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Mitral Gradients and Frequency of Recurrence of Mitral Regurgitation After Ring Annuloplasty for Ischemic Mitral Regurgitation
Matthew L. Williams, MD, Mani A. Daneshmand, MD, James G. Jollis, MD, John R. Horton, MS, Linda K. Shaw, MS, Madhav Swaminathan, MD, Robert D. Davis, MD, Donald D. Glower, MD, Peter K. Smith, MD, and Carmelo A. Milano, MD Divisions of Cardiothoracic Surgery and Cardiovascular Medicine, Duke University Medical Center, and Duke Clinical Research Institute, Durham, North Carolina
Background. Undersized ring annuloplasty and surgical revascularization are commonly used to correct ischemic mitral regurgitation (MR), but published series have failed to demonstrate a benefit compared with revascularization alone. We hypothesized that surgical revascularization and annuloplasty lead to a durable repair, but may also lead to increased mitral gradients that could limit the benefit of the repair technique. Methods. Data were collected for 222 consecutive patients who underwent combined revascularization and repair for ischemic MR between 1999 and 2006. The most recent transthoracic echocardiogram available for each patient (namely, the study that occurred at the latest date after surgery) was reviewed to define the fate of ischemic MR. When present, the mean gradient across the mitral valve was measured. Cox regression modeling was then performed to determine whether increasing gradients were associated with decreased long-term survival or increased hospitalization for heart failure.
Results. For the group of 222 patients, echocardiographic follow-up was available for 68% (149 patients). At follow-up, 1.3% had severe MR and 9.4% had moderate MR; 54% of patients (66 of 123) were found to have gradients of 5 mm or greater across the mitral valve, with 11% demonstrating gradients of 8 mm or more. Cox proportional hazards models failed to show adverse effects of increasing mitral gradient on outcomes analyzed: survival hazard ratio ⴝ 0.95 (95% confidence interval: 0.82 to 1.11, p ⴝ 0.527) and survival/heart failure hospitalization hazard ratio ⴝ 1.04 (95% confidence interval: 0.93 to 1.17, p ⴝ 0.488). Conclusions. Undersized ring annuloplasty and revascularization can provide a durable correction of ischemic mitral regurgitation. This technique frequently increases the gradient across the mitral valve, but increasing mitral gradient does not appear to adversely impact survival or heart failure hospitalization. (Ann Thorac Surg 2009;88:1197–201) © 2009 by The Society of Thoracic Surgeons
T
plete rigid annuloplasty rings should be utilized, and have shown a decrease in need for reoperation as evidence that this technique provides a more durable correction for ischemic MR [7]. It would appear that a more durable correction of ischemic MR performed concurrently with CABG would yield greater benefits for patients, although at the risk of creating iatrogenic mitral stenosis. Concerns have previously been raised that an aggressively undersized annuloplasty ring may lead to increased gradients across the mitral valve, which could have a deleterious effect on outcome [8]. Clearly, moderately increased gradients have been described in patients with rheumatic mitral stenosis that were well tolerated for long periods of time with few deleterious effects [9, 10]. However, it is unknown what the effect of increased gradient is after repair of ischemic MR. The population of ischemic MR patients would certainly be expected to have a higher left ventricular end-diastolic pressure than rheumatic patients and would therefore be at higher risk of heart failure symptoms after the creation of moderate stenosis by undersized annuloplasty.
he presence of mitral regurgitation (MR) has been shown to adversely impact outcomes in patients who undergo coronary artery bypass grafting [1]. The technique of undersized annuloplasty for the treatment of functional MR in patients with cardiomyopathy was popularized by Bolling and associates [2]. Currently, undersized ring annuloplasty and coronary artery bypass grafting (CABG) are frequently applied to patients with ischemic MR, but published series to date have thus far failed to show a benefit relative to revascularization alone [3, 4]. Furthermore, it has been demonstrated in some surgical series that recurrent MR occurs in one third of patients when echocardiographic follow-up is available [5, 6]. Some authors have argued that to avoid recurrent mitral regurgitation, undersized, com-
Accepted for publication June 1, 2009. Presented at the Poster Session of the Forty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Francisco, CA, Jan 26 –28, 2009. Address correspondence to Dr Williams, University of Louisville Health Sciences, Division of Cardiovascular and Thoracic Surgery, 201 Abraham Flexner Way, Suite 1200, Louisville, KY 40202; e-mail: mwilliams@ ucsamd.com.
© 2009 by The Society of Thoracic Surgeons Published by Elsevier Inc
0003-4975/09/$36.00 doi:10.1016/j.athoracsur.2009.06.022
ADULT CARDIAC
Mitral Gradients and Frequency of Recurrence of Mitral Regurgitation After Ring Annuloplasty for Ischemic Mitral Regurgitation
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WILLIAMS ET AL RECURRENCE OF MR AFTER RING ANNULOPLASTY
ADULT CARDIAC
In surgical patients with ischemic MR, the dominant (although not uniform) strategy at our institution has been to undersize the valve with a complete, nonflexible annuloplasty ring. We hypothesized that this, along with revascularization, would lead to a durable repair and would reduce left ventricular diameters. We sought to determine if this strategy led to increased gradients across the repaired valve, and if this had any measurable impact on fatal or nonfatal outcomes.
