The Italian Network of Cardiac Care Units and the … Italian Network of. Cardiac Care Units and ....
Transcript of The Italian Network of Cardiac Care Units and the … Italian Network of. Cardiac Care Units and ....
Leonardo De Luca, M.D., Ph.D., F.A.C.C.
Department of Cardiovascular SciencesInterventional Cardiology UnitEuropean HospitalRome, [email protected]
Conflict of interest: none
The Italian Network ofCardiac Care Units and the STEMI System of Care
2010 Annual Chapter MeetingNemacolin Woodlands ResortFarmington, PA
Pittsburgh, PA. October 16th 2010
* Percentages refer to pts with complete data receiving reperfusion TxANC=Australia, New Zeland, CanadaAB=Argentina, Brazil
Reperfusion Therapy by Geographic Region*:Findings From the GRACE Registry
Eagle KA, et al. Lancet 2002;359:373
Single χ2 test, p<0.001 for each four-by-four comparison
%
Hospitalized STEMI Treatment in Europe**data from national registries or surveys
Widimsky P, et al. Eur Heart J 2010;31: 943
Countries abbreviations: CZ, Czech Republic; SLO, Slovenia; DE, Germany; CH, Switzerland; PL, Poland; HR, Croatia; SE, Sweden; HU, Hungary; BE, Belgium; IL, Israel; IT, Italy; FIN, Finland; AT, Austria; FR, France; SK, Slovakia; LAT, Latvia; UK, United Kingdom; BG, Bulgaria; PO, Portugal; SRB, Serbia; GR, Greece; TR, Turkey; RO, Romania
Improving Patient Care by Linking Evidence-Based Medicine and Evidence-Based Management
Two components
Advances in evidence-based medicine (EBM)
Knowledge of how to put this content into routine practice (EBMgt)
EBMgt focuses on the underlying organizational issues that influence how care is delivered.
Advances in EBMgt identify the organizational strategies, structures, and management practice that enable to provide
evidence-based care, i.e., the context of providing care.
Managed Clinical Networks
Linked groups of health professionalsand organizations from primary, secondary, and tertiary care working in a coordinated manner, unconstrained by existing professionals and organisational boundaries to ensure equitable provision of high quality effective services
The Scottish Office, Department of Health. Introduction of managed ClinicalNetworks within the NHS in Scotland. Leeds: NHS Executive, 1999.
Practical Limitations of Primary PCI as a Universal Reperfusion Strategiy
Time delays (DBT, transfer time, waiting time for next available ambulance etc.)
Availability of invasive facilities
Operators’ skillness and cath lab volume load
Reorganization of EMS systems not conducive to making PPCI
EMS lacking 12-lead ECG capabilitiesNot all patients having STEMI are transported by EMSMandates to transport patients to the nearest facility
Transport in STEMI Networks:a Continous Odissey
Organization of ambulance systems, prehospital management, and adequate PCI capacity appear now to be the key issues in providing
reperfusion therapy for AMI.
Terkeisen et al. J Electrocardiology 2005; 36: 187
0
50
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300
Sym
ptom
ons
et to
bal
loon
infla
tion
(min
utes
)
No prehospital diagnosisAdmission to local hospitalSubsequently transferredto interventional hospital
Prehospital diagnosisAdmission to local hospitalSubsequently transferredto interventional hospital
Prehospital diagnosisLocal hospital bypassed.Patients rerouted directlyto interventional hospital
PRAGUE-1PRAGUE-2MAASTRICTDANAMI-2Terkelsen et al.Aashein et al.
Clinical impact of direct referral to primary PCI following pre-hospital diagnosis of STEMI
Is Possible to Apply These Findings in a “Real World” Setting?
