TRATTAMENTO in RETE INTEROSPEDALIERA di un INFARTO MIOCARDICO ACUTO ST ELEVATO (Dalle Linee Guida alla Realtà Clinica) Nazario Carrabba Cardiologia 1 - Dipartimento del Cuore e dei Vasi, Azienda Ospedaliera - Universitaria di Careggi, Firenze Firenze, 15 Marzo 2008 EDUCATORIO del FULIGNO “Difendiamo il cuore” Campagna Educazionale Regionale ANMCO Toscana

Primary PTCA vs Thrombolysis for AMI: Review of 23 Randomized Trials Primary PTCA vs Thrombolysis for AMI: Review of 23 Randomized Trials. Long- term Outcome % PTCA n= 3872 Pz p< 0.0001 Thrombolysis n= 3867 Pz p< 0.0001 p= 0.0019 p= 0.0053 p< 0.0001 Ormai è noto come la angioplastica primaria abbia mostrato la sua superiorità sulla fibrinolisi come confermato dalla celebre metaanalisi di 23 studi randomizzati. Death Death excluding Shock Non Fatal MI Recurrent Ischemia Death, Non Fatal MI or Stroke Keeley EC, Lancet 2003; 361: 13-20

The Transfer for Primary Angioplasty: The Evidences According to ESC guidelines (and AHA/ACC guidelines too) when primary angioplasty is available in a “timely fashion” and procedure can be performed by an “experienced” operator in a “large volume centre”, primary PCI should be considered the preferred reperfusion strategy However, which is the best modality of reperfusion treatment for patients admitted to community hospitals without invasive facilities is less clear

The Importance of Time to Transfer The time delay for transferring patients to PCI centers could reduce or even nullify the potential benefit of reperfusion Gersh, B. J. et al. JAMA 2005;293:979-986

ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction—Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction) Writing Committee Members: Elliott M. Antman, MD, FACC, FAHA, Chair; Daniel T. Anbe, MD, FACC, FAHA; Paul Wayne Armstrong, MD, FACC, FAHA; Eric R. Bates, MD, FACC, FAHA; Lee A. Green, MD, MPH; Mary Hand, MSPH, RN, FAHA; Judith S. Hochman, MD, FACC, FAHA; Harlan M. Krumholz, MD, FACC, FAHA; Frederick G. Kushner, MD, FACC, FAHA; Gervasio A. Lamas, MD, FACC; Charles J. Mullany, MB, MS, FACC; Joseph P. Ornato, MD, FACC, FAHA; David L. Pearle, MD, FACC, FAHA; Michael A. Sloan, MD, FACC; Sidney C. Smith, Jr, MD, FACC, FAHA                                                          Tuttavia, dal 1990, la commissione di esperti delle 2 principali associazioni di cardiologi americani ha fornito periodicamente alla comunità scientifica delle rasserenanti raccomandazioni che tenessero di conto i numerosi progressi realizzati nel campo della diagnosi e del trattamento dell’IMA. Nel luglio 2004 sono state aggiornate le linee guida compilate nel 1999. (Circulation. 2004;110:588-636.)

ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction Class I. If immediately available, primary PCI should be performed in patients with STEMI (including true posterior MI) or MI with new or presumably new LBBB who can undergo PCI of the infarct artery within 12 hours of symptom onset, if performed in a timely fashion (balloon inflation within 90 minutes of presentation) by persons skilled in the procedure (individuals who perform more than 75 PCI procedures per year). The procedure should be supported by experienced personnel in an appropriate laboratory environment (performs more than 200 PCI procedures per year, of which at least 36 are primary PCI for STEMI, and has cardiac surgery capability). (Level of Evidence: A)                                                          Per quanto riguarda le indicazioni all’angioplastica primaria, (Circulation. 2004;110:588-636.)

ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction Strict performance criteria must be mandated for primary PCI programs so that long door-to-balloon times and performance by low- volume or poor-outcome operators/laboratories do not occur. Interventional cardiologists and centers should strive for outcomes to include: (1) door-to-balloon times less than 90 minutes; (2) TIMI 2/3 flow rates obtained in more than 90% of patients; (3) emergency CABG rate less than 2%; Le linee guida americane oltre alla quantità si preoccupano anche della qualità delle procedure dei singoli centri. Vengono quindi elencati criteri minimi da raggiungere. Tali criteri includono: Un tempo intercorso tra la presentazione e la riperfusione inferiore a 90’ Un flusso epicardico TIMI 2-3 in almeno 90% dei pazienti. La necessità di intervento cardiochirurgico d’urgenza in meno del 2% Il realizzo effettivo della angioplastica in almeno l’85% dei pazienti Una mortalità intraospedaliera inferiore al 7% (4) actual performance of PCI in >85% of patients brought to the lab; (5) risk-adjusted in-hospital mortality rate less than 7% in patients without cardiogenic shock.

