Advances in Rheumatic Mitral Stenosis: Echocardiographic, Pathophysiologic, and Hemodynamic Considerations

•Decreased ejection fraction in mitral stenosis is caused by reduced preload.•Low-flow, low-gradient mitral stenosis occurs when ventricular compliance is low.•Patients with Cn < 4 mm Hg/mL may remain symptomatic after successful valvuloplasty.•Low Nunes scores correctly predict good outcomes even when Wilkins scores are >8.•For any given valve area, gradients are lower in calcific than rheumatic valves. Echocardiography is the primary imaging modality used in patients with mitral stenosis. Doppler-derived measurements of mitral pressure half-time are commonly used to calculate mitral valve area, but a number of hemodynamic confounders associated with advanced age limit its utility. Planimetry remains the gold standard for determining mitral valve area and may be performed using two- or three-dimensional imaging. Although the Wilkins score has been used for >30 years to predict balloon mitral valvuloplasty outcomes, newer scoring systems have been proposed to improve predictive accuracy. Some patients undergoing technically successful balloon mitral valvuloplasty may not have satisfactory clinical outcomes. These individuals may be identified by the presence of reduced net atrioventricular compliance, which can be measured echocardiographically. Exercise testing may be useful in patients with mitral stenosis whose symptomatic status is incongruous their mitral valve area. Last, reduced left atrial systolic strain, an indicator of poor left atrial compliance, has been shown to reliably predict adverse outcomes in patients with mitral stenosis. The author discusses the hemodynamics and path ophysiology of mitral stenosis and reviews current and emerging roles of echocardiography in its evaluation. Echocardiography is the primary imaging modality used in patients with mitral stenosis. Doppler-derived measurements of mitral pressure half-time are commonly used to calculate mitral valve area, but a number of hemodynamic confounders associated with advanced age limit its utility. Planimetry remains the gold standard for determining mitral valve area and may be performed using two- or three-dimensional imaging. Although the Wilkins score has been used for >30 years to predict balloon mitral valvuloplasty outcomes, newer scoring systems have been proposed to improve predictive accuracy. Some patients undergoing technically successful balloon mitral valvuloplasty may not have satisfactory clinical outcomes. These individuals may be identified by the presence of reduced net atrioventricular compliance, which can be measured echocardiographically. Exercise testing may be useful in patients with mitral stenosis whose symptomatic status is incongruous their mitral valve area. Last, reduced left atrial systolic strain, an indicator of poor left atrial compliance, has been shown to reliably predict adverse outcomes in patients with mitral stenosis. The author discusses the hemodynamics and path ophysiology of mitral stenosis and reviews current and emerging roles of echocardiography in its evaluation. Attention ASE Members:Login at www.ASELearningHub.org to earn continuing medical education credit through an online activity related to this article. Certificates are available for immediate access upon successful completion of the activity and postwork. This activity is free for ASE Members, and $25 for nonmembers. Attention ASE Members: Login at www.ASELearningHub.org to earn continuing medical education credit through an online activity related to this article. Certificates are available for immediate access upon successful completion of the activity and postwork. This activity is free for ASE Members, and $25 for nonmembers. The decline of acute rheumatic fever in industrialized countries has resulted in a significant decrease in the incidence of mitral stenosis. In underdeveloped countries, however, where rheumatic fever continues to remain a significant public health concern, its incidence remains high. In the West, rheumatic heart disease generally comes to clinical attention during middle age or later. In developing countries, where rheumatic disease is