INTERVENCIONISMO EN EL SIGLO XXI NUEVAS FRONTERAS

Daniel Berrocal, MD, FACC

Jefe de Cardiologia Intervencionista

daniel.berrocal@hiba.org.ar

Andreas Gruentzig September 1977

Balloon angioplasty

Roads opened by insane will be later traveled by the wise man C. Dossi

Response to vascular injury

Proliferation

Elastic recoil

Thrombosis Neointimal Inflamation

hyperplasia

Remodeling
70% 30%

RESTENOSIS

Clinical Trials evaluating Antithrombotic and anticoagulants

Trial year N Control Angio
157 376 71% 66%

Drug(s) /dose

Stenosis definition
70% 50%

Restenosis Drug
18% 38%

Restenosis Placebo
20% 39%

Odds ratio

ASA vs. Placebo

White Schwartz 1987 1988 AAS 990mg/DIP 225mg AAS 990mg/DIP 225mg

ASA high vslow dosis

Dyckmans Mufson 1988 1988 203 453 42% 37% AAS 1500mg vs 320mg AAS 1500mg vs 80mg

50% 50%

21% 51%

31% 47%

Ticlopidin
White Kitazume Bertrand 1987 1988 1990 157 189 266 76% 100% 92% Ticlopidina 750mg Ticlopidina 200mg Ticlopidina 200mg

70% 50% 50% lost

29% 27% 50%

20% 38% 41%

Tromboxan A2 blocker
Serruys Feldman 1991 1992 649 1192 89% 59%

GR 32191 80mg 0.72mm lost GR 32191 40-80mg 70%

21% 28%

19% 31%

Prostaciclin and analogous vs Placebo

Knudston Raizner 1990 1993 270 247 83% 85% Prostaciclina 5ng/kg/min Ciprostene 120ng/Kg/min

50% 50%

27% 26%

32% 38%

Anticoagulants
Thornton Urban Ellis Faxon 1984 1988 1989 1994 248 110 416 394 72% 77% 61% 86% Warfarina Warfarina Heparina Enoxaparina 40mg 50% lost 50% 50% 50% 36% 29% 41% 52% 27% 37% 37% 51%

10

Clinical trials evaluating Antiproliferative agents

Trial year N Control Angio Droug (s) /dose Stenosis Restenosis Definition Drug Restenosis Placebo Odds ratio

Steroids vs Placebo
Rose Stone Pepine 1987 1989 1990 66 102 722 88% 53% 71% Medrol 48mg Metilprednisolona 125mg + Prednisolona 60mg/d Mtilprednisolona 1mg/d 50% 50% 50% 33% 59% 43% 33% 58% 43%

Colchicina vs Placebo
OKeefe 1992 197 74% Colchicina 1.2mg

70%

41%

45%

Trapidil vs AAS
Okamoto Maresta 1992 1994 90 254 80% 74%

TP 600mg vs AAS 300mg prdida 50% TP300mg vs AAS 300mg prdida 50%

19% 24%

42% 40%

Angiopeptin vs Placebo
Kent 1993 Emanuelsson 1995 Eriksen 1995 1246 546 112 87% 76% 94% AP 190-300g/10das AP pre y post ATC AP pre y post ATC

50% 50% 50%

35-38% 37% 12%

39% 36% 40%

Transilast vs Placebo
Ueda 1995 205 les. 100% Transilast 600mg/d prdida 50% 22% 46%

10

Clinical trials evaluating oral lipid lowering

Trial year N Control Angio Drug(s) /dosis Stenosis definition Restenosis Drug Restenosis Placebo Odds ratio

Hidroximetilglutamil-coenzima A (HMG-Co A) Reductase inhibitors vs Placebo

Sahni Weintraub Yui Mufson 1990 1994 1995 1995 157 404 208 453 50% 79% 100% 37% Lovastatin 20mg/d Lovastatin 80mg/d Pravastatin 20mg/d Lov 40mg/d + Prav 1g/d 50% 50% 50% 12% 39% 41% 45% 42% 52%

Fish oil vs Placebo

Denher Grigg Reis Nye Bairati Bellamy Kaul Franzen Leaf Cairns 1988 1989 1989 1990 1992 1992 1992 1993 1994 1994 82 108 186 73 119 120 107 200 551 668 100% 93% 30% 95% 100% 94% 100% 65% 81% 88%

3FA 5.4gr 3FA 3.0gr 3FA 6.0gr 3FA 2.2gr 3FA 4.5gr 3FA 3.0gr 3FA 3.0gr 3FA 3.2gr 3FA 6.9gr 3FA 5.4gr

50% prdida 50% 70% prdida 50% 50% prdida 50% 50% 50% 50% prdida 50%

19% 34% 34% 11% 31% 21% 35% 33% 52% 47%

46% 33% 23% 30% 48% 18% 27% 35% 46% 46%

LDL Apheresis vs Placebo

Daida 1994 203 100% LDL Aferesis 50% 32% 46%

10

BOAT
Baloon vs Optimal Atherectomy Trial
Baim D; Cutlip D; Sharma S. Circulation 1998

COBRA
Rotablator
Erbel. Circulation 1997

Excimer Laser
Ligth Amplification by Stimulated Emission of Radiation

F. Litvack. Am J Cardiol 1994

Palmaz balloon expandable stent

Balloon expanded stent

Balloon angioplasty

Stent implanted

Balloon result

Stent result

First Palmaz-SchatzTM (1986)

13-years post stent

First CypherTM (1999)

2-years post DES stenting

MEGAMETANALISIS

Target-vessel revascularization
Study type RCT: all RCT: on-label RCT: off-label Registries
*Random-effects model

Patients, n Trials, n Relative risk 7291 4618 2673 73 819 16 9 8 17 0.45 0.53 0.38 0.53

P* <0.001 <0.001 <0.001 <0.001

47 to 62%

Kirtane AJ, Stone GW. Comprehensive meta-analysis of DES vs BMS randomized trials and registries; March 28, 2008; Chicago, IL.

MEGAMETANALISIS

All-cause mortality
Study type RCT: all RCT: on-label RCT: off-label Registries Patients, n Trials, n Relative risk 8867 4818 4049 161 232 21 10 12 28 0.97 1.05 0.84 0.80 p 0.72a 0.69a 0.24a <0.001b

20%

a. Fixed-effects model b. Random-effects model

Kirtane AJ, Stone GW. Comprehensive meta-analysis of DES vs BMS randomized trials and registries; March 28, 2008; Chicago, IL.

De la prctica a la evidencia
1977: Angioplasta por baln 1984: Atherectomy (directional) 1988: Atherectomy (rotational) 1987: Stent angioplasty 1981 (Registro NHBLI) 1993 (CAVEAT) 1993 (Registro multicntrico) 1994 (BENESTENT)

De la evidencia a la prctica
2001 2002 2003 FIM RAVEL SIRIUS = 30 patients = 238 pacients = 1100 patients

TAXUS I, