Mitral Regurgitation Francesca N. Delling, MD July 8, 2009

Outline Anatomy Diagnosis - Two-dimensional echocardiography (etiology) - Doppler methods (assessment of severity) - Role of 2D and 3D-TEE - Role of CMR Treatment

Anatomy: The mitral valve apparatus Subvalvular apparatus (papillary muscles with their supporting left ventricular walls and chordae tendineae) Mitral annulus Mitral valve leaflets

Anatomy: The mitral valve Reference view from the left ventricular apex Surgical view from the left atrium with the heart rotated

Diagnosis

2D Echocardiography: Etiology of mitral regurgitation Primary: - Myxomatous - Endocarditis - Rheumatic - Trauma - Congenital - Drugs (ergotamines, methysergide, pergolide, fen fen) Secondary: - Non-ischemic dilated CMP - Ischemic heart disease - HCM

Carpentier classification Type I = normal leaflet motion but with annular dilatation or leaflet perforation Type II = leaflet prolapse (eg myxomatous disease) or papillary muscle rupture Type III = restricted leaflet motion. IIIa = rheumatic disease IIIb = ischemic or idiopathic cardiomyopathy.

2D Echocardiography: additional information Left ventricular size and function and left atrial size as clues to: - severity of MR - acuteness or chronicity - necessity and timing of surgery

Mitral valve prolapse Occurs in 2.4% of the population (Freed at al. NEJM 1999) Patients exhibit fibromyxomatous changes in the mitral leaflet tissue that cause superior displacement of the leaflets into the left atrium (by definition > 2 mm) The most common primary cause of isolated MR requiring surgical repair Both familial (loci identified: chromosomes 11, 16, 13) and “sporadic” cases observed

Mitral valve prolapse

Mitral valve prolapse

Mitral valve prolapse Leaflet elongation can manifest itself not only by superior motion into the LA but also by anterior motion that shifts the coaptation point toward the aortic root and septum. ANTERIOR Septum Septum AO AO Chromosome 13 study: while phenotyping family members we observed that….This has led to the identification of a “prodromal form” or form fruste LV A A Coaptation P SUPERIOR Normal MVP 3

Nesta et al. Circulation 2005 Interestingly, these individuals were all carriers of the locus Nesta et al. Circulation 2005

Prodromal form Anterior displacement of the coaptation point. Mild bulging of the posterior leaflet relative to the anterior. Normal Prodromal

Functional Mitral Regurgitation: Incomplete Mitral Leaflet Closure IMI or global LVD NORMAL MR Papillary Muscle Displacement Mitral Valve Tethering IMLC LV Fig 2. Left panel depicts normal mitral valve geometry. Right panel shows restricted leaflet closure termed incomplete mitral leaflet closure. Several mechanisms have been proposed, including abnormal tethering of the mitral valve by displacement of the papillary muscles in the ischemic territory and by annular dilatation. LA AO Courtesy of Judy Hung, MD 3

Functional Mitral regurgitation

Leaflet concavity (PS view) in functional MR

MR related to HOCM LV ejection through an LVOT narrowed by both septal hypertrophy and anterior displacement of MV apparatus (PM + MV) causes the Venturi effect or “drag forces” which drag the MV leaflets and chordae towards the septum MR is related to SAM of the anterior mitral leaflet AND failure of post leaflet to move anteriorly with consequent gap between the two leaflets

Yu et al. Mitral regurgitation in hypertrophic cardiomyopathy: relationship to obstruction and relief with myectomy. J Am Coll Cardiol 2000;36;2219-2225

Doppler Methods for assessment of severity Color flow Doppler - Regurgitant jet area - Vena contracta - Flow convergence (PISA) Continuous wave Doppler Pulsed Doppler - Mitral inflow pattern - Quantitative parameters (regurgitant volume, fraction, EROA)

Regurgitant jet area Pros: - Simple, quick screen for mild or severe central MR - Evaluates spatial orientation of jet Cons: - Subject to technical, hemodynamic variation - Underestimates severity in eccentric jets Mild: < 4 cm2 or < 20% of LA area Moderate: variable Severe: > 10 cm2 or > 40% of LA area Small central jet Large central jet or variable size wall-impinging jet

Vena contracta width SAX LAX Mild: < 0.3 cm Narrowest portion of a jet that occurs at or just downstream from the orifice. The examiner must search in multiple planes perpendicular to the commissural line (such as the PLA view). Widths are not additive, but their cross sectional areas (in SAX view) are Mild: < 0.3 cm Severe  0.7 with large central jet or with wall impinging jet of any size

Proximal isovelocity surface area (PISA) Based on the hydrodynamic principle that the flow profile of blood approaching a circular orifice forms concentric, hemispheric shells of increasing velocity and decreasing surface area. Color flow mapping able to image one of these hemispheres that corresponds to the aliasing velocity or Nyquist limit of the instrument. The aliasing velocity should be adjusted to identify a flow convergence region with a hemispheric shape.

