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HEART   INSTITUTE
Prediction of restenosis after PCI with
            contemporary drug-eluting stents
                       DR. ASHOK SETH
        FRCP (LOND), FRCP (EDIN), FRCP (IREL), FACC, FSCAI, FCSI, DSc.

                                CHAIRMAN
                         CHIEF OF CARDIOLOGY
CHAIRMAN – CARDIOLOGY COUNCIL, FORTIS GROUP OF HOSPITALS
                    FORTIS ESCORTS HEART INSTITUTE

             PRESIDENT – CARDIOLOGICAL SOCIETY OF INDIA



HEART   INSTITUTE
Restenosis After BA and Stent
   • Most significant problem for years
   • DES have dramatically reduced instent
     restenosis.
   • Low rates of ISR in DES still a problem.




HEART   INSTITUTE
Classification of Restenosis
                      (Mehran et al. Circulation 1999;100:1872-8)




HEART   INSTITUTE
Incidence of DES ISR
        12%                             11-12%
        10%

        8%                                                    6-7%
        6%          5-6%

        4%

        2%

        0%
                Native Denovo      Real Life Patients   Real Life Patients
              Lesion 1st Gen DES     1st Gen DES          2nd Gen DES


HEART   INSTITUTE
Delayed Restenosis
        • Late ‘Catch Up’
             Modest increase in NIH beyond 1-year on IVUS
             study follow up.
           – Delayed healing response
           – Persistent biological reaction
           – Hypersensitivity reaction to durable polymer

             ‘Therefore longer term follow up’

HEART   INSTITUTE
Stent Thrombosis vs Restenosis
   • ISR Presents as effort angina while stent
     thrombosis usually presents MI.
   • TVF within 30-days is usually stent thrombosis
     while ISR is usually later.
   • DES has delayed the time frame of ISR
   • Both ISR and Stent thrombosis may co-exist.


HEART   INSTITUTE
Definitions and Classification of Restenosis and
                   Stent Thrombosis
          Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907




HEART   INSTITUTE
Possible Mechanisms of Restenosis After DES
          Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907




HEART   INSTITUTE
Biologic Factors
   • Drug Resistance
   • Hyper sensitivity
         – Allergy to Nickel / Molybdenum of 316 to stenosis
           steel.
         – RADAR STUDY (Research on Adverse Drug / Device
           Adverse Reports) - Drug Hypersensitivity for DES.



HEART   INSTITUTE
RADAR (Research on Adverse Drug Events
                 & Reports)
             (Nebeker JR et al. J Am Coll Cardiol 2006;47:175-181)


        •   5783      AE after DES
        •   261       Hypersensitivity Reaction
        •   17        DES cause of HS
        •   4         Died of stent thrombosis between
                      4-18 months


HEART   INSTITUTE
HEART   INSTITUTE
Mechanical Factors
              (Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907)

                              Stent Under expansion




HEART   INSTITUTE
Mechanical Factors
                (Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907)

                                                   Stent Fracture
   • Incidence: 2-8%
   • Rigid closed cell stents,
        overlapping stents, longer
        stents, vessel tortuousity,
        angulation and torsion




HEART   INSTITUTE
Technical Factors
        • ‘Geographical Miss’
        • Uncovered atherosclerotic plaque
               • Baro trauma outside stented segment




HEART   INSTITUTE
Technical Factors
   • Stent Gap
             • Gap between two overlapping stents
   • Bends and Curves




HEART   INSTITUTE
Predictors of ISR or TLR After DES Implantation
         Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907




HEART   INSTITUTE
Risk Scoring to Predict TLR in DES
           (Stolker et al. Circ Cardiovasc Interv. 2010;3:327-334)




HEART   INSTITUTE
Predictors of DES Restenosis
                    (Corbett et al. Circulation. 2006;114:II_688)

        • 2269 lesions  1283 patients (2003-2005)
        • Angio FU 70% DES ISR      : SES 16.9%
                                    : PES 16.8%




HEART   INSTITUTE
Morphologic Pattern of SES, PES, and BMS ISR
         Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907




HEART   INSTITUTE
Clinical and Angiographic Outcomes After Percutaneous
                          Treatment of DES ISR
         Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907




HEART   INSTITUTE
Morphological Pattern of Restenosis as a Predictor of Repeat
                  ISR after DES ISR Treatment
           (Dangas et al. JACC 2010; 56: 1897-907)
                    Repeat ISR     TLR
        60%                                      57%

        50%

        40%

        30%
                                                            23%
        20%         18%
                                 10%
        10%

        0%
                      Focal ISR                   Non Focal ISR
                                       DES ISR
HEART   INSTITUTE
Treatment of DES ISR
                    ‘Difficult Disease Process’
        • IVUS or other imaging essential to understand
          the underlying mechanism.
        • OPTIONS
           – Balloon angioplasty
           – DEB
           – DES     : Same DES
                     : Different DES
           – VBT
           – CABG


HEART   INSTITUTE
Algorithm for the Treatment of DES Restenosis
            Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907




HEART   INSTITUTE
Conclusion
  • Though DES has lowered the restenosis rates of PCI, the
    increased complexity of lesions being treated has resulted in
    DES ISR being an important problem.
  • The predictors of restenosis in DES era are similar to the BMS
    era, but DES ISR can occur later and tends to be more focal and
    this has a better prognosis than BMS ISR.
  • Diffuse DES ISR is a very ‘difficult animal’ as the pathophysiology
    and causative mechanism of DES ISR are in many cases unclear
    and hence treatment options are ‘hit and trial’.
  • Further studies new DES and Bioresorbable stents are on the
    way to overcome this important problem.