66%
86.6%
PRE POST PRE POST
16%
9.5%
Implementation of Guidelines Improve the Standard of Care
The Vienna STEMI RegistryREPERFUSION THERAPY MORTALITY
Kalla K, et al. Circulation 2006;113:2398
%
EMS coordinated with 5 Heart Hospitals Rotated 24 hr PCI availability Evaluated frequency of PCI and Lytics Evaluated Mortality
Ting HH et al. Circulation 2007; 116:729*Bradley EH, et al. N Engl J Med 2006;355:2308
28 regional hospitals without PCI capability located up to 150 miles away across 3 states
The Mayo Clinic STEMI Protocol
A Regional System to Provide Timely Access to PPCI Centers
ACC D2B Alliance*• emergency medicine physicians activate catheterization laboratory; • single phone call activates catheterization laboratory; • catheterization laboratory staff arrive at hospital within 20 min after activation; • real-time data feedback given to emergency medicine and cardiology staff
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20
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37.5%
51%
85.7%
EMS12 LeadPre-Arrival Activation
No EMS12 Lead
EMS12 Lead
Prehosp Emerg Care 2006;10:374-377
Door to Balloon Time < 90 min
Establishing Infarct NetworksMedical Response Delay
The Ottawa Hospital Institute STEMI Regional Program
DTB<90 min DTB<120 min
%
Le May RM et al. N Engl J Med 2008;358:231
Field transfInter-hosp. transf
Interhospitaltransfers
Fieldtransfers
P<0.001
Minutes
ECG
to B
allo
on T
ime
Prop
ortio
n of
Pat
ient
s (%
)The Citywide Ottawa ProgramTime to Treatment
p<0.001 p<0.001
ThrombolysisPTCA shock and ctd. to TBLThrombolysis and transfer to HubHigh risk PCIHigh and not high risk PCI
2002 2004
2003
AMI Network and Reperfusion Strategies in STEMI. Health Care Agency of the Italian region Emilia-Romagna
January 2003ESC Guidelines:
Primary PCIGold standard for
STEMI
Network implementation(transition) Saia F. et al, Heart 2008
Reperfusion TreatmentPatients with STEMI < 12h (85%)
Saia F. et al, Heart 2008
58,876,3
41,223,7
0
20
40
60
80
100
2002 2004
%
No reperfusionReperfusion
AMI Network and Reperfusion Strategies in STEMI. Health Care Agency of the Italian region Emilia-Romagna
In-hospital mortality
17
12,3
0
5
10
15
20
2002 2004
%
4.7 % ARR
p = 0.00528 % RRR
Saia F. et al, Heart 2008
AMI Network and Reperfusion Strategies in STEMIHealth Care Agency of the Italian region Emilia-Romagna
Clinical Impact of an Interhospital Transfer Strategy in Patients with STEMI Undergoing Primary PCI
The Emilia-Romagna STEMI network
Manari A et al. Eur Heart J 2008;29:1834
0
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0 1 2 3 4 5 6 7 8 9 10 11 12
On-site p-PCITransfer p-PCI
9.2%
7.4%
HR: 0.8295% CI: 0.62 – 1.08; P=0.16
Months
1-Ye
ar
Car
diac
Mor
talit
y (%
)
47,90%
29,00%23,10%
ECG senza teletrasmissione
ECG con teletrasmissione
No ECG sul territorio
ECG and TNK
other combinationsECG and TNK sul territorio
ECG with teletransmission
ECG without teletransmission
No ECG
White: No ECGLight Blue:ECG without teletransmissionDark Blue:ECG with teletransmission
Pre-Hospital ECGand Teletransmission
Areas >60’ from Hub PPCI all ptsPPCI all pts (except for low risk <3h)PPCI for pts at high riskPPCI for pts at high risk >3hPPCI in case of shock or contraindications to TBLNo ECG transfer to ER
Reperfusion Strategiesby 118 Areas
1,6%4,1%
41,6%
6,8%
14,2%
31,8%
Sempre PPCIPPCI (TBL basso rischio <3h) Mix PPCI/TBLPPCI solo alto rischio > 3hSempre TBLSolo trasporto al PS
Strategie di Riperfusioneby 118 areas
Missing data (0)PCI for all patients (47)
PCI for all patients (except low risk, <3h) (16)PCI for all high risk patients (9)
PCI for high risk patients >3h (1)Thrombolysis; PCI only for shock or counterindication TBL (7)
No ECG / Direct Transport (54)
Percentage of STEMI Patients Arriving to the First Hospital via EMS Services
Widimsky P, et al. Eur Heart J 2010;31: 943
Italy
Primary PCIs per Year per Million Inhabitantsin European Countries
Widimsky P, et al. Eur Heart J 2010;31: 943
23
Primary PCIIn Italy (year 2009)
2007 2008 ∆% 2009 ∆%
22.421 24.101 7,5% 25.697
6,6%
7.601
5.200
4.6364.984
8.175
5.366
4.705
5.855
8.270
5.499
5.065
6.863
Nord Ovest Nord Est Centro Sud e Isole
2007 2008 2009
www.gise.it
24
Italiy tot. primary PCI./mlninhabitants 2009: 428(404 in 2008)
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Abru
zzo
Alto A
dig
e
Basi
licata
Cala
bria
Cam
pania
Em
ilia R
.