Reg volume = EROA x VTIreg jet PkVreg = the peak velocity of the regurgitant jet by continuous wave Doppler Reg volume = EROA x VTIreg jet The radius of the hemisphere is then measured… The regurgitant volume can be estimated as EROA multiplied by the velocitiy time integral of the regurgitant jet Since PISA calculation provides an instantaneous peak flow rate, EROA is the maximal EROA

Proximal isovelocity surface area (PISA) Mild: EROA <0.2cm2 Severe: EROA >/=0.4cm2 Pros: - Presence of flow convergence at Nyquist limit of 50-60 cm/s alerts to significant MR - Provides both lesion severity (EROA) and volume overload (R Vol) Cons: - Less accurate in eccentric jets - Not valid in multiple jets - Any error is determining the location/radius of the orifice is squared Therefore PISA is more accurate if the aliasing velocity can be adjusted to obtain a radius of >/=1cm.

Example of PISA calculation r = 0.8 cm Radius is 0.8, the color Doppler scale has been shifted down so that the MR aliasing velocity has been reduced to 36 cm/s, thus maximizing resolution for measuring the aliasing radius EROA = [6.28 x (.8)(.8) ml/s x 36] / [480 cm/s] = 0.3cm2

Supportive signs of MR severity Example of findings of continuous wave (CW) Doppler recordings and pulmonary vein flow by pulsed Doppler in a case with mild and another with severe mitral regurgitation (MR). In mild MR, spectral recording of the jet has a soft density with a parabolic, rounded contour of the regurgitant velocity whereas in severe MR, the jet is dense with a triangular, early peaking of the velocity (arrow). Pulmonary vein flow is normal in mild MR with predominance of systolic flow (S). In contrast, the case with severe MR displays systolic flow reversal. D, Diastolic flow velocity.

Other supportive signs of MR severity Mild MR: - A-wave dominant mitral inflow ** - Normal LV size Severe MR: - E-wave dominant mitral inflow (E > 1.2 m/s) ** - Enlarged LV and LA size ** Usually above 50 years or in conditions of impaired relaxation, in the absence of mitral stenosis or other causes of elevated LA pressure Greater E because of increased diastolic flow

Quantitative pulsed Doppler parameters ann In the absence of regurgitation, stroke volume should be equal at different sites, e.g. the mitral and aortic annulus. In the presence of regurgitation (assuming the absence of an intracardiac shunt), the flow through the affected valve is larger than through other competent valves. Stroke volume = product of CSA and the velocity time integral of flow at the annulus

Quantitative pulsed Doppler parameters Supportive signs of severity Need to add pros/cons of CW, PW and pulm vein CW jet profile Pros: simple, readily available Cons: qualitative PW peak mitral E velocity Pros simple, readily available, A wave dominance excludes severe MR (severe MR = increased diastolic flow across the mitral valve = increased E velocity) Cons: influenced by LA pressure, LV relaxation, MV area, and atrial fibrillation Quantitative Pw Cons: measurement of flow at the MV annulus less reliable in calcific MV. Not valid with concomitant significant AR unless pulmonic site is used Pulm veins Pros: simple Cpms: influenced by LA pressure, afib.

Summary JASE 2003;16:777

2D-TEE localization of MR defects Probe in Standard mid esophageal position Tee provides a systematic method to accurately localize MR defects and improves preoperative assessment Foster et al. Ann Thorac Surg 1998;65:1025

2D-TEE localization of MR defects Probe at 0 degrees, effects of flexion or withdrawal and retroflexion or advancement Foster et al. Ann Thorac Surg 1998;65:1025

2D-TEE localization of MR defects 40 to 90 degrees, effect of clockwise and counterclockise probe rotation Foster et al. Ann Thorac Surg 1998;65:1025

3D-TEE To simulate a surgeon’s view of the valve, the 3D TEE image is positioned with the aortic valve the 11-o’clock position.