HEART   INSTITUTE

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Prediction of Restenosis After PCI with Contemporary Drug-Eluting Stents

  • 1. HEART INSTITUTE
  • 2. Prediction of restenosis after PCI with contemporary drug-eluting stents DR. ASHOK SETH FRCP (LOND), FRCP (EDIN), FRCP (IREL), FACC, FSCAI, FCSI, DSc. CHAIRMAN CHIEF OF CARDIOLOGY CHAIRMAN – CARDIOLOGY COUNCIL, FORTIS GROUP OF HOSPITALS FORTIS ESCORTS HEART INSTITUTE PRESIDENT – CARDIOLOGICAL SOCIETY OF INDIA HEART INSTITUTE
  • 3. Restenosis After BA and Stent • Most significant problem for years • DES have dramatically reduced instent restenosis. • Low rates of ISR in DES still a problem. HEART INSTITUTE
  • 4. Classification of Restenosis (Mehran et al. Circulation 1999;100:1872-8) HEART INSTITUTE
  • 5. Incidence of DES ISR 12% 11-12% 10% 8% 6-7% 6% 5-6% 4% 2% 0% Native Denovo Real Life Patients Real Life Patients Lesion 1st Gen DES 1st Gen DES 2nd Gen DES HEART INSTITUTE
  • 6. Delayed Restenosis • Late ‘Catch Up’ Modest increase in NIH beyond 1-year on IVUS study follow up. – Delayed healing response – Persistent biological reaction – Hypersensitivity reaction to durable polymer ‘Therefore longer term follow up’ HEART INSTITUTE
  • 7. Stent Thrombosis vs Restenosis • ISR Presents as effort angina while stent thrombosis usually presents MI. • TVF within 30-days is usually stent thrombosis while ISR is usually later. • DES has delayed the time frame of ISR • Both ISR and Stent thrombosis may co-exist. HEART INSTITUTE
  • 8. Definitions and Classification of Restenosis and Stent Thrombosis Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907 HEART INSTITUTE
  • 9. Possible Mechanisms of Restenosis After DES Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907 HEART INSTITUTE
  • 10. Biologic Factors • Drug Resistance • Hyper sensitivity – Allergy to Nickel / Molybdenum of 316 to stenosis steel. – RADAR STUDY (Research on Adverse Drug / Device Adverse Reports) - Drug Hypersensitivity for DES. HEART INSTITUTE
  • 11. RADAR (Research on Adverse Drug Events & Reports) (Nebeker JR et al. J Am Coll Cardiol 2006;47:175-181) • 5783 AE after DES • 261 Hypersensitivity Reaction • 17 DES cause of HS • 4 Died of stent thrombosis between 4-18 months HEART INSTITUTE
  • 12. HEART INSTITUTE
  • 13. Mechanical Factors (Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907) Stent Under expansion HEART INSTITUTE
  • 14. Mechanical Factors (Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907) Stent Fracture • Incidence: 2-8% • Rigid closed cell stents, overlapping stents, longer stents, vessel tortuousity, angulation and torsion HEART INSTITUTE
  • 15. Technical Factors • ‘Geographical Miss’ • Uncovered atherosclerotic plaque • Baro trauma outside stented segment HEART INSTITUTE
  • 16. Technical Factors • Stent Gap • Gap between two overlapping stents • Bends and Curves HEART INSTITUTE
  • 17. Predictors of ISR or TLR After DES Implantation Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907 HEART INSTITUTE
  • 18. Risk Scoring to Predict TLR in DES (Stolker et al. Circ Cardiovasc Interv. 2010;3:327-334) HEART INSTITUTE
  • 19. Predictors of DES Restenosis (Corbett et al. Circulation. 2006;114:II_688) • 2269 lesions 1283 patients (2003-2005) • Angio FU 70% DES ISR : SES 16.9% : PES 16.8% HEART INSTITUTE
  • 20. Morphologic Pattern of SES, PES, and BMS ISR Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907 HEART INSTITUTE
  • 21. Clinical and Angiographic Outcomes After Percutaneous Treatment of DES ISR Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907 HEART INSTITUTE
  • 22. Morphological Pattern of Restenosis as a Predictor of Repeat ISR after DES ISR Treatment (Dangas et al. JACC 2010; 56: 1897-907) Repeat ISR TLR 60% 57% 50% 40% 30% 23% 20% 18% 10% 10% 0% Focal ISR Non Focal ISR DES ISR HEART INSTITUTE
  • 23. Treatment of DES ISR ‘Difficult Disease Process’ • IVUS or other imaging essential to understand the underlying mechanism. • OPTIONS – Balloon angioplasty – DEB – DES : Same DES : Different DES – VBT – CABG HEART INSTITUTE
  • 24. Algorithm for the Treatment of DES Restenosis Dangas et al. J Am Coll Cardiol. 2010;56(23):1897-1907 HEART INSTITUTE
  • 25. Conclusion • Though DES has lowered the restenosis rates of PCI, the increased complexity of lesions being treated has resulted in DES ISR being an important problem. • The predictors of restenosis in DES era are similar to the BMS era, but DES ISR can occur later and tends to be more focal and this has a better prognosis than BMS ISR. • Diffuse DES ISR is a very ‘difficult animal’ as the pathophysiology and causative mechanism of DES ISR are in many cases unclear and hence treatment options are ‘hit and trial’. • Further studies new DES and Bioresorbable stents are on the way to overcome this important problem. HEART INSTITUTE