Friuli
V.G
.
Lazi
o
Lig
uria
Lom
bard
ia
Marc
he
Molis
e
Pie
monte
Puglia
Sard
egna
Sic
ilia
Tosc
ana
Tre
ntino
Um
bria
V. d'A
ost
a
Veneto
2007 2008 2009
www.gise.it
Primary PCI /millions Inhabitants (year 2009)
Incidence
STEMINSTEMIUA
Epidemiology of ACS in Italy
6 months mortality
www.istat.it
411 CCUs in Italy2005
De Luca L, et al. G it Cardiol 2008;9(Suppl. 1)
728 Hospitals with a Cardiology Unit
CCUs
Cath LabPCI
Cardiac Surg
CCU+Cath lab
CCU+Cath +Cardiac Surg
Nuclear medicine
E.P.Ablations
North (%) Center (%) South (%)
CCUs in Italy2005
De Luca L, et al. G it Cardiol 2008;9(Suppl. 1)
Population/CCU Bed1 CCU bed/21816 inhabitants – 1 CCU/136577 inhabitants
•1888 patients, 257 centers, May 2003 (3 weeks)
•ACS admitted within 24 hours from last episode of chest pain, and biochemical evidence of myocardial necrosis a/o ECG changes, w/o ST elevation
•1959 patients, 296 centers, October 2001 (2 weeks)
•Patients with AMI (STEMI and NSTEMI) within 48 hours from symptoms onset (biochemical evidence of myocardial necrosis a/o acute ischemic ECG changes
IN ACS
Outcome
•5869 patients, 41 centers, 2006-2007 (12 months)
•ACS admitted within 48 hours from symptoms onset, with biochemical a/o ECG changes a/o known CAD/MI
ANMCO Registrieson ACS
BackgroundThe BLITZ History
Katz JN, et al. J Am Coll Cardiol 2007;49:1279
BackgroundCardiology and the Critical Care Crisis
0 10 20 30 40 50 60 70
Acute Coronary Syndromes
Acute Renal Failure
Ischemic Cardiomyopathy
Vasopressors/Inotropes used
PCI Performed
Respiratory Failure
Invasive Mechanical Ventilation
Chronic Kidney Disease/ESRD
STEMI
Acute Decompensated Heart Failure
Pneumonia
Sepsis/Septic shock
VT/VF
IABP Used
Gastrointestinal Bleed
Nonischemic Cardiomyopathy
Cardiogenic Shock
Thrombolytics Given
Infective Endocarditis
Pulmonary Embolism
Jul-06 Jul-01 Jul-96
Prevalence (%)
To Describe in Italian CCUs :
• epidemiology of admissions• main management aspects • most used resources for diagnosis, therapy and
management • in-CCU patients outcomes • organizing pathways • frequency of the most important co-morbidities
Blitz-3Aims of the Study
N° of Invited CCUs: 409N° of Partecipating CCUs: 332 (81%)
Blitz-3Results
80 79 84
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20
40
60
80
100
North Central South
79 85 81
0
20
40
60
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CCU CCU+Cath Lab CCU+CathLab+Cardiac
Surgery
% %
Blitz-3Diagnosis at Discharge from CCUs
%
21
31
13
7 7 6
2 2 2 2 1 1 1 1 0,5 0,4 0,3 0,3 0,20
20
40
STE ACS
NSTE ACS
Heart f
ailure
AF/SVT
Bradya
rrhyth
mias
Chest p
ainVT/VF
Synco
pe
Post-PCI/s
urgery
Other con
ditions
Pulmona
ry Embolis
m
Out-ho
spita
l Arre
st
Shock no ACS
Myo-peri
carditis
Post-PM-A
blatio
n
Tampo
nade
Aortic Diss
ectio
n
Stable
CAD
Endocarditis
Blitz-3Resources Use
79
3524
105 5 3 2 2 1
8
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100
Echo
Coro
PCI
Pacem
aker CT
Ventila
tion
CVETEE
IABP
Ultrafi
ltrati
onNon
e
%
Number of procedures/patient