Material and Methods All data collection and analysis was performed with waiver of consent with Institutional Review Board approval. Between February 1999 and August 2006, we identified 222 consecutive patients who underwent CABG and annuloplasty for ischemic mitral regurgitation. Preoperative clinical characteristics as well as longitudinal data for survival and heart failure hospitalization were collected as part of the Duke Cardiovascular Databank and were 98% complete. The most recent transthoracic echocardiogram available for each patient (namely, the echocardiogram that occurred at the latest date after surgery) was reviewed to determine the extent of MR in patients who underwent surgical repair and revascularization for ischemic MR. If moderate or severe MR was identified, an attempt was made to determine the cause from the echocardiogram. If available, left ventricular diameters were compared using a sign-rank test. In addition, if measured, the mean gradient across the mitral valve was recorded. Two endpoints were examined in time-to-event analyses: all-cause mortality and a composite of death or heart failure hospitalization. Unadjusted Kaplan-Meier plots were generated and stratified by low mitral gradient (gradient 5 or less) versus high mitral gradient (gradient more than 5). Kaplan-Meier methods were also used to examine survival differences for patients with follow-up echocardiogram versus no follow-up echocardiogram. Unadjusted Cox-proportional hazards were examined to assess relationships with outcomes. Multivariable Cox proportional hazards models were used to assess relationships between clinical characteristics and both endpoints. The following covariates were examined in the unadjusted and adjusted models: mitral gradient, history of diabetes, renal disease, male, chronic obstructive pulmonary disease, baseline ejection fraction, pulmonary gradient, surgery redo, preoperative balloon bump, age, prior CABG, history of myocardial infarction, and number of grafts, number of disease vessels, onpump, race, and New York Heart Association (NYHA) class. Mean mitral gradient was assessed in an adjusted model with all significant components to determine if increasing gradients were associated with decreased survival or increased hospitalization for heart failure. All analyses were performed utilizing SAS version 8.1 or higher (SAS Institute, Cary, NC).
Ann Thorac Surg 2009;88:1197–201
Table 1. Patient Characteristics
Characteristic Age, median years (IQR) Male (%) Black (%) Preoperative ejection fraction, median (IQR) Renal failure (%) Diabetes mellitus (%) COPD (%) History of CABG (%) History of myocardial infarction (%) History of stroke (%) Class III or IV heart failure (%) Number of diseased vessels (SD) Cerebrovascular disease (%) Peripheral vascular disease (%) Smoking (%) Hypertension (%) Hypercholesterolemia (%) Preoperative inotropes (%) Emergency status (%) Preoperative IABP (%) Redo operation (%)
All Patients (n ⫽ 222)
Patients with Paired Echocardiographic Data (n ⫽ 83)
67 (59, 74) 101 (46) 48 (22) 30 (20, 40)
65 (58, 73) 39 (47) 23 (28) 30 (20, 40)
16 (7) 86 (39) 46 (21) 18 (8) 106 (48)
9 (11) 33 (40) 22 (27) 8 (10) 43 (52)
17 (8) 99 (45)
7 (8) 40 (48)
2.6 (⫾ 0.1)
2.6 (⫾ 0.6)
23 (10) 37 (17)
10 (12) 18 (18)
117 (53) 159 (72) 126 (57) 5 (2) 32 (14) 18 (8) 22 (10)
42 (51) 59 (71) 51 (61) 2 (3) 15 (18) 6 (7) 9 (10)
CABG ⫽ coronary artery bypass graft surgery; COPD ⫽ chronic obstructive pulmonary disease; IABP ⫽ intra-aortic balloon pump; IQR ⫽ interquartile range.