Caso clinico numero 1 Nazario Carrabba, MD

Caratteristiche Cliniche del Paziente Maschio, 59 anni Fattori di rischio cardiovascolare: Fumatore, Ipercolesterolemia, Diabete Riferisce da circa 5 ore dispnea e dolore toracico posteriore Killip class: 1 Nazario Carrabba, MD

Primo ECG eseguito

Iter Diagnostico-Terapeutico? Ricovero nell’UTIC più vicina per eseguire fibrinolisi 2. Fibrinolisi in ambulanza (pre-ospedaliera) 3. PCI facilitata (trombolitici/inibitori IIb/IIIa prima del trasferimento per PCI - 2 ambulanze -) 4. Trasferimento diretto in sala di emodinamica per una PCI (2-ambulanze)

Trasferimento per una PCI una scelta appropriata?

Coronaria destra

ECG post-angioplastica primaria

The Florence Reperfusion Experience Andando ad analizzare l’esperienza ormai decennale conseguita a Firenze…… Spontaneous organization with Spoke centers

FLORENCE DISTRICT REGISTRY Location of the Participating Hospitals AMI-Florence Florence District 2,205 Kmq 798.000 residents 33 municipalities Careggi Hospital: 2 PCI centers 5 community hospitals Distance range: 5-33 Km N Mugello H 33 km/20 miles Careggi 2 PCI centers OSMA 12 km/7 miles NSGD 7 km/4 miles * SMN 5 km/3 miles Historic area Urban area Figline H 33 km/20 miles Chianti area Mugello area

Use of Reperfusion Treatment: AMI-Florence Use of Reperfusion Treatment: March 1, 2000 to February 28, 2001 746 reperfusion treatment eligible patients (<12h) No reperfusion treatment n=274 (36.7 %) Reperfusion treatment n=472 (63.3 %) 91.5% with P- PCI (n°432 patients) 7.4% with thrombolysis (n°35 patients) 1.1% rescue PCI (n°5 patients) Buiatti E. Eur Heart J. 2003;24:1195-203

Underuse of Reperfusion Therapy in Registry Studies 60 % 50 40 MITRA-MIR 36.8 <12h 94-98 No Reperfusion FRENCH 34 <6h nov. 95 AMI-Florence 36.7 <12h 00-01 BLITZ 35 <6h oct. 01 30 GRACE <12h 99-01 30 NRMI-2 24 <6 94-96 20 10 Delay (h) Period

AMI-Florence Registry In-hospital and 6-month Mortality 30 P<.000 25 20 P<.000 % 15 14.9 24.4 10 9.1 5 5.7 In hospital 6 months Reperfusion therapy No reperfusion therapy

Factors Influencing the use of Reperfusion AMI-Florence Factors Influencing the use of Reperfusion by Multivariate Regression Analysis HR 95% CI 0.97 0.96 - 0.99 0.26 0.11 - 0.65 0.55 0.33 - 0.93 0.91 0.84 - 0.99 0.32 0.21 - 0.50 0.44 0.24 - 0.83 0.59 0.39 - 0.88 7.8 5.1 - 11.8 Age (years) Previous CHF Previous MI Time delay>6 h Non anterior MI Killip >II Non-office hours Hospitals with P-PCI facilities 0.5 1 3 6 9 Reduced probability Increased probability

Caso clinico numero 2 Nazario Carrabba, MD

Caratteristiche Cliniche del Paziente Donna, 62 anni Fattori di rischio cardiovascolare: Ipertensione arteriosa, ipercolesterolemia, Riferisce da >12 ore fastidio epigastrico, Killip class: 3 Nazario Carrabba, MD

Primo ECG eseguito

Iter Diagnostico-Terapeutico? Ricovero nell’UTIC più vicina per eseguire fibrinolisi 2. Fibrinolisi in ambulanza (pre-ospedaliera) 3. PCI facilitata (trombolitici/inibitori IIb/IIIa prima del trasferimento per PCI - 2 ambulanze -) 4. Trasferimento diretto in sala di emodinamica per una PCI (2-ambulanze)

Trasferimento per una PCI una scelta appropriata?

