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EDITORIAL COMMENT

Ischemic mitral regurgitation, the dynamic lesion: clues to the cure^*

Robert A. Levine, MD, FACC^,* and Judy Hung, MD, FACC

Cardiac Ultrasound Laboratory, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA

^* Reprint requests and correspondence: Dr. Robert A. Levine, Massachusetts General Hospital, Cardiac Ultrasound Laboratory, 55 Fruit Street, VBK 508, Boston, Massachusetts 02114, USA.
rlevine{at}partners.org

	Changes with exercise

Top Changes with exercise Balance of forces Changes with loading Exercise-induced variation Clinical implications Is bypass alone sufficient... Caveats Clues to the cure References

 
Until now, ischemic MR has been evaluated almost exclusively at rest. In this issue of the Journal, Lancellotti et al. (10) for the first time quantitatively measured changes in ischemic MR with semi-supine exercise. The dynamic changes they observed provide mechanistic insights that can sharpen the therapeutic approach in general and clarify the course of action in the individual patient.

	Balance of forces

Top Changes with exercise Balance of forces Changes with loading Exercise-induced variation Clinical implications Is bypass alone sufficient... Caveats Clues to the cure References

 
These dynamic changes in MR can best be understood by considering the basic forces acting on the mitral leaflets. Ischemic MR occurs in the setting of normal mitral leaflets but abnormal left ventricular (LV) function and geometry. Ischemic LV distortion leads to papillary muscle displacement and annular dilatation, tethering the mitral leaflets and restricting their ability to close effectively (Fig. 1) (11–21). Annuloplasty addresses only one end of this "tug of war" (22–25). Tethering is compounded by LV dysfunction, which decreases the force needed to close the leaflets in opposition to the tethering (26). This interplay of competing forces creates a dynamic lesion that varies during the cardiac cycle. Noninvasively emulating the approach of Yoran et al. (27,28) and Keren et al. (29), Schwammenthal (30) showed that effective regurgitant orifice area in ischemic MR typically peaks in early and late systole and decreases in midsystole as LV pressure rises and the transmitral closing force increases. This behavior was reproduced in vitro by He et al. (14) and shown by Hung et al. (31) to be determined in patients primarily by the midsystolic rise in LV pressure, closing the mitral leaflets more completely, with a lesser contribution from midsystolic annular contraction. Thus, MR variation within the cardiac cycle (32) provides clues to the basic forces influencing leaflet closure (33).

View larger version (29K): [in this window] [in a new window]   Figure 1 Mechanism of functional mitral regurgitation (MR). AO = aorta; LA = left atrium; LV = left ventricle.

	Changes with loading

Top Changes with exercise Balance of forces Changes with loading Exercise-induced variation Clinical implications Is bypass alone sufficient... Caveats Clues to the cure References

	Exercise-induced variation

Top Changes with exercise Balance of forces Changes with loading Exercise-induced variation Clinical implications Is bypass alone sufficient... Caveats Clues to the cure References

 
The current article provides further insight into the pathophysiology of postinfarction MR as a characteristically dynamic lesion. The authors prospectively examined 70 patients with at least mild MR and LV ejection fraction <45%, excluding patients with evidence of exercise-induced ischemia. During semi-supine exercise, the effective regurgitant orifice area was quantified by two complementary Doppler methods. The observed changes were important and largely adverse, with orifice area increasing by >20 mm² (enough to change grade of severity) in nearly 30% of patients. The exception was patients with inferior myocardial infarctions and recruitable systolic function, in whom regurgitant orifice area tended to decrease. Exercise-induced changes in MR did not correlate with degree of MR or LV dysfunction at rest. Instead, they correlated best with changes in mitral valve configuration and mitral apparatus geometry at both ends of the tethered leaflets, including annular dilatation and posterior displacement of the papillary muscles (10).

	Clinical implications

Top Changes with exercise Balance of forces Changes with loading Exercise-induced variation Clinical implications Is bypass alone sufficient... Caveats Clues to the cure References

 
Patients with milder degrees of MR at rest who undergo coronary revascularization are not generally considered to require additional efforts to address the mitral valve. Yet, as this study demonstrates, patients with milder MR may actually have more severe regurgitation when provoked by exercise. These same authors have shown that such exercise-induced increases in MR are accompanied by increases in pulmonary artery pressure (39). These adverse exercise hemodynamics could potentially explain the clinical puzzle of patients who have exertional dyspnea out of proportion to their degree of dysfunction or MR at rest if exercise increases their MR and pulmonary pressures (assuming this scenario is not due to intermittent ischemia with "flash pulmonary edema"). Thus, assessing the true impact of ischemic MR often becomes a "moving target," engendering discussions among echocardiographers, surgeons, and anesthesiologists. The dynamic nature of ischemic MR can support the contention of some surgeons that decisions should not be based on MR assessment alone, given its dependence on load and volume, but rather on the appearance of restricted leaflet closure, which sets the stage for important MR. This study naturally leads to the question of whether exercise testing should be performed on all patients with ischemic MR. That will require further investigation, but we can anticipate that provocative testing could be most useful when the quantitative and clinical importance of MR are unclear, particularly when MR is mild to moderate at rest.

