Increasing Disadvantage of “Watchful Waiting” for Repairing Degenerative Mitral Valve Disease Farhang Yazdchi, MD, MS, Colleen G. Koch, MD, MS, Tomislav Mihaljevic, MD, Rory Hachamovitch, MD, Ashley M. Lowry, MS, Jiayan He, ScD, A. Marc Gillinov, MD, Eugene H. Blackstone, MD, and Joseph F. Sabik, III, MD Departments of Thoracic and Cardiovascular Surgery, Cardiothoracic Anesthesia, and Cardiovascular Medicine, Heart and Vascular Institute; and Department of Quantitative Health Sciences, Research Institute, Cleveland Clinic, Cleveland, Ohio
Background. Successful durable repair of severe degenerative mitral regurgitation with low operative mortality encourages intervention in asymptomatic patients rather than “watchful waiting.” Our objectives were to assess trends in patient characteristics, timing of intervention, and evolving surgical techniques at a highvolume center, and determine effects of these changes on outcomes after mitral valve (MV) repair over a 25-year period. Methods. From January 1, 1985, to January 1, 2011, 5,902 patients underwent isolated repair (with or without tricuspid repair for functional regurgitation) for degenerative MV disease at Cleveland Clinic. For illustration, the experience is presented in 3 eras: 1985 to 1997 (era 1, n [ 1,184), 1997 to 2005 (era 2, n [ 2,400), and 2005 to 2011 (era 3, n [ 2,318). Results. In era 3, more patients were asymptomatic on presentation (44% in New York Heart Association [NYHA] class I vs 25% in era 1), with less heart failure
(11% vs 29%) and atrial fibrillation (9.9% vs 23%). Full sternotomy decreased from era 1 (n [ 1,100/93%) to era 2 (n [ 602/25%) (era 3, n [ 717/31%), and robotic surgery emerged (n [ 577/25%) in era 3. Median length of stay shortened (era 1 [ 7 days, era 2 [ 5.9 days, era 3 [ 5.2 days, p < 0.0001), and in-hospital mortality remained low (era 1 [ 5/0.42%, era 2 [ 5/0.21%, era 3 [ 1/0.043%); 0.73% overall required reoperation on the repaired valve before discharge, and 97% had 0 to 1D regurgitation at discharge. Conclusions. Treatment trends over 25 years reveal that rather than watchful waiting, a more aggressive approach to degenerative MV disease, with earlier intervention for severe regurgitation in asymptomatic patients and less invasive operative techniques, is successful, safe, and effective.
S
without tricuspid valve repair or surgery for atrial fibrillation) for degenerative mitral valve disease and severe (3þ/4þ) regurgitation at Cleveland Clinic. Among these, 6,013 were intended primary isolated mitral valve repairs and 318 mitral valve replacements. Of the included repairs, 111 (1.8%) were converted intraoperatively to mitral valve replacement; 13 in era 1 (1.1%; see text that follows for definition), 44 (1.8%) in era 2, and 54 (2.3%) in era 3 (Fig 1A). The remaining as-treated cohort of 5,902 is the focus of this study.
urgery for degenerative mitral valve disease has evolved, with a higher percentage of patients undergoing intervention before symptoms arise [1], repair rather than replacement of the valve [1, 2], and less invasive surgical approaches [3–9] . However, debate continues about the value of “watchful waiting” versus early surgical intervention for asymptomatic patients [10–13]. Our hypothesis is that an aggressive strategy, rather than watchful waiting, is successful, safe, and effective. We tested this hypothesis by the following: (1) assessing trends in patient characteristics, timing of intervention, and evolution of surgical techniques at a single institution over a 25-year period; and (2) determining the effects of these changes on hospital length of stay and mortality after mitral valve repair.
Patients and Methods Patients From January 1, 1985, to January 1, 2011, 6,331 patients underwent primary isolated mitral valve surgery (with or Accepted for publication Jan 19, 2015. Address correspondence to Dr Sabik, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, 9500 Euclid Ave/Desk J4-1, Cleveland, OH 44195; e-mail: [email protected].
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2015;-:-–-) Ó 2015 by The Society of Thoracic Surgeons
Statistical Methods For illustration, the experience is presented both year-byyear and in some instances by era stratified arbitrarily. Era 1 is 1985 to 1997 (n ¼ 1,184); era 2 is 1997 to 2005 (n ¼ 2,400); and era 3 is 2005 to 2011 (n ¼ 2,318). Continuous variables are summarized as mean standard deviation or as 15th, 50th (median), and 85th Dr Gillinov discloses financial relationships with Edwards Lifesciences, Medtronic, On-X, Abbott, Tendyne, and St Jude; and Dr Sabik with Medtronic, Sorin, Edwards Lifesciences, and Abbott.
