HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Edward H. Kincaid John W. Hammon Neal D. Kon Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kincaid, E. H. Articles by Kon, N. D. Search for Related Content PubMed PubMed Citation Articles by Kincaid, E. H. Articles by Kon, N. D. Related Collections Valve disease

Ann Thorac Surg 2007;83:964-968
© 2007 The Society of Thoracic Surgeons

---

Original Articles: Cardiovascular

Coronary Insufficiency After Stentless Aortic Root Replacement: Risk Factors and Solutions

Department of Cardiothoracic Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina

Accepted for publication September 1, 2006.

^_* Address correspondence to Dr Kincaid, Department of Cardiothoracic Surgery, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157 (Email: tkincaid{at}wfubmc.edu).

Presented at the Fifty-second Annual Meeting of the Southern Thoracic Surgical Association, Orlando, FL, Nov 10–12, 2005.

Adult cardiac surgery: The Annals of Thoracic Surgery CME Program is located online at http://cme.ctsnetjournals.org. To take the CME activity related to this article, you must have either an STS member or an individual non-member subscription to the journal.

 

	Abstract

Top Abstract Introduction Material and Methods Results Comment Discussion References

 
Background: Coronary insufficiency is a dreaded complication of total aortic root replacement (ARR) with few defined risk factors. This study describes the incidence, risk factors, management options, and outcomes of this condition after ARR with stentless porcine valves.

Methods: The study consisted of a retrospective analysis of 503 patients (mean age, 68.9 ± 10.2 years) undergoing stentless porcine total ARR (Medtronic Freestyle and St. Jude Toronto) between the years 1993 and 2005 at a single institution. Coronary insufficiency was defined as the need for unplanned bypass grafting during, or after removal from cardiopulmonary bypass to correct wall motion abnormalities, arrhythmias, or right ventricular failure in the absence of known obstructive coronary disease.

Results: A total of 13 cases of right coronary artery and no cases of left coronary insufficiency were identified (overall incidence 13 of 503, 2.6%). All were treated with aortocoronary bypass grafting to the right coronary artery using saphenous vein. Compared with patients who did not have coronary insufficiency, patients with this complication were more likely to be female (11 of 13, 85%, versus 201 of 490, 41%; p = 0.006), had higher mean body mass index (34.6 ± 12.0 kg/m² versus 28.3 ± 3.8 kg/m², p = 0.04), and were implanted with smaller prostheses (23.9 ± 2.1 mm versus 25.6 ± 2.4 mm, p = 0.026), a finding not explained by the preponderance of female sex. Mean age, ejection fraction, and other demographic variables were similar. Despite longer cardiopulmonary bypass times (238 ± 61 minutes versus 180 ± 35 minutes, p = 0.005), operative mortality was not significantly different (1 of 13, 7.7%, versus 29 of 490, 5.9%; p = not significant).

Conclusions: Coronary artery insufficiency is uncommon after stentless aortic root replacement and more often affects the right coronary artery. Risk factors appear to be female sex, higher body mass index, and small aortic root. Preventive measures include recognition of coronary orientation, routine valve rotation, and adequate coronary button mobilization. When this complication occurs, good outcomes can still be obtained with early recognition and prompt bypass grafting.

Over the past decade, aortic valve replacement (AVR) with stentless porcine bioprostheses has become an accepted technique for routine treatment of aortic valve and root diseases. Compared with traditional stented bioprostheses, touted advantages of stentless valves include better hemodynamics [1–3], improved regression of left ventricular mass [3–5], less risk of patient-prosthesis mismatch in the small aortic root [6], and possibly improved long-term survival [7, 8]. Some of these advantages appear to be maximized with implantation using a total root replacement technique, which also is associated with less risk of late valve failure [9]. However, the potential benefits of stentless valves may come at the cost of increased operative risks, including a higher operative mortality compared with subcoronary stentless or stented AVR [9]. While other large series have reported low operative mortality with stentless root replacement [10–12], a learning curve of more than 20 cases has been described [13]. Besides a learning curve for this more complex procedure, other factors that could potentially contribute to excess mortality include longer perfusion and myocardial ischemic times, and more suture lines exposed to the pericardial space.

