2. B.G. 62 aa. Fumatore attivo, IA, dislipidemia 2009 SCA Malattia a. circonflessa : PTCA con stent “metallico”(BMS) 27/12/2013 Ricovero programmato per TE positivo 75 W 28/12/2013 Coronarografia : restenosi subocclusiva intra-stent arteria circonflessa prox ; lesione 50% c destra ; IVA “irregolarità” Angioplastica PCI: impianto di DES (tecnica “stent in stent”) 30/12/2014 Dimissione. Asa 100, Clopidogrel 75, bisoprololo 2,5, atorvastatina 20

3. B.G. 62 aa. 05/01/2014 ore 14:00 dolore tipico a riposo ore 14:30 giunge in DEA (Pescia)con mezzi propri (!)

4. B.G. 62 aa. 05/01/2014 ore 15:30 entra in Sala di Emodinamica al San Jacopo Coronarografia per via radiale destra Diagnosi: Occlusione trombotica in ingresso stent: “Trombosi Subacuta di Stent” Trattamento : In DEA :eparina 5000 U ev In Emodinamica Carico orale Prasugrel Avanzato catetere Export: Reo-Pro (Abcximab) i.c. & Trombectomia manuale

5. Fine art of thrombus suction in STEMI ! February 29, 2012 by dr s venkatesan dr s venkatesan

6. B.G. 62 aa. 05/01/2014 ore 15:45 Trombectomia

7. B.G. 62 aa. 05/01/2014 ore 15:50 ripristinato flusso TIMI 3 2)Trattamento: PTCA palloncino, con distensione alta pressione dello stent

8. B.G. 62 aa. 05/01/2014 ore 17:00 in reparto Liv 1 S.I.

11. Stent Thrombosis (ARC Definite + Probable) 0 1 2 3 0306090180270360450 HR 0.48 P <0.0001 Prasugrel Clopidogrel 2.4 (142) NNT= 77 1.1 (68) Days Endpoint (%) Any Stent at Index PCI N= 12,844

12. R I V A L NSTE-ACS and STEMI (n=7021) Radial Access (n=3507) Femoral Access (n=3514) Primary Outcome: Death, MI, stroke or non-CABG-related Major Bleeding at 30 days Randomization RIVAL Study Design Key Inclusion: Intact dual circulation of hand required Interventionalist experienced with both (minimum 50 radial procedures in last year) Jolly SS et al. Am Heart J. 2011;161:254-60. Blinded Adjudication of Outcomes

13. R I V A L Site of Non-CABG Major Bleeds (RIVAL definition) * Sites of Non Access site Bleed: Gastrointestinal (most common site), ICH, Pericardial Tamponade and Other

14. 0.251.004.00 16.00 Radial better Femoral better Hazard Ratio(95% CI) High Medium Low High Medium Low High Medium Low High Medium Low High Medium Low 0.021 0.013 0.538 0.019 0.003 Interaction p-value HR (95% CI) Primary Outcome Death, MI or stroke Non CABG Major Bleed Major Vascular Complications Access site Cross-over Results stratified by High*, Medium* and Low* Volume Radial Centres R I V A L No significant interaction by Femoral PCI center volume Tertiles of Radial PCI Centre Volume/yr *High (>146 radial PCI/year/ median operator at centre), Medium (61-146), Low (≤60)

15. Impact of Therapies on Outcomes Bleeding Ischemic events: MI/CKMB↑ Stent Thrombosis

16. Bleeding and Mortality Major Bleeding TransfusionHypotension IschemiaStent ThrombosisInflammation Mortality Cessation of ASA/Clop Bhatt DL. In Braunwald EB, Harrison’s Online. 2005.

