New Approaches to Assessment and Management of Tricuspid Regurgitation Before Intervention.

Severe tricuspid regurgitation (TR) is a progressive condition associated with substantial morbidity, poor quality of life, and increased mortality. Patients with TR commonly have coexisting conditions including congestive heart failure, pulmonary hypertension, chronic lung disease, atrial fibrillation, and cardiovascular implantable electronic devices, which can increase the complexity of medical and surgical TR management. As such, the optimal timing of referral for isolated tricuspid valve (TV) intervention is undefined, and TV surgery has been associated with elevated risk of morbidity and mortality. More recently, an unprecedented growth in TR treatment options, namely the development of a wide range of transcatheter TV interventions (TTVI) is stimulating increased interest and referral for TV intervention across the entire medical community. However, there are no stepwise algorithms for the optimal management of symptomatic severe TR before TTVI. This article reviews the contemporary assessment and management of TR with addition of a medical framework to optimize TR before referral for TTVI.

Mitral Annulus Calcium Score in Patients With Calcific Mitral Stenosis Undergoing Invasive Hemodynamic Assessment.

BACKGROUND: Aortic valve calcium score is associated with hemodynamic severity of aortic stenosis. Whether this association is present in calcific mitral stenosis remains unknown. METHODS AND RESULTS: This study was a retrospective analysis of consecutive patients with mitral stenosis secondary to mitral annular calcification (MAC) undergoing transseptal catheterization. All patients underwent invasive mitral valve assessment via direct left atrial and left ventricular pressure measurement. Computed tomography within 1 year of cardiac catheterization and with adequate visualization of the mitral annulus was included. MAC calcium score quantification by Agatston method was obtained offline using dedicated software (Aquarius, TeraRecon, V.4). Median patient age was 66.9±11.2 years, 47% of patients were women, 50% had coronary artery disease, 40% had atrial fibrillation, 47% had prior cardiac surgery, and 33% had prior chest radiation. Median diastolic mitral valve gradient was 9.4±3.4 mm Hg on echocardiography and 8.5±4 mm Hg invasively. Invasive median mitral valve area using the Gorlin formula was 1.87±0.9 cm2. Median MAC calcium score for the cohort was 7280±7937 Hounsfield units. MAC calcium score correlated with the presence of atrial fibrillation (P=0.02) but was not associated with other comorbidities. There was no correlation between MAC calcium score and mitral valve area (r=0.07; P=0.6) or mitral valve gradient (r=-0.03; P=0.8). CONCLUSIONS: MAC calcium score did not correlate with invasively measured mitral valve gradient and mitral valve area in patients with MAC-related mitral stenosis, suggesting that calcium score should not be used as a surrogate for invasive hemodynamic parameters.

Incremental Prognosis by Left Atrial Functional Assessment: The Left Atrial Coupling Index in Patients With Floppy Mitral Valves.

Background Emerging data suggest important prognostic value to left atrial (LA) characteristics, but the independent impact of LA function on outcome remains unsubstantiated. Thus, we aimed to define the incremental prognostic value of LA coupling index (LACI), coupling volumetric and mechanical LA characteristics and calculated as the ratio of left atrial volume index to tissue Doppler imaging a', in a large cohort of patients with isolated floppy mitral valve. Methods and Results All consecutive 4792 patients (61±16 years, 48% women) with isolated floppy mitral valve in sinus rhythm diagnosed at Mayo Clinic from 2003 to 2011, comprehensively characterized and with prospectively measured left atrial volume index and tissue Doppler imaging a' in routine practice, were enrolled, and their long-term survival analyzed. Overall, LACI was 5.8±3.7 and was <5 in 2422 versus ≥5 in 2370 patients. LACI was independently higher with older age, more mitral regurgitation (no 3.8±2.3, mild 5.1±3.0, moderate 6.5±3.8, and severe 7.8±4.3), and with diastolic (higher E/e') and systolic (higher end-systolic dimension) left ventricular dysfunction (all P≤0.0001). At diagnosis, higher LACI was associated with more severe presentation (more dyspnea, more severe functional tricuspid regurgitation, and elevated pulmonary artery pressure, all P≤0.0001) independently of age, sex, comorbidity index, ventricular function, and mitral regurgitation severity. During 7.0±3.0 years follow-up, 1146 patients underwent mitral valve surgery (94% repair, 6% replacement), and 880 died, 780 under medical management. In spline curve analysis, LACI ≥5 was identified as the threshold for excess mortality, with much reduced 10-year survival under medical management (60±2% versus 85±1% for LACI <5, P<0.0001), even after comprehensive adjustment (adjusted hazard ratio, 1.30 [95% CI, 1.10-1.53] for LACI ≥5; P=0.002). Association of LACI ≥5 with higher mortality persisted, stratifying by mitral regurgitation severity of LA enlargement grade (all P<0.001) and after propensity-score matching (P=0.02). Multiple statistical methods confirmed the significant incremental predictive power of LACI over left atrial volume index (all P<0.0001). Conclusions LA functional assessment by LACI in routine practice is achievable in a large number of patients with floppy mitral valve using conventional Doppler echocardiographic measurements. Higher LACI is associated with worse clinical presentation, but irrespective of baseline characteristics, LACI is strongly, independently, and incrementally determinant of outcome, demonstrating the crucial importance of LA functional response to mitral valve disease.