If stentless root replacement is associated with higher operative risks, technical factors must also play some role, although little information is published on this topic. Coronary complications have been described for aortic root replacement procedures and may be more common in autografts than other types of prostheses [14]. Additionally, reimplantation of a severely atherosclerotic coronary button can lead to other complications including obstruction, dissection, and bleeding. In 2004, Byrne and colleagues [15] reported a large series of root replacements, mostly with homografts and mechanical valve conduits, and found that 2% of patients required "bailout" coronary artery bypass grafting (CABG) for wall motion abnormalities or bleeding from coronary buttons after completion of the root replacement. Mortality in these patients was 25%. Westaby and associates [11] also described the need for bypass grafting of right coronary artery (RCA) for right ventricular failure after allograft root replacement. Less information on coronary insufficiency is available for stentless porcine root replacements, an odd finding given that coronary orientation is significantly different between porcine and human aortic roots. With this background, the purposes of this study are to determine risk factors for the development of coronary insufficiency after stentless porcine root replacement, determine the effect of this complication on mortality, and discuss potential solutions to this problem.

	Material and Methods

Top Abstract Introduction Material and Methods Results Comment Discussion References

 
This project consisted of a retrospective analysis of data stored in the cardiovascular services database of the Wake Forest University Baptist Medical Center. The study was approved by this Institutional Review Board. Additional data fields were added through review of the departmental study valves database and existing electronic medical records. The need for written informed consent was waived.

The patient population included all adult patients undergoing aortic root replacement using stentless porcine valves, either as isolated or combined procedures during the years 1993 to 2005 at the single institution. During the study period, procedures were performed by five surgeons with minor variations in surgical practice. Conduct of cardiopulmonary bypass for all cases included general anesthesia, roller pumps, membrane oxygenation, blood cardioplegia, and alpha-stat pH management. Aprotinin was used in the majority of cases including those involving CABG or hypothermic circulatory arrest.

All valves were implanted using a total root technique, which has been previously described [16]. In general, this is performed with complete transection of the aorta just above the sinotubular junction. Both coronary ostia are mobilized on generous buttons of aortic wall. The remaining tissue of each sinus of Valsalva and the diseased aortic valve are excised. The proximal, or inflow, anastomosis is accomplished using 28 to 35 simple interrupted sutures of 3-0 braided Dacron (C. R. Bard, Haverhill, Pennsylvania) tied around a 1-mm strip of Teflon felt (Impra, subsidiary of L. R. Baird, Tempe, Arizona). The sutures are placed in a single plane in the left ventricular outflow tract to conform to the round inflow of the prosthesis. The coronary arteries on their buttons of aortic wall are sewn end to side to the corresponding sinus of Valsalva of the bioprosthesis with a continuous 5-0 polypropylene suture. For severely atherosclerotic coronary artery buttons, we routinely perform endarterectomy or bypass grafting, or both, to facilitate reattachment. The decision to rotate the valve 120 degrees depended on native coronary orientation. In the usual scenario, the coronary ostia are at 140 to 160 degrees apart compared with the porcine relationship of 90 to 110 degrees. Most valves are thus rotated to facilitate coronary alignment.

Definitions and Data Analysis
Coronary insufficiency was defined as the need for unplanned bypass grafting for wall motion abnormalities or electrocardiographic changes on weaning from cardiopulmonary bypass in patients with no preexistent obstructive coronary lesions in the involved territory. Patients who required coronary reconstruction with saphenous vein for severe button atherosclerosis before cross-clamp removal, therefore, do not meet the definition. Body mass index was calculated using the standard equation of weight/height [2]. Mortality was defined as 30-day or in-hospital death.

Patients with and without coronary insufficiency were compared with determine potential risk factors for the development of this complication. Demographic variables included age, sex, body mass index, body surface area, aortic stenosis versus insufficiency, diabetes mellitus, left ventricular ejection fraction, New York Heart Association class, left ventricular hypertrophy, and planned concomitant procedures. Intraoperative variables included cardiopulmonary bypass time, aortic cross-clamp time, valve size, and valve rotation for implant. Outcome variables included intensive care unit length of stay, hospital length of stay, and mortality (30-day and in-hospital death). Univariate predictors of coronary insufficiency were determined using t tests and ² where appropriate. For each outcome, an overall two-sided type-1 error rate of 5% was preserved using Holm’s sequentially rejective multiple comparisons procedure. Unless otherwise stated, all numerical data are expressed as mean ± SD.

