. CONCLUSION: The integrated 2D/3D protocol approach to stress echocardiography is technically feasible and maximizes image quality of dobutamine stress echocardiography, improving patient assessment.

Diagnostic value of vena contracta area in the quantification of mitral regurgitation severity by color Doppler 3D echocardiography.

BACKGROUND: Accurate quantification of mitral regurgitation (MR) is important for patient treatment and prognosis. Three-dimensional echocardiography allows for the direct measure of the regurgitant orifice area (ROA) by 3D-guided planimetry of the vena contracta area (VCA). We aimed to (1) establish 3D VCA ranges and cutoff values for MR grading, using the American Society of Echocardiography-recommended 2D integrative method as a reference, and (2) compare 2D and 3D methods of ROA to establish a common calibration for MR grading. METHODS AND RESULTS: Eighty-three patients with at least mild MR underwent 2D and 3D echocardiography. Direct planimetry of VCA was performed by 3D echocardiography. Two-dimensional quantification of MR included 2D ROA by proximal isovelocity surface area (PISA) method, vena contracta width, and ratio of jet area to left atrial area. There were significant differences in 3D VCA among patients with different MR grades. As assessed by receiver operating characteristic analysis, 3D VCA at a best cutoff value of 0.41 cm(2) yielded 97% of sensitivity and 82% of specificity to differentiate moderate from severe MR. There was significant difference between 2D ROA and 3D VCA in patients with functional MR, resulting in an underestimation of ROA by 2D PISA method by 27% as compared with 3D VCA. Multivariable regression analysis showed functional MR as etiology was the only predictor of underestimation of ROA by the 2D PISA method. CONCLUSIONS: Three-dimensional VCA provides a single, directly visualized, and reliable measurement of ROA, which classifies MR severity comparable to current clinical practice using the American Society of Echocardiography-recommended 2D integrative method. The 3D VCA method improves accuracy of MR grading compared with the 2D PISA method by eliminating geometric and flow assumptions, allowing for uniform clinical grading cutoffs and ranges that apply regardless of etiology and orifice shape.

Unusual position of a prosthetic mitral valve.

Extensive calcification of the mitral annulus in patients who require mitral valvereplacement presents a significant challenge to the surgeon. Several techniques, includingdebridement of the calcium, reconstruction of the annulus, and insertion of the prosthesis in a locationother than the annulus, have been used in such patients. We report the echocardiographictechniques used to evaluate the case of a woman with an unusually positioned prosthetic mitralvalve.

Mitral leaflet adaptation to ventricular remodeling: occurrence and adequacy in patients with functional mitral regurgitation.

BACKGROUND: Functional mitral regurgitation (MR) is caused by systolic traction on the mitral leaflets related to ventricular distortion. Little is known about whether chronic tethering causes the mitral leaflet area to adapt to the geometric needs imposed by tethering, in part because of inability to reconstruct leaflet area in vivo. Our aim was to explore whether adaptive increases in leaflet area occur in patients with functional MR compared with normal subjects and to test the hypothesis that leaflet area influences MR severity. METHODS AND RESULTS: A new method for 3-dimensional echocardiographic measurement of mitral leaflet area was developed and validated in vivo against 15 sheep heart valves, later excised. This method was then applied in 80 consecutive patients from 3 groups: patients with normal hearts by echocardiography (n=20), patients with functional MR caused by isolated inferior wall-motion abnormality or dilated cardiomyopathy (n=29), and patients with inferior wall-motion abnormality or dilated cardiomyopathy but no MR (n=31). Leaflet area was increased by 35+/-20% in patients with LV dysfunction compared with normal subjects. The ratio of leaflet to annular area was 1.95+/-0.40 and was not different among groups, which indicates a surplus leaflet area that adapts to left-heart changes. In contrast, the ratio of total leaflet area to the area required to close the orifice in midsystole was decreased in patients with functional MR compared with those with normal hearts (1.29+/-0.15 versus 1.78+/-0.39, P=0.001) and compared with patients with inferior wall-motion abnormality or dilated cardiomyopathy but no MR (1.81+/-0.38, P=0.001). After adjustment for measures of LV remodeling and tethering, a leaflet-to-closure area ratio <1.7 was associated with significant MR (odds ratio 23.2, 95% confidence interval 2.0 to 49.1, P=0.02). CONCLUSIONS: Mitral leaflet area increases in response to chronic tethering in patients with inferior wall-motion abnormality and dilated cardiomyopathy, but the development of significant MR is associated with insufficient leaflet area relative to that demanded by tethering geometry. The varying adequacy of leaflet adaptation may explain in part the heterogeneity of this disease among patients. The results suggest the need to understand the mechanisms that underlie leaflet adaptation and whether leaflet area can potentially be modified as part of the therapeutic approach.