Results For the group of 222 patients, preoperative data can be seen in Table 1. The intraoperative transesophageal echocardiogram demonstrated moderate MR in 138 of 222 (62%) and severe MR in 78 of 222 patients (35%). Six patients (3%) had mild MR. Median follow-up time for all surviving patients was 2.20 years with an interquartile range (IQR) of 1.04 years to 4.42 years, and 2.22 years with an IQR of 1.1 to 4.26 years for surviving patients with a follow-up echocardiograph. This is a very high risk group of patients: 30-day mortality was 6.3% (14 of 222). A nonflexible ring was utilized in 98% of patients, with an average ring size of 24.8 mm (⫾ 1.3 mm). A complete ring was used in 91% of patients, and the average number of bypass grafts was 2.8 (⫾ 0.9). A preoperative chest wall echocardiogram was available for 134 patients. Average preoperative left ventricular end-diastolic diameter for this group was 5.4 cm (⫾ 0.8 cm), and left ventricular end-systolic diameter was 4.3 cm (⫾ 1.0 cm). Echocardiographic follow-up was available for 149 of 222 patients (68%). Median time to latest echocardiographic follow-up was 321 days; the IQR was 17 to 918 days. At the time of follow-up echocardiograph, 1.3% (2 of 149 patients) had severe MR and 9.4% (14 of 149) had moderate MR. Upon
WILLIAMS ET AL RECURRENCE OF MR AFTER RING ANNULOPLASTY
Table 2. Left Ventricular (LV) Diameters (n ⫽ 83) Diameter Preoperative LV end-diastolic diameter Postoperative LV end-diastolic diameter Delta ⫽ ⫺0.4 cm, p ⬍ 0.001 Preoperative LV end-systolic diameter Postoperative LV end-systolic diameter Delta ⫽ ⫺0.1 cm, p ⫽ 0.08
5.5 cm (⫾ 0.8) 5.1 cm (⫾ 1.0) 4.3 cm (⫾ 1.0) 4.2 cm (⫾ 1.2)
review of the echocardiograms, 81% (13 of 16 patients) with moderate or severe MR were determined to have progressive posterior leaflet tethering as the etiology for failure of repair. No patients underwent reoperation for mitral regurgitation; 2 patients did go on to receive cardiac transplantation. Paired preoperative and postoperative transthoracic echocardiograms were available for 37% of patients (83 of 222). Left ventricular end-diastolic diameter was significantly decreased relative to preoperative transthoracic echocardiogram; left ventricular end-systolic diameter was decreased but did not reach statistical significance (Table 2). Measurement of the transmitral gradient was available for 123 patients; 54% of patients were found to have mean gradients of 5 mm Hg or greater across the mitral valve, with 13% demonstrating gradients of 8 mm Hg or more (average 5.0 ⫾ 2.2 mm Hg). Diabetes mellitus, preoperative intra-aortic balloon pump, increased age, history of myocardial infarction, number of grafts, and higher NHYA class were found to be significantly associated with increased mortality (p values ⬍ 0.05) in the multivariable proportional hazards model, following stepwise selection of all candidate variables. Diabetes, male, chronic obstructive pulmonary disease, baseline ejection fraction, and preoperative intra-aortic balloon pump were found be associated with increased risk for the composite of death or heart failure rehospitalization. When mitral gradient was forced into these models, there was no indication of an association with either endpoint (p values ⫽ 0.527 and 0.488, respectively; Table 3). No difference in these endpoints was observed when comparing patients with follow-up echocardiogram to patients without follow-up echocardiogram (Fig 1A, B). No differences in the unadjusted plots were observed for patients with a mitral gradient of 5 mm Hg compared with patients having a gradient of 5 mm Hg or less (death, p ⫽ 0.274; death/rehospitalization, p ⫽ 0.560; Fig 2A, B). Actuarial survival of the entire cohort was 72% at 2 years and 55% at 5 years.
Comment In this series of patients who underwent undersized ring annuloplasty and surgical revascularization for treatment of ischemic MR, a durable correction of the ischemic MR was achieved. The rate of recurrent MR in this cohort of patients was less than that reported in other series with comparable rates of echocardiographic follow-up [5, 6].
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Possible explanations for this finding include differences in patient population or the incomplete echocardiographic follow-up. More likely, though, this finding represents a true decrease in recurrent MR secondary to the strategy of aggressive undersizing and the utilization of complete, rigid annuloplasty rings. It appears that this technique does reduce the rate of recurrent MR, but at the price of increased mitral gradients, as the majority of those patients in whom it was measured demonstrated a mean transmitral gradient of 5 mm Hg or more. This is a higher proportion than has usually been reported in series of repairs of ischemic MR or functional MR, even after aggressive undersizing [11], although one other group has reported a mean mitral gradient of greater than 5 mm Hg afater restrictive annuloplasty for functional MR[12]. In addition, left ventricular diameters were decreased after surgical revascularization and mitral annuloplasty. The modest decrease in left ventricular diameter may not be clinically significant, but increasing chamber size is associated with worse outcome in patients with heart failure and after myocardial infarction [13, 14]. Using proportional hazards models, we were unable to demonstrate any adverse relationship between mitral gradient and survival or the composite of survival and hospitalization for heart failure. Although the number of patients analyzed was low (123 patients), this is a cohort of patients with high event rates, and there appeared to be no trend toward an adverse effect. This finding runs counter to recent descriptions of the adverse effect of patient-prosthesis mismatch at the mitral position [15, 16]. Table 3. Adjusted Proportional Hazards Survival Survival/ Hospitalization for Heart Failure Variable
Wald 2
Hazard Ratio (95% CI)
p Value
Adjusted proportional hazards survival (n ⫽ 123) Mitral gradient 0.400 0.95 (0.82–1.11) 0.527 Diabetes mellitus 10.047 3.10 (1.54–6.24) 0.002 Preoperative IABP 6.408 3.56 (1.33–9.51) 0.011 Age 4.764 1.05 (1.10–1.09) 0.029 History of myocardial 9.646 3.74 (1.63–8.59) 0.002 infarction Number of grafts 3.257 1.43 (0.97–2.12) 0.071 NYHA class CHF 8.119 1.60 (1.16–2.20) 0.004 Adjusted proportional hazards survival/hospitalization for heart failure (n ⫽ 123) Mitral gradient 0.481 1.042 (0.93–1.17) 0.488 Diabetes mellitus 5.639 1.90 (1.12–3.21) 0.018 Male 4.576 1.78 (1.05–3.02) 0.032 COPD 3.541 1.73 (0.98–3.07) 0.060 Ejection fraction 6.990 0.97 (0.94–0.99) 0.008 Preoperative IABP 22.057 5.81 (2.79–12.12) ⬍0.0001 CHF ⫽ congestive heart failure; CI ⫽ confidence interval; COPD ⫽ chronic obstructive pulmonary disease; IABP ⫽ intra-aortic balloon pump; NYHA ⫽ New York Heart Association.