17. HORIZONS: 1-Year All-Cause Mortality Number at risk Bivalirudin alone Heparin+GPIIb/IIIa 18001705168416691520 18021678166316461486 Mortality (%) 0 1 2 3 4 5 Time in Months 0123456789101112 Bivalirudin alone (n=1800) Heparin + GPIIb/IIIa (n=1802) 4.8% 3.4% HR [95%CI] = 0.69 [0.50, 0.97] P=0.029 3.1% 2.1% Δ = 1.0% P=0.049 Δ = 1.4% Mehran R et al. Lancet 2009:on-line

18. HORIZONS: 30 Day Adverse Events *Not related to CABG ** Plat cnt <100,000 cells/mm 3 P<0.001 P = 0.90 Stone GW et al. NEJM 2008;358:2218-30

21. 1:1 1:1 NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker Trans-Femoral Access Heparin ±GPI Bivalirudin Mono-Tx Stop Infusion Prolong≥ 6 hs infusion 1:1 Trans-Radial Access Is TRI superior to TFI ? Is Bivalirudin superior to UFH ? Should Bivalirudin be prolonged after PCI ? MATRIX Trial NCT01433627 http://www.cardiostudy.it/matrix

22. paziente procedura farmacologia Rischio ischemico vs Rischio emorragico Trattamento delle SCA Accesso Trombectomia Stenting IABP Nuovi devices ASA +Clopidogrel ASA + nuovi bloccanti 2Py12 Uso selettivo dei GP2b3a Eparina vs Bivaluridina MATRIX Trial

24. B.F. 76 aa Familiarità per CI, IA, DM tipo 2, dislipidemia 25/10/2013 : dolore toracico tipico insorto a riposo FMC (118) ad un ora circa dall’esordio. Diagnosi ecg di IM anteriore (ST sopra V2-V5) “door to balloon (D2B)” time di 75 min Coronarografia : stenosi “significativa” TC, occlusione trombotica di IVA, stenosi critica 75% “ulcerata” di C.dx prossimale, arteria CX indenne

25. B.F. coronarografia sinistra Occlusione IVA Stenosi TC

26. B.F.Angioplastica primaria tramite trombectomia ed impianto di stent (DES) IVA

27. B.F….Ad un mese ( 11/12/2013) controllo con “IVUS” su TC ….. Stenosi TC Stent di IVA IVUS : intra vascular ultra sound

28. ….Ad un mese (13/12/2013) controllo con “IVUS” su TC…. Stenosi TC Stent di IVA IVUS : intra vascular ultra sound

29. ….Ad un mese controllo con “IVUS” su TC : MLA 4,2 mm2 Stenosi TC Stent di IVA IVUS : intra vascular ultra sound Area luminale minima 4,2 mm2 Valori cut off per TC 6,0 mm2

30. Stent su TC Stent su IVA B.F. (14/12/2013) PCI di TC mediante impianto di stent su TC-IVA

31. Stent su TC Stent su IVA B.F. (13/12/2013) PCI di TC mediante impianto di stent su TC-IVA 25/10/2013

32. Stent su C destra PCI di c destra con impianto di stent DES 1° tratto

33. Stent C. destra Ottimizzazione tecnica impianto “Clear Stent”

34. PROVE-IT TIMI-22 4,162 Randomized Pts with ACS 16% RR  P = 0.005 Pravastatin 40 mg/d Atorvastatin 80 mg/d 26.3% 22.4% Death, MI, UA requiring hosp, revasc >30d, or stroke (%) Cannon CP et al. NEJM 2004;350:1495-1504 How many events were attributable to: 1) Restenosis, stent thrombosis, etc. vs. 2) Significant disease left behind, vs. 3) VP with rapid lesion progression? ACS median 7d PCI 69%

35. We therefore performed a prospective, multicenter natural history study using 3 vessel multimodality intracoronary imaging to quantify the clinical event rate due to atherosclerotic progression and to identify those lesions which place pts at risk for unexpected adverse cardiovascular eventsWe therefore performed a prospective, multicenter natural history study using 3 vessel multimodality intracoronary imaging to quantify the clinical event rate due to atherosclerotic progression and to identify those lesions which place pts at risk for unexpected adverse cardiovascular events The PROSPECT Trial Background