	Results

Top Abstract Introduction Material and Methods Results Comment Discussion References

 
During the 12-year study period, 503 patients underwent full root replacement with stentless porcine valves (477 Medtronic Freestyle [Medtronic, Inc, Minneapolis, MN] and 26 St. Jude Toronto Root [St. Jude Medical, St. Paul, MN]). A total of 13 cases of right coronary insufficiency and no cases of left coronary insufficiency were identified, yielding an overall incidence of 2.6% for this complication. These cases occurred in years 1993, 1994, and 2000 to 2005. Twelve cases involved the Freestyle valve, and one involved the Toronto valve. In 12 cases, right ventricular dilation and failure developed; and in 1 case, left ventricular inferior wall contractility deteriorated. Ventricular arrhythmias were also common. All cases were treated by resumption of cardiopulmonary bypass and aortocoronary bypass grafting of the right main coronary artery with reversed saphenous vein and without additional aortic cross clamping. In no case was the cause of RCA insufficiency immediately apparent. It is assumed that most would be related to changes in proximal RCA orientation that occur in the dynamic situation of right ventricular filling upon emergence from cardiopulmonary bypass. Visualization of this portion of the RCA, however, is difficult with a filled right ventricle, whereas full cardiopulmonary bypass with an empty right ventricle, or cardiac arrest, may not allow for determination of a kink or malalignment.

Compared with patients who did not develop this complication, female sex was more common, as was higher body mass index. Other demographic variables were similar (Table 1). Operative data revealed more concomitant procedures, including planned CABG, among patients who did not develop this complication, an expected finding as CABG should be protective. Cardiopulmonary bypass times were longer for patients in whom coronary insufficiency developed, but that did not translate into longer length of stays or higher mortality (Table 2). Compared with patients with no coronary insufficiency, patients with coronary insufficiency were implanted with smaller valves (25.6 ± 2.4 mm versus 23.9 ± 2.1 mm, p = 0.026), a finding not explained by a higher percentage of women in the group who had coronary insufficiency. No patients in this series have had late RCA ostial occlusion.

	Comment

Top Abstract Introduction Material and Methods Results Comment Discussion References

Coronary insufficiency is not unique to root replacement and can occur after any procedure involving the aortic valve [17]. However, root replacement, especially with porcine bioprostheses entails specific risks. As discussed above, coronary anatomy in the usual setting is significantly different between human and porcine aortic roots. Our solution of rotating the valve 120 degrees does not appear to be completely protective of right coronary insufficiency. Other techniques we employ include liberal use of endarterectomy or bypass grafting for the severely atherosclerotic ostium, generous dissection of the aortic root, and extensive mobilization of the buttons. Perhaps the most important implication of this study is that one should make an early decision to perform RCA grafting in patients with poor right ventricle function, inferior left ventricular wall motion abnormalities or significant unexplained arrhythmias. While these conditions can also be caused by other factors such coronary air emboli, poor myocardial protection, or protamine/transfusion reactions, these etiologies should be uncommon and often transient. With prompt recognition of these concerns, we have demonstrated that acceptable operative mortality can be maintained.

Our data suggest that women are more prone than men to have the complication of coronary insufficiency after aortic root replacement. Reasons for this are unclear but do not appear to be related to valve sizing issues. Women have also been shown to have worse overall outcomes with CABG, and with AVR [18, 19], for mechanisms that have not been completely elucidated. It is known, however, that left ventricular adaptation to severe aortic stenosis is sex specific, with less compensatory increase in left ventricular mass and wall tension in females compared with males [20, 21]. However, a better indicator of hypertrophy may be the left ventricular mass/volume ratio, a ratio that is increased in women with aortic stenosis compared with men [21, 22]. Consequently, women with aortic stenosis tend to have worse diastolic function and exercise capacity [23]. Given that aortic stenosis is manifest differently in women, it is not surprising that operative outcomes and complications are different. Little information exists on the effects of the combination of sex and obesity on AVR outcomes, although Florath and colleagues [12] did show that women with higher body mass index who also underwent AVR with concomitant CABG had much higher mortality rates.