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It could be that mitral gradients more commonly found in this series (between 5 mm and 8 mm Hg) are simply well tolerated, and gradients at this level are a good trade for lower rates of MR recurrence. Other interpretations are possible. Mitral gradient measurement with echocardiography relies on a number of assumptions, and the lack of an apparent effect of increased gradients could simply reflect a lack of accuracy using this technique. In addition, increasing cardiac output—all other factors being equal—would tend to increase the mitral gradient. The finding of increased gradient alone then could reflect increased cardiac output relative to other patients, rather than greater restriction at the level of the mitral valve. Despite the low rate of MR recurrence and the apparently benign nature of the increased gradients, survival of this very ill group of patients remained poor, with only about half expected to survive 5 years after operation. Weaknesses of this study are the drawbacks of retrospective analysis, including the absence of a significant group of
Fig 2. Mitral gradients: (A) survival probability; (B) freedom from death or hospitalization for heart failure. (Solid line ⫽ gradient more than 5; broken line ⫽ gradient 5 or less.)
patients who received flexible or larger rings. In addition, echocardiographic follow-up is not available for the entire cohort and is based on a variable time interval from operation, which weakens conclusions drawn from those data. It is reassuring to note, however, that there does not appear to be any significant difference with respect to long-term outcomes between patients who did or did not undergo follow-up echocardiography (Figs 1A and B). In conclusion, undersized ring annuloplasty and surgical revascularization provide a durable correction of ischemic MR that reduces left ventricular diameters. This technique frequently increases the gradient across the mitral valve as measured by echocardiography, but increasing mitral gradient does not appear to adversely impact survival or heart failure hospitalization (Table 3). Fig 1. Echocardiographic follow-up: (A) survival probability; (B) freedom from death or hospitalization for heart failure. (Solid line ⫽ with echocardiographic follow-up; broken line ⫽ without echocardiographic follow-up.)
References 1. Schroder JN, Williams ML, Hata JA, et al. Impact of mitral valve regurgitation evaluated by intraoperative transesopha-
2. 3.
4.
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6.
7. 8.
geal echocardiography on long-term outcomes after coronary artery bypass grafting. Circulation 2005;112(Suppl 1):293– 8. Bolling SF, Deeb GM, Brunsting LA, et al. Early outcome of mitral valve reconstruction in patients with end-stage cardiomyopathy. J Thorac Cardiovasc Surg 1995;109:676 – 82. Mihaljevic T, Lam BK, Rajeswaran J, et al. Impact of mitral valve annuloplasty combined with revascularization in patients with functional ischemic mitral regurgitation. J Am Coll Cardiol 2007;49:2191–201. Diodato MD, Moon MR, Pasque MK, et al. Repair of ischemic mitral regurgitation does not increase mortality or improve long-term survival in patients undergoing coronary artery revascularization: a propensity analysis. Ann Thorac Surg 2004;78:794 –9. Crabtree TD, Bailey MS, Moon MR, et al. Recurrent mitral regurgitation and risk factors for early and late mortality after mitral valve repair for functional ischemic mitral regurgitation. Ann Thorac Surg 2008;85:1537– 42. McGee EC, Gillinov AM, Blackstone EH, et al. Recurrent mitral regurgitation after annuloplasty for functional ischemic mitral regurgitation. J Thorac Cardiovasc Surg 2004; 128:916 –24. Spoor MT, Geltz A, Bolling SF. Flexible versus nonflexible mitral valve rings for congestive heart failure: differential durability of repair. Circulation 2006;114(Suppl 1):67–71. Magne J, Sénéchal M, Mathieu P, et al. Restrictive annuloplasty for ischemic mitral regurgitation may induce
WILLIAMS ET AL RECURRENCE OF MR AFTER RING ANNULOPLASTY
9. 10. 11.
12.
13. 14. 15. 16.