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.01.065
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YAZDCHI ET AL WATCHFUL WAITING: MITRAL VALVE DISEASE
Ann Thorac Surg 2015;-:-–-
Fig 1. Temporal trends in mitral valve surgery. Yearly frequencies are presented as symbols; lines are smoothing spline curves. (A) Proportion of 6,331 primary isolated operations that were actual repairs (closed squares and solid line, n ¼ 5,902), intended replacements (closed circles and dashed line, n ¼ 318), and repairs converted to replacement intraoperatively (closed triangles and dotted line, n ¼ 111). (B) Temporal number of actual mitral valve repairs.
percentiles when data were skewed; comparisons were made using a linear regression model with eras 2 and 3 compared with era 1. Categoric data are summarized as frequencies and percentages; comparisons were made using a logistic regression model with eras 2 and 3 compared with era 1. Trends were modeled using a smoothing spline and R-statistical software [14–16].
Results
(Fig 3B). Mean left atrial diameter decreased from severe left atrial enlargement in era 1 (5.4 1.0 cm) to less severe enlargement in eras 2 and 3 (4.8 0.88 cm and 4.6 0.80 cm, respectively, p < 0.0001; Fig 3C), paralleling the decreased prevalence of preoperative atrial fibrillation in this patient cohort. Left ventricular ejection fraction remained constant at about 0.60 (Table 2). Occurrence of mild mitral valve calcification trended downward (Table 1) (patients with severe mitral annular calcification did not undergo mitral valve repair).
Repair Trends From 1985 to 2011, the number of mitral valve repair procedures increased nearly linearly, from 1,184 in era 1 to 2,318 in era 3 (Fig 1B).
Clinical Presentation Trends An increasing proportion of patients were asymptomatic on presentation. In era 3, more than 40% were in New York Heart Association (NYHA) functional class I, compared with 25% in era 1 (Table 1, Fig 2A). In era 1, 29% (n ¼ 349) had a history of heart failure; this decreased to 16% (n ¼ 390) in era 2 and 11% (n ¼ 248) in era 3 (Fig 2B). Preoperative atrial fibrillation also decreased during the same period: era 1, 23% (n ¼ 241); era 2, 13% (n ¼ 264); and era 3, 9.9% (n ¼ 226); p value less than 0.0001 (Fig 2C).
Heart Structure and Function Trends Echocardiographic trends in left atrial and ventricular morphology paralleled temporal trends in clinical presentation. Left ventricular end-systolic volume index decreased from 33 16 mL $ m2 in era 1 to 24 11 mL $ m2 in era 3 (p < 0.0001), as did end-diastolic volume index (p < 0.0001; Fig 3A). Mean left ventricular mass index decreased from 161 43 g $ m2 in era 1 to 125 46 in era 3, p value less than 0.0001, although these exceeded the upper limit of normal for both men and women
Surgical Approach Trends In era 1, full sternotomy was performed in 93% of cases (n ¼ 1,100), decreasing to 25% (n ¼ 602) in era 2 and 31% (n ¼ 717) in era 3. Less invasive surgical approaches (partial sternotomy, right anterior thoracotomy, and robotic) were used in a large percentage of cases in eras 2 (75%) and 3 (69%), but rarely in era 1 (n ¼ 84, 7.0%). In era 3, 577 patients underwent robotic mitral valve repairs. Cardiopulmonary bypass and myocardial ischemic times increased over time (Table 2). An annuloplasty ring was used in almost all cases in recent eras (Table 2). Use of artificial chordae increasingly replaced chordal transfer techniques. Leaflet resection was performed in 81% of cases, with a decreasing trend in era 3 (73%). In 1997, we began using edge-to-edge repair [17] for complex disease, averaging about 2.7% per year.
Outcome Trends Fifteen of the 5,902 patients (0.25%) required mitral valve replacement before hospital discharge, primarily for repair of dehiscence and systolic anterior motion (SAM); 28 (0.47%) required re-repair, primarily for SAM and dehiscence, 97% left the hospital with 0 to 1þ mitral regurgitation, and 7 (0.12%) had moderate to severe mitral regurgitation at discharge.
