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Circulation. 1996;94:2355-2357

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(Circulation. 1996;94:2355-2357.)
© 1996 American Heart Association, Inc.

Articles

Aortic Regurgitation in Women

Does the Measuring Stick Need a Change?

Blase A. Carabello, MD

the Department of Medicine and the Gazes Cardiac Research Institute, Medical University of South Carolina, and the Ralph H. Johnson Department of Veterans Affairs, Charleston, SC.

Correspondence to Blase A. Carabello, MD, Charles Ezra Daniel Professor of Cardiology, Cardiology Division, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425-221.


Key Words: Editorials • regurgitation • aorta • surgery


*    Introduction
up arrowTop
 *Introduction
down arrowReferences
 
The outlook for patients with aortic regurgitation has improved dramatically over the past two decades. Operative mortality has decreased from as high as 20% in the early 1970s to 2% to 4% today.1 2 3 Survivorship after aortic valve replacement for aortic regurgitation has also improved so that there now is approximately an 85% 5-year and 70% 10-year survivorship.3 4 5

Improvement in survival derives from several underlying factors, including (1) newer prosthetic valves, which have improved hemodynamic profiles and a reduced risk of thromboembolism; (2) the almost universal use of intraoperative cardioplegia, which protects the enlarged left ventricle of aortic regurgitation from ischemic damage; and (3) progressively earlier surgery performed on candidates with better preoperative left ventricular function resulting, in turn, in better postoperative left ventricular function. While once surgery was delayed until the patient suffered from far-advanced symptoms refractory to medical therapy,6 now patients with mild symptoms and even asymptomatic patients are referred for surgery if preoperative echocardiographic evaluation demonstrates evidence of early left ventricular dysfunction.7 Although valvular heart disease imparts abnormal loading conditions on the left ventricle, making load-sensitive ejection phase indexes such as ejection fraction sometimes difficult to interpret, the "55" rule has been extremely effective in helping physicians time aortic valve replacement for patients with aortic regurgitation. By operating on patients before ejection fraction falls below 55%8 or before the left ventricle can no longer contract to an end-systolic dimension of 55 mm or less,9 low operative mortality and normal postoperative ejection fraction is expected unless an unusual event such as perioperative myocardial infarction or an unexpectedly long extracorporeal perfusion time is encountered. Even if left ventricular function has begun to deteriorate and markers of dysfunction have been exceeded, ejection fraction usually becomes normal after surgery because careful surveillance, which is now standard practice, has prevented dysfunction from being present for a prolonged period of time.10 11

Thus, while in the late 1970s and early 1980s depressed preoperative ejection fraction inconsistently improved after aortic valve replacement for aortic regurgitation,12 today depressed ejection fraction almost always increases after surgery.13 Improved ejection performance stems from afterload reduction and possibly an improvement in contractile function permitted by timely surgery performed before ventricular dysfunction has become irreversible.13 In this regard, it should be remembered that afterload on the left ventricle can be as high in aortic regurgitation as it is in aortic stenosis.14 15 High afterload accrues from preoperative systolic hypertension and left ventricular dilatation, which are normalized after surgery.

Although I have read the literature concerning aortic regurgitation with great interest, I failed to recognize that the overwhelming number of patients studied with this disease were male until it was pointed out by the provocative study of Klodas and colleagues5 presented in this month's journal. They reported that most of their patients with aortic regurgitation who underwent aortic valve replacement also were men but because of their high volume they were able to examine a subset of 51 women. To my knowledge, this study represents the largest investigation of women with aortic regurgitation. It found remarkably unfavorable results. Despite similar operative mortalities for men and women, 10-year survivorship was only 39% in women-much less than the 72% for men.

An interesting issue raised by the investigators is whether the currently used prognosticators developed from mostly male patients also apply to women. The issue is an important one, not yet settled in my view. In the current study, 31 of the 51 female patients had either coronary disease or the presence of an aortic aneurysm, both of which impacted negatively on survival, possibly subjugating the relevance of ventricular performance in those patients. Female sex was not a significant risk factor in the remaining 20 patients with isolated aortic regurgitation, although as the authors note, it would be hard to define significant prognosticators in such a small series of patients. Reduced ejection fraction was a negative prognosticator in both men and women, which is not surprising since ejection fraction is a dimensionless property unaffected by body size.