Assessing mitral valve area and orifice geometry in calcific mitral stenosis: a new solution by real-time three-dimensional echocardiography.

BACKGROUND: Planimetry of mitral valve area (MVA) is difficult in calcific mitral stenosis (CaMS) in which limiting orifice is near the annulus, and unlike rheumatic mitral stenosis (RhMS), does not present an area for planimetry at the leaflet tips. Moreover, pressure half time (PHT)-derived MVA (MVA(PHT)) has limitations in patients with CaMS in whom there are coexisting conditions that affect LV chamber compliance. We tested the hypothesis that real-time 3-dimensional echocardiography (RT3D) can guide measurement at the narrowest orifice in CaMS. METHODS: In 34 patients with CaMS, MVA by RT3D (MVA(RT3D)) was obtained using a color-defined planimetry technique performed "en face" at the smallest annular orifice cross-section (diastolic maximum). MVA(RT3D) and MVA(PHT) were compared with an independent standard: MVA by continuity equation (MVA(CEQ)). In a subgroup of 10 patients with CaMS or RhMS, the 3-dimensional shape of the stenotic mitral valve was examined, guided by color flow mapping. RESULTS: MVA(PHT) overestimated the mitral orifice area compared with MVA(CEQ) (2.01 +/- 0.52 cm(2) vs 1.75 +/- 0.46 cm(2); P = .037), whereas there was no significant difference in MVA(RT3D) and MVA(CEQ) (1.83 +/- 0.52 cm(2) vs 1.75 +/- 0.46 cm(2), respectively, P = .61). MVA(RT3D) had a greater correlation with MVA (CEQ) than MVA(PHT) (R = 0.86 vs 0.59 MVA(RT3D) vs MVA(PHT), respectively). There was better agreement between MVA by RT3D and MVA by continuity equation than MVA by PHT and MVA by continuity equation (difference in MVA: 0.23 +/- 0.15 cm(2) vs 0.43 +/- 0.29 cm(2); P < .0001, MVA(RT3D) - MVA(CEQ) vs MVA(PHT) - MVA(CEQ,) respectively). In CaMS, there was a tubular geometry to the valve shape. In contrast, RhMS had a doming funnel-shaped geometry. CONCLUSION: RT3D provides an accurate measurement of MVA in CaMS. In contrast with the doming valve shape present in RhMS, the limiting anatomic orifice area occurs at the annulus in CaMS as measured by RT3D and reflects the effective orifice area as present in a tubular valve geometry.

Geometric determinants of functional tricuspid regurgitation: insights from 3-dimensional echocardiography.

BACKGROUND: Tricuspid regurgitation (TR) is an important predictor of morbidity and mortality in heart failure. We aimed to examine the 3D geometry of the tricuspid valve annulus (TVA) in patients with functional TR, comparing them with patients with normal tricuspid valve function and relating annular geometric changes to functional TR. METHODS AND RESULTS: TVA shape was examined by real-time 3D echocardiography in 75 patients: 35 with functional TR and 40 with normal tricuspid valve function (referent group). The 3D shape of the TVA was reconstructed from rotated 2D planes, and the annular plane was computed by least-squares fitting. Annular area and mediolateral, anteroposterior, and high (superior)-low (inferior) distances were calculated. TR was assessed by vena contracta width. The normal TVA has a bimodal pattern (high-low distance=7.23+/-1.05 mm). High points were located anteroposteriorly, and low points were located mediolaterally. With moderate or greater TR (vena contracta width 5.80+/-2.62 mm), the TVA became dilated (17.24+/-4.75 versus 9.83+/-2.18 cm2, P<0.0001, TR versus referent), more planar with decreased high-low distance (4.14+/-1.05 mm), and more circular with decreased ratio of mediolateral/anteroposterior (1.11+/-0.09 versus 1.32+/-0.09, P<0.0001, TR versus referent). CONCLUSIONS: The normal TVA has a bimodal shape with distinct high points located anteroposteriorly and low points located mediolaterally. With functional TR, the annulus becomes larger, more planar, and circular. These changes in annular shape with TR have potentially important mechanistic and therapeutic implications for tricuspid valve repair.