1. Mitral Valve Surgery: Lessons from New York State
Joanna Chikwe, MD
Professor of Cardiovascular Surgery
Icahn School of Medicine at Mount Sinai, New York
Chairman, Department of Cardiovascular Surgery
Mount Sinai St. Luke’s, New York
This afternoon I’m going to present an analysis of New York State Data focusing on long term outcomes after mitral valve surgery. It comes from a collaboration with the Department of Population Health Science and Policy at Mount Sinai

2. This paritculalr analsysis is in this months’s issue of JAMAI aim to achieve two things - firstly provide you information that may inform your conversation with non-elderly patients sent to you for mitral valve replacement, and secondly highlight the strengths and the limiitations of this analysis (which are really the strneghs and limitations of the dataset) because if the limitations can be successfully addressed there is an exciting opportunity here for some very impactfult rsearch.. .

3. Disclosures
Icahn School of Medicine at Mount Sinai receives royalties from Edwards Lifesciences and Medtronic for Dr. David Adams’ involvement in developing two mitral valve repair rings and one tricuspid valve repair ring.
Dr. David Adams is the National Co-Principal Investigator of the CoreValve United States Pivotal Trial, which is supported by Medtronic. 
None of the sponsoring organizations had any role in the design and conduct of the study.
None of the other authors have any conflicts of interest to disclose..  
The senior author of this studiy, Dr David Adams, has the following disclosures.

4. Background
In non-elderly patients undergoing mitral valve replacement, the optimal prosthesis type is subject to debate.
Current guidelines recommend either mechanical or bioprosthetic valves in patients under 70 years of age,1,2 and state that the balance of risks favors mechanical valves in patients <60 years.2
While the balance of risks in elderly patients clearly favours bioprosthetic over mechanical mitral valve replacement, the best prosthesis type for middle-aged patients undergoing mitral valve replacement is less clear cut. This equivocacy is encapsulated by current consensus guidelines which recommend either prosthesis type in patients under 70 years. Fpr patients under 60 years guidance is that the balance of risks favours mechanical valves
1 Nishimura RA et al. J Thorac Cardiovasc Surg 2014; 148: e1-e132
2 Vahanian A et al. Eur Heart J 2012; 33:

5. Evidence
Three randomized clinical trials of mechanical versus bioprosthetic valves
Showed no difference in late survival
But two trials followed patients operated on in 1970’s and 1980’s 1, 2
And the most recent trial included only aortic valve replacement 3
Three single center series
Suggested that a survival benefit was associated with mechanical valves
But prone to selection bias
These guidelines are based primarily on the results of three randomized controlled trials which found no significant difference in late survival between prosthesis types.. But, the Edinburgh study and the VA study compared mechanical and bioprosthetic valve models implanted in the 1970s and 1980s. The more recent trial by Stassano et al included only patients undergoing aortic valve replacement. A recent retrospective analysis from the Brigham of 125 propensity matched pairs suggested a possible survival benefit with mechanical valves.
1 Oxenham H et al. Heart 2003; 89:
2 Hammermeister K et al. J Am Coll Cardiol 2000; 36:
3 Stassano P et al. J Am Coll Cardiol 2009; 54:
4 Badhwar V et al. Ann Thorac Surg 2012; 93:
5 Kaneko T et al. J Thorac Cardiovasc Surg 2014; 147:
6 Daneshund MA et al. Ann Thorac Surg 2010; 90:

6. Research question
In non-elderly patients undergoing mitral valve replacement:
Is there a survival difference between prosthesis types?
If not, does the balance of complications such as stroke, reoperation, or major bleeding favor one prosthesis type over the other?
Statewide Planning and Research Cooperative System (SPARCS)
Mandatory
All admissions, all visits to the emergency room, all ambulatory visits
We posed two questions: in patients aged 50 to 69 years undergoing mitral valve replacement, is there a survival difference between mechanical and bioprosthetic valves? And if not, does the balance of major comorbidities i.e. reoperation, stroke and major bleeding favour one prosthesis type over another? To answer this question we used the Statewide Planning and Research Cooperative System (SPARCS) dataset. This is very differerent form the New York State Cardiac Surgery Report Cards data – insofar as it contains informatopm on every hospital admission, emergecy room visit and ambulatory visit of every patient in every hospital in New York State. Thusit does not only contain 30-day outcome data and long-term sutvival data, but also long-term clinical data on any diagnois made in a hospital visit.