Performance of Echocardiographic Algorithms for Assessment of High Aortic Bioprosthetic Valve Gradients.

BACKGROUND: Bioprosthetic aortic valve dysfunction (BAVD) is a challenging diagnosis. Commonly used algorithms to classify high-gradient BAVD are the 2009 American Society of Echocardiography, 2014 Blauwet-Miller, and 2016 European Association of Cardiovascular Imaging algorithms. We sought (1) to evaluate the accuracy of existing algorithms against objectively proven BAVD and (2) to propose an improved algorithm. METHODS: This was a retrospective study of 266 patients with objectively proven BAVD (pathology of explanted valves, four-dimensional computed tomography prior to transcatheter valve-in-valve replacement, or therapeutically confirmed bioprosthetic thrombosis) who were treated. Of those, 191 had obstruction, 48 had regurgitation, 15 had mixed stenosis and regurgitation, and 12 had patient-prosthesis mismatch (PPM). Normal controls were matched 1:1 (age, prosthesis size, and type), of which 43 had high gradients (PPM in 30, high flow in nine, and normal prosthesis in nine). Algorithm assignment was based on the echocardiogram leading to BAVD diagnosis and the predischarge "fingerprint" echocardiogram after surgical or transcatheter aortic valve replacement. A novel algorithm (Mayo Clinic algorithm) incorporating valve appearance in addition to Doppler parameters was developed to improve observed deficiencies. RESULTS: The accuracy of existing algorithms was suboptimal (2009 American Society of Echocardiography, 62%; 2014 Blauwet-Miller, 62%; 2016 European Association of Cardiovascular Imaging, 57%). The most common overdiagnosis was PPM (22%-29% of patients and controls with high gradients). The novel Mayo Clinic algorithm correctly identified the mechanism in 256 of 307 patients and controls (83%). Recognition of regurgitation was substantially improved (42 of 47 patients, 89%), and the number of PPM misdiagnoses was significantly reduced (five patients). CONCLUSION: Currently recommended algorithms misclassify a significant number of BAVD patients. The accuracy was improved by a newly proposed algorithm.

Numerical wave speed sensitivity study for assessment of myocardial elasticity in a simplified linear elastic and isotropic left ventricle model.

Since tissue elasticity can change with pathology, noninvasive assessment of elasticity has received increasing attention. Emerging methods for assessing cardiac elasticity utilize either an external source to induce propagating shear waves or intrinsic longitudinal waves created by natural cardiac events such as left ventricle stretching that occurs due to atrial kick during late diastole. However, the effect of morphological variations that occur in diseased hearts on this longitudinal stretch wave and the corresponding estimate of elasticity is not well understood and is an active area of research. This study investigated the sensitivity of longitudinal wave speed to material properties and chamber geometry parameters through numerical simulations using a finite element model of a bullet-shaped chamber with homogeneous isotropic linear elastic material properties. A longitudinal impulse displacement was applied to the base edge of the model to investigate wave propagation from this boundary. Parametric studies were performed for variables of interest related to geometry and material properties. The wave speeds estimated from simulation results were used to determine wave speed sensitivity to each variable. Wave speed was found to be a strong function of material elasticity and a weak function of chamber geometry and viscous damping. Simulated wave speed as a function of elasticity was in good agreement with wave speeds determined from an analytical expression for longitudinal wave speed in elastic thin plates. These promising preliminary results increase our understanding of how these parameters affect intrinsic longitudinal wave speed and warrant future studies addressing the impact of patient-specific model geometry, material anisotropy and hyperelasticity, and boundary conditions on wave speed.