more rapidly progressive, disease onset typically occurs in the second and third decades of life.1Iung B. Mitral stenosis: still a concern in heart valve disease.Arch Cardiovasc Dis. 2018; 101: 597-599Crossref Scopus (5) Google Scholar In fact, women of childbearing age may first present with acute pulmonary edema during pregnancy because of the rise in circulating blood volume. The mitral valve (MV) is the most commonly affected in rheumatic heart disease. Rheumatic valvulitis is believed to be triggered by an autoimmune process caused by cross-reactivity between streptococcal antigens and native heart valve proteins (molecular mimicry).2Cunningham M.W. Rheumatic fever, autoimmunity and molecular mimicry: the Streptococcal connection.Int Rev Immunol. 2014; 33: 314-329Crossref PubMed Scopus (97) Google Scholar Echocardiography plays a key role in the diagnosis of mitral stenosis and, when indicated, in the selection of the most appropriate intervention. In this review I discuss the hemodynamics, pathophysiology, and echocardiographic assessment of this disorder. Mitral stenosis restricts blood flow into the left ventricle during diastole. The accompanying rise in left atrial (LA) pressure increases the transmitral gradient (TMG), which helps maintain forward ventricular filling. At the same time, increased LA pressure causes a passive upstream rise in pulmonary venous pressure. This is thought to trigger pulmonary arteriolar vasoconstriction, which increases pulmonary artery (PA) pressure. Over time, irreversible obliterative changes may develop in the pulmonary vasculature,3Tandon H.D. Kasturi I. Pulmonary vascular changes associated with isolated mitral stenosis in India.Br Heart J. 1975; 37: 26-36Crossref PubMed Scopus (40) Google Scholar which lead to fixed pulmonary hypertension, sometimes referred to as the “second stenosis.” Interestingly, the second stenosis reduces congestive symptoms by decreasing venous return, albeit at the expense of a reduction in cardiac output. The development of pulmonary hypertension increases right ventricular afterload, which over time results in right ventricular hypertrophy, dilatation, and failure. Enlargement of the right ventricle causes tricuspid annular dilatation as well as tricuspid leaflet tethering, resulting in functional tricuspid regurgitation.4Hung J. The pathogenesis of functional tricuspid regurgitation.Sem Thorac Cardiovasc Surg. 2010; 22: 76-78Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar There are a number of characteristic two-dimensional echocardiographic findings in rheumatic mitral stenosis (Figure 1).5Jain S. Mankad S.V. Echocardiographic assessment of mitral stenosis: features of mitral stenosis.Cardiol Clinics. 2013; 3: 177-191Abstract Full Text Full Text PDF Scopus (9) Google Scholar,6Feigenbaum H. Echocardiography.4th ed. Lea & Febiger, Philadelphia1986: 249-364Google Scholar Increased leaflet thickness typically begins at the free margins of the MV and gradually extends toward its base. The distinctive diastolic doming (hockey-stick appearance) of the anterior mitral leaflet, caused by commissural fusion, is best appreciated in long-axis views. The posterior leaflet may also dome, although it is more often immobile. Fusion of the medial and lateral commissures of the MV, which progresses inward, produces the characteristic fish-mouth appearance of the rheumatic MV in the short-axis view. Last, the chordae tendineae shorten, thicken, and become fused together. Chordal abnormalities typically begin at points of leaflet attachment and progress toward the papillary muscles. Importantly, these abnormalities, which are often underestimated echocardiographically, can be seen to advantage with intentional off-axis imaging (Figure 1C). Several early studies demonstrated abnormalities of left ventricular (LV) systolic contractility in about 25% of patients with mitral stenosis, with a predilection for the posterior wall. LV ejection is usually mildly decreased. Early workers suggested that this is due to chronic (“smoldering”) rheumatic carditis,7Klein A.J.P. Carroll J.D. Left ventricular dysfunction and mitral stenosis.Heart Failure Clin. 2006; 2: 3-52Abstract Full Text Full Text PDF