7. Research question
In non-elderly patients undergoing mitral valve replacement:
Is there a survival difference between prosthesis types?
If not, does the balance of complications such as stroke, reoperation, or major bleeding favor one prosthesis type over the other?
Statewide Planning and Research Cooperative System (SPARCS)
Mandatory
All admissions, all visits to the emergency room, all ambulatory visits
We posed two questions: in patients aged 50 to 69 years undergoing mitral valve replacement, is there a survival difference between mechanical and bioprosthetic valves? And if not, does the balance of major comorbidities i.e. reoperation, stroke and major bleeding favour one prosthesis type over another? To answer this question we used the Statewide Planning and Research Cooperative System (SPARCS) dataset. This is very differerent form the New York State Cardiac Surgery Report Cards data – insofar as it contains informatopm on every hospital admission, emergecy room visit and ambulatory visit of every patient in every hospital in New York State. Thusit does not only contain 30-day outcome data and long-term sutvival data, but also long-term clinical data on any diagnois made in a hospital visit.
NYS Cardiac surgery
report cards

8. Research question
In non-elderly patients undergoing mitral valve replacement:
Is there a survival difference between prosthesis types?
If not, does the balance of complications such as stroke, reoperation, or major bleeding favor one prosthesis type over the other?
Statewide Planning and Research Cooperative System (SPARCS)
Mandatory
All admissions, all visits to the emergency room, all ambulatory visits
We posed two questions: in patients aged 50 to 69 years undergoing mitral valve replacement, is there a survival difference between mechanical and bioprosthetic valves? And if not, does the balance of major comorbidities i.e. reoperation, stroke and major bleeding favour one prosthesis type over another? To answer this question we used the Statewide Planning and Research Cooperative System (SPARCS) dataset. This is very differerent form the New York State Cardiac Surgery Report Cards data – insofar as it contains informatopm on every hospital admission, emergecy room visit and ambulatory visit of every patient in every hospital in New York State. Thusit does not only contain 30-day outcome data and long-term sutvival data, but also long-term clinical data on any diagnois made in a hospital visit.
SPARCS
NYS Cardiac surgery
report cards

9. Trends in mitral prosthesis choice
Between 1997 and 2012, there was a steady increase in the proportion of patients in this age group who received a bioprosthetic mitral valve replacement in NYS - from just 6% in 1997 to over 60% in 2012 – mirroring STS data on aortic vlave replacement over a similar timeframe

10. Methodology Inclusion criteria (n=8410) 1997-2007 Age 50-69
Mitral valve replacement
Exclusion criteria
Out-of-state residents (7.0%)
Prior replacement of any valve (7.8%)
Concomitant valve replacement (21.9%)
Concomitant aortic/pulmonary valve repair (1.1%)
Concomitant CABG (33.4%)
Concomitant thoracic aortic surgery (1.2%)
We identified every patient aged 50 to 69 years that underwent mitral valve replacement in NYS between 1997 and We chose this timeframe to represent relatively contemporary practice with prosthetic valves in current use, with a cut-off selected to maximise the number of patients included and the length of clinical follow-up. We excluded out of state residents because of the difficulty in obtaining follow-up information, and also exlcuded patients undergoing concomitant coronary bypass surgery or other valve replacement.

11. Patient characteristics
Study cohort consisted of 3343 patients
Bioprosthetic valve patients were older, with more comorbidity
Propensity score matching, for year of surgery as well as demographics and comorbidity, produced 664 patient pairs
We excluded X patients, and propensity matching for 21 clinical characteristics produced 664 patient pairs. The baseline clinical characteristics are similar to those in single institution and other clinical registry series, including the proportion of patients with a pre-operative history of atrial fibrillation who received bioprosthetic valves – which at 46% was higher than might be expected.

12. Patient characteristics
Study cohort consisted of 3343 patients
Bioprosthetic valve patients were older, with more comorbidity
Propensity score matching, for year of surgery as well as demographics and comorbidity, produced 664 patient pairs
Patient characteristics
Bioprosthetic
(n=664)
Mechanical
P value
Male
42%
0.7
Age
60.8
61.0
0.58
Coronary artery disease
39%
0.11
Peripheral vascular disease 3% 5%
0.43
Cerebrovascular disease 8% 9%
0.63
Congestive heart failure
57%
60%
0.28
Atrial fibrillation
46%
44%
0.35
Chronic airways disease
21%
23%
0.47
Chronic kidney disease
10%
We excluded X patients, and propensity matching for 21 clinical characteristics produced 664 patient pairs. The baseline clinical characteristics are similar to those in single institution and other clinical registry series, including the proportion of patients with a pre-operative history of atrial fibrillation who received bioprosthetic valves – which at 46% was higher than might be expected.

13. 30-day outcomes Complication Bioprosthetic (n=664) Mechanical P value
Mortality 5% 4%
0.12
Stroke 2%
0.85
Atrial fibrillation
13%
10%
0.13
Acute kidney injury
0.67
Respiratory failure
21%
16%
0.014
Readmission
22%
20%
0.41
We excluded X patients, and propensity matching for 21 clinical characteristics produced 664 patient pairs. The baseline clinical characteristics are similar to those in single institution and other clinical registry series, including the proportion of patients with a pre-operative history of atrial fibrillation who received bioprosthetic valves – which at 46% was higher than might be expected.

14. 30-day outcomes Complication Bioprosthetic (n=664) Mechanical P value
Mortality 5% 4%
0.12
Stroke 2%
0.85
Atrial fibrillation
13%
10%
0.13
Acute kidney injury
0.67
Respiratory failure
21%
16%
0.014
Readmission
22%
20%
0.41
We excluded X patients, and propensity matching for 21 clinical characteristics produced 664 patient pairs. The baseline clinical characteristics are similar to those in single institution and other clinical registry series, including the proportion of patients with a pre-operative history of atrial fibrillation who received bioprosthetic valves – which at 46% was higher than might be expected.