A Novel Assessment Using Projected Transmitral Gradient Improves Diagnostic Yield of Doppler Hemodynamics in Rheumatic and Calcific Mitral Stenosis.

OBJECTIVES: The aims of this study were to: 1) develop a formula for projected transmitral gradient (TMG), expected gradient under normal heart rate (HR), and stroke volume (SV); and 2) assess the prognostic value of projected TMG. BACKGROUND: In mitral stenosis (MS), TMG is highly dependent on hemodynamics, often leading to discordance between TMG and mitral valve area. METHODS: All patients with suspected MS based on echocardiography from 2001 to 2017 were analyzed. Data were randomly split (2:1); projected TMG was modeled in the derivation cohort, then tested in the validation cohort. The composite endpoint was death or mitral valve intervention. RESULTS: Of 4,973 patients with suspected MS, severe and moderate MS, defined as mitral valve area ≤1.5 and >1.5 to 2.0 cm2, were present in 437 (9%) and 936 (19%), respectively. In the derivation cohort (n = 3,315; age 73 ± 12 years; 34% male), corresponding gradients were TMG ≥6 and 4 to <6 mm Hg, respectively, under normal hemodynamics. Based on the impact of hemodynamics on TMG, the formula was projected TMG = TMG - 0.07 (HR - 70) - 0.03 (SV - 97) in men and projected TMG = TMG - 0.08 (HR - 72) - 0.04 (SV - 84) in women. In the validation cohort (n = 1,658), projected TMG had better agreement with MS severity than TMG (kappa 0.61 vs. 0.28). Among 281 patients with TMG ≥6 mm Hg, projected TMG ≥6 mm Hg, present in 171 patients (61%), was associated with higher probability of the endpoint versus projected TMG <6 mm Hg (adjusted hazard ratio: 1.8; 95% confidence interval: 1.2 to 2.6; p < 0.01). CONCLUSIONS: The novel concept of projected TMG, constructed using the observed impact of HR and SV on TMG, significantly improved the concordance of gradient and valve area in MS and provided better risk stratification than TMG.

Noninvasive Hemodynamic Assessment of Shock Severity and Mortality Risk Prediction in the Cardiac Intensive Care Unit.

OBJECTIVES: This study sought to define the 2-dimensional and Doppler echocardiographic hemodynamics associated with each Society for Cardiovascular Angiography and Interventions (SCAI) stage, and to determine their association with mortality. BACKGROUND: The SCAI shock stages classification stratifies mortality risk in cardiac intensive care unit (CICU) patients, but the echocardiographic and hemodynamic parameters that define these SCAI shock stages are unknown. METHODS: Unique CICU patients admitted from 2007 to 2015 who had a transthoracic echocardiogram within 1 day of CICU admission were included. Echocardiographic variables were evaluated as a function of SCAI shock stage. Multivariable logistic regression determined the association between echocardiographic parameters with adjusted hospital mortality. RESULTS: We included 5,453 patients with a median age of 69.3 years (interquartile range: 58.2 to 79.0 years) (37% women), and a median left ventricular ejection fraction (LVEF) of 50% (interquartile range: 35% to 61%). Higher SCAI shock stages were associated with lower LVEF and worse systemic hemodynamics. Hospital mortality was higher in patients with LVEF <40%, cardiac index <1.8 l/min/m2, stroke volume index <35 ml/m2, cardiac power output <0.6 W, or medial early mitral valve inflow velocity to early diastolic annular velocity (E/e') ratio >15 (particularly in SCAI shock Stages A to C). After multivariable adjustment, only stroke volume index <35 ml/m2 (adjusted odds ratio: 2.0; 95% confidence interval: 1.4 to 3.0; p < 0.001) and E/e' ratio >15 (adjusted odds ratio: 1.52; 95% confidence interval: 1.04 to 2.23; p = 0.03) remained associated with higher hospital mortality. CONCLUSIONS: Noninvasive 2-dimensional and Doppler echocardiographic parameters correlate with the SCAI shock stages and improve risk stratification for hospital mortality in CICU patients. Low stroke volume index and high E/e' ratio demonstrated the strongest association with hospital mortality.