1 42%2 26%≥3 24%
Overall Population
Overall Mortality in CCU: 3.34 %
Blitz-3Complications in CCU
6
4
23
0,9 0,5
9
3
0,81,5
66,9
0
5
10
15
Supraven
tricular
arrhyth
Major v
entric
ular ar
rhth
AV Block
Angina
Re-IMA
Stroke
HF or worse
ning
Cardiac arre
st
Sepsis
Cardiogenic
Shock
Major B
leeding
Other
%
Hospital-based quality improvement initiative created by the ANMCO to improve the care as suggested by
current guidelines of patients with ACS admitted in CCUs
Aimand Methods
• Survey• Performance measures• Rapid feedback to partecipating centers• Snapshot on actual management of ACS pts
admitted to CCUs in Italy
PartecipatingCCUs (n=163)
The ANMCO Network
Nearly 5500 cardiologists N. 754 hospitals
N. 871 cardiological centers N. 403 CCUs
Cardiology Centers involved in ANMCO research projects
(total number 549)
> 5 projects 21 3 projects 78
5 projects 38 2 projects 147
4 Projects 49 1 project 216
Further, 60 Internal Medicine Divisions, 40 diabetologycenters, nearly 300 GPs are collaborating in ANMCO
projects
ANMCO Research Center
Epidemiology (E) Clinical Trial (RCT) Outcomes Research (OR)
IN-CHF (E)Survey Acute HF (E)
AREA IN-CHF (RCT)GISSI-HF (RCT)
CandHeart * (RCT)EVEREST* (RCT)
ALOFT* (RCT)
BLITZ 2 (E)OAT (RCT)•
Diabete e SCA# (RCT)G-CSF ISS# (RCT)Eplerenone* (RCT)
IN-ACS Outcome (OR)
IN-CP# (E)HEART Survey (E)•
DYDA (E)GOSPEL (RCT)
CARDIO-SIS (RCT)ORIGIN * (RCT)SCOUT * (RCT)
ONTARGET* (RCT)BEAUTIFUL* (RCT)
Total: 24 projects
Euro Heart Surveys, Osservatorio MinSal, Censimento
ACTIVE * (RCT)GISSI-AF (RCT)
• In collaborazione* Endorsement # Forthcoming
Heart FailureArrhythmiasCHDCV Prevention
The GISSI-1 Trial
GISSI Responsibilities
Study Design
Protocol Development + CRFsSelection of CommitteesImplementation of study protocolCentral RandomizationInvestigator’s Meetings Communication with CentersRecruitmentMonitoring Database set up + Data ManagementStatistical AnalysisSubstudies & Core LabEvent Adjudication ProcessPrimary Publication and Approval of secondary publications
The GISSI Collaboration
The enduring lessons of GISSI provide us with guidance about how to proceed:
- Focus trials aimed at drug development on questions that willinform clinical practice.
- Keep the mechanisms and bureaucracy of trials to a minimum.
- The spirit of the GISSI organization must be replicated to provide a mechanism that can deliver the evidence for thepractice of evidence-based medicine.
Califf RM Circulation. 1998;98:2649
Am Heart J 2004;148:187-193
…………The Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardio (GISSI) trial was the first megatrial (commonly defined as a trial enrolling10,000 patients) in STEMI and provided an unambiguous, affirmative answer. GISSI 1 (the number 1 was added later, when the group wisely decided to conduct additional trials) was more than a landmark trial—it was a bombshell. Like the development of thecoronary care unit 2 decades earlier, it immediatelyimproved the treatment of these patients……
Am Heart J 2004;148:187.