	Is bypass alone sufficient to reduce ischemic MR?

Top Changes with exercise Balance of forces Changes with loading Exercise-induced variation Clinical implications Is bypass alone sufficient... Caveats Clues to the cure References

 
Although several studies demonstrate frequent persistence of ischemic MR after revascularization alone (34), others maintain that coronary bypass is sufficient therapy in most patients (40). Moreover, no approach currently predicts in which patients MR will resolve with revascularization alone. Exercise testing may be informative in this controversial decision. This study suggests that exercise-induced reduction in MR caused by improved motion of the inferior LV base would predict that revascularization alone is likely to reduce the MR. If MR persists or increases with exercise, however, the implications are not obvious. Evidence of myocardial viability with low-dose dobutamine could provide comparable information, but the decrease in LV volume with higher dobutamine doses may decrease tethering and MR without predicting lasting benefit off inotropic support (41).

	Caveats

Top Changes with exercise Balance of forces Changes with loading Exercise-induced variation Clinical implications Is bypass alone sufficient... Caveats Clues to the cure References

 
Patient position during exercise testing may also influence the degree of MR. This study evaluated MR during semi-supine exercise. As Kelbaek et al. (42) have shown, exercise ventricular volumes are smaller in the sitting than in the supine position, causing functional MR to decrease in the more upright position. However, Osbakken et al. (43) showed that LV end-systolic volume increased with supine exercise in patients with coronary artery disease; the decrease in volume seen in the patients of Lancellotti et al. (10) suggests that they resemble patients exercising in the sitting position (44,45). The increases in MR, therefore, cannot be simply ascribed to positional variation. The authors acknowledge the technical challenges of quantifying MR during exercise, with substantial limits of variation and standard deviations between observers and methods (39), and they recognize the limitations of applying the proximal flow convergence method at only one time point and velocity (30,46).

	Clues to the cure

Top Changes with exercise Balance of forces Changes with loading Exercise-induced variation Clinical implications Is bypass alone sufficient... Caveats Clues to the cure References

 
Returning to the principle that successful valve repair must address mechanism, this study provides further evidence for the decisive role of adverse mitral and ventricular geometry in the mechanism of ischemic MR. Increased MR with exercise is associated with greater tethering at both the annular and papillary muscle ends of the leaflets. Unbalanced tethering can therefore be addressed by papillary muscle repositioning, achieved by infarct plication (18,47,48), by external constraint applied to reverse LV remodeling locally (49,50), or by direct traction (51,52). Biventricular pacing can potentially reduce tethering (related to LV end-systolic volume) (53–55) as well as increase mitral valve closing force (56). Additionally, specific chordal modification can minimize mitral leaflet deformity and MR, either alone or combined with annular ring reduction (57). In summary, therefore, the dynamic changes in ischemic MR with exercise provide clues to increasing the effectiveness of therapy by addressing the geometric culprits.

	Acknowledgments

 
The authors thank Shirley Sims for her excellent editorial assistance.

	Footnotes

 
Supported in part by grants R01 HL38176, K24 HL67434, and K23 HL04504 of the National Institutes of Health, Bethesda, Maryland.

^* Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.

	References

Top Changes with exercise Balance of forces Changes with loading Exercise-induced variation Clinical implications Is bypass alone sufficient... Caveats Clues to the cure References

 