36. 700 pts with ACS UA (with ECGΔ) or NSTEMI or STEMI >24º undergoing PCI of 1 or 2 major coronary arteries at up to 40 sites in the U.S. and Europe at up to 40 sites in the U.S. and Europe PCI of culprit lesion(s) Successful and uncomplicated Formally enrolled Metabolic S. Waist circumWaist circum Fast lipidsFast lipids Fast gluFast glu HgbA1CHgbA1C Fast insulinFast insulin CreatinineCreatinineBiomarkers Hs CRPHs CRP IL-6IL-6 sCD40LsCD40L MPOMPO TNFαTNFα MMP9MMP9 Lp-PLA2Lp-PLA2 othersothers PI: Gregg W. Stone Sponsor: Abbott Vascular; Partner: Volcano The PROSPECT Trial

37. 3-vessel imaging post PCI Culprit artery, followed by non-culprit arteries Angiography (QCA of entire coronary tree) IVUS Virtual histology Palpography (n=~350) Repeat imaging in pts with events Meds rec Aspirin Plavix 1yr Statin Repeat biomarkers @ 30 days, 6 months Proximal 6-8 cm of each coronary artery MSCTSubstudyN=50-100 F/U: 1 mo, 6 mo, 1 yr, 2 yr, ±3-5 yrs F/U: 1 mo, 6 mo, 1 yr, 2 yr, ±3-5 yrs The PROSPECT Trial

38. Lesions are classified into 5 main types 1. Fibrotic 2. Fibrocalcific 3. Pathological intimal thickening (PIT) 4. Thick cap fibroatheroma (ThCFA) 5. VH-thin cap fibroatheroma (VH-TCFA) (presumed high risk) PROSPECT: Methodology Virtual histology lesion classification

39. Index 2/13/06 Event 2/6/07 QCA PLCX DS 28.6% QCA PLCX DS 71.3% PROSPECT 82910-012: 52 yo♂ 2/13/06: NSTEMI, PCI of MLAD 2/6/07 (51 weeks later): NSTEMI attributed to LCX

40. 38 1. ThCFA * OM 5.3 mm 2 Lesion * 1 prox PROSPECT 82910-012: Index 2/13/06 Baseline PLCX QCA: RVD 2.82 mm, DS 28.6%, length 6.8 mm IVUS: MLA 5.3 mm 2 VH: ThCFA

41. PROSPECT: MACE MACE (%) Time in Years 0123 All Culprit lesion (CL) related Non culprit lesion (NCL) related Indeterminate 0 5 10 15 20 25 Number at risk ALL697 557 557506 480 480 CL related 697 590 590543 518 518 NCL related 697 595 595553 521 521 Indeterminate697 634 634604 583 583 12.9% 20.4% 11.6% 2.7%

42. PROSPECT: Multivariable Correlates of Non Culprit Lesion Related Events Independent predictors of lesion level events by logistic regression analysis Variables entered into the model: Minimal luminal area (MLA); plaque burden at the MLA (PB MLA ); external elastic membrane at the MLA (EEM MLA ) <median; lesion length ≥ median (mm); VH-TCFA. VariableOR [95% CI] P value PB MLA ≥70%<0.0001 PB MLA ≥70%4.99 [2.54, 9.79] <0.0001 VH-TCFA 0.0002 VH-TCFA 3.00 [1.68, 5.37]0.0002 MLA ≤4.0 mm 2 0.007 MLA ≤4.0 mm 2 2.77 [1.32, 5.81]0.007 Lesion length ≥11.6 mm]0.07 Lesion length ≥11.6 mm1.97 [0.94, 4.16]0.07 EEM MLA <14.3 mm 2 ]0.49 EEM MLA <14.3 mm 2 1.30 [0.62, 2.75]0.49

43. I LIMITI DELLA CORONAROGRAFIA NELLO STUDIO DELL’ATS CORONARICA (MALATTIA DI PARETE)

44. IVUS=intravascular ultrasound AngiogramIVUS Little evidence of disease Atheroma No evidence of disease The IVUS technique can detect angiographically ‘silent’ atheroma NEW Reproduced from Circulation 2001;103:604–616, with permission from Lippincott Williams & Wilkins. RIMODELL.POSIT.