“Dal territorio alla preservazione della funzione ventricolare” Versilia 7-8 ottobre 2011 Sergio Berti Fondazione CNR-Reg. Toscana G. Monasterio Ospedale del Cuore, Massa 1

Importance of Prompt Treatment Prompt treatment increases the likelihood of survival for patients with myocardial infarction with ST-segment elevation (Berger et al., 1999; Cannon et al., 2000, McNamara et al., 2006). McNamara et al., JACC, 2006

Mortality and Doorn to Balloon Time Ting HH, et al. Circulation 2007;116:729-736

Beyond a D2B of 90 minutes…. Every 15-min delay adds mortality (Nallamothu 2007 NEJM 357:1631)‏

2008 ESC STEMI GUIDELINES Key Messages remain unchanged: Early diagnosis Reperfusion therapy as soon as possible Optimal secondary prevention 2008 ESC GUIDELINES

Ritardo Evitabile (tempo decisionale)‏ Ritardo extraospedaliero sanitario Ritardo extraospedaliero NON sanitario Ritardo intraospedaliero Campagne educazionali Percorsi extraospedalieri Percorsi intraospedalieri

Fonti di possibili ritardi tra comparsa sintomi e inizio terapia riperfusiva Problema Soluzione Ritardo del paziente: Tempo tra la comparsa sintomi e chiamata 118 Educazione del paziente Ritardo nel trasporto Strategia organizzativa 118 Da qui la necessità di realizzare una strategia organizzativa interospedaliera e territoriale che potesse coinvolgere ed inglobare tutti i tempi (dall’inizio del dolore del pz ed al tentativo di riapertura del vaso)- Ritardo inizio del trattamento Strategia organizzativa Inter-intraospedaliera 8

Strategia concordata:

Modello di Rete per l’emergenza coronarica Obiettivi Favorire una diagnosi precoce, un trasporto rapido ed un ottimale trattamento riperfusivo a tutti i pazienti 10

La “realtà” italiana: la “Rete” Documento di consenso La rete interospedaliera per l’emergenza coronarica FIC SICI SIMEU SIS 118 IHJ Nov. 2005 Vol.6/Suppl.6 11

365 Hospitals E. H. Bradley, N Engl J. Med 13, 2006;335

28 Key hospital strategies 32 Items 28 Key hospital strategies Six strategies associated with a faster door to balloon time

Door to Balloon Times: Achieving 90 Minutes and Less W. Douglas Weaver, MD President-Elect ACC November 2007 Una recente iniziativa americana chiamata DtB : an alliance for quality organizzata dall’ACC e AHA ha l’obiettivo di proporre alcune strategie operative sul territorio nazionale con lo scopo di raggiungere un DtB in almeno il 75% dei pz con STEMI 14

Strategies that Reduce Treatment Delays 1. ED physician activates the cath lab 2. Single call activates the cath lab 3. Cath lab team ready in 20-30 minutes 4. Prompt data feedback for case review Pre-hospital ECG to activate the cath lab while patient is en route Having attending cardiologist always on site Core of the D2B campaign. The basic strategies are just the beginning… As more evidence is generated, the D2B Alliance may add new strategies. Lots of processes being uses successfully that are not on this list. 15

D2B Alliance Goal Goal: To achieve a door-to-balloon time of ≤ 90 minutes for at least 75% of non-transfer primary PCI patients with STEMI Here is our goal. Here is the essence of the goal: Excludes transfer patients Only STEMI patients Only Primary PCI hospitals 75% of all those folks are 90 minutes or less.