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functional mitral stenosis. J Am Coll Cardiol 2008;51:1692– 701. Rapaport E. Natural history of aortic and mitral valve disease. Am J Cardiol 1975;35:221–7. Selzer A, Cohn KE. Natural history of mitral stenosis: a review. Circulation 1972;45:878 –90. Tulner SA, Steendijk P, Klautz RJ, et al. Acute hemodynamic effects of restrictive mitral annuloplasty in patients with end-stage heart failure: analysis by pressure-volume relations. J Thorac Cardiovasc Surg 2005;130:33– 40. Walls MC, Cimino N, Bolling SF, et al. Persistent pulmonary hypertension after mitral valve surgery: does surgical procedure affect outcome? J Heart Valve Dis 2008;17:1–9. Lee TH, Hamilton MA, Stevenson LW, et al. Impact of left ventricular cavity size on survival in advanced heart failure. Am J Cardiol 1993;72:672– 6. Pfeffer MA, Lamas GA, Vaughan DE, et al. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med 1988;319:80 – 6. Lam BK, Chan V, Hendry P, et al. The impact of patientprosthesis mismatch on late outcomes after mitral valve replacement. J Thorac Cardiovasc Surg 2007;133:1464 –73. Li M, Dumesnil JG, Mathieu P, et al. Impact of valve prosthesis/patient mismatch on pulmonary arterial pressure after mitral valve replacement. J Am Coll Cardiol 2005;45: 1034 – 40.
The Society of Thoracic Surgeons Policy Action Center The Society of Thoracic Surgeons (STS) is pleased to announce a new member benefit—the STS Policy Action Center, a website that allows STS members to participate in change in Washington, DC. This easy, interactive, hassle-free site allows members to: ● Personally contact legislators with one’s input on key issues relevant to cardiothoracic surgery ● Write and send an editorial opinion to one’s local media
© 2009 by The Society of Thoracic Surgeons Published by Elsevier Inc
● E-mail senators and representatives about upcoming medical liability reform legislation ● Track congressional campaigns in one’s district—and become involved ● Research the proposed policies that help— or hurt— one’s practice ● Take action on behalf of cardiothoracic surgery This website is now available at www.sts.org/takeaction.
Ann Thorac Surg 2009;88:1201
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0003-4975/09/$36.00
ADULT CARDIAC
Ann Thorac Surg 2009;88:1197–201
Background. Undersized ring annuloplasty and surgical revascularization are commonly used to correct ischemic mitral regurgitation (MR), but published series have failed to demonstrate a benefit compared with revascularization alone. We hypothesized that surgical revascularization and annuloplasty lead to a durable repair, but may also lead to increased mitral gradients that could limit the benefit of the repair technique. Methods. Data were collected for 222 consecutive patients who underwent combined revascularization and repair for ischemic MR between 1999 and 2006. The most recent transthoracic echocardiogram available for each patient (namely, the study that occurred at the latest date after surgery) was reviewed to define the fate of ischemic MR. When present, the mean gradient across the mitral valve was measured. Cox regression modeling was then performed to determine whether increasing gradients were associated with decreased long-term survival or increased hospitalization for heart failure.
Results. For the group of 222 patients, echocardiographic follow-up was available for 68% (149 patients). At follow-up, 1.3% had severe MR and 9.4% had moderate MR; 54% of patients (66 of 123) were found to have gradients of 5 mm or greater across the mitral valve, with 11% demonstrating gradients of 8 mm or more. Cox proportional hazards models failed to show adverse effects of increasing mitral gradient on outcomes analyzed: survival hazard ratio ⴝ 0.95 (95% confidence interval: 0.82 to 1.11, p ⴝ 0.527) and survival/heart failure hospitalization hazard ratio ⴝ 1.04 (95% confidence interval: 0.93 to 1.17, p ⴝ 0.488). Conclusions. Undersized ring annuloplasty and revascularization can provide a durable correction of ischemic mitral regurgitation. This technique frequently increases the gradient across the mitral valve, but increasing mitral gradient does not appear to adversely impact survival or heart failure hospitalization. (Ann Thorac Surg 2009;88:1197–201) © 2009 by The Society of Thoracic Surgeons
T
plete rigid annuloplasty rings should be utilized, and have shown a decrease in need for reoperation as evidence that this technique provides a more durable correction for ischemic MR [7]. It would appear that a more durable correction of ischemic MR performed concurrently with CABG would yield greater benefits for patients, although at the risk of creating iatrogenic mitral stenosis. Concerns have previously been raised that an aggressively undersized annuloplasty ring may lead to increased gradients across the mitral valve, which could have a deleterious effect on outcome [8]. Clearly, moderately increased gradients have been described in patients with rheumatic mitral stenosis that were well tolerated for long periods of time with few deleterious effects [9, 10]. However, it is unknown what the effect of increased gradient is after repair of ischemic MR. The population of ischemic MR patients would certainly be expected to have a higher left ventricular end-diastolic pressure than rheumatic patients and would therefore be at higher risk of heart failure symptoms after the creation of moderate stenosis by undersized annuloplasty.
