Testing Drug Eluting Paclitaxel Balloon Valvuloplasty in an Experimental Model of Aortic Stenosis

  • Konstantinos Spargias
  • Mariann Gyöngyösi
  • Rayyan Hemetsberger
  • Aniko Posa
  • Noemi Pavo
  • Imre J. Pavo
  • Kurt Huber
  • Zsolt Petrasi
  • Ors Petnehazy
  • Rembert Pogge von Strandmann
  • Jeffrey Park
  • Dietmar Glogar
  • Gerald Maurer
  • Nalini M. Rajamannan


Balloon aortic valvuloplasty (BAV) was introduced in 1986 as an alternative non- surgical therapeutic option in elderly and high-risk patients with aortic stenosis [1]. It generates small to moderate increase in the effective aortic valve area (AVA) and decline in the transvalvular pressure gradient (by average 50 %) which results in early symptomatic improvements in the majority of patients [2–5]. Nonetheless, clinical data demonstrates restenosis rates of the aortic valve occurring up to 83 % observed at 6 months and is almost universal within 1 year after the procedure [3, 6, 7]. Restenosis promptly revokes the improvement in symptoms and quality of life, which is so much valued especially in the elderly population with multiple comorbidities and limited life expectancy. The initial enthusiasm about BAV led to its more liberal use in high-risk patients but registry data indicated that it does not alter the natural history of aortic stenosis [8].