D2B Alliance Participants Over 900 hospitals currently participating Representing 45 states and 8 countries 15.6 West 12.7 Southwest 27.5 Midwest 26.8 Southeast 16.2 Northeast % Region 17

ottimizzando tempi e modalità di soccorso 2008-2010 CAMPAGNA RITARDO EVITABILE RITARDO EVITABILE La Campagna presentata in tutte le Regioni ha proposto una semplice scheda di automisurazione dei dati Disponibili i dati dei Centri che hanno accettato di centralizzare i dati Salvare il miocardio dei Pazienti con SCA ottimizzando tempi e modalità di soccorso e di intervento medico SVILUPPANDO UN DISEGNO STRATEGICO DI CONTINUITA’ In tutte le Regioni la Campagna ha coinvolto Cardiologi, 118, Medicina Urgenza, Assessorati e Agenzie COORDINAMENTO F. Chiarella L. Oltrona Visconti A. Di Chiara

Obiettivo: Ottenere nel 75% dei pazienti: D2B entro 90 minuti Un intervento mirato ai singoli Ospedali ed alla rete. Obiettivo: Ottenere nel 75% dei pazienti: D2B entro 90 minuti D2N entro 30 minuti

Cardiologie aderenti alla raccolta dati n = 78 Milano Centri N. 4 - Treviglio – Lecco – Tradate - Pavia – Saronno - Varese - Lodi - Gravendona – Sondrio - Desenzano - Gallarate Bolzano – Merano Rovereto - Trento Pordenone - Trieste – Udine – Gorizia -Tolmezzo - San Daniele - Palmanova Latisana - San Vito al Tagliamento Bolzano Trento FVG Lombardia Veneto Treviso -Castelfranco Veneto - Mestre Ivrea - Novara Torino Centri N.2 Moncalieri Valle d'Aosta Piemonte Emilia Romagna Rimini - Sassuolo Liguria Ascoli Piceno - Pesaro Genova Centri N. 2 Pietra Ligure - Sanremo Marche Toscana Città di Castello - Foligno Gubbio - Perugia - Terni Empoli - Grosseto – Lucca – Massa - Piombino - Pisa Umbria Avezzano - Pescara Teramo - Vasto Lazio Abruzzo Roma Centri N.6 AlbanoTerme Rieti Andria – Bari - Gallipoli – Scorrano - Terlizzi Puglia Salerno Vallo della Lucania Nocera Inferiore Pozzuoli Campania Basilicata Tutte le Regioni hanno partecipato Sardegna Cagliari – Olbia Carbonia Lagonegro - Matera Policoro - Potenza Calabria Catanzaro - Cosenza Crotone - Vibo Valentia Sicilia Siracusa – Ragusa Cardiologie aderenti alla raccolta dati n = 78

Zona Apuane-Versilia 21

Zona Lunigiana 55 Km 58 Km 74 Km 22

Triage diretto Paziente con IMA Unità 118 - PS I° LIV TELECONSULTO FTGM Ospedale del Cuore IMA ST Protocollo Terapeutico Concordato SALA DI EMODINAMICA ECG normale o ST PS - UTIC 23

La Trasmissione ECG HWS SERVER Hospital 1 Hospital 2 MobiMed System 24

25

Matrix Network STEMI 1227 Pazienti

Network STEMI “Zona Apuane-Versilia” D2B (1227 Pz) 107.5 n=166 107.7 n=220 109.7 n=219 99.7 n=238 p<0.0001 82.3 n=247 2006 2007 2008 2009 2010

% pazienti con DtB ≤ 90 min (1227 Pz) Network STEMI “Zona Apuane-Versilia” % pazienti con DtB ≤ 90 min (1227 Pz) 104 (72.3%) p<0.0001 89 (46.3%) 81 (40.0%) 80 (36.4%) 58 (34.9%) 2006 2007 2008 2009 2010

Network STEMI “Zona Apuane-Versilia” 1227 pts 72.3% EF% DtB (minutes)

Network STEMI “Zona Apuane-Versilia” 1227 pts

How Effective is the Hub? 31

Reperfusion Therapy: Primary PCI Recommendations Class LoE I A Preferred reperfusion treatment if performed by an experienced team as soon as possible after FMC

Physician Volume and Hospital Volume and Mortality during Primary PCI Srinivas VS J Am Coll Cardiol 2009: 53:574-9 33