he presence of mitral regurgitation (MR) has been shown to adversely impact outcomes in patients who undergo coronary artery bypass grafting [1]. The technique of undersized annuloplasty for the treatment of functional MR in patients with cardiomyopathy was popularized by Bolling and associates [2]. Currently, undersized ring annuloplasty and coronary artery bypass grafting (CABG) are frequently applied to patients with ischemic MR, but published series to date have thus far failed to show a benefit relative to revascularization alone [3, 4]. Furthermore, it has been demonstrated in some surgical series that recurrent MR occurs in one third of patients when echocardiographic follow-up is available [5, 6]. Some authors have argued that to avoid recurrent mitral regurgitation, undersized, com-
Accepted for publication June 1, 2009. Presented at the Poster Session of the Forty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Francisco, CA, Jan 26 –28, 2009. Address correspondence to Dr Williams, University of Louisville Health Sciences, Division of Cardiovascular and Thoracic Surgery, 201 Abraham Flexner Way, Suite 1200, Louisville, KY 40202; e-mail: mwilliams@ ucsamd.com.
© 2009 by The Society of Thoracic Surgeons Published by Elsevier Inc
0003-4975/09/$36.00 doi:10.1016/j.athoracsur.2009.06.022
ADULT CARDIAC
Mitral Gradients and Frequency of Recurrence of Mitral Regurgitation After Ring Annuloplasty for Ischemic Mitral Regurgitation
1198
WILLIAMS ET AL RECURRENCE OF MR AFTER RING ANNULOPLASTY
ADULT CARDIAC
In surgical patients with ischemic MR, the dominant (although not uniform) strategy at our institution has been to undersize the valve with a complete, nonflexible annuloplasty ring. We hypothesized that this, along with revascularization, would lead to a durable repair and would reduce left ventricular diameters. We sought to determine if this strategy led to increased gradients across the repaired valve, and if this had any measurable impact on fatal or nonfatal outcomes.
Material and Methods All data collection and analysis was performed with waiver of consent with Institutional Review Board approval. Between February 1999 and August 2006, we identified 222 consecutive patients who underwent CABG and annuloplasty for ischemic mitral regurgitation. Preoperative clinical characteristics as well as longitudinal data for survival and heart failure hospitalization were collected as part of the Duke Cardiovascular Databank and were 98% complete. The most recent transthoracic echocardiogram available for each patient (namely, the echocardiogram that occurred at the latest date after surgery) was reviewed to determine the extent of MR in patients who underwent surgical repair and revascularization for ischemic MR. If moderate or severe MR was identified, an attempt was made to determine the cause from the echocardiogram. If available, left ventricular diameters were compared using a sign-rank test. In addition, if measured, the mean gradient across the mitral valve was recorded. Two endpoints were examined in time-to-event analyses: all-cause mortality and a composite of death or heart failure hospitalization. Unadjusted Kaplan-Meier plots were generated and stratified by low mitral gradient (gradient 5 or less) versus high mitral gradient (gradient more than 5). Kaplan-Meier methods were also used to examine survival differences for patients with follow-up echocardiogram versus no follow-up echocardiogram. Unadjusted Cox-proportional hazards were examined to assess relationships with outcomes. Multivariable Cox proportional hazards models were used to assess relationships between clinical characteristics and both endpoints. The following covariates were examined in the unadjusted and adjusted models: mitral gradient, history of diabetes, renal disease, male, chronic obstructive pulmonary disease, baseline ejection fraction, pulmonary gradient, surgery redo, preoperative balloon bump, age, prior CABG, history of myocardial infarction, and number of grafts, number of disease vessels, onpump, race, and New York Heart Association (NYHA) class. Mean mitral gradient was assessed in an adjusted model with all significant components to determine if increasing gradients were associated with decreased survival or increased hospitalization for heart failure. All analyses were performed utilizing SAS version 8.1 or higher (SAS Institute, Cary, NC).
Ann Thorac Surg 2009;88:1197–201
Table 1. Patient Characteristics
Characteristic Age, median years (IQR) Male (%) Black (%) Preoperative ejection fraction, median (IQR) Renal failure (%) Diabetes mellitus (%) COPD (%) History of CABG (%) History of myocardial infarction (%) History of stroke (%) Class III or IV heart failure (%) Number of diseased vessels (SD) Cerebrovascular disease (%) Peripheral vascular disease (%) Smoking (%) Hypertension (%) Hypercholesterolemia (%) Preoperative inotropes (%) Emergency status (%) Preoperative IABP (%) Redo operation (%)
All Patients (n ⫽ 222)
Patients with Paired Echocardiographic Data (n ⫽ 83)
67 (59, 74) 101 (46) 48 (22) 30 (20, 40)
65 (58, 73) 39 (47) 23 (28) 30 (20, 40)
16 (7) 86 (39) 46 (21) 18 (8) 106 (48)
9 (11) 33 (40) 22 (27) 8 (10) 43 (52)
17 (8) 99 (45)
7 (8) 40 (48)
2.6 (⫾ 0.1)
2.6 (⫾ 0.6)
23 (10) 37 (17)
10 (12) 18 (18)
117 (53) 159 (72) 126 (57) 5 (2) 32 (14) 18 (8) 22 (10)
42 (51) 59 (71) 51 (61) 2 (3) 15 (18) 6 (7) 9 (10)
CABG ⫽ coronary artery bypass graft surgery; COPD ⫽ chronic obstructive pulmonary disease; IABP ⫽ intra-aortic balloon pump; IQR ⫽ interquartile range.