Intra-Operative 2D and 3D TEE Depiction of MV Prolapse and Leaflet Flail Schematic (upper row) and 2D as well as 3D echocardiographic examples of a patient with a normal mitral valve (left panels), mitral valve prolapse (P1, middle panels) and a flail mitral valve (P2, right panels) as visualized with 2D TEE (long-axis mid esophageal TEE views (middle row) and real-time 3D TEE volume rendering from the left atrial perspective (bottom row). The surgical views obtained with real-time 3D TEE provide unique visualization and better understanding of the anatomic relationships of the mitral valve annulus, commissures and leaflets. Abbreviations as in Figures 1 and 2.

3D-TEE quantitative analysis of the mitral apparatus Examples of 3D renderings of the mitral valve obtained from 3D-TEE dataset using software designed for quantitative analysis of the mitral apparatus. (Top, Left) Antero-posterior diameter is shown in green. (Top, Right) Annular height. (Bottom Left) Anterior mitral leaflet surface area (hatched) with posterior middle scallop leaflet prolapse. (Bottom, Right) Angle between the mitral and aortic annuli. A anterior, P posterior, AL anterolateral, PM posteromedial, Ao aorta, TEE transesophageal echocardiography.

CMR Etiology of mitral regurgitation Quantitation of mitral regurgitation Better determination of volumes and LVEF (facilitating surgical decision making in asymptomatic patients)

LVOT stack A) Left ventricular outflow tract (LVOT) stack prescription is created by obtaining parallel slices across the mitral valve perpendicular to the long axis of the valve.

LVOT Borderline-severe MR Eccentric anteriorly-directed flow jet MVP of P2 scallop with flail posterior leaflet Mildly enlarged LV with NL systolic function LVEF was normal at 68% Effective forward LVEF moderately at 35% LV Stroke volume 145 ml Mitral Valve regurgitant volume 70 ml Normal RV cavity size and systolic function RVEF normal at 53% Mild RAE. Mild-to-moderate LAE.

Therapy

Therapy The distinction between primary and secondary MR is key Correction of primary MR in a timely fashion reverses LV remodeling, PHTN, and heart failure It is less obvious that correcting secondary MR will be curative or beneficial

Primary MR No conclusive data showing that medical therapy (vasodilators or beta-blockers) is effective in primary MR without heart failure (however recommended for heart failure) Surgical therapy - Mitral valve repair instead of replacement is the preferred method in non-rheumatic valves

Survival MV repair vs replacement Survival after mitral valve repair (MVP) is compared with MVR for propensity-matched groups Carabello, B. A. J Am Coll Cardiol 2008;52:319-326 Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.

ACC/AHA 2006 guidelines

Secondary MR Should be treated with standard heart failure therapy In selected patients, CRT reduces amount of MR No evidence of improved survival with annuloplasty Also divergence of opinion about whether MR should be corrected during revascularization

Results of Mitral Surgery in CHF Unadjusted (A) and propensity-adjusted (B) survival of patients with secondary MR are shown and separated into groups of CABG alone or CABG plus annuloplasty. No difference in survival was detected Carabello, B. A. J Am Coll Cardiol 2008;52:319-326 Copyright ©2008 American College of Cardiology Foundation. Restrictions may apply.

Limitations of ring annuloplasty AO LA LV Papillary Muscle Tethering Forces Ring Annuloplasty Ischemic Doesn’t address tethering Further ventricular remodeling after ring

Percutaneous therapies Alfieri procedure Schematic of edge-to-edge MV repair (Alfieri procedure; (top) and percutaneous mitral annuloplasty (bottom), capitalizing on the relationship between the coronary sinus and the annulus. Percutaneous mitral annuloplasty

Noninvasive assessment for percutaneous MVR Role of TEE

Take home points Need to use multiple criteria for more accurate assessment of MR Importance of distinguishing primary from secondary MR In secondary MR, indications for mitral valve intervention are less certain and more data are needed

References Recommendations for evaluation of the severity of native valvular regurgitation with 2D and Doppler echocardiography. J Am Soc Echocardiogr 2003;16 O’Gara et al. The role of imaging in chronic degenerative mitral regurgitation. JACC Cardiovascular Imaging 2008;1 Carabello. The current therapy for mitral regurgitation. JACC 2008;52