1. Lamas GA, Mitchell GF, Flaker MD, et alfor the Survival and Ventricular enlargement Investigators. Clinical significance of mitral regurgitation after acute myocardial infarction. Circulation. 1997;96:827–833[Abstract/Free Full Text]
2. Grigioni F, Enriquez-Sarano M, Zehr KJ, et al. Ischemic mitral regurgitation: long-term outcome and prognostic implications with quantitative Doppler assessment. Circulation. 2001;103:1759–1764[Abstract/Free Full Text]
3. Rumberger JA. Ventricular dilatation and remodeling after myocardial infarction. Mayo Clin Proc. 1994;69:664–674[Medline]
4. Bolling SF, Pagani FD, Deeb GM, Bach DS. Intermediate-term outcome of mitral reconstruction in cardiomyopathy. J Thorac Cardiovasc Surg. 1998;115:381–388[Abstract/Free Full Text]
5. St. John Sutton M, Ferrari VA. Prevention of left ventricular remodeling after myocardial infarction. Curr Treatment Options Cardiovasc Med. 2002;4:97–108
6. Cohn LH, Rizzo RJ, Adams DH, et al. The effect of pathophysiology on the surgical treatment of ischemic mitral regurgitation: operative and late risks of repair versus replacement. Eur J Cardiothorac Surg. 1995;9:568–574[Abstract]
7. David TE. Techniques and results of mitral valve repair for ischemic mitral regurgitation. J Card Surg. 1994;9(Suppl 2):274–277[Medline]
8. Frater RWM, Cornelissen P, Sisto D. Mechanisms of ischemic mitral insufficiency and their surgical correction. Vetter HO, Hetzer R, Schmutzler H. Ischemic Mitral Incompetence. New York, NY: Springer-Verlag; 1991. p. 117–130
9. Gillinov AM, Wierup PN, Blackstone EH, et al. Is repair preferable to replacement for ischemic mitral regurgitation? J Thorac Cardiovasc Surg. 2001;122:1125–1141[Abstract/Free Full Text]
10. Lancellotti P, Lebrun F, Piérard LA. Determinants of exercise-induced changes in mitral regurgitation in patients with coronary artery disease and left ventricular dysfunction. J Am Coll Cardiol 2003;42:1921–8
11. Godley RW, Wann LS, Rogers EW, et al. Incomplete mitral leaflet closure in patients with papillary muscle dysfunction. Circulation. 1981;63:565–571[Abstract/Free Full Text]
12. Kono T, Sabbah HN, Rosman H, et al. Mechanism of functional mitral regurgitation during acute myocardial ischemia. J Am Coll Cardiol. 1992;19:1101–1105[Abstract]
13. Otsuji Y, Handschumacher MD, Schwammenthal E, et al. Insights from three-dimensional echocardiography into the mechanism of functional mitral regurgitation: direct in vivo demonstration of altered leaflet tethering geometry. Circulation. 1997;96:1999–2008[Abstract/Free Full Text]
14. He S, Fontaine AA, Schwammenthal E, et al. An integrated mechanism for functional mitral regurgitation: leaflet restriction vs. coapting force—in vitro studies. Circulation. 1997;96:1826–1834[Abstract/Free Full Text]
15. Gorman JH 3rd, Jackson BM, Gorman RC, Kelley ST, Gikakis N, Edmunds LH Jr. Papillary muscle discoordination rather than increased annular area facilitates mitral regurgitation after acute posterior myocardial infarction. Circulation. 1997;96:II124–127
16. Komeda M, Glasson JR, Bolger AF, et al. Geometric determinants of ischemic mitral regurgitation. Circulation. 1997;96:II128–133
17. Timek TA, Lai DT, Tibayan F, et al. Ischemia in three left ventricular regions: insights into the pathogenesis acute ischemic mitral regurgitation. J Thorac Cardiovasc Surg. 2003;125:559–569[Abstract/Free Full Text]
18. Liel-Cohen N, Guerrero JL, Otsuji Y, et al. Design of a new surgical approach for ventricular remodeling to relieve ischemic mitral regurgitation. Insights from three-dimensional echocardiography. Circulation. 2000;101:2756–2763[Abstract/Free Full Text]
19. Messas E, Guerrero JL, Handschumacher MD, et al. Paradoxic decrease in ischemic mitral regurgitation with papillary muscle dysfunction: insights from three-dimensional and contrast echocardiography with strain rate measurement. Circulation 2001;104:1952–7
20. Yiu SF, Enriquez-Sarano M, Tribouilloy C, et al. Determinants of the degree of functional mitral regurgitation in patients with systolic left ventricular dysfunction: a quantitative clinical study. Circulation. 2000;102:1400–1406[Abstract/Free Full Text]