Scopus (17) Google Scholar but this has not been borne out by histopathologic studies.8Saikia U.N. Kumar R.M. Pandian R.P. Gupta S. Dhaliwal R.S. Talwar K.K. Adhesion molecule expression and ventricular remodeling in chronic rheumatic heart disease: a cause or effect in the disease progression—a pilot study.Cardiovasc Path. 2012; 21: 83-88Crossref PubMed Scopus (8) Google Scholar Moreover, recent invasive hemodynamic studies have demonstrated that end-systolic elastance, the gold standard of intrinsic LV contractility, is normal in mitral stenosis.9El Sabbagh A. Reddy Y.N.V. Barros-Gomez S. Borlaug B.A. Miranda W.R. Pislaru S.V. et al.Low-gradient severe mitral stenosis: hemodynamic profiles, clinical characteristics, and outcomes.J Am Heart Assoc. 2019; 8: e010736Crossref PubMed Scopus (14) Google Scholar Some workers have alternatively proposed that decreased LV systolic contractility is caused by reduced LV filling in accordance with the Starling mechanism. Specifically, it has been suggested that the scarred and foreshortened chords seen in mitral stenosis tether, and thus prevent, the LV free wall from expanding during diastole.7Klein A.J.P. Carroll J.D. Left ventricular dysfunction and mitral stenosis.Heart Failure Clin. 2006; 2: 3-52Abstract Full Text Full Text PDF Scopus (17) Google Scholar Reduced LV filling may also be caused by exaggeration of the otherwise modest leftward motion of the interventricular septum normally seen in early diastole (Figure 2). The resulting paradoxical (leftward diastolic) motion of the septum has been attributed to predominance of early diastolic right ventricular filling resulting from the marked disparity in area between the mitral and tricuspid valves (Figure 2, Video 1 available at www.onlinejase.com).10Weyman A.E. Heger J.J. Kronik G. Wann L.S. Dillon J.C. Feigenbaum H. Mechanism of paradoxical early diastolic septal motion in patients with mitral stenosis: a cross-sectional echocardiographic study.Am J Cardiol. 1977; 40: 691-699Abstract Full Text PDF PubMed Scopus (26) Google Scholar Deformation studies11Bilen E. Kurt M. Tanboga I.H. Kaya A. Isik T. Ekinci M. et al.Severity of mitral stenosis ans left ventricular mechanics: a speckle tracking study.Cardiology. 2011; 119: 108-115Crossref PubMed Scopus (31) Google Scholar performed in patients with mitral stenosis demonstrate a significant reduction in LV global longitudinal strain compared with normal control subjects, suggesting the presence of intrinsic myocardial disease. However, when global longitudinal strain is indexed to LV volume, these differences disappear, indicating that the reduction in global longitudinal strain is related to reduced preload rather than to a “myocardial factor.”12Sengupta S.P. Amaki M. Bansal M. Fulwani M. Washimkar S. Hofstra L. et al.Effects of percutaneous balloon valvuloplasty on left ventricular deformation in patients with isolated severe mitral stenosis: a speckle tracking strain echocardiographic study.J Am Soc Echocardiogr. 2014; 27: 639-647Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Severe mitral stenosis is defined as an MV area ≤ 1.5 cm2 and very severe mitral stenosis as an MV area ≤ 1.0 cm2.13Nishimura R.A. Bonow R.A. Carabello B.A. Erwin III, J.P. Guyton R.A. O’Gara P.T. et al.2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary.J Am Coll Cardiol. 2014; 63: 2438-2488Crossref PubMed Scopus (1338) Google Scholar An MV area between 1.6 and 2.0 cm2 is not usually associated with symptoms and is variably referred to as “moderate” or “nonsevere” mitral stenosis. Of note, there are no established indexed values for MV area. Last, it is important to emphasize that TMGs cannot be used as reliable surrogates for MV area, because of their dependence upon heart rate and blood flow.14Rahimtoola S.H. Durairaj A. Mehra A. Nuno I. Current evaluation and management of patients with mitral stenosis.Circulation. 2002; 106: 1183-1188Crossref PubMed Scopus (86) Google Scholar Accordingly, expected mean TMGs, at a heart rate between 60 and 80 beats/min (assuming normal transmitral flow, i.e., no anemia, hyperthyroidism, etc.) for moderate, severe, and very severe mitral stenosis are <5, 5 to 10, and >10 mm Hg, respectively.15Baumgartner H. Hung J. Burmejo J. Chambers J.B. Evangelista A. Griffin B.P. et al.Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice.J Am Soc Echocardiogr. 2009; 22: 1-23Abstract Full Text Full Text PDF PubMed Scopus (1235) Google Scholar MV area is most commonly measured directly using planimetry or indirectly using the pressure half-time (P½t) method. Methods involving the continuity principle are seldom used. Planimetry is considered the echocardiographic gold standard for measuring MV area because it is not subject to the various confounders that influence Doppler-based methods. Because the MV domes in diastole, it is critical that planimetry is performed at the leaflet tips, otherwise MV area will be overestimated. MV area measurement is greatly simplified with three-dimensionally guided biplane imaging (Figure 3). When the cursor is positioned across the tips of both leaflets in the parasternal long-axis view, the orthogonal short-axis view is simultaneously displayed, such that the MV can be planimetered along its free margin.16Sebag I.A. Morgan J.G. Handschumacher M.D. Marshall J.E. Nesta F. Hung J. et al.Usefulness of three-dimensionally guided assessment of mitral stenosis using matrix-array ultrasound.Am J Cardiol. 2005; 96: 1151-1156Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar Real-time three-dimensional imaging permits visualization of the mitral leaflets in multiple planes and thus facilitates accurate identification of the narrowest opening of the MV (Figure 4). Last, cardiac computed tomography has been successfully used to measure MV area in patients with rheumatic mitral stenosis who have suboptimal echocardiographic images.17Messika-Zeitoun D. Sefaty J. Laissy J. Berhili M. Brochet E. Iung B. et al.Assessment of mitral valve area in patients with mitral stenosis by multislice computed tomography.J Am Coll Cardiol. 2006; 48: 411-413Crossref PubMed Scopus (93) Google ScholarFigure 4Real-time three-dimensional measurement of MV area. Multiplane reconstruction allows precise identification of the narrowest opening of the MV. Images courtesy of Gila Perk, MD, Mount Sinai Medical Center.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The mitral P½t is the time it takes for the peak LA-LV pressure gradient to fall by a factor of one half. This is determined by the rate at which falling LA and rising LV diastolic pressures come into equilibrium. When equilibrium is reached slowly, P½t is prolonged and mitral stenosis is severe, and vice versa (Figure 5). Empiric observations from invasive hemodynamic studies reveal18Hatle L. Angelsen B. Tromsdal A. Noninvasive assessment of atrioventricular pressure half-time by Doppler ultrasound.Circulation. 1979; 60: 1096-1104Crossref PubMed Scopus (571) Google Scholar that when P½t is 220 msec, MV area equals 1.0 cm2. Hence, MV area can be calculated using the formula: 220/P½t (the Hatle formula). Doppler-derived P½t (Figure 6) can be used to calculate MV area using the same formula, but it does not perform accurately unless the MV is stenotic.19Firstenberg M.S. Abel E.E. Papadimos T.J. Tripathi R.S. Nonconvective forces: a critical and often ignored component in the echocardiographic assessment of transvalvular pressure gradients.Cardiol Res Pract. 2012; 2012: e383217Crossref PubMed Scopus (8) Google ScholarFigure 6P½t can be ascertained using Doppler imaging by measuring the time offset between peak E-wave transmitral velocity (Vmax) and the velocity at Vmax/√2. See text.View Large Image Figure ViewerDownload Hi-res image Download (PPT) It is important to point out that P½t is influenced by a number of factors that render calculation of MV area inaccurate.20Thomas J.D. Wilkins G.T. Choong C.Y.P. Abascal V.M. Palacios I.F. Block P.C. Inaccuracy of mitral pressure half-time immediately after percutaneous mitral valvotomy: dependence on transmitral gradient and left atrial and ventricular compliance.Circulation. 