Continuity and Consistency:the Main Result of GISSI
GISSI 1 GISSI 2 GISSI 3 GISSI P
Enrollment 1984-85 1988-89 1991-93 1993-96
Publication 1986 1990 1993 1998
No Centers 176 223 200 172
No Patients 11,806 12,490 19,394 11,379
Total costs 350,000 € 4,000,000 € 6,000,000 € 4,000,000 €
Cost per pt Reg Auth
30 € SK by FDA
320 € 309 € Lisinopril by FDA
350 € n-3 PUFA by IMH and EMEA
GISSI-1 GISSI-2 GISSI-3 GISSI-P
GISSI-HF : 2002-2007A large randomized multi-center double blind, placebo controlled clinical trial testing the effects of n-3 PUFA (fish oil) and a statin on mortality and morbidity of patients with symptomatic Congestive Heart Failure.
GISSI: Recent Clinical Trials
GISSI-AF : 2005-2008Randomized, multi-center double blind, placebo controlled clinical trial on the use of valsartan, an angiotensin II AT1-receptor blocker, in the prevention of Atrial Fibrillation recurrence.
GISSI-HF Study Design
At each visit, the following assessments were performed: CV examination, vital signs, 12-lead electrocardiogram, compliance check, serious adverse events assessment and blood chemistryNYHA=New York Heart Association; R1=randomization 1; R2=randomization 2; D=drug distribution
Rosuvastatin 10 mg q.d.(n=2285)
Placebo (n=2289)
Median follow-up 3.9 years
Visit:
Month: 101 2
33
D
64
D
125
D
186
D
247
D
308
D
369
D
R1, R2
Placebo (n=3481)
n-3 PUFA 1 g q.d.(n=3494)
R1 (n=6975)
R2 (n=4574)
Adapted from: Tavazzi et al. Eur J Heart Fail 2004;6: 635.GISSI-HF Investigators. Lancet 2008; 372(9645):1231
GISSI-HF (n 3 PUFA)Co-primary End Points
Adapted from GISSI-HF Investigators. Lancet 2008; 372(9645):1223
HR = hazard ratio; CI = confidence interval*adjusted HR
0.90
0.94
P value
[99% CI 0.91-1.11]
[95.5% CI 0.90-1.12]
CI
1.01
1.00
HR*
1283 (56)1305 (57)All-cause mortality or CV hospitalizations
644 (28)657 (29)All-cause mortalityPrimary end points
Placebo(n=2289)
n (%)
Rosuvastatin(n=2285)
n (%)
(i) All-cause mortality and (ii) all-cause mortality or hospitalizations for CV reasons
GISSI-HF (Rosuva)Co-primary End Points
Adapted from GISSI-HF Investigators. Lancet 2008; 372(9645):1231
Visit 1 2
Week Days-5 to -1
Day 0
Randomization
3
2
4
4
5
8
6
24
7
52
Study Drug Treatment
placebo
placebo
placebo
80 mg valsartan160 mg valsartan
320 mg valsartan
GISSI-AFStudy Design
All patients have been provided with a transtelephonic monitoring tool N Engl J Med. 2009;360:1606
TRATTAMENTO A B
0.0
0.1
0.2
0.3
0.4
0.5
0.6
timefirstFA
0 30 60 90 120 150 180 210 240 270 300 330 360
Time to first recurrence of AF(n. 1442)
Valsartan: 371/722 (51.4%)Placebo: 375/720 (52.1%)
Adjusted* HR 0.9996%CI 0.85-1.15P value 0.84
Pts at riskValsartanPlacebo* Adjusted for ACE-I, amiodarone use, cardioversion, PAD, CAD
722 586 524 491 465 445 423 398 383 368 356 343 260720 589 520 484 454 435 407 387 377 359 344 334 254
Days
N Engl J Med. 2009;360:1606
Focus of Innovative Research: From Lumpers to Splitters
not treated
treated
MAC
E %
0102030405060708090
100
Time
70% event-freewithout treatment
18% MACEwith treatment
40% MACEreduction
Maseri A, Circulation 2006
GISSI OUTLIERSProjects
1. Post-MI LV Remodelling
2. Risk Factors for Atherosclerosis
3. Determinants of coronary instability and healing
4. Idiopathic Heart Failure
5. Biomolecular Research in Cardiac Surgery