Ann Thorac Surg 2015;-:-–-
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YAZDCHI ET AL WATCHFUL WAITING: MITRAL VALVE DISEASE
Table 1. Trends in Patient Characteristics 1985 to 1997 (n ¼ 1,184) Variable Demography Age (years) Female Race Black White Other Body surface area (m2) Symptoms NYHA functional class I II III IV Preoperative valve pathology Mitral valve Mild calcificationc Chordal rupture Tricuspid valve Regurgitation grade 0 1þ 2þ 3þ 4þ Cardiac comorbidity LA diameter (cm) LV end-diastolic volume index (mL m2) LV end-systolic volume index (mL m2) LV mass index (g m2) Atrial fibrillation or flutter Pacemaker Ventricular arrhythmia Heart failure History of endocarditis Prior MI LV systolic function Normal Mild dysfunction Moderate dysfunction >Moderate dysfunction Noncardiac comorbidity Peripheral arterial disease Carotid disease Prior stroke Hypertension Pharmacologically treated diabetes COPD Smoking Bilirubin (mg dL1)
na
1,184 1,184 1,180
1,043
No. (%) or Mean SD 58 13 426 (36) 24 (2.0) 1,134 (96) 22 (1.9) 1.9 0.23
1,182
263 (22) 799 (67)
2,058
No. (%) or Mean SD 57 13 757 (32) 36 (1.5) 2,287 (96) 69 (2.9) 2.0 0.24
2,400 2,400
(55) (24) (14) (5.4) (1.5)
5.4 1.0 107 30 33 16 161 43 241 (23) 13 (1.3) 119 (15) 349 (29) 39 (7.0) 62 (5.2) 90 3 1 0
(96) (3.2) (1.1) (0)
30 (2.5) 31 (2.6) 49 (4.1) 273 (30) 24 (2.2) 16 (1.8) 447 (38) 0.86 0.50
2,318 2,318 2,310
2,301
No. (%) or Mean SD 58 12 728 (31) 54 (2.3) 2,146 (93) 110 (4.8) 2.0 0.25
2,316 2,316
(52) (27) (14) (5.6) (1.2)
4.8 0.88 82 23 2513 136 36 264 (13) 30 (1.5) 270 (13) 390 (16) 150 (6.3) 114 (4.8) (95) (3.3) (0.94) (0.42)
38 (1.6) 152 (6.3) 43 (1.8) 929 (39) 33 (1.4) 155 (6.5) 914 (39) 0.76 0.46
0.2 0.0002
Background. Successful durable repair of severe degenerative mitral regurgitation with low operative mortality encourages intervention in asymptomatic patients rather than “watchful waiting.” Our objectives were to assess trends in patient characteristics, timing of intervention, and evolving surgical techniques at a highvolume center, and determine effects of these changes on outcomes after mitral valve (MV) repair over a 25-year period. Methods. From January 1, 1985, to January 1, 2011, 5,902 patients underwent isolated repair (with or without tricuspid repair for functional regurgitation) for degenerative MV disease at Cleveland Clinic. For illustration, the experience is presented in 3 eras: 1985 to 1997 (era 1, n [ 1,184), 1997 to 2005 (era 2, n [ 2,400), and 2005 to 2011 (era 3, n [ 2,318). Results. In era 3, more patients were asymptomatic on presentation (44% in New York Heart Association [NYHA] class I vs 25% in era 1), with less heart failure
(11% vs 29%) and atrial fibrillation (9.9% vs 23%). Full sternotomy decreased from era 1 (n [ 1,100/93%) to era 2 (n [ 602/25%) (era 3, n [ 717/31%), and robotic surgery emerged (n [ 577/25%) in era 3. Median length of stay shortened (era 1 [ 7 days, era 2 [ 5.9 days, era 3 [ 5.2 days, p < 0.0001), and in-hospital mortality remained low (era 1 [ 5/0.42%, era 2 [ 5/0.21%, era 3 [ 1/0.043%); 0.73% overall required reoperation on the repaired valve before discharge, and 97% had 0 to 1D regurgitation at discharge. Conclusions. Treatment trends over 25 years reveal that rather than watchful waiting, a more aggressive approach to degenerative MV disease, with earlier intervention for severe regurgitation in asymptomatic patients and less invasive operative techniques, is successful, safe, and effective.