21. Miller DC. Ischemic mitral regurgitation redux—to repair or to replace? J Thorac Cardiovasc Surg. 2001;122:1059–1062[Free Full Text]
22. Liel-Cohen N, Otsuji Y, Vlahakes GJ, et al. Functional ischemic mitral regurgitation can persist despite ring annuloplasty: mechanistic insights. Circulation. 1997;96:I540
23. Hung J, Handschumacher MD, Rudski L, et al. Persistence of ischemic mitral regurgitation despite annular ring reduction: mechanistic insights from 3D echocardiography. Circulation. 1999;100(Suppl I):1–1052
24. Calafiore AM, Gallina S, DiMauro M, et al. Mitral valve procedure in dilated cardiomyopathy: repair or replacement. Ann Thorac Surg. 2001;71:1146–1152[Abstract/Free Full Text]
25. Tahta SA, Oury JH, Maxwell JM, et al. Outcome after mitral valve repair for functional ischemic mitral regurgitation. J Heart Valve Dis. 2002;11:11–19[Medline]
26. Kaul S, Spotnitz WD, Glasheen WP, et al. Mechanism of ischemic mitral regurgitation: an experimental evaluation. Circulation. 1991;84:2167–2180[Abstract/Free Full Text]
27. Yoran C, Yellin EL, Becker RM, Gabbay S, Frater RW, Sonnenblick EH. Dynamic aspects of acute regurgitation: effects of ventricular volume, pressure and contractility on the effective regurgitant orifice area. Circulation. 1979;60:170–176[Abstract/Free Full Text]
28. Yoran C, Yellin EL, Becker RM, Gabbay S, Frater RWM, Sonnenblick EH. Mechanism of reduction of mitral regurgitation with vasodilator therapy. Am J Cardiol. 1979;43:773–777[CrossRef][Medline]
29. Keren G, Bier A, Strom JA, Laniado S, Sonnenblick EH, LeJemtel TH. Dynamics of mitral regurgitation during nitroglycerin therapy: a Doppler echocardiographic study. Am Heart J. 1986;112:517–525[CrossRef][Medline]
30. Schwammenthal E, Chen C, Benning F, et al. Dynamics of mitral regurgitant flow and orifice area in different forms of mitral regurgitation: physiologic application of the proximal flow convergence method. Circulation. 1994;90:307–322[Abstract/Free Full Text]
31. Hung J, Otsuji Y, Handschumacher MD, et al. Mechanism of dynamic regurgitant orifice area variation in functional mitral regurgitation: physiologic insights from the proximal flow convergence technique. J Am Coll Cardiol. 1999;33:538–545[Abstract/Free Full Text]
32. Braunwald E. Mitral regurgitation: physiologic, clinical and surgical considerations. N Engl J Med. 1969;281:425–433[Medline]
33. Schwammenthal E, Popescu AC, Popescu BA, et al. Mechanism of mitral regurgitation in inferior wall acute myocardial infarction. Am J Cardiol. 2002;90:306–309[CrossRef][Medline]
34. Aklog L, Filsoufi F, Flores KQ, et al. Does coronary artery bypass grafting alone correct moderate ischemic mitral regurgitation? Circulation. 2001;104(Suppl I):68–75[Abstract/Free Full Text]
35. Bach DS, Deeb GM, Bolling SF. Accuracy of intraoperative transesophageal echocardiography for estimating the severity of functional mitral regurgitation. Am J Cardiol. 1995;76:508–512[CrossRef][Medline]
36. Grewal KS, Malkowski MJ, Piracha AR, et al. Effect of general anesthesia on the severity of mitral regurgitation by transesophageal echocardiography. Am J Cardiol. 2000;85:199–203[CrossRef][Medline]
37. Kizilbash AM, Willett DL, Brickner E, Heinle SK, Grayburn PA. Effects of afterload reduction on vena contracta width in mitral regurgitation. J Am Coll Cardiol. 1998;32:427–431[Abstract/Free Full Text]
38. Rosario LB, Stevenson LW, Solomon SD, Lee RT, Reimold SC. The mechanism of decrease in dynamic mitral regurgitation during heart failure treatment: importance of reduction in the regurgitant orifice size. J Am Coll Cardiol. 1998;32:1819–1824[Abstract/Free Full Text]
39. Lebrun F, Lancellotti P, Pierard LA. Quantitation of functional mitral regurgitation during bicycle exercise in patients with heart failure. J Am Coll Cardiol. 2001;38:1685–1692[Abstract/Free Full Text]
40. Tolis GA Jr, Korkolis DP, Kopf GS, Elefteriades JA. Revascularization alone (without mitral valve repair) suffices in patients with advanced ischemic cardiomyopathy and mild-to-moderate mitral regurgitation. Ann Thorac Surg. 2002;74:1476–1480[Abstract/Free Full Text]