15. Results: survival 59.9% 57.5% Long term survival 15 years identical
2 caveats - Number at risk low – does not represent lifetime risk

16. Results: mitral valve reoperation
11.1%
5.0%
Firstly reoperation. We defined reoperation as any subsequent operation involving the mitral valve – Patients with bioprosthetic valves, obviously, had with significantly higher risk of s at 15 years. there are 3 takehomes from this reoperation data. Firstly, in the matched cohort of over one throusand patients, in 15 years of followup 65 patients needed reoperation on the mitral valve..secondly, 1 in 20 patients with mechanical valve prostheses needed reoperation on that mechancial valve within 15 years. And thirdly, the 30-day mortality of reoperation, which was usually elective, was 5.3% - 95% of patients of patients left hospitalafter a planned procedure without residual disability. Contrast this with stroke

17. Results: stroke
14.0%
6.8%
Stroke is never planned, is by definition associated with significant residual disability, and in this cohort carried a 30-day mortality of over 8%. This is particulalry orth emphasizing as paititents with echanical valves were twice as likely to experience astroke in long-term follow=up compred to patients with bioprosthetic valves. .

18. Results: major bleeding
14.9%
9.0%
This was similar to of major bleeding – which we defined as any bleeding event necessitating a hospital admission,.- and was significantly ore common in patients with mechanical valves which was also associated the 30-day mortality was 9%. .

19. Summary of findings
No survival difference between mechanical and bioprosthetic mitral valves in propensity matched patients aged 50 to 69 years.
The 15-year cumulative incidence of stroke and major bleeding were both significantly higher in patients with mechanical valves
The risk of reoperation was lower in the mechanical prosthesis group
In summary, we saw no survival benefit with either valve type. Bioprosthetic valves had the advantage of lower risk of stroke and major bleeding, at the cost of increased risk of reoperation in long-term follow-up.

20. Conclusions
The main trade-off for non-elderly patients is between the distant risk of reoperation, versus the increased lifelong risk of both stroke and major bleeding, AND the lifestyle restrictions imposed by lifelong anticoagulation.
These findings support the expanded use of bioprosthetic valves in younger patients undergoing mitral valve replacement.
The main trade-off between prosthesiis type in patients aged 50 to 69 years of age is between the distant risk of reoperation, versus the increased lifelong risk of stroke, and amjor bleeding; and the lifestyle restrictions associated with lifelong anticoagulation. It is our view that these findings support the expanded use of bioprosthetic valves in younger patients undergoing mitral valve replacement.

21. Strengths Large sample size
All levels of care represented – tertiary centers to community hospitals
Important clinical endpoints , long duration of follow-up
The main strengths of our study include the large sample size, and the representative nature of the sample - all levels of care were represented.
There are many limitations to this dataset – firstly coding is performed by administrative personnel, and the accuracy of this has been questioned. Possibly the greater limitation is the absence of information on key variables that – n this study could not be adjusted for, and which would limit the scope of questions that this dataset on its own could address – missing data includes specific descriptors of degenerative and ischemic mitral valeb disease (rheumatic and endcarditis is well coded for), the severity of coronary artery disease, and ventricular dysfunction. As a result, selection bias may not have been completely controlled for. Finally we were unable to determine when patients were hospitalized out of state, potentially causing us to underestimate the rate of the secondary endpoints: we believe that movement out of state would affect both groups equally.

22. Strengths Limitations Large sample size
All levels of care represented – tertiary centers to community hospitals
Important clinical endpoints, long duration of follow-up
Administrative data
Limited to New York State
Absence of information on etiology of valve disease, extent of coronary artery disease, and ventricular dysfunction
Limitations

23. NYS work in progress
Validating method of reliably identifying degenerative and ischemic mitral patients
Combining SPARCS data with clinical datasets such as New York State report cards:

24. NYS work in progress
Validating method of reliably identifying degenerative and ischemic mitral patients
Combining SPARCS data with clinical datasets such as New York State report cards:
Degenerative mitral repair
Surgical strategies in Ischemic MR
Surgical revascularization strategies e.g. BIMA vs. LIMA
Comparative clinical outcomes in patients under-represented in clinical trials

25. Thank you Yuting Chiang MSc, MD Shinobu Itagaki MD David H. Adams MD
Natalia Egorova PhD
Annetine Gellijns MD
Alan Moskowitz MD
Nana Toyoda MD
We would not be at this exciting point without the efforts of many people. In particular I’d like to highlight the contributions of two exceptional future cardiac surgeons that’s it’s been my prviledge to mentor in this research, who were the backbone of this work, and definitely “ones to watch” – firstly, Dr Shinobu Itagaki our PGY2 I6 resident, and secondly, Mr Yuting Chiang who gets his MD from Mount Sinai in 10 days, and is probably the only medical graduating this year with not one but 2 papers in JAMA..
Thank you