S
without tricuspid valve repair or surgery for atrial fibrillation) for degenerative mitral valve disease and severe (3þ/4þ) regurgitation at Cleveland Clinic. Among these, 6,013 were intended primary isolated mitral valve repairs and 318 mitral valve replacements. Of the included repairs, 111 (1.8%) were converted intraoperatively to mitral valve replacement; 13 in era 1 (1.1%; see text that follows for definition), 44 (1.8%) in era 2, and 54 (2.3%) in era 3 (Fig 1A). The remaining as-treated cohort of 5,902 is the focus of this study.
urgery for degenerative mitral valve disease has evolved, with a higher percentage of patients undergoing intervention before symptoms arise [1], repair rather than replacement of the valve [1, 2], and less invasive surgical approaches [3–9] . However, debate continues about the value of “watchful waiting” versus early surgical intervention for asymptomatic patients [10–13]. Our hypothesis is that an aggressive strategy, rather than watchful waiting, is successful, safe, and effective. We tested this hypothesis by the following: (1) assessing trends in patient characteristics, timing of intervention, and evolution of surgical techniques at a single institution over a 25-year period; and (2) determining the effects of these changes on hospital length of stay and mortality after mitral valve repair.
Patients and Methods Patients From January 1, 1985, to January 1, 2011, 6,331 patients underwent primary isolated mitral valve surgery (with or Accepted for publication Jan 19, 2015. Address correspondence to Dr Sabik, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, 9500 Euclid Ave/Desk J4-1, Cleveland, OH 44195; e-mail: [email protected].
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
(Ann Thorac Surg 2015;-:-–-) Ó 2015 by The Society of Thoracic Surgeons
Statistical Methods For illustration, the experience is presented both year-byyear and in some instances by era stratified arbitrarily. Era 1 is 1985 to 1997 (n ¼ 1,184); era 2 is 1997 to 2005 (n ¼ 2,400); and era 3 is 2005 to 2011 (n ¼ 2,318). Continuous variables are summarized as mean standard deviation or as 15th, 50th (median), and 85th Dr Gillinov discloses financial relationships with Edwards Lifesciences, Medtronic, On-X, Abbott, Tendyne, and St Jude; and Dr Sabik with Medtronic, Sorin, Edwards Lifesciences, and Abbott.
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.01.065
2
YAZDCHI ET AL WATCHFUL WAITING: MITRAL VALVE DISEASE
Ann Thorac Surg 2015;-:-–-
Fig 1. Temporal trends in mitral valve surgery. Yearly frequencies are presented as symbols; lines are smoothing spline curves. (A) Proportion of 6,331 primary isolated operations that were actual repairs (closed squares and solid line, n ¼ 5,902), intended replacements (closed circles and dashed line, n ¼ 318), and repairs converted to replacement intraoperatively (closed triangles and dotted line, n ¼ 111). (B) Temporal number of actual mitral valve repairs.
percentiles when data were skewed; comparisons were made using a linear regression model with eras 2 and 3 compared with era 1. Categoric data are summarized as frequencies and percentages; comparisons were made using a logistic regression model with eras 2 and 3 compared with era 1. Trends were modeled using a smoothing spline and R-statistical software [14–16].
Results
(Fig 3B). Mean left atrial diameter decreased from severe left atrial enlargement in era 1 (5.4 1.0 cm) to less severe enlargement in eras 2 and 3 (4.8 0.88 cm and 4.6 0.80 cm, respectively, p < 0.0001; Fig 3C), paralleling the decreased prevalence of preoperative atrial fibrillation in this patient cohort. Left ventricular ejection fraction remained constant at about 0.60 (Table 2). Occurrence of mild mitral valve calcification trended downward (Table 1) (patients with severe mitral annular calcification did not undergo mitral valve repair).
Repair Trends From 1985 to 2011, the number of mitral valve repair procedures increased nearly linearly, from 1,184 in era 1 to 2,318 in era 3 (Fig 1B).
Clinical Presentation Trends An increasing proportion of patients were asymptomatic on presentation. In era 3, more than 40% were in New York Heart Association (NYHA) functional class I, compared with 25% in era 1 (Table 1, Fig 2A). In era 1, 29% (n ¼ 349) had a history of heart failure; this decreased to 16% (n ¼ 390) in era 2 and 11% (n ¼ 248) in era 3 (Fig 2B). Preoperative atrial fibrillation also decreased during the same period: era 1, 23% (n ¼ 241); era 2, 13% (n ¼ 264); and era 3, 9.9% (n ¼ 226); p value less than 0.0001 (Fig 2C).