Assessment of Right Ventricular-Pulmonary Arterial Coupling in Chronic Pulmonary Regurgitation.

BACKGROUND: We hypothesized that noninvasively measured right ventricular (RV) to pulmonary arterial (RV-PA) coupling would be abnormal in chronic pulmonary regurgitation (PR) even in the setting of normal RV ejection fraction, and that RV-PA coupling indices would have a better correlation with peak oxygen consumption (VO2) compared with RV systolic indices alone. METHODS: This was a retrospective study of 129 adults (repaired tetralogy of Fallot [TOF] n = 84 and valvular pulmonic stenosis [VPS] with previous intervention n = 45) with ≥ moderate native PR and RV ejection fraction > 50%. The 84 TOF patients were propensity matched with 84 patients with normal echocardiogram (control); age 28 ± 7 years and male sex n = 39 (46%). RV-PA coupling was measured according to fractional area change (FAC)/RV systolic pressure (RVSP) and tricuspid annular plane systolic excursion (TAPSE)/RVSP. RESULTS: RV systolic function indices were similar between TOF and control groups (FAC 43 ± 6% vs 41 ± 5% [P = 0.164] and TAPSE 22 ± 5 mm vs 24 ± 6 mm [P = 0.263]). However, RV-PA coupling was lower in the TOF group (FAC/RVSP 1.10 ± 0.29 vs 1.48 ± 0.22 [P < 0.001]; TAPSE/RVSP 0.51 ± 0.15 vs 0.78 ± 0.11 [P < 0.001]) because of higher RV afterload (RVSP 42 ± 3 mm Hg vs 31 ± 3 mm Hg [P = 0.012]). FAC/RVSP (r = 0.61; P < 0.001) and TAPSE/RVSP (r = 0.69; P < 0.001) correlated with peak VO2 especially in the patients with impaired exercise capacity whereas FAC and TAPSE were independent of peak VO2. Similar comparisons between VPS and control groups showed no difference in TAPSE and FAC between groups, but lower FAC/RVSP and TAPSE/RVSP in the VPS group. CONCLUSIONS: There is abnormal RV-PA coupling in chronic PR, and noninvasively measured RV-PA coupling might potentially be prognostic because of its correlation with exercise capacity.

The role of echocardiography for quantitative assessment of right ventricular size and function in adults with repaired tetralogy of Fallot.

BACKGROUND: Quantitative assessment of right ventricular (RV) systolic function by echocardiography is challenging in patients with congenital heart disease because of the complex geometry of the RV and the iatrogenic structural abnormalities resulting from prior cardiac surgeries. The purpose of this study was to determine the correlation between echocardiographic indices of RV systolic function and cardiac magnetic resonance imaging (CMRI) derived RV ejection fraction (RVEF) in adults with repaired tetralogy of Fallot (TOF). METHODS: Quantitative assessment of RV function was performed with RV tissue Doppler systolic velocity (RV s'), tricuspid annular plane systolic excursion (TAPSE), and fractional area change (FAC). These echocardiographic indices were compared to RVEF from CMRI performed on the same day as echocardiogram. RESULTS: Of 209 patients, the mean RV FAC was 39 ± 9%, TAPSE was 18 ± 4 mm, RV s' was 10 ± 2 cm/s, and RVEF was 40 ± 10%. There was a good correlation between TAPSE and RVEF (r = 0.79, P < .001), good correlation between RV s' and RVEF (r = 0.71, P < .001), and modest correlation between FAC and RVEF (r = 0.66, P < .001). TAPSE < 17 mm effectively discriminated between patients with RV systolic dysfunction defined as RVEF < 47% (sensitivity 81%, specificity 79%, area under the curve [AUC] 0.805). FAC < 40% was associated with RVEF < 47% (sensitivity 72%, specificity 63%, AUC 0.719). RV s' < 11 cm was associated with RVEF < 47% (sensitivity 83%, specificity 68%, AUC 0.798). CONCLUSION: Despite the structural and functional abnormalities of the RV in patients with repaired TOF, quantitative assessment of RV systolic function by echocardiography is feasible and had good correlation with CMRI-derived RVEF.

Incidence and Management of Hemopericardium: Impact of Changing Trends in Invasive Cardiology.