On the other hand, the fact that women are smaller in size than men might indicate that a cutoff value for end-systolic dimension developed primarily in men might be too large to detect early ventricular dysfunction in women. If this were the case, then delaying valve replacement until end-systolic dimension reached 55 mm might be waiting too long because left ventricular dysfunction would have already developed. Had that occurred, the women in this study should have suffered from postoperative left ventricular dysfunction, and heart failure should have been a major cause of death. This was not the case. Although more women had severe preoperative symptoms, they did not have lower postoperative ejection fractions in the group of patients who received postoperative echocardiograms. Thus, the higher symptom class in women probably did not indicate more impaired preoperative systolic function, since it did not lead to impaired postoperative systolic function gauged by ejection fraction. Although ejection fraction is a problematic indicator of ventricular function because of ejection fraction load dependence, load dependence should not cause a problem of interpretation after surgery, when the abnormal loading conditions have been removed by restoration of valve competence.16 Thus, I do not believe that reliance on currently recognized indexes of ventricular function led to unrecognized systolic dysfunction in women.

Because heart failure can develop either from systolic or diastolic dysfunction and because there was no evidence that women had a higher incidence of systolic dysfunction, it is possible that their higher symptom class was due to the unmeasured presence of diastolic dysfunction that put them at higher risk after surgery.

Whether there was systolic dysfunction, diastolic dysfunction, both, or neither, I do find it worrisome that such advanced symptoms were present before surgery in patients studied in the relatively recent period from 1980 to 1989. The intent of the investigators who developed the indexes discussed above was to determine objective markers of ventricular dysfunction on which to base the timing of surgery in a disease in which ventricular dysfunction could develop insidiously in even asymptomatic patients. The use of these markers in my view has been largely responsible for earlier surgery resulting in reduced operative mortality and for the overall improved outcome for aortic regurgitation patients today versus two decades ago. However, these studies do not infer that severely symptomatic patients should be treated only medically if they have no echocardiographic evidence of ventricular dysfunction. The presence of severe symptoms indicates disordered physiology, many facets of which cannot be measured echocardiographically. I believe that symptoms alone can be an indication for surgery, and I agree with the authors that surgery should not be delayed until class III or class IV symptoms have developed. On the other hand, it is hard to understand how earlier surgery would have improved late survival for the women studied by Klodas et al, since much of the late mortality stemmed from the presence of coronary disease and the presence of aortic root aneurysms. Perhaps the early and aggressive therapy for hypertension and the early recognition of the Marfan syndrome could help to reduce that portion of the excess mortality caused by aortic aneurysm. Mitigation of higher mortality in women with coronary disease awaits further understanding of coronary disease in general and of revascularization in women in particular.

In the past two decades there has been an impressive improvement in the outlook for patients with aortic regurgitation, resulting in part from earlier surgery performed before advanced left ventricular dysfunction has developed. More timely surgery has been based on effective markers that define the presence of ventricular dysfunction. On this basis, surgery should be performed even in asymptomatic patients if ejection fraction has fallen below 55% or if end-systolic dimension approaches 55 mm. Whether a smaller end-systolic dimension should be recommended for the timing of surgery in women versus men is still in question. If increased end-systolic dimension is a marker for systolic dysfunction that carries over into the postoperative period, the current study suggests that most women are already being operated before substantial dysfunction has developed, since postoperative heart failure and ventricular dysfunction were not noted to be the cause of excess mortality in women in this study. On the other hand, if end-systolic dimension also indicates some other negative factor yet to be explained, then perhaps applying a smaller value in women might improve outcome. In any case, it was reassuring to find that for the most part both sexes are being referred for surgery before the left ventricle reaches an end-systolic dimension of 55 mm. Indeed, 73% of men and 89% of women in the current study were so referred. However, aortic valve surgery should also be extended to those patients with more than mild symptoms even if the echocardiogram demonstrates that left ventricular function is normal. Such patients will have an improvement in lifestyle at a low operative mortality, which are major goals of surgery.


*    Footnotes
 
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.


