Will

Accelerated failure of biological valve replacements due to diabetes, atherosclerosis, metabolic syndrome, hypercholesterolemia and patient-prosthesis mismatch puts patients at risk.^1-5

Recently published studies describe a variety of conditions common in patients with heart valve disease that can cause early tissue valve failure.

Diabetes is a 3X higher risk factor for biological valve failure
In a twelve center study in Italy of 6184 bioprosthetic patients, 1731 (27.9%) exhibited type II diabetes mellitus (DM).1 1113 pairs of patients with and without diabetes were propensity matched and compared after a median follow-up of 7 years.

“Patients with type II DM showed higher 30-day mortality, longer intensive care unit stay, longer assisted ventilation time and higher incidence of early postoperative complications. . . . One-hundred-twenty-one patients (10.8%) in the type II DM group, and 43 (3.8%) patients in the no DM group had reoperation as a result of primary tissue valve failure.”¹

Metabolic syndrome accelerates bioprosthetic valve failure
Briand and associates of Quebec after finding that the presence of metabolic syndrome was a predictor of disease progression in patients with aortic valve stenosis, hypothesized that it would also influence bioprosthetic valve deterioration.² Thirty three per cent of their aortic patients exhibited metabolic syndrome—a grouping of inflammatory abnormalities associated with abdominal obesity and insulin resistance. Their findings:

• Progression of valve regurgitation was twice as high in the group with metabolic syndrome compared to those that did not have it, and
• Deterioration of hemodynamic function was higher in patients with metabolic syndrome.
• Young patients with high cholesterol are at risk for early valve failure

A study from Munich, Germany, showed that a cholesterol level greater than 240 mg/dL in patients less than 57 years old was associated with faster valve degeneration and failure prior to 10 years after implant.³ This study also showed that young women experienced early valve failure more frequently than younger men. Smoking and diabetes were also risk factors in younger valve patients.

A Harvard study found increasing serum cholesterol levels are associated with implanted bioprosthetic valve calcification and that patients who had their valves explanted exhibited higher cholesterol levels than a matched group of valve patients who did not have their valves explanted.⁴ These authors also found a link to younger age and increased calcification.

Patient-prosthesis mismatch and poor hemodynamics as risk factors
A study of patient-prosthesis mismatch5 in biological valve patients showed that those who were mismatched experienced stenotic valve failure more often than those who were not mismatched. 50% of 564 biological implants were mismatched in this study. These authors state:

“Because it is obvious that only patients prone to P-PtM develop stenosis-type SVD over time, there must be a link between disturbed hemodynamics and this kind of pathology.”⁵

With poor effective orifice areas and gradients typically displayed by biological valves in small sizes^7-12 it is probable that patient-prosthesis mismatch, i.e.,“disturbed hemodynamics” and early failure of the implanted valves would be more frequent. This would contribute to the increased mortality seen in several matched or randomized studies between biological and mechanical valve patients.^{6, 13-17}





With the common occurrence of these risk factors for bioprosthetic valve failure especially in younger patients needing replacement, shouldn’t these risks be factored into valve choice favoring the mechanical option in patients younger than 65?