Results For the group of 222 patients, preoperative data can be seen in Table 1. The intraoperative transesophageal echocardiogram demonstrated moderate MR in 138 of 222 (62%) and severe MR in 78 of 222 patients (35%). Six patients (3%) had mild MR. Median follow-up time for all surviving patients was 2.20 years with an interquartile range (IQR) of 1.04 years to 4.42 years, and 2.22 years with an IQR of 1.1 to 4.26 years for surviving patients with a follow-up echocardiograph. This is a very high risk group of patients: 30-day mortality was 6.3% (14 of 222). A nonflexible ring was utilized in 98% of patients, with an average ring size of 24.8 mm (⫾ 1.3 mm). A complete ring was used in 91% of patients, and the average number of bypass grafts was 2.8 (⫾ 0.9). A preoperative chest wall echocardiogram was available for 134 patients. Average preoperative left ventricular end-diastolic diameter for this group was 5.4 cm (⫾ 0.8 cm), and left ventricular end-systolic diameter was 4.3 cm (⫾ 1.0 cm). Echocardiographic follow-up was available for 149 of 222 patients (68%). Median time to latest echocardiographic follow-up was 321 days; the IQR was 17 to 918 days. At the time of follow-up echocardiograph, 1.3% (2 of 149 patients) had severe MR and 9.4% (14 of 149) had moderate MR. Upon
WILLIAMS ET AL RECURRENCE OF MR AFTER RING ANNULOPLASTY
Table 2. Left Ventricular (LV) Diameters (n ⫽ 83) Diameter Preoperative LV end-diastolic diameter Postoperative LV end-diastolic diameter Delta ⫽ ⫺0.4 cm, p ⬍ 0.001 Preoperative LV end-systolic diameter Postoperative LV end-systolic diameter Delta ⫽ ⫺0.1 cm, p ⫽ 0.08
5.5 cm (⫾ 0.8) 5.1 cm (⫾ 1.0) 4.3 cm (⫾ 1.0) 4.2 cm (⫾ 1.2)
review of the echocardiograms, 81% (13 of 16 patients) with moderate or severe MR were determined to have progressive posterior leaflet tethering as the etiology for failure of repair. No patients underwent reoperation for mitral regurgitation; 2 patients did go on to receive cardiac transplantation. Paired preoperative and postoperative transthoracic echocardiograms were available for 37% of patients (83 of 222). Left ventricular end-diastolic diameter was significantly decreased relative to preoperative transthoracic echocardiogram; left ventricular end-systolic diameter was decreased but did not reach statistical significance (Table 2). Measurement of the transmitral gradient was available for 123 patients; 54% of patients were found to have mean gradients of 5 mm Hg or greater across the mitral valve, with 13% demonstrating gradients of 8 mm Hg or more (average 5.0 ⫾ 2.2 mm Hg). Diabetes mellitus, preoperative intra-aortic balloon pump, increased age, history of myocardial infarction, number of grafts, and higher NHYA class were found to be significantly associated with increased mortality (p values ⬍ 0.05) in the multivariable proportional hazards model, following stepwise selection of all candidate variables. Diabetes, male, chronic obstructive pulmonary disease, baseline ejection fraction, and preoperative intra-aortic balloon pump were found be associated with increased risk for the composite of death or heart failure rehospitalization. When mitral gradient was forced into these models, there was no indication of an association with either endpoint (p values ⫽ 0.527 and 0.488, respectively; Table 3). No difference in these endpoints was observed when comparing patients with follow-up echocardiogram to patients without follow-up echocardiogram (Fig 1A, B). No differences in the unadjusted plots were observed for patients with a mitral gradient of 5 mm Hg compared with patients having a gradient of 5 mm Hg or less (death, p ⫽ 0.274; death/rehospitalization, p ⫽ 0.560; Fig 2A, B). Actuarial survival of the entire cohort was 72% at 2 years and 55% at 5 years.
Comment In this series of patients who underwent undersized ring annuloplasty and surgical revascularization for treatment of ischemic MR, a durable correction of the ischemic MR was achieved. The rate of recurrent MR in this cohort of patients was less than that reported in other series with comparable rates of echocardiographic follow-up [5, 6].