Limitations of the present study include its retrospective nature and low number of index events. That such a large number of patients was required to generate these few events attests to the safety of aortic root replacement with respect to coronary complications. An additional weakness of the study is that, with these data, we can not mechanistically explain why the identified risk factors are associated with RCA complications. Such answers may be found in further anatomic studies or additional retrospective studies from other centers with a large aortic root experience.

The literature is replete with conflicting data on the benefits of stentless AVR. Most randomized data have compared stentless subcoronary implants with stented AVRs [24], a comparison that may not demonstrate the full benefits of stentless technology. It has been established that total root replacement more accurately reproduces native aortic root anatomy, leads to better flow characteristics with larger effective orifice areas, results in less aortic insufficiency, and although not proven, most likely allows for implantation of a larger valve without any distortions of valve geometry. Unless operative mortality can remain universally low, however, a randomized comparison between stentless root replacement and stented AVR may also not demonstrate the potential advantages of routine application of stentless technology. It is hoped that studies such as the present one can help identify technical pitfalls, shorten learning curves, and lead to appropriate comparisons between valve substitutes.

	Discussion

Top Abstract Introduction Material and Methods Results Comment Discussion References

 
DR MARC MOON (St. Louis, MO): In your retrospective review you identified three factors you thought were related to coronary insufficiency, but really there were not enough patients in that subset to allow you to develop any sort of an algorithm or predict which patients were at risk for this complication. Therefore, it seems that a high index of suspicion in anybody with right ventricular dysfunction coming off-pump should lead to at least an initial attempt to rule out coronary insufficiency.

My first question is, how was your diagnosis differentiated from air embolism or inadequate myocardial protection, which both can cause the same symptomatology initially but don’t need bypass grafting, and when you opened the coronary, did you have a diminution in flow or absent flow that would verify your diagnosis?

Secondly, did right ventricular function improve immediately after you did the bypass or were there some patients that required support for an extended period of time postoperatively?

Finally, I would like to congratulate you on achieving excellent results with such a potentially fatal complication.

DR KINCAID: Thank you, Dr Moon. Regarding the first question, how to differentiate coronary insufficiency from other causes of right ventricular dysfunction such as air embolism or protamine reaction, in general we find these complications to be fairly unusual and transient. RCA insufficiency does not resolve with time. Regarding your second question about recovery after bypass grafting, we have found this to be surprisingly prompt upon revascularization of the right coronary artery.

DR JOSEPH S. COSELLI (Houston, TX): Nice presentation. Just one technical question. Before deciding the location for reattachment of the right coronary artery, do you fill and expand the heart to make that selection or do you do that with the heart collapsed?

One little comment. In more than 100 of these tissue roots in the last few years, about 80 of which have been the St. Jude Toronto, we rotated a different way. We bring the right coronary to the left main and take the root’s right coronary artery to the native left main, and we take the patient’s right coronary artery and attach it to the noncoronary sinus. It gives us flexibility as to where to attach the right coronary artery, and, as a consequence, we haven’t really identified the problem at the level you have.

DR KINCAID: Thank you for your comments. We have reimplanted the right coronary artery using both ways you described, including with the heart empty and with the heart full. We have not noticed that this makes a tremendous difference, because in either way we are able to line up the right coronary artery pretty much where we want it using the rotation that we described. One of the other tricks that we have noted over time is that we try to prevent overdistension of the right ventricle upon emerging from cardiopulmonary bypass, make sure that we limit the amount of filling that occurs, and limit the amount of central venous pressure that is obtained by the perfusionist and anesthesiologist.

And your point about rotation of the valve is well taken. We have decided to use the noncoronary sinus for reimplantation of the left coronary artery because we have always felt that is the most important artery, but given the fact that we have seen trouble with the right coronary artery, one could certainly rotate in the other direction, especially in a high risk patient.