Physician Volume and Hospital Volume and Mortality during Primary PCI Physicians High Volume Low Volume (N=92) (N= 174) Odds Ratio (95% CI) Mortality 3.25% 4.9% 0.66 (0.48-0.92)

Physician Volume and Hospital Volume and Mortality during Primary PCI Hospitals High Volume Low Volume (N=23) (N= 18) Odds Ratio (95% CI) Mortaliy 3.4% 5.4% 0.58 (0.38-0.88)

PCI for STEMI Less Safe, Effective When Performed Off-Hours Routine Hours p Device use Stent 76% 82.4% 0.04 IVUS 0.8% 4.6% 0.005 Thrombectomy 1.9% 6.3% 0.007 Periprocedural Clopidogrel 48.2% 58.2% 0.01 Major Dissections 10.3% 5.2% 0.2 Glaser R J Am Coll Cardiol Intv 2008;1:681-8 36

PCI for STEMI Less Safe, Effective When Performed Off-Hours Combined End Point: In HospitalDeath, MI, Target Vessel Revascularization: Off Hours: 16.2% p=0.002 Routine Hours 6.8% Glaser R J Am Coll Cardiol Intv 2008;1:681-8 37

Mechanical strategies to prevent distal embolization

Primary endpoint: Myocardial Blush Grade TAPAS Trial Primary endpoint: Myocardial Blush Grade P < 0.001 Patients (%) Thrombus aspiration Conventional PCI Svilaas T, et al N Engl J Med 2008;358:557 39

TAPAS: 1,071 pts with STEMI undergoing PCI randomized to thrombus aspiration vs control Vlaar P et al. Lancet 2008; 371:1915

Cardiac Magnetic Resonance Imaging Results Thrombus aspiration during Primary Percutaneous Coronary Intervention: myocardial reperfusion and infarct size The EXPIRA (Thrombectomy With Export Catheter in Infarct-Related Artery During Primary Percutaneous Coronary Intervention) Prospective, Randomized Trial Cardiac Magnetic Resonance Imaging Results G Sardella, MD, M Mancone, MD, C Bucciarelli-Ducci, MD et al; JACC Vol. 53, No. 4, 2009

Thrombus Aspiration Reduces Microvascular Obstruction After Primary Coronary Intervention A Myocardial Contrast Echocardiography Substudy of the REMEDIA Trial *p 0.05 vs. control patients †p 0.05 compared to 24 h In thrombus-aspiration patients, at each time point, ejection fraction was significantly better compared with control patients, and it further improved at 1 week and 6 months L Galiuto, MD, PHD, B Garramone, MD, F Burzotta, MD, PHD et al, JACC Vol. 48, No. 7, 2006

Illusion of reperfusion In 1993, at the peak of the thrombolytic era, Lincoff and Topol wrote a provocative editorial wondering whether reperfusion was just an illusion. At that time, they estimated that only “25% or less” of patients treated by thrombolysis had an optimal reperfusion. Lincoff AM, Topol EJ. Illusion of reperfusion. Does anyone achieve optimal reperfusion during acute myocardial infarction? Circulation 1993;88:1361–74. defined as a rapid, complete, and sustained coronary recanalization with adequate myocardial tissue perfusion.

The No-Reflow Phenomenon: Defining the Problem The no-reflow phenomenon is the inability to reperfuse a portion of the myocardium after re-establishment of patency of previously occluded epicardial coronary artery Despite the proven success of restoration of epicardial coronary blood flow in a reasonably timely fashion, reperfusion on the myocardial level is not accomplished in 50% of patients with STEMI. The common denominator of prevailing theories for this phenomenon is the development of myocardial microvascular dysfunction as a consequence of the primary epicardial event and/or perhaps of reperfusion per se Indeed, patients with no-reflow exhibit a higher prevalence of: 1) early post-infarction complications (arrhythmias, pericardial effusion, cardiac tamponade, early congestive heart failure); 2) left adverse ventricular remodelling; 3) late re-hospitalizations for heart failure; 4) mortality 44