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Possible explanations for this finding include differences in patient population or the incomplete echocardiographic follow-up. More likely, though, this finding represents a true decrease in recurrent MR secondary to the strategy of aggressive undersizing and the utilization of complete, rigid annuloplasty rings. It appears that this technique does reduce the rate of recurrent MR, but at the price of increased mitral gradients, as the majority of those patients in whom it was measured demonstrated a mean transmitral gradient of 5 mm Hg or more. This is a higher proportion than has usually been reported in series of repairs of ischemic MR or functional MR, even after aggressive undersizing [11], although one other group has reported a mean mitral gradient of greater than 5 mm Hg afater restrictive annuloplasty for functional MR[12]. In addition, left ventricular diameters were decreased after surgical revascularization and mitral annuloplasty. The modest decrease in left ventricular diameter may not be clinically significant, but increasing chamber size is associated with worse outcome in patients with heart failure and after myocardial infarction [13, 14]. Using proportional hazards models, we were unable to demonstrate any adverse relationship between mitral gradient and survival or the composite of survival and hospitalization for heart failure. Although the number of patients analyzed was low (123 patients), this is a cohort of patients with high event rates, and there appeared to be no trend toward an adverse effect. This finding runs counter to recent descriptions of the adverse effect of patient-prosthesis mismatch at the mitral position [15, 16]. Table 3. Adjusted Proportional Hazards Survival Survival/ Hospitalization for Heart Failure Variable
Wald 2
Hazard Ratio (95% CI)
p Value
Adjusted proportional hazards survival (n ⫽ 123) Mitral gradient 0.400 0.95 (0.82–1.11) 0.527 Diabetes mellitus 10.047 3.10 (1.54–6.24) 0.002 Preoperative IABP 6.408 3.56 (1.33–9.51) 0.011 Age 4.764 1.05 (1.10–1.09) 0.029 History of myocardial 9.646 3.74 (1.63–8.59) 0.002 infarction Number of grafts 3.257 1.43 (0.97–2.12) 0.071 NYHA class CHF 8.119 1.60 (1.16–2.20) 0.004 Adjusted proportional hazards survival/hospitalization for heart failure (n ⫽ 123) Mitral gradient 0.481 1.042 (0.93–1.17) 0.488 Diabetes mellitus 5.639 1.90 (1.12–3.21) 0.018 Male 4.576 1.78 (1.05–3.02) 0.032 COPD 3.541 1.73 (0.98–3.07) 0.060 Ejection fraction 6.990 0.97 (0.94–0.99) 0.008 Preoperative IABP 22.057 5.81 (2.79–12.12) ⬍0.0001 CHF ⫽ congestive heart failure; CI ⫽ confidence interval; COPD ⫽ chronic obstructive pulmonary disease; IABP ⫽ intra-aortic balloon pump; NYHA ⫽ New York Heart Association.
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It could be that mitral gradients more commonly found in this series (between 5 mm and 8 mm Hg) are simply well tolerated, and gradients at this level are a good trade for lower rates of MR recurrence. Other interpretations are possible. Mitral gradient measurement with echocardiography relies on a number of assumptions, and the lack of an apparent effect of increased gradients could simply reflect a lack of accuracy using this technique. In addition, increasing cardiac output—all other factors being equal—would tend to increase the mitral gradient. The finding of increased gradient alone then could reflect increased cardiac output relative to other patients, rather than greater restriction at the level of the mitral valve. Despite the low rate of MR recurrence and the apparently benign nature of the increased gradients, survival of this very ill group of patients remained poor, with only about half expected to survive 5 years after operation. Weaknesses of this study are the drawbacks of retrospective analysis, including the absence of a significant group of
Fig 2. Mitral gradients: (A) survival probability; (B) freedom from death or hospitalization for heart failure. (Solid line ⫽ gradient more than 5; broken line ⫽ gradient 5 or less.)
patients who received flexible or larger rings. In addition, echocardiographic follow-up is not available for the entire cohort and is based on a variable time interval from operation, which weakens conclusions drawn from those data. It is reassuring to note, however, that there does not appear to be any significant difference with respect to long-term outcomes between patients who did or did not undergo follow-up echocardiography (Figs 1A and B). In conclusion, undersized ring annuloplasty and surgical revascularization provide a durable correction of ischemic MR that reduces left ventricular diameters. This technique frequently increases the gradient across the mitral valve as measured by echocardiography, but increasing mitral gradient does not appear to adversely impact survival or heart failure hospitalization (Table 3). Fig 1. Echocardiographic follow-up: (A) survival probability; (B) freedom from death or hospitalization for heart failure. (Solid line ⫽ with echocardiographic follow-up; broken line ⫽ without echocardiographic follow-up.)
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The Society of Thoracic Surgeons Policy Action Center The Society of Thoracic Surgeons (STS) is pleased to announce a new member benefit—the STS Policy Action Center, a website that allows STS members to participate in change in Washington, DC. This easy, interactive, hassle-free site allows members to: ● Personally contact legislators with one’s input on key issues relevant to cardiothoracic surgery ● Write and send an editorial opinion to one’s local media
© 2009 by The Society of Thoracic Surgeons Published by Elsevier Inc
● E-mail senators and representatives about upcoming medical liability reform legislation ● Track congressional campaigns in one’s district—and become involved ● Research the proposed policies that help— or hurt— one’s practice ● Take action on behalf of cardiothoracic surgery This website is now available at www.sts.org/takeaction.
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