DR ROSS M. UNGERLEIDER (Portland, OR): I noticed you had a lot of patients with coronary bypass grafting, especially in the noncoronary insufficiency group, which makes me wonder about how that contaminates what you are looking for, because as soon as you do a coronary bypass graft, you may take away the possibility of identifying coronary insufficiency from coronary ostial implantation. So the question is, have you looked at the data by taking all those coronary bypass patients out and just looking at your data with the noncoronary bypass patients to look for coronary insufficiency?

DR KINCAID: Yes, we have, and I will freely admit that there were certainly cases that we could have missed; there could have been patients who were doing poorly for reasons that we didn’t identify as being right coronary insufficiency. So this is really a descriptive study to try to identify some risk factors and also to mention that be cautious in this patient population.

DR MICHAEL MACK (Dallas, TX): You also mentioned that you are very liberal in the use of coronary ostial endarterectomy. Did you look at that in these patients and was that a risk factor for coronary insufficiency? I tend to avoid touching the calcium in the coronary ostia at all costs and tend to take a larger button, if possible. So was coronary endarterectomy associated with coronary insufficiency?

DR KINCAID: No, not at all, in none of the patients was coronary endarterectomy associated with insufficiency.

	References

Top Abstract Introduction Material and Methods Results Comment Discussion References

 