OBJECTIVE: As invasive cardiovascular care has become increasingly complex, cardiac perforation leading to hemopericardium is a progressively prevalent complication. We sought to assess the frequency, etiology, and outcomes of hemorrhagic pericardial effusions managed through a nonsurgical echo-guided percutaneous strategy. PATIENTS AND METHODS: Over a 10-year period (January 1, 2007, to December 31, 2016), 1097 unique patients required pericardiocentesis for clinically important pericardial effusions. Of these 411 had drainage of hemorrhagic effusions (defined as a pericardial hemoglobin level >50% of serum hemoglobin or frank blood in the setting of cardiac perforation). Clinical characteristics, echocardiographic data, details of the procedure, and outcomes were determined. RESULTS: Median patient age was 67 years (interquartile range, 56-76 years), and 60% were men. The procedure was emergent in 83% and elective in 17%. The site of pericardiocentesis was determined by echo-guidance in all: 68% from the left para-apical region, 18% from the left or right parasternal areas, and 14% were subxyphoid. Half (n=215 [52%]) occurred after cardiac perforation with percutaneous interventional procedure (ablation, n=94; device lead implantation, n=65; percutaneous coronary intervention, n=22; other, n=34), whereas 30% followed cardiac or thoracic surgery. Pericardial fluid volume drained was 546±440 mL. In 94% of cases, echo-guided pericardiocentesis was the only treatment of the effusion needed, whereas definitive surgery was required in 25 (6%) cases for persistent bleeding or acute management of the underlying etiology. There was no procedural mortality. Late mortality was better for hemorrhagic effusions compared with a contemporary cohort with nonhemorrhagic effusions. CONCLUSION: Echocardiographic guidance allows rapid successful pericardiocentesis in the setting of hemopericardium related to microperforation with interventional procedures, malignancy, or pericarditis, with most not requiring surgical intervention. Surgery should remain the first-line approach for aortic dissection or myocardial rupture.

Residual leaks following percutaneous left atrial appendage occlusion: assessment and management implications.

Left atrial appendage (LAA) closure for stroke prevention in the setting of non-valvular atrial fibrillation is an alternative to oral anticoagulation in patients with increased bleeding risk. It allows similar reduction in thromboembolic events, in particular stroke, compared to warfarin. A common clinical dilemma is the management of patients with peri-device leak after LAA occlusion. This has been documented in both percutaneous as well as surgical approaches. The specific definitions of leak severity, and the longer-term clinical implications are poorly understood. Here we review the mechanisms of incomplete occlusion for the different percutaneous closure devices, the data regarding thromboembolic risk in patients with incomplete appendage closure for both percutaneous and surgical strategies, and provide recommendations for management in these patients.

Assessment of Prosthetic Valve Function After TAVR.

Calcific aortic valve stenosis is a common valve pathology that increases in prevalence with advancing age. Transcatheter aortic valve (TAV) replacement has now emerged as the preferred treatment for patients at high risk for surgery and for those who are inoperable. However, the use of this ground-breaking technology has inevitably been associated with a host of new problems. These new types of complications are frequently unrecognized or underestimated due to lack of familiarity with the normal and pathological appearance of TAV and often require redefining strategies for diagnosis and treatment. This review presents a systematic approach for follow-up assessment of TAV function, as well as pathology uniquely related to TAV. Because the worldwide transcatheter aortic valve replacement experience has been dominated by the Edwards Sapien (Irvine, California) and Medtronic CoreValve (Minneapolis, Minnesota) family of bioprosthetic aortic valves, we will focus our review on these valves, each with their unique set of advantages and technological challenges.

Aortic Stenosis and Noncardiac Surgery: Managing the Risk.

Managing the risk of noncardiac surgery in patients with aortic stenosis is a problem that is frequently confronted in clinical practice. Traditionally, patients with severe aortic stenosis were considered to be at substantial risk during noncardiac surgery, and as such, elective procedures were avoided before intervention on the aortic valve in most patients other than those who were ineligible or refused aortic valve replacement. Recent data suggest that with contemporary anesthesia and surgical techniques, the risk of noncardiac surgery is substantially lower than previously believed. We review the existent literature in the field, and propose a practical approach to complex patients.

Comparison of semiquantitative and quantitative assessment of severity of aortic regurgitation: clinical implications.