Coronaria Destra

Coronaria Sinistra

ECG post-angioplastica primaria

Study Population 746 Patients AMI-Florence Study Population 746 Patients Admitted to hospitals with PCI facilities n=351 (47%) Admitted to hospitals without PCI facilities n=395 (53%) On-site P-PCI n=286 (81.5%) Transf. for P-PCI n=146 (37%) Presented ESC-2006

Kaplan-Meier Survival Curves by Hospital of Admission AMI-Florence Kaplan-Meier Survival Curves by Hospital of Admission % 100 91.3% On-site P-PCI 89.7% Transf. P-PCI 75 50 25 Log – rank test p = 0.305 2 4 6 Time (months) Presented ESC-2006

Kaplan Meyer survival curves after 3 years: comparison between on-site and after transferal primary PCI. AMI-Florence log-rank test: p<0.20 Variables independently associated with the risk of death at 3 years. Variable HR1 95%CI p value Age in years (continuous variable) 1.07 1.05-1.10 <0.001 Killip class > 1 (reference: class 1) 3.20 1.94-5.26 Use of Glycoprotein IIb/IIIa inhibitors 0.57 0.35-0.93 0.024 Paper submitted

Angioplasty: Evidences Transfer for Primary Angioplasty: Evidences Metanalysis considering five randomized Trials (n=2909) (+ CAPTIM, n=3750) showed a benefit of transfer for primary PCI compared to on-site fibrinolysis in term of combined endpoint (death, reinfarction, stroke) Dalby, M. et al. Circulation 2003;108:1809-1814

Asymptomatic patients with STEMI and symptom onset > 12 h BRAVE-2 Trial: Asymptomatic patients with STEMI and symptom onset > 12 h % 13% Final Infarct size 8% Invasive strategy Conservative strategy Schömig, A. et al. JAMA 2005;293:2865-2872

Should patients with STEMI and symptom onset > 12 h be treated with PCI? Schömig, A. et al. JAMA 2005;293:2865-2872

Practical Messages The policy of transferring STEMI patients with symptom onset <12 h initially admitted to community hospitals to centres which offer primary PCI seem feasible and safe, with the “useful window for transfer of 90 min”. For patients with STEMI and symptom onset 12 h (8-31% of all patients with STEMI), the transfer from community hospitals to PCI centres could represent a “missed opportunity”. However, more trials are needed to confirm this policy.

CONCLUSIONE Indipendentemente dal tipo di “rete interospedaliera” che si viene a realizzare, deve essere perseguito l’obiettivo di garantire il trattamento riperfusivo più rapido ed efficace al “maggior numero possibile di pazienti”.

AHA Consensus Statement Recommendation to Develop Strategies to Increase the Number of ST-Segment–Elevation Myocardial Infarction Patients With Timely Access to Primary Percutaneous Coronary Intervention The American Heart Association’s Acute Myocardial Infarction (AMI) Advisory Working Group Alice K. Jacobs, MD, FAHA, Chair; Elliott M. Antman, MD, FAHA; Gray Ellrodt, MD; David P. Faxon, MD, FAHA; Tammy Gregory; George A. Mensah, MD, FAHA; Peter Moyer, MD; Joseph Ornato, MD, FAHA; Eric D. Peterson, MD, FAHA; Larry Sadwin; Sidney C. Smith, MD, FAHA (Circulation. 2006;113:2152-2163) AHA Policy Recommendations

Guiding Principles Patient-centered care as the No. 1 priority High-quality care that is safe, effective, and timely Stakeholder consensus on systems infrastructure Increased operational efficiencies Appropriate incentives for quality, such as "pay for performance," "pay for value," or "pay for quality" Measurable patient outcomes An evaluation mechanism to ensure quality-of-care measures reflect changes in evidence-based research, including consensus-based treatment guidelines A role for local community hospitals so as to avoid a negative impact that could eliminate critical access to local health care A reduction in disparities of healthcare delivery, such as those across economic, education, racial/ethnic, or geographic lines

Guiding Principles Patient-centered care as the No. 1 priority High-quality care that is safe, effective, and timely Stakeholder consensus on systems infrastructure Increased operational efficiencies Appropriate incentives for quality, such as "pay for performance," "pay for value," or "pay for quality" Measurable patient outcomes An evaluation mechanism to ensure quality-of-care measures reflect changes in evidence-based research, including consensus-based treatment guidelines A role for local community hospitals so as to avoid a negative impact that could eliminate critical access to local health care A reduction in disparities of healthcare delivery, such as those across economic, education, racial/ethnic, or geographic lines

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