Aortic Valve Aortic Stenosis Aortic Valve Stenosis Transcatheter Aortic Valve Replacement Aortic Valve Disease 
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  1. 1.
    Cribier A, Savin T, Saoudi N, Rocha P, Berland J, Letac B. Percutaneous transluminal valvuloplasty of acquired aortic stenosis in elderly patients: an alternative to valve replacement. Lancet. 1986;11(1):63–7.CrossRefGoogle Scholar
  2. 2.
    McKay RG, Safian RD, Lock JE, et al. Assessment of left ventricular and aortic valve function after aortic balloon valvuloplasty in adult patients with critical aortic stenosis. Circulation. 1987;75:192–203.PubMedCrossRefGoogle Scholar
  3. 3.
    Harrison JK, Davidson CJ, Leithe ME, Kisslo KB, Skelton TN, Bashore TM. Serial left ventricular performance evaluated by cardiac catheterization before, immediately after and at 6 months after balloon aortic valvuloplasty. J Am Coll Cardiol. 1990;16:1351–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Dorros G, Lewin RF, Stertzer SH, et al. Percutaneous transluminal aortic valvuloplasty: the acute outcome and follow-up of 149 patients who underwent the double balloon technique. Eur Heart J. 1990;11:429–40.PubMedGoogle Scholar
  5. 5.
    NHLBI Balloon Valvuloplasty Registry Participants. Percutaneous balloon aortic valvuloplasty. Acute and 30-day follow-up results from the NHLBI balloon valvuloplasty registry. Circulation. 1991;84:2383–97.Google Scholar
  6. 6.
    Otto CM, Mickel MC, Kennedy JW, et al. Three-year outcome after balloon aortic valvuloplasty: insights into prognosis of valvular aortic stenosis. Circulation. 1994;89:642–50.PubMedCrossRefGoogle Scholar
  7. 7.
    Tuzcu EM. Clinical outcomes from “Standard Therapy” in the P AR TNER inoperable patients. In: Paper presented at: Transcatheter cardiovascular therapeutics 2010, Washington, DC, 24 Sept 2010.Google Scholar
  8. 8.
    Lieberman EB, Bashore TM, Hermiller JB, et al. Balloon aortic valvuloplasty in adults: failure of procedure to improve longterm survival. J Am Coll Cardiol. 1995;26:1522–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Hara H, Pedersen WR, Ladich E, et al. Percutaneous balloon aortic valvuloplasty revisited: time for a renaissance? Circulation. 2007;115:334–8.CrossRefGoogle Scholar
  10. 10.
    Klein A, Lee K, Gera A, Ports TA, Michaels AD. Long-term mortality, cause of death, and temporal trends in complications after percutaneous aortic balloon valvuloplasty for calcific aortic stenosis. J Interv Cardiol. 2006;19:269–75.PubMedCrossRefGoogle Scholar
  11. 11.
    Shareghi S, Rasouli L, Shavelle DM, Burstein S, Matthews RV. Current results of balloon aortic valvuloplasty in high-risk patients. J Invasive Cardiol. 2007;19:1–5.PubMedGoogle Scholar
  12. 12.
    Pedersen WR, Klaassen PJ, Boisjolie CR, et al. Feasibility of transcatheter intervention for severe aortic stenosis in patients 90 years of age: aortic valvuloplasty revisited. Catheter Cardiovasc Interv. 2007;70:149–54.PubMedGoogle Scholar
  13. 13.
    Descoutures F, Himbert D, Lepage L, et al. Contemporary surgical or percutaneous management of severe aortic stenosis in the elderly. Eur Heart J. 2008;29:1410–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Leon M. Lessons learned from the PARTNER experience in the United States. In: Paper presented at: Transcatheter valve therapies 2010, Seattle, 6–9 June 2010.Google Scholar
  15. 15.
    Rajamannan NM, Subramaniam M, Springett M, et al. Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and bone matrix production in the rabbit aortic valve. Circulation. 2002;105:2660–5.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Feldman T, Glagov S, Carroll JD. Restenosis following successful balloon valvuloplasty: bone formation in aortic valve leaflets. Cathet Cardiovasc Diagn. 1993;29:1–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Van Den Brand M, Essed CE, DiMario C, et al. Histological changes in the aortic valve after balloon dilatation: evidence for a delayed healing process. Br Heart J. 1992;67:445–9.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Waller BF, Dorros G, Lewin RF, King JF, McKay C, van Tassel JW. Catheter balloon valvuloplasty of stenotic aortic valves. Part II: Balloon valvuloplasty during life subsequent tissue examination. Clin Cardiol. 1991;14:924–30.PubMedCrossRefGoogle Scholar
  19. 19.
    McKay RG, Safian RD, Lock JE, et al. Balloon dilatation of calcific aortic stenosis in elderly patients: postmortem, intraoperative, and percutaneous valvuloplasty studies. Circulation. 1986;74:119–25.PubMedCrossRefGoogle Scholar
  20. 20.
    Moses JW, Leon MB, Popma JJ, SIRIUS Investigators, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med. 2003;349:1315–23.PubMedCrossRefGoogle Scholar
  21. 21.
    Stone GW, Ellis SG, Cox DA, TAXUS-IV Investigators, et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med. 2004;350:221–31.PubMedCrossRefGoogle Scholar
  22. 22.
    Rajamannan NM, Subramaniam M, Caira F, Stock SR, Spelsberg TC. Atorvastatin inhibits hypercholesterolemia-induced calcification in the aortic valves via the Lrp5 receptor pathway. Circulation. 2005;112:I229–34.PubMedCentralPubMedGoogle Scholar
  23. 23.
    Rajamannan NM, Subramaniam M, Rickard D, et al. Human aortic valve calcification is associated with an osteoblast phenotype. Circulation. 2003;107:2181–4.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Rajamannan NM, Subramaniam M, Stock SR, et al. Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve. Heart. 2005;91:806–10.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Spargias K, Milewski K, Debinski M, et al. Drug delivery at the aortic valve tissues of healthy domestic pigs with a paclitaxel-eluting valvuloplasty balloon. J Interv Cardiol. 2009;22:291–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Drolet MC, Arsenault M, Couet J. Experimental aortic valve stenosis in rabbits. J Am Coll Cardiol. 2003;41:1211–7.PubMedCrossRefGoogle Scholar
  27. 27.
    Posa A, Hemetsberger R, Petnehazy O, et al. Attainment of local drug delivery with paclitaxel-eluting balloon in porcine coronary arteries. Coron Artery Dis. 2008;19:243–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Baumgartner H, Hung J, Bermejo J, EAE/ASE, et al. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr. 2009;10:1–25.PubMedCrossRefGoogle Scholar
  29. 29.
    Rajamannan NM, Nealis TB, Subramaniam M, et al. Calcified rheumatic valve neoangiogenesis is associated with vascular endothelial growth factor expression and osteoblast-like bone formation. Circulation. 2005;111:3296–301.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Rajamannan NM. Mechanisms of aortic valve calcification: the LDL-density-radius theory: a translation from cell signaling to physiology. Am J Physiol. 2010;298:H5–15.Google Scholar
  31. 31.
    Rajamannan NM, Edwards WD, Spelsberg TC. Hypercholesterolemic aortic-valve disease. N Engl J Med. 2003;349:717–8.PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Rajamannan NM, Gersh B, Bonow RO. Calcific aortic stenosis: from bench to the bedside-emerging clinical and cellular concepts. Heart. 2003;89:801–5.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Rajamannan NM. Calcific aortic stenosis: lessons learned from experimental and clinical studies. Arterioscler Thromb Vasc Biol. 2009;29:162–8.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Ong AT, Serruys PW. Technology Insight: an overview of research in drug-eluting stents. Nat Clin Pract Cardiovasc Med. 2005;2:647–58.PubMedCrossRefGoogle Scholar
  35. 35.
    Herdeg C, Oberhoff M, Baumbach A, et al. Local paclitaxel delivery for the prevention of restenosis: biological effects and efficacy in vivo. J Am Coll Cardiol. 2000;35:1969–76.PubMedCrossRefGoogle Scholar
  36. 36.
    Sheikh SH, Mulchandani A. Continuous-flow fluoroimmunosensor for paclitaxel measurement. Biosens Bioelectron. 2001;16:647–52.PubMedCrossRefGoogle Scholar
  37. 37.
    Axel DI, Kunert W, Goggelmann C, et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation. 1997;96:636–45.PubMedCrossRefGoogle Scholar
  38. 38.
    Mullins DW, Koci MD, Burger CJ, Elgert KD. Interleukin-12 overcomes paclitaxel- mediated suppression of T -cell proliferation. Immunopharmacol Immunotoxicol. 1998;20:473–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Konstantinos Spargias
    • 1
  • Mariann Gyöngyösi
    • 2
  • Rayyan Hemetsberger
    • 2
  • Aniko Posa
    • 2
  • Noemi Pavo
    • 2
  • Imre J. Pavo
    • 2
  • Kurt Huber
    • 3
  • Zsolt Petrasi
    • 4
  • Ors Petnehazy
    • 4
  • Rembert Pogge von Strandmann
    • 5
  • Jeffrey Park
    • 6
  • Dietmar Glogar
    • 2
  • Gerald Maurer
    • 2
  • Nalini M. Rajamannan
    • 6
  1. 1.Department of Transcatheter Heart ValvesHygeia HospitalAthensGreece
  2. 2.Department of CardiologyMedical University of ViennaViennaAustria
  3. 3.3rd Department MedicineWilhelminen HospitalViennaAustria
  4. 4.Diagnostic Imaging and Radiation OncologyUniversity of KaposvarKaposvar, SomogyHungary
  5. 5.Department of ClinicalEurocor GmbHBonnGermany
  6. 6.Division of Biochemistry and Molecular BiologyMayo ClinicRochesterUSA

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