1988; 78: 980-993Crossref PubMed Scopus (219) Google Scholar Among older patients, in whom heart failure with preserved ejection fraction (LV diastolic dysfunction) is common, reduced ventricular compliance may cause a steep rise in LV diastolic pressure leading to a shortened P½t and overestimation of MV area. Significant aortic regurgitation similarly increases the rate of diastolic LV pressure rise, thereby shortening the P½t. When significant mitral regurgitation (MR) complicates mitral stenosis, the marked rise in peak E-wave velocity prolongs the time required for transmitral velocity to decrease to peak E-wave velocity/√2, thereby lengthening P½t (Figure 6). At the same time, LA volume overload from MR decreases the operational compliance of the atrium by shifting its pressure-volume relationship onto the steep upper portion of its pressure-volume curve. As a result, there is a rapid decline in LA pressure (and E-wave velocity), which shortens the P½t. The utility of the P½t for estimating MV area rests in the fact that peak transmitral pressure gradient (peak E-wave velocity) and LA compliance influence the P½t in opposite directions. However, in some patients with mixed mitral stenosis and MR, this balance becomes disturbed, and LA compliance change predominates, rendering the Hatle formula (220/P½t) inaccurate.21Mohan J.C. Mukherjee S. Kumar A. Arora R. Patel A.R. Pandian N.G. Does chronic mitral regurgitation influence Doppler pressure half-time-derived calculation of the mitral valve area in patients with mitral stenosis?.Am Heart J. 2004; 148: 703-709Crossref PubMed Scopus (17) Google Scholar Volume overload of the left atrium during pregnancy may cause overestimation of the MV area by the P½t method for similar reasons.22Rokey R. Hsu H.W. Moise K.J. Adam K. Wasserstrum N. Inaccurate noninvasive mitral valve area during pregnancy.Obstet Gynecol. 1994; 84: 950-955PubMed Google Scholar Last, P½t is decreased when an atrial septal defect is present because of simultaneous runoff into the right atrium and left ventricle.23Levin T.N. Feldman T. Carroll J.D. Effect of atrial septal occlusion on mitral area after Inoue balloon valvotomy.Cathet Cardiovasc Diagn. 1994; 33: 308-314Crossref PubMed Scopus (16) Google Scholar When MV area is measured using the Doppler P½t method, deceleration of the continuous-wave Doppler signal occasionally displays an early, steep fall in velocity followed by a more gradual fall, producing a “ski-slope” appearance23Levin T.N. Feldman T. Carroll J.D. Effect of atrial septal occlusion on mitral area after Inoue balloon valvotomy.Cathet Cardiovasc Diagn. 1994; 33: 308-314Crossref PubMed Scopus (16) Google Scholar (Figure 7). The mid-diastolic decrease in slope is caused by the increase in operational compliance that takes place as the left atrium empties (shifts onto the less steep portion of its pressure-volume curve).24Gonzalez M.A. Child K.S. Krivokapich J. Comparison of two-dimensional and Doppler echocardiography and intracardiac hemodynamics for quantification of mitral stenosis.Am J Cardiol. 1987; 60: 327-332Abstract Full Text PDF PubMed Scopus (52) Google Scholar In such instances, it is recommended that the P½t be measured using the less steep mid-diastolic slope.25Flachskampf F.A. Weyman A.E. Guerrero J.L. Thomas J.D. Calculation of atrioventricular compliance from the mitral flow profile: analytic and in vitro study.J Am Coll Cardiol. 1992; 19: 998-1004Crossref PubMed Scopus (71) Google Scholar The operational compliance of the left atrium is reduced in mitral stenosis because of the rise in atrial volume that attends decreased chamber emptying.26Athayde G.R.S. Nascimento B.R. Elmariah S. Lodi-Junqueira L. Soares J.R. Saad G.P. et al.Impact of left atrial compliance improvement on functional status after percutaneous mitral valvuloplasy.Catheter Cardiovasc Interv. 2019; 93: 156-163Crossref PubMed Scopus (4) Google Scholar Additional perturbations common in older individuals further decrease atrial compliance. First, comorbidities prevalent among the elderly (diabetes mellitus, hypertension, obesity, and coronary artery disease) reduce LA compliance by promoting atrial fibrosis.27Morris D.A. Gailani M. Pere A.M. Blaschke Dietz R. Haverkamp W. et al.Left atrial systolic and diastolic dysfunction in heart failure with normal left ventricular ejection fraction.J Am Soc Echocardiogr. 