References

1. Lorusso R, Gelsomino S, Lucá F, et al. Type II diabetes mellitus is associated with faster degeneration of bioprosthetic valve: Results from a propensity score-matched Italian multicenter study. Circulation 2011;on-line publication available at: http://circ.ahajournal.org/content/early/2011/12/27/CIRCUALTIONAHA.111.025064
2. Briand M, Pibarot P, Despres JP, et al. Metabolic syndrome is associated with faster degeneration of bioprosthetic valves. Circulation 2006;114:I-512-I-517
3. Nollert G, Miksch J, Kreuzer E, et al. Risk factors for atherosclerosis and the degeneration fo pericardial valves after aortic valve replacement. J Thorac Cardiovasc Surg 2003;126:965-68
4. Farivar RS, Cohn LH. Hypercholesterolemia is a risk factor for bioprosthetic valve calcification and explantation. J Thorac Cardiovasc Surg 2003;126:969-75
5. Flameng W, Herregods M, Vercalsteren M, et al. Prosthesis-patient mismatch predicts structural valve degeneration in bioprosthetic heart valves. Circulation 2010;121:2123-29
6. Weber A, Noureddine H, Englberger L, et al. Ten-year comparison of pericardial bioprostheses and mechanical aortic valve replacement in patients less than 60 years of age. The Society of Thoracic Surgeons 47th Annual Meeting Program Book, Abstract 47, page 182
7. Edwards Life Sciences Carpentier-Edwards Perimount Magna Pericardial Bioprosthesis. Instructions for Use. © 2003
8. Mitroflow Aortic Pericardial Heart Valve. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P060038. Approval date October 23, 2007
9. SJM Biocor® Valve and SJM Biocor® Supra Valve. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P040021. Approval date August 5, 2005
10. Medtronic Freestyle® Aortic Root Prosthesis. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P970031 Approval date November 26, 1997
11. Mosaic Heart Valve. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P990064. Approval date July 14, 2000
12. ATS 3f® Aortic Bioprosthesis, Model 1000. Instructions for Use
13. Brown ML, Schaff HV, Lahr BD, et al. Aortic valve replacement in patients aged 50 to 70 years: Improved outcome with mechanical versus biologic prostheses. J Thorac Cardiovasc Surg 2008;135:878-84
14. Daneshmand MA, Milano CA, Rankin JS, et al. Influence of patient age on procedural selection in mitral valve surgery. Ann Thorac Surg 2010;90:1479-86
15. Badhwar V. Ofenloch J, Rovin J, et al. Equivalency of closely monitored mechanical valves to bioprostheses overshadowed by early mortality benefit in younger patients. The Society of Thoracic Surgeons 47th Annual Meeting Program Book, Poster Abstract 12, page 359
16. Vicchio M, Della Corte A, De Santo LS, et al. Tissue versus mechanical prostheses: Quality of life in octogenarians. Ann Thorac Surg 2008;85:1290-95
17. de Vincentiis C, Kunkl AB, Trimarchi S, et al. Aortic valve replacement in octogenarians: Is biologic valve the unique solution? Ann Thorac Surg 2008;85:1296-302

On-X aortic and mitral valves are FDA approved.
CAUTION: Federal law restricts this device to sale by or on the order of a physician. Refer to the Instructions for Use that accompany each valve for indications, contraindications, warnings, precautions and possible complications. For further information, visit www.onxlti.com.

Headquarters and Manufacturing Facilities:
1300 East Anderson Lane, Building B Austin, Texas 78752 U.S.A. – Telephone: (512) 339-8000 – Facsimile: (512) 339-3636 – www.onxlti.com – onx@onxlti.com
010006 202 012612 © 2012 On-X Life Technologies, Inc.

AUSTIN, TX – January 24, 2012 – On-X^® Life Technologies, Inc. (On-X LTI) announced today that it is highlighting the interim results of the potentially game-changing PROACT Anticoagulation Trial, two clinical studies completed during the first 15 years of the On-X® Prosthetic Heart Valve implant experience and several recent studies that indicate patients survive longer with mechanical rather than tissue valve prosthesis. The reports will be available to surgeons in the On-X Life Technologies, Inc. booth 508 at the 48^th Annual Meeting of The Society of Thoracic Surgeons, taking place January 29-31, 2012, in Fort Lauderdale, Florida.

The preliminary report of PROACT (Prospective Randomized On-X Clinical Trial) trial data presented at the American College of Cardiology meeting in 2011 for the high risk aortic patient test and control groups showed that as hypothesized, patients in the test group with INRs between 1.5 and 2.0 are currently equal in composite thromboembolism and hemorrhage rates compared to the control group of patients. All patients received an On-X valve as a replacement for their aortic valve. High-risk aortic patients are those who have a higher potential for thrombotic or bleeding events. These were randomized into Test and Control groups for the trial. Both patient groups were maintained with standard anticoagulation therapy for the first three months after surgery and then randomized into their groups. The Test group was maintained with a daily dose of 81milligrams of baby aspirin plus warfarin to achieve an INR target of 1.5 to 2.0. The Control group continued with standard anticoagulation therapy throughout the trial.

The recently presented South African study provides a stunning example of the On-X valve’s ability to reduce complications despite adverse anticoagulation compliance. For example, with an approximately 50 percent noncompliant patient group in this study, the thrombosis rate remains 0.2 percent per patient-year comparing favorably to competitive valves with 2.0 percent per patient-year to 6.0 percent per patient-year thrombosis rates in this same patient population.¹

Several recent studies, which provide evidence of durability, reoperation and mortality benefits received by mechanical valve recipients in comparison with matched patient groups receiving biologic valves, will available to participants of the meeting. These data provide new and compelling evidence that mechanical valve patients with equal disease severity and age to those with tissue valves can expect a survival advantage and an equivalent combined morbid event rate compared to their matched biological valve recipients. 