41. Jiang L, Ye Q-W, Gilon D, et al. Dobutamine stress echo in patients with inferior wall motion abnormalities: insights into the mechanism of incomplete mitral leaflet closure. J Am Soc Echocardiogr. 1996;9:S45
42. Kelbaek H, Aldershvile J, Skagen K, Hildebrandt P, Nielsen SL. Mitral regurgitation determined by radionuclide cardiography: dependence on posture and exercise. Br Heart J. 1994;72:156–160[Abstract/Free Full Text]
43. Osbakken MD, Boucher CA, Okada RD, Bingham JB, Strauss HW, Pohost GM. Spectrum of global left ventricular responses to supine exercise. Am J Cardiol. 1983;51:28–35[CrossRef][Medline]
44. Poliner LR, Dehmer GJ, Lewis SE, Parkey RW, Blomqvist CG, Willerson JT. Left ventricular performance in normal subjects: a comparison of the responses to exercise in the upright and supine positions. Circulation. 1980;62:528–534[Free Full Text]
45. Manyari DE, Kostuk WJ, Purves PP. Left and right ventricular function at rest and during bicycle exercise in the supine and sitting positions in normal subjects and patients with coronary artery disease. Am J Cardiol. 1983;51:36–42[CrossRef][Medline]
46. Schwammenthal E, Chen C, Giesler M, et al. New method for accurate calculation of regurgitant flow rate based on analysis of Doppler color flow maps of the proximal flow field: validation in a canine model of mitral regurgitation with initial application in patients. J Am Coll Cardiol. 1996;27:161–172[Abstract]
47. Kaza AK, Patel MR, Fiser SM, et al. Ventricular reconstruction results in improved left ventricular function and amelioration of mitral insufficiency. Ann Surg. 2002;235:828–832[CrossRef][Medline]
48. RESTORE GroupMenicanti L, Di Donato M, Frigiola A, Buckberg G, Santambrogion C, Ranucci M, San D. Ischemic mitral regurgitation: intraventricular papillary muscle imbrication without mitral ring during left ventricular restoration. J Thorac Cardiovasc Surg. 2002;123:1041–1050[Abstract/Free Full Text]
49. Hung J, Guerrero JL, Handschumacher BS, Supple G, Sullivan S, Levine RA. Reverse ventricular remodeling reduces ischemic mitral regurgitation: echo-guided device application in the beating heart. Circulation. 2002;106:2594–2600[Abstract/Free Full Text]
50. Moainie SL, Guy TS, Gorman JH III, et al. Infarct restraint attenuates remodeling and reduces chronic ischemic mitral regurgitation after posterolateral infarction. Ann Thorac Surg. 2002;74:444–449[Abstract/Free Full Text]
51. Kron IL, Green GR, Cope JT. Surgical relocation of the posterior papillary muscle in chronic ischemic mitral regurgitation. Ann Thorac Surg. 2002;74:600–601[Abstract/Free Full Text]
52. Hvass U, Tapia M, Baron F, Pouzet B, Shafy A. Papillary muscle sling: a new functional approach to mitral repair in patients with ischemic left ventricular dysfunction and functional mitral regurgitation. Ann Thorac Surg. 2003;75:809–811[Abstract/Free Full Text]
53. Lau CP, Yu CM, Chau E, et al. Reversal of left ventricular remodeling by synchronous biventricular pacing in heart failure. Pacing Clin Electrophysiol 2000;23:1722–5
54. Kim WY, Sogaard P, Mortensen PT, et al. Three dimensional echocardiography documents haemodynamic improvement by biventricular pacing in patients with severe heart failure. Heart. 2001;85:514–520[Abstract/Free Full Text]
55. Yu CM, Lin H, Fung WH, Zhang Q, Kong SL, Sanderson JE. Comparison of acute changes in left ventricular volume, systolic and diastolic functions, and intraventricular synchronicity after biventricular and right ventricular pacing for heart failure. Am Heart J. 2003;145:E18[CrossRef][Medline]
56. Breithardt OA, Sinha AM, Schwammenthal E, et al. Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. J Am Coll Cardiol. 2003;41:765–770[Abstract/Free Full Text]
57. Messas E, Guerrero JL, Handschumacher MD, et al. Chordal cutting: a new therapeutic approach for ischemic mitral regurgitation. Circulation. 2001;104:1958–1963[Abstract/Free Full Text]

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This Article Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Levine, R. A. Articles by Hung, J. Search for Related Content PubMed PubMed Citation Articles by Levine, R. A. Articles by Hung, J.