2011; 24: 651-662Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar In addition, reduced LV compliance, common among older individuals, decrease operational LA compliance because of the attendant rise in atrial volume (atrioventricular coupling). Concomitant reduction of atrial and ventricular compliance, commonplace among older individuals, may result in the novel clinical entity low-flow, low-gradient (LF-LG) mitral stenosis. The reduced atrial compliance seen in this disorder increases the LA V wave (and hence mean LA pressure; Figure 8), resulting in dyspnea and effort intolerance.28Ha J.W. Chung N. Jang Y. Kang W.C. Kang S.M. Rim S.J. et al.Is the left atrial v wave the determinant of peak pulmonary artery pressure in patients with pure mitral stenosis.Am J Cardiol. 2000; 85: 986-992Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar Poor LA compliance also causes a rapid decline in the LA y-descent (Figure 8), because the atrium is operating on the steep upper portion of its pressure-volume curve.29Nunes M.C.P. Hung J. Barbosa M.M. Esteves W.A. Carvalho V.T. Lodi-Junqueira L. et al.Impact of atrioventricular compliance on clinical outcome in mitral stenosis.Circ Cardiovasc Img. 2013; 6: 1001-1008Crossref PubMed Scopus (22) Google Scholar This, combined with a rapid rise in LV diastolic pressure caused by poor ventricular compliance (Figure 8), decreases the magnitude of the TMG. In practical terms, LF-LG mitral stenosis is characterized by the constellation of (1) low flow (stroke volume < 35 mL/m2 by the continuity equation) due to reduced MV area and decreased LV filling due to a stiff ventricle, (2) a low gradient (reduced out of proportion to the planimetered MV area) due to low flow as well as rapid equalization of LA and LV pressures, and (3) dyspnea resulting from increased mean LA pressure (tall LA V wave).9El Sabbagh A. Reddy Y.N.V. Barros-Gomez S. Borlaug B.A. Miranda W.R. Pislaru S.V. et al.Low-gradient severe mitral stenosis: hemodynamic profiles, clinical characteristics, and outcomes.J Am Heart Assoc. 2019; 8: e010736Crossref PubMed Scopus (14) Google Scholar,30Cho I. Hong G. Lee S.H. Chang B. Shim C.Y. Chang H. et al.Differences in characteristics, left atrial reverse remodeling, and functional outcomes after mitral valve replacement in patients with low-gradient very severe mitral stenosis.J Am Soc Echocardiogr. 2016; 29: 757-767Abstract Full Text Full Text PDF Scopus (14) Google Scholar Additional factors such as right ventricular and LV systolic dysfunction may also decrease stroke volume (and transmitral flow) in LF-LG mitral stenosis. Decreased stroke volume can also result from reduced LV filling associated with severe subvalvular disease, LV concentric remodeling, loss of LA kick due to atrial fibrillation (AF), paradoxical septal motion, and pulmonary hypertension (the second stenosis).9El Sabbagh A. Reddy Y.N.V. Barros-Gomez S. Borlaug B.A. Miranda W.R. Pislaru S.V. et al.Low-gradient severe mitral stenosis: hemodynamic profiles, clinical characteristics, and outcomes.J Am Heart Assoc. 2019; 8: e010736Crossref PubMed Scopus (14) Google Scholar,30Cho I. Hong G. Lee S.H. Chang B. Shim C.Y. Chang H. et al.Differences in characteristics, left atrial reverse remodeling, and functional outcomes after mitral valve replacement in patients with low-gradient very severe mitral stenosis.J Am Soc Echocardiogr. 2016; 29: 757-767Abstract Full Text Full Text PDF Scopus (14) Google Scholar Increased afterload associated with hypertension and aortic stiffness, common in older individuals, can similarly reduce LV stroke volume.9El Sabbagh A. Reddy Y.N.V. Barros-Gomez S. Borlaug B.A. Miranda W.R. Pislaru S.V. et al.Low-gradient severe mitral stenosis: hemodynamic profiles, clinical characteristics, and outcomes.J Am Heart Assoc. 2019; 8: e010736Crossref PubMed Scopus (14) Google Scholar,30Cho I. Hong G. Lee S.H. Chang B. Shim C.Y. Chang H. et al.Differences in characteristics, left atrial reverse remodeling, and functional outcomes after mitral valve replacement in patients with low-gradient very severe mitral stenosis.J Am Soc Echocardiogr. 