“We are very pleased with the continuing record of clinical evidence demonstrating the benefit of the On-X valve’s unique design with many categories of patients in diverse geographic and clinical settings,” saidClyde Baker, On-X LTI’s president. “The results emphasize the ability of the On-X valve to tolerate an inconsistent INR level, to provide the lowest possible levels of clinical complications and to help heart valve replacement patients maintain an active life, without severe risk of reoperation at an advanced age.”

The On-X valve is the result of a breakthrough in medical grade carbon technology—On-X^® pure pyrolytic carbon. In addition to providing a more thromboresistant surface, the comparatively high strength of pure On-X Carbon^® enabled On-X LTI to make significant valve design changes that resulted in a prosthesis that acts more like a natural valve in its treatment of blood. It is well documented that the On-X valve does not produce the turbulence and blood damage commonly produced by other mechanical heart valve prostheses and, therefore, significantly reduces the potential for life-threatening blood clots.

About On-X LTI

On-X^® Life Technologies, Inc. (On-X LTI) develops heart valve replacements that significantly improve the quality of life of patients. Jack Bokros, Ph.D., and his associates founded On-X LTI in 1994 to further advance prosthetic heart valve technology by capitalizing on their new form of pyrolytic carbon. The company has FDA, CE and Japanese approval for sale of the On-X^® valve. On-X LTI also provides contract-manufacturing services utilizing its patented pyrolytic carbon to manufacturers of other medical products, including orthopedic joint and spine prostheses. Headquartered in Austin, Texas, On-X LTI is a privately held company. More information is located at www.onxlti.com.

1. Williams MA, Crause L, Van Riet S. A comparison of mechanical valve performance in a poorly anticoagulated community. J Card Surg 2004;19:410-14

# # #

On-X is a registered trademark of On-X Life Technologies, Inc. All other trademarks mentioned herein belong to their respective companies.

Media Contact:  Clyde Baker, On-X Life Technologies, Inc., 512-339-8000 ext. 269, cbaker@onxlti.com

 It was a very long surgery,(wife said I was in the OR for 13 hrs) and took 30 days in the hospital. The surgeon replaced my previous mechanical heart valve (other brand), rebuilt my aortic root, and made his own graft. This had to be done due to pannus which was causing my valve to not function properly.   A vascular surgeon addressed my dissection and aneurysm issues.  My carotid artery came into the aneurysm, so he had to do a bypass to move it to a more stable area. He then coiled off the aneurysm, and then inserted a stent with 22 cm of dacron tubing attached to it into my aorta to help support my dissected artery.  He calls this the “frozen elephant procedure”.   The stent is sewn in, and the tubing hangs down from it inside the aorta.

 I only got 10 yrs with my previous heart valve replacement.  I sure hope my On-X heart valve can do better.  I am hopeful that it does a better job protecting against pannus interference.

 Rob

 So, here I am 3+ years later, a survivor, and finally feeling like myself again. I never really cried or dealt with this whole process but every now and then I get a little emotional and I’m in awe of the surgery, the docs, the technology, the On-X heart valve. So, as odd as it may seem, being a part of the On-X Club does mean so much to me as I’m sure it does to everyone else.

–Erika

Several recent clinical trials provide evidence of superior durability, reoperation rates and mortality for mechanical valve recipients compared to biological valve recipients.^1-9

Matched study results favor mechanical valves
In an abstract presented earlier this year at the Society of Thoracic Surgery, Weber, et al., of Switzerland offered the following about aged-matched patients:
“In our cohort of patients less than 60 years of age, biological AVR is associated with reduced ten year survival compared to mechanical valve implantation. Despite similar valve-related event rates in both groups, better hemodynamic performance of mechanical valves determines outcomes.”¹

Brown, et al., of the Mayo Clinic in a retrospective matched study similarly noted:
“We observed improved survival of patients who received mechanical prostheses. There is insufficient evidence to recommend bioprosthetic valves in the aortic position for patients younger than 65 years . . .” ²

In a propensity matched study, Badhwar, et al., observed:
“Mechanical valves begin to confer mortality benefit over bioprostheses as early as 7.5 years postoperatively.”⁴

In a study of mitral valves, Daneshmand and associates found:
“However, after adjustment for differences in preoperative baseline characteristics, mitral repair still had the best predicted survival, followed by mechanical valve replacement . . , and tissue valves seemed inferior to both of the other options.”³