*    References
up arrowTop
 up arrowIntroduction
 *References
 

  1. Scott WC, Miller DC, Haverich A, Dawkins K, Mitchell RS, Jamieson SW, Oyer PE, Stinson EB, Baldwin JC, Shumway NE. Determinants of operative mortality for patients undergoing aortic valve replacement: discriminant analysis of 1,479 operations. J Thorac Cardiovasc Surg.. 1985;89:400-413.[Abstract]
  2. Di Lello F, Flemma RJ, Anderson AJ, Mullen DC, Kleinman LH, Werner PH. Improved early results after aortic valve replacement: analysis by surgical time frame. Ann Thorac Surg.. 1989;47:51-56.[Abstract]
  3. Morris JJ, Schaff HV, Mullany CJ, Rastogi A, McGregor CG, Daly RC, Frey RL, Orszulak TA. Determinants of survival and recovery of left ventricular function after aortic valve replacement. Ann Thorac Surg.. 1993;56:22-29.[Abstract]
  4. Lindblom D, Lindblom U, Qvist J, Lundstrom H. Long-term relative survival rates after heart valve replacement. J Am Coll Cardiol.. 1990;15:566-573.[Abstract]
  5. Klodas E, Enriquez-Sarano M, Tajik AJ, Mullany CJ, Bailey KR, Seward JB. Surgery for aortic regurgitation in women: contrasting indications and outcomes as compared with men. Circulation.. 1996;94:2472-2478.[Abstract/Free Full Text]
  6. Schwarz F, Flameng W, Langebartels F, Sesto M, Walter P, Schlepper M. Impaired left ventricular function in chronic aortic valve disease: survival and function after replacement by Bjork-Shiley prosthesis. Circulation.. 1979;60:48-58.[Abstract]
  7. Bonow RO, Lakatos E, Maron BJ, Epstein SE. Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function. Circulation.. 1991;84:1625-1635.[Abstract/Free Full Text]
  8. Bonow RO, Rosing DR, McIntosh CL, Jones M, Maron BJ, Lann KKG, Lakatos E, Bacharach SL, Green MV, Epstein SE. The natural history of asymptomatic patients with aortic regurgitation and normal left ventricular function. Circulation.. 1983;68:509-517.[Free Full Text]
  9. Henry WL, Bonow RO, Borer JS, Ware JH, Kent KM, Redwood DR, McIntosh CL, Morrow AG, Epstein SE. Observations on the optimum time for operative intervention for aortic regurgitation, I: evaluation of the results of aortic valve replacement in symptomatic patients. Circulation.. 1980;61:471-483.[Abstract/Free Full Text]
  10. Bonow RO, Rosing DR, Maron BJ, McIntosh CL, Jones M, Bacharach SL, Green MV, Clark RE, Epstein SE. Reversal of left ventricular dysfunction after aortic valve replacement for chronic aortic regurgitation: influence of duration of preoperative left ventricular dysfunction. Circulation.. 1984;70:570-579.[Abstract/Free Full Text]
  11. Carabello BA, Usher BW, Hendrix GH, Assey ME, Crawford FA, Leman RB. Predictors of outcome in patients with aortic regurgitation and left ventricular dysfunction: a change in the measuring stick. J Am Coll Cardiol.. 1987;10:991-997.[Abstract]
  12. Clark DG, McAnulty JH, Rahimtoola SH. Valve replacement in aortic insufficiency with left ventricular dysfunction. Circulation.. 1980;61:411-421.[Free Full Text]
  13. Taniguchi K, Nakano S, Kawashima Y, Sakai K, Kawamoto T, Sakaki S, Kobayashi J, Morimoto S, Matsuda H. Left ventricular ejection performance, wall stress, and contractile state in aortic regurgitation before and after aortic valve replacement. Circulation.. 1990;82:798-807.[Abstract/Free Full Text]
  14. Wisenbaugh T, Spann JF, Carabello BA. Differences in myocardial performance and load between patients with similar amounts of chronic aortic versus chronic mitral regurgitation. J Am Coll Cardiol.. 1984;3:916-923.[Abstract]
  15. St John Sutton M, Plappert T, Spiegel A, Raichlen J, Douglas P, Reichek N, Edmunds L. Early post-operative changes in left ventricular chamber size, architecture, and function in aortic stenosis and aortic regurgitation and their relation to intraoperative changes in afterload: a prospective two-dimensional echocardiographic study. Circulation.. 1987;76:77-89.[Abstract/Free Full Text]
  16. Bonow RO, Dodd JT, Maron BJ, O'Gara PT, White GG, McIntosh CL, Clark RE, Epstein SE. Long-term serial changes in left ventricular function and reversal of ventricular dilatation after valve replacement for chronic aortic regurgitation. Circulation.. 1988;78:1108-1120.[Abstract/Free Full Text]




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