Heart Structure and Function Trends Echocardiographic trends in left atrial and ventricular morphology paralleled temporal trends in clinical presentation. Left ventricular end-systolic volume index decreased from 33 16 mL $ m2 in era 1 to 24 11 mL $ m2 in era 3 (p < 0.0001), as did end-diastolic volume index (p < 0.0001; Fig 3A). Mean left ventricular mass index decreased from 161 43 g $ m2 in era 1 to 125 46 in era 3, p value less than 0.0001, although these exceeded the upper limit of normal for both men and women
Surgical Approach Trends In era 1, full sternotomy was performed in 93% of cases (n ¼ 1,100), decreasing to 25% (n ¼ 602) in era 2 and 31% (n ¼ 717) in era 3. Less invasive surgical approaches (partial sternotomy, right anterior thoracotomy, and robotic) were used in a large percentage of cases in eras 2 (75%) and 3 (69%), but rarely in era 1 (n ¼ 84, 7.0%). In era 3, 577 patients underwent robotic mitral valve repairs. Cardiopulmonary bypass and myocardial ischemic times increased over time (Table 2). An annuloplasty ring was used in almost all cases in recent eras (Table 2). Use of artificial chordae increasingly replaced chordal transfer techniques. Leaflet resection was performed in 81% of cases, with a decreasing trend in era 3 (73%). In 1997, we began using edge-to-edge repair [17] for complex disease, averaging about 2.7% per year.
Outcome Trends Fifteen of the 5,902 patients (0.25%) required mitral valve replacement before hospital discharge, primarily for repair of dehiscence and systolic anterior motion (SAM); 28 (0.47%) required re-repair, primarily for SAM and dehiscence, 97% left the hospital with 0 to 1þ mitral regurgitation, and 7 (0.12%) had moderate to severe mitral regurgitation at discharge.
Ann Thorac Surg 2015;-:-–-
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YAZDCHI ET AL WATCHFUL WAITING: MITRAL VALVE DISEASE
Table 1. Trends in Patient Characteristics 1985 to 1997 (n ¼ 1,184) Variable Demography Age (years) Female Race Black White Other Body surface area (m2) Symptoms NYHA functional class I II III IV Preoperative valve pathology Mitral valve Mild calcificationc Chordal rupture Tricuspid valve Regurgitation grade 0 1þ 2þ 3þ 4þ Cardiac comorbidity LA diameter (cm) LV end-diastolic volume index (mL m2) LV end-systolic volume index (mL m2) LV mass index (g m2) Atrial fibrillation or flutter Pacemaker Ventricular arrhythmia Heart failure History of endocarditis Prior MI LV systolic function Normal Mild dysfunction Moderate dysfunction >Moderate dysfunction Noncardiac comorbidity Peripheral arterial disease Carotid disease Prior stroke Hypertension Pharmacologically treated diabetes COPD Smoking Bilirubin (mg dL1)
na
1,184 1,184 1,180
1,043
No. (%) or Mean SD 58 13 426 (36) 24 (2.0) 1,134 (96) 22 (1.9) 1.9 0.23
1,182
263 (22) 799 (67)
2,058
No. (%) or Mean SD 57 13 757 (32) 36 (1.5) 2,287 (96) 69 (2.9) 2.0 0.24
2,400 2,400
(55) (24) (14) (5.4) (1.5)
5.4 1.0 107 30 33 16 161 43 241 (23) 13 (1.3) 119 (15) 349 (29) 39 (7.0) 62 (5.2) 90 3 1 0
(96) (3.2) (1.1) (0)
30 (2.5) 31 (2.6) 49 (4.1) 273 (30) 24 (2.2) 16 (1.8) 447 (38) 0.86 0.50
2,318 2,318 2,310
2,301
No. (%) or Mean SD 58 12 728 (31) 54 (2.3) 2,146 (93) 110 (4.8) 2.0 0.25
2,316 2,316
(52) (27) (14) (5.6) (1.2)
4.8 0.88 82 23 2513 136 36 264 (13) 30 (1.5) 270 (13) 390 (16) 150 (6.3) 114 (4.8) (95) (3.3) (0.94) (0.42)
38 (1.6) 152 (6.3) 43 (1.8) 929 (39) 33 (1.4) 155 (6.5) 914 (39) 0.76 0.46
0.2 0.0002