These differences are shown in Table 1 along with other similar findings.^1-9

Table 1. Mortality rates of tissue valves (BP) versus mechanical valves (MP)
*significant difference in age defined in study
BP = biological prosthesis, MP = mechanical prosthesis
CE = Carpentier Edwards, SJM = St. Jude Medical, ATS = Advancing the Standard (Medtronic)



Unexpected similarity in bleeding and thromboembolic rates
In a randomized eight-year study of middle-aged tissue and mechanical patients in Italy, Stassano, et al.,¹⁰ reported differences in valve failure and reoperation between the groups, but, as with Weber, et al.,¹ no other major valve-related events reached significance. Additionally, 21% of the tissue valve recipients in this study needed continued warfarin therapy after surgery.

Dramatic failure rates at ten to twelve years for tissue valves
The Stassano study results mirror a similar finding from the Cleveland Clinic1¹ showing that the peak time for structural valve deterioration in patients less than 50 years old is between ten and twelve years after implant. This is not the 20-year life touted by some tissue valve manufacturers even though it is often erroneously the rationale given for implant of tissue valves implants in younger and younger patients.

“Valve-in-valve” in younger patients not justified
Another misleading and unproven claim is the “valve-in-valve” theory of a transcatheter valve as a possibility of a second implant after a failed tissued valve. Because of reduced survival in patients less than 60 with biological valves, Weber, et al., concluded, “The later possibility of a transcatheter valve in valve intervention does not justify the indication for biological AVR in younger patients.”¹

Tissue valves produce complications equal to those of mechanical valves
Recent findings at the Mayo Clinic show unacceptable thrombosis rates for porcine tissue valve implants.¹² As found in the studies cited above, complication rates for tissue valves are commonly the same as those for mechanical valves. Pannus can cause failure of tissue valve implants as well (Figure 1).

Figure 1. Pannus ingrowth causes failure of explanted tissue valve¹³

Matched studies and FDA approval clinical trials show that the On-X Heart Valve offers the lowest mortality and morbidity rates for your patients.^1-9

References

1. Weber A, Noureddine H, Englberger L, et al. Ten-year comparison of pericardial bioprostheses and mechanical aortic valve replacement in patients less than 60 years of age. The Society of Thoracic Surgeons 47th Annual Meeting Program Book, Abstract 47, page 182
2. Brown ML, Schaff HV, Lahr BD, et al. Aortic valve replacement in patients aged 50 to 70 years: Improved outcome with mechanical versus biologic prostheses. J Thorac Cardiovasc Surg 2008;135:878-84
3. Daneshmand MA, Milano CA, Rankin JS, et al. Influence of patient age on procedural selection in mitral valve surgery. Ann Thorac Surg 2010;90:1479-86
4. Badhwar V. Ofenloch J, Rovin J, et al. Equivalency of closely monitored mechanical valves to bioprostheses overshadowed by early mortality benefit in younger patients. The Society of Thoracic Surgeons 47th Annual Meeting Program Book, Poster Abstract 12, page 359
5. Vicchio M, Della Corte A, De Santo LS, et al. Tissue versus mechanical prostheses: Quality of life in octogenarians. Ann Thorac Surg 2008;85:1290-95
6. de Vincentiis C, Kunkl AB, Trimarchi S, et al. Aortic valve replacement in octogenarians: Is biologic valve the unique solution? Ann Thorac Surg 2008;85:1296-302
7. On-X® Prosthetic Heart Valve. Summary of Safety and Effectiveness Data submitted to the United States Food and Drug Administration. PMA P000037. Approval date May 30, 2001 and October 11, 2002
8. Edwards Life Sciences Carpentier-Edwards Perimount Magna Pericardial Bioprosthesis. Instructions for Use. © 2003
9. Palatianos GM, Laczkovics AM, Simon P, et al. Multicentered European study on safety and effectiveness of the On-X Prosthetic Heart Valve: Intermediate follow-up. Ann Thorac Surg 2007;83:40-46
10. Stassano P, Di Tommaso L, Monaco M, et al. Aortic valve replacement: A prospective randomized evaluation of mechanical versus biological valves in patients ages 55 to 70 years. J Am Coll Cardiol 2009;54:1862–68
11. Smedira NG, Blackstone EH, Roselli EE, et al. Are allografts the biologic valve of choice for aortic valve replacement in nonelderly patients? Comparison of explantation for structural valve deterioration of allograft and pericardial prostheses. J Thorac Cardiovasc Surg 2006;131:558-64
12. Brown ML, Park SJ, Sundt TM, Schaff HV. Early thrombosis risk in patients with biologic valves in the aortic position. Article in press. © 2011 The American Association for Thoracic Surgery, Published by Elsevier Inc.
13. Photo courtesy of On-X Life Technologies, Inc., Austin, TX, USA 2011

On-X aortic and mitral valves are FDA approved.
CAUTION: Federal law restricts this device to sale by or on the order of a physician. Refer to the Instructions for Use that accompany each valve for indications, contraindications, warnings, precautions and possible complications. For further information, visit www.onxlti.com.