BACKGROUND: Recent studies have emphasized the importance of quantitative assessment of the degree of aortic regurgitation (AR). However, semiquantitative methods have remained mainly used despite their unclear diagnostic value. The aim of this study was to define the sensitivity and specificity of semiquantitative methods compared with the proximal isovelocity surface area method as a reference for the diagnostic of severe AR. METHODS: The degree of AR was evaluated using the proximal isovelocity surface area method and four semiquantitative measurements (left ventricular cardiac output, pressure half-time, diastolic flow reversal, and vena contracta) in 224 patients with a wide range of AR severity. RESULTS: The mean effective regurgitant orifice area was 25 ± 14 mm(2) (range, 3-69 mm(2)), the mean regurgitant volume was 57 ± 31 mL (range, 9-183 mL), and 100 patients (44%) had severe AR (effective regurgitant orifice area ≥ 30 mm(2) or regurgitant volume ≥ 60 mL). Overall, semiquantitative methods had good specificity but poor sensitivity, except the vena contracta, which had good sensitivity and specificity. Sensitivity, specificity, and positive and negative predictive values of the recommended thresholds for severe AR of the four semiquantitative methods were 53%, 89%, 77%, and 73% for left ventricular cardiac output ≥ 10 L/min; 12%, 100%, 100%, and 52% for pressure half-time < 200 msec; 45%, 87%, 79%, and 60% for diastolic flow reversal ≥ 18 cm/sec; and 81%, 83%, 78%, and 85% for vena contracta ≥ 6 mm, respectively. CONCLUSIONS: For the assessment of AR severity, current thresholds appear specific but poorly sensitive, except for vena contracta, which provides good discriminative value. Semiquantitative methods should be integrated into the comprehensive evaluation of AR severity, but severe AR should not be excluded only on the basis of semiquantitative criteria. These results emphasize the need for the quantitative assessment of AR severity.

Pathophysiology of tricuspid regurgitation: quantitative Doppler echocardiographic assessment of respiratory dependence.

BACKGROUND: Respiratory dependence of tricuspid regurgitation (TR), a long-held concept suggested by murmur variation, remains unproven and of unclear mechanisms. METHODS AND RESULTS: In 41 patients with mild or greater TR (median age, 67 years), we performed triple Doppler echocardiographic quantification (TR severity, right ventricular, and right atrial quantification) with simultaneous respirometer recording of respiratory phases. Expiration to inspiration changes (median) affected TR peak velocity (-40 cm/s; 25th to 75th percentile, -60 to -30 cm/s), duration (-12 milliseconds; 25th to 75th percentile, -45 to 2 milliseconds), and time-velocity integral (-17 cm; 25th to 75th percentile, -23.4 to -10 cm; all P<0.001), consistent with decreased TR driving force. Nevertheless, inspiratory TR augmentation was demonstrated by increased effective regurgitant orifice (0.21 cm(2); 25th to 75th percentile, 0.09 to 0.34 cm(2)) and volume (18 mL per beat; 25th to 75th percentile, 10 to 25 mL per beat; all P<0.001) infrequently detected clinically (2 of 41, 5). As a result of reduced TR driving force, regurgitant volume increased less than effective regurgitant orifice (120 [25th to 75th percentile, 78.6 to 169] versus 169 [ 25th to 75th percentile, 12.9 to 226.1]; P<0.001). During inspiration, right ventricular area increased (diastolic, 27.8 [25th to 75th percentile, 22.6 to 36.3] versus 26.5 [21.1 to 31.9]; P<0.0001) with widening of right ventricular shape (length-to-width ratio, 1.6 [ 25th to 75th percentile, 1.37 to 1.95] versus 1.7 [1.46 to 2.1]; P<0.0001), increased systolic annular diameter (P=0.003), valve tenting height (P<0.0001) and area (P<0.0001), and reduced valvular-to-annular ratio (P=0.006). Effective regurgitant orifice during inspiration was independently determined by inspiratory valvular-to-annular ratio (P=0.026) and inspiratory change in right ventricular length-to-width ratio (P=0.008) and valve tenting area (P=0.015). CONCLUSIONS: TR is dynamic with almost universal respiratory changes of large magnitude and complex pathophysiology. During inspiration, a large increase in effective regurgitant orifice causes, despite a decline in regurgitant gradient, a notable increase in regurgitant volume. Effective regurgitant orifice changes are independently linked to inspiratory annular enlargement (decreased valvular coverage) and to inspiratory right ventricular shape widening with increased valvular tenting. These novel physiological insights into TR respiratory dependence underscore right-side heart plasticity and are important for clinical TR severity evaluation.