The No-Reflow Phenomenon: Defining the Problem The no-reflow phenomenon is the inability to reperfuse a portion of the myocardium after re-establishment of patency of previously occluded epicardial coronary artery Despite the proven success of restoration of epicardial coronary blood flow in a reasonably timely fashion, reperfusion on the myocardial level is not accomplished in 50% of patients with STEMI. The common denominator of prevailing theories for this phenomenon is the development of myocardial microvascular dysfunction as a consequence of the primary epicardial event and/or perhaps of reperfusion per se Indeed, patients with no-reflow exhibit a higher prevalence of: 1) early post-infarction complications (arrhythmias, pericardial effusion, cardiac tamponade, early congestive heart failure); 2) left adverse ventricular remodelling; 3) late re-hospitalizations for heart failure; 4) mortality 45

Agents studied to reduce reperfusion injury Mechanism proposed Trial Fluosol Neutr.inhib., O2 delivery TAMI 9 Magnesium Membrane stabilisation ISIS4,MAGIC RheothRX O2 delivery CORE Trimetazidine H+, free radicals, neutr. EMIP-FR hSOD Prevent free radicals Flaherty Cylexin Inhib.p-selectin, neutr. CALYPSO Adenosine Neutr.inhib, vasodil, metab. AMISTAD I,II ANTI CD-18 Neutr.inhib. HALT, LIMIT Eniporide Na+/H+ exchange inhib. ESCAMI

Agents studied to reduce reperfusion injury Trial N° Primary endpoint Result TAMI 9 430 Infarct size, EF  (22 v.17%) ISIS4 58,050 35 d. mortality  (7.6 v. 7.2%) CORE pilot 114 Infarct size  (16 v.26%) CORE 2,607 Death, shock, reMI  (14 v. 26%) EMIP-FR 19,665 35 d.mortality  (12.2 v.12.3%) CALYPSO 153  (larger) AMISTAD I 236  (ant. 20 v.13%) AMISTAD II 2,118 30-d.death, CHF  (18 v. 16%) ISz+ HALT MI 420  (no effect) LIMIT MI 413 Patency, infarct size ESCAMI 1389

Ormoni tiroidei ed IMA: evidenze cliniche Wiersinga WM et al. Thyroid hormones in acute myocardial infarction. Clin Endocrinol 1981; 14: 367-74. Friberg L et al. Association between increased levels of reverse triiodothyronine and mortality after acute myocardial infarction. Am J Med. 2001; 111: 699-703. Friberg L et al. Rapid down-regulation of thyroid hormones in acute myocardial infarction: is it cardioprotective in patients with angina? Arch Intern Med. 2002; 162: 1388-94.

Tiride e Cuore Nei pazienti con STEMI la riduzione dei livelli di fT3 durante la degenza correla con un peggiore recupero funzionale delle aree infartuali, come ben evidenziato dallo scarso recupero in termini di WMSI alla dimissione

Recommended Logistics Pre-hospital triage/care: EMS unique telephone number tele-consultation Ambulance 12-ECG recorder/defibrillator staff able to provide basic and advanced life support

Recommended Logistics Pre-hospital triage/care: EMS unique telephone number tele-consultation Ambulance 12-ECG recorder/defibrillator staff able to provide basic and advanced life support Networks: implementation of a network of hospitals with different levels of technology connected by an efficient ambulance service using the same protocol Targets: < 10 min ECG transmission < 5 min tele-consultation < 120 min to first balloon inflation < 30 min start fibrinolytic therapy

Mille ragioni per vivere, Dom Helder Camara (Profeta del Terzo Mondo)

“Dal territorio alla preservazione della funzione ventricolare” Versilia 7-8 ottobre 2011 Sergio Berti Fondazione CNR-Reg. Toscana G. Monasterio Ospedale del Cuore, Massa 53