2016; 29: 757-767Abstract Full Text Full Text PDF Scopus (14) Google Scholar Given the impact that reduced LA and LV compliance have on the hemodynamics of mitral stenosis, it would be useful to be able to measure these parameters noninvasively. Although the individual compliances of the left atrium and left ventricle cannot be measured,31Li M. Dery J.P. Dumesnil J.G. Bourdreault J.R. Jobin J. Pibarot P. Usefulness of measuring net atrioventricular compliance by Doppler echocardiography in patients with mitral stenosis.Am J Cardiol. 2005; 96: 432-435Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar net atrioventricular compliance (Cn)32Schwammenthal E. Vered Z. Agranat O. Kaplinsky E. Rabinowitz B. Feinberg M.S. Impact of atrioventricular compliance on pulmonary artery pressure in mitral stenosis: an exercise echocardiographic study.Circulation. 2000; 102: 2378-2384Crossref PubMed Scopus (118) Google Scholar can be measured echocardiographically using the simple Doppler-based formula Cn (mL/mm Hg) = 1,270 × (planimetered MV area [cm2]/mitral E-wave deceleration slope [cm/s2]) (see Appendix). It is intuitive from this formula that Cn is reduced when LA or LV compliance is decreased, as both prolong E-wave downslope (shorten P½t; Figure 9). In patients with pure mitral stenosis, reduced Cn is due to decreased LA compliance. Among older individuals with LF-LG mitral stenosis, however, Cn is further reduced by decreased LV compliance.29Nunes M.C.P. Hung J. Barbosa M.M. Esteves W.A. Carvalho V.T. Lodi-Junqueira L. et al.Impact of atrioventricular compliance on clinical outcome in mitral stenosis.Circ Cardiovasc Img. 2013; 6: 1001-1008Crossref PubMed Scopus (22) Google Scholar Not surprisingly, low Cn (<4 mL/mm Hg) in patients with LF-LG mitral stenosis has been shown to worsen prognosis and has been linked to an increased likelihood of downstream AF, heart failure, repeat MV intervention, and death.33Mahfouz R.A. Elawady W. Hossein E. Yosri A. Impact of atrioventricular compliance on clinical outcome of patients undergoing successful percutaneous balloon mitral valvuloplasty.Echocadiography. 2012; 30: 1187-1193Crossref Scopus (15) Google Scholar,34Nunes M.C.P. Tan T.C. Elmariah S. Lodi-Junquiera L. Nascimento B.R. do Lago R. et al.Net atrioventricular compliance is an independent predictor of cardiovascular death in mitral stenosis.Heart. 2017; 103: 1891-1898Crossref PubMed Scopus (14) Google Scholar Moreover, symptomatic improvement may not occur in as many as 40% of such patients, despite technically successful balloon mitral valvuloplasty (BMV). This is thought to be due to the tall LA V wave (high mean LA pressure), which remains unaffected by the procedure9El Sabbagh A. Reddy Y.N.V. Barros-Gomez S. Borlaug B.A. Miranda W.R. Pislaru S.V. et al.Low-gradient severe mitral stenosis: hemodynamic profiles, clinical characteristics, and outcomes.J Am Heart Assoc. 2019; 8: e010736Crossref PubMed Scopus (14) Google Scholar (Figure 8). Echocardiographically, such “BMV nonresponders” may demonstrate a tall mitral E wave with an E/A ratio > 1 and a short P½t. Potentially salutary interventions in such patients include vasodilator therapy for those with increased LV afterload (hypertension and increased aortic stiffness) and restoration of sinus rhythm in those with AF. The utility of these therapeutic measures, however, remains to be substantiated.9El Sabbagh A. Reddy Y.N.V. Barros-Gomez S. Borlaug B.A. Miranda W.R. Pislaru S.V. et al.Low-gradient severe mitral stenosis: hemodynamic profiles, clinical characteristics, and outcomes.J Am Heart Assoc. 2019; 8: e010736Crossref PubMed Scopus (14) Google Scholar LF-LG mitral stenosis should be distinguished from so-called pseudosevere MS. Low flow associated with the latter is insufficient to adequately open the MV despite the negligible resistance it offers.9El Sabbagh A. Reddy Y.N.V. Barros-Gomez S. Borlaug B.A. Miranda W.R. Pislaru S.V. et al.Low-gradient severe mitral stenosis: hemodynamic profiles, clinical characteristics, and outcomes.J Am Heart Assoc. 2019; 8: e010736Crossref PubMed Scopus (14) Google Scholar Unfortunately, these two disorders cannot be readily distinguished. Mitral stenosis has a number of effects on LA strain. Peak LA systolic (reservoir) strain, a reflection of atrial compliance, has been shown to correlate with functional capacity.35Chien C. Chen C. Lin T. Lin Y