1. Sensky PR, Loubani M, Keal RP, Samani NJ, Sosnowski AW, Galinanes M. Does the type of prosthesis influence early left ventricular mass regression after aortic valve replacement?Assessment with magnetic resonance imaging. Am Heart J 2003;146:e13.[Medline]
2. Maselli D, Pizio R, Bruno LP, Di Bella I, De Gasperix C. Left ventricular mass reduction after aortic valve replacement: homografts, stentless and stented valves Ann Thorac Surg 1999;67:966-971.[Abstract/Free Full Text]
3. Walther T, Falk V, Langebartels G, et al. Prospectively randomized evaluation of stentless versus conventional biological aortic valves: impact on early regression of left ventricular hypertrophy Circulation 1999;100(19 Suppl):II6-II10.[Medline]
4. Jin XY, Zhang ZM, Gibson DG, Yacoub MH, Pepper JR. Effects of valve substitute on changes in left ventricular function and hypertrophy after aortic valve replacement Ann Thorac Surg 1996;62:683-690.[Abstract/Free Full Text]
5. Thomson HL, O’Brien MF, Almeida AA, Tesar PJ, Davison MB, Burstow DJ. Haemodynamics and left ventricular mass regression: a comparison of the stentless, stented and mechanical aortic valve replacement Eur J Cardiothorac Surg 1998;13:572-575.[Medline]
6. Yun KL, Jamieson WR, Khonsari S, Burr LH, Munro AI, Sintek CF. Prosthesis-patient mismatch: hemodynamic comparison of stented and stentless aortic valves Semin Thorac Cardiovasc Surg 1999;11:98-102.[Medline]
7. Luciani GB, Casali G, Auriemma S, Santini F, Mazzucco A. Survival after stentless and stented xenograft aortic valve replacement: a concurrent, controlled trial Ann Thorac Surg 2002;74:1443-1449.[Abstract/Free Full Text]
8. Casali G, Auriemma S, Santini F, Mazzucco A, Luciani GB. Survival after stentless and stented xenograft aortic valve replacement: a concurrent, case-match trial Ital Heart J 2004;5:282-289.[Medline]
9. Bach DS, Kon ND, Dumesnil JG, Sintek CF, Doty DB. Ten-year outcome after aortic valve replacement with the freestyle stentless bioprosthesis Ann Thorac Surg 2005;80:480-486.[Abstract/Free Full Text]
10. Kon ND, Riley RD, Adair SM, Kitzman DW, Cordell AR. Eight-year results of aortic root replacement with the freestyle stentless porcine aortic root bioprosthesis Ann Thorac Surg 2002;73:1817-1821.[Abstract/Free Full Text]
11. Westaby S, Katsumata T, Vaccari G. Aortic root replacement with coronary button re-implantation: low risk and predictable outcome Eur J Cardiothorac Surg 2000;17:259-265.[Abstract/Free Full Text]
12. Florath I, Rosendahl UP, Mortasawi A, et al. Current determinants of operative mortality in 1400 patients requiring aortic valve replacement Ann Thorac Surg 2003;76:75-83.[Abstract/Free Full Text]
13. Sonnad SS, Bach DS, Bolling SF, et al. The impact of new technology on a clinical practice Semin Thorac Cardiovasc Surg 1999;11:79-82.[Medline]
14. Luciani GB, Casali G, Mazzucco A. Risk factors for coronary complications after stentless aortic root replacement Semin Thorac Cardiovasc Surg 1999;11:126-132.[Medline]
15. Byrne JG, Karavas AN, Leacche M, et al. Impact of concomitant coronary artery bypass grafting on hospital survival after aortic root replacement Ann Thorac Surg 2005;79:511-516.[Abstract/Free Full Text]
16. Kon ND, Cordell AR, Adair SM, Dobbins JE, Kitzman DW. Aortic root replacement with the freestyle stentless porcine aortic root bioprosthesis Ann Thorac Surg 1999;67:1609-1615.[Abstract/Free Full Text]
17. Salerno TA, Bergsland J, Calafiore AM, Cordell AR, Kon ND, Bhayana JN. Acute right ventricular failure during aortic valvular operation due to mechanical problem in the right coronary artery Ann Thorac Surg 1996;61:706-707.[Abstract/Free Full Text]
18. Astor BC, Daczmeare RG, Hefflin B, Daley WR. Mortality after aortic valve replacement: results from a nationally representative database Ann Thorac Surg 2000;70:1939-1945.[Abstract/Free Full Text]
19. Maganti MD, Rao V, Borger MA, Ivanov J, David TE. Predictors of low cardiac output syndrome after isolated aortic valve surgery Circulation 2005;112(9 Suppl):I448-I452.[Medline]
20. Favero L, Giordan M, Tarantini G, et al. Gender differences in left ventricular function in patients with isolated aortic stenosis J Heart Valve Dis 2003;12:313-318.[Medline]
21. Bech-Hanssen O, Wallentin I, Houltz E, Beckman Suurkula M, Larsson S, Caidahl K. Gender differences in patients with severe aortic stenosis: impact on preoperative left ventricular geometry and function, as well as early postoperative morbidity and mortality Eur J Cardiothorac Surg 1999;15:24-30.[Abstract/Free Full Text]
22. Rohde LE, Zhi G, Aranki SF, Beckel NE, Lee RT, Reimold SC. Gender-associated differences in left ventricular geometry in patients with aortic valve disease and effect of distinct overload subsets Am J Cardiol 1997;80:475-480.[Medline]
23. Legget ME, Kuusisto J, Healy NL, Fujioka M, Schwaegler RG, Otto CM. Gender differences in left ventricular function at rest and with exercise in asymptomatic aortic stenosis Am Heart J 1996;131:94-100.[Medline]
24. Perez de Arenaza D, Lees B, Flather M. Randomized comparison of stentless versus stented valves for aortic stenosis: effects on left ventricular mass Circulation 2005;112:2696-2702.[Abstract/Free Full Text]

This article has been cited by other articles:

				O. E. Dapunt, J. Easo, P. P.F. Holzl, P. Murin, M. Sudkamp, M. Horst, and E. Natour Stentless full root bioprosthesis in surgery for complex aortic valve-ascending aortic disease: a single center experience of over 300 patients Eur. J. Cardiothorac. Surg., April 1, 2008; 33(4): 554 - 559. [Abstract] [Full Text] [PDF]

				E. H. Kincaid Reply Ann. Thorac. Surg., March 1, 2008; 85(3): 1144 - 1145. [Full Text] [PDF]

				A. D'Onofrio, S. Auriemma, P. Magagna, N. Abbiate, and A. Fabbri The Inclusion Technique Reduces Ischemia After Stentless Aortic Root Replacement Ann. Thorac. Surg., March 1, 2008; 85(3): 1143 - 1144. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Edward H. Kincaid John W. Hammon Neal D. Kon Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kincaid, E. H. Articles by Kon, N. D. Search for Related Content PubMed PubMed Citation Articles by Kincaid, E. H. Articles by Kon, N. D. Related Collections Valve disease