Headquarters and Manufacturing Facilities:
1300 East Anderson Lane, Building B Austin, Texas 78752 U.S.A. – Telephone: (512) 339-8000 – Facsimile: (512) 339-3636 – www.onxlti.com – onx@onxlti.com
010006 201 121611 © 2011 On-X Life Technologies, Inc.

I read all the “Clinical Updates” issued by the manufacturer and also watched a surgical video.

Knowing that the On-X valve is a most advanced product with improved design features, my concern about surgery was swept away. I was strongly convinced I would be more active postoperatively and underwent surgery in a positive frame of mind.

One month after surgery, I started exercising on the treadmill, together with walking and jogging, aimed to finish a full-length marathon at one year anniversary of my surgery. I had made a quick recovery and 10km running became my daily routine after two months following surgery.

I am now gradually increasing running distance every day.

I always feel “joie de vivre” when hearing the sound of my On-X.  I hope someday, I will be released from Warfarin intake.

I will enjoy my life as a lifelong runner, following up my first grandchild’s growth who was born in the same month as my surgery.

-Minoru from Japan

1.The PROACT study

2. On-X Carbon (big seller)

3. The fact that it was made with pure carbon

4. The fact that On-X company founder was the pioneer of this technology

5. Many patient testimonials that were already on the site.

In February, 2011 my cardiologist determined that yes, I needed a new valve and yes, I was eligible for surgery and would be looking at it in the next year. I asked her about the On-X valve and she told me that was the preferred choice of my surgeon. So that was the final selling point and I officially decided right then that I definitely wanted the On-X heart valve.  I still continued to research other valves , but the On-X heart valve always came out on top.

  
After a few more tests, it was determined that there was also a small aneurism in my descending aorta and my ascending aorta was also enlarged and would most likely be replaced. I asked my surgeon about the combined On-X aortic heart valve and aortic graft but this was just 2 weeks prior to surgery and he hadn’t heard about it yet nor would it be available to him just yet, so he had to do it the old fashioned way (sew the graft to the valve).
 
On August 17, 2011, the surgeon and his team replaced my 21mm Bjork-Shiley valve with a 23 mm On-X aortic heart valve and replaced my ascending aorta in a 6 hour surgery.  I was in the ICU for 24 hours and on my way home exactly 7 days post surgery. Recovery has been uneventful with my return to work 12 weeks post op.
 
The big benefits I have noticed so far are YES, the On-X heart valve is definitely quieter than the old Bjork-Shiley and my INR range is now lower–between 2 and 3 now where before it was 2.5 – 3.5.  I have not noticed too much on the physical side, as far as improvements go, but I have noticed a bit more energy and longevity  and I am still only 3 months post op so there is still lots of room for improvement!
 
My biggest disappointment with the surgery is that I really wanted and waited 25 years to have my old heart valve as a souvenir and they would not let me keep it.  It was against hospital policy !!!!!!

Thank you very much!
 
Trevor

I have had such a great experience with the On-X heart valve during this challenging time. I am so happy that my surgeon recommended the On-X valve for my aortic heart valve replacement. Not being from the medical community myself, I did some research and found out just how great this heart valve is! Everyone I speak to that has had heart valve replacement tells me how lucky I am to have received the very best on the market.

It has been almost 4 months since my surgery and I am feeling great. In fact, I never knew I could ever feel like this again! I am still going through physical therapy, but I can do anything I set my mind to these days thanks to my new valve. I am completely confident in its operation and function. It is so nice not to be afraid.

 Thanks once again, not only for the quality product and helpful service to my Doctor (who had to work hard to get the heart valve approved and On-X was there to assist and deliver!), but also for the care and concern you have expressed to me during the past few months. I know of no company that would go out of their way to make the patient feel more comfortable and well informed, and do it in a manner that felt like….well…family!

 God Bless you, and the On-X Heart Valve, for helping save my life. (That is NOT something you write truthfully very often, but in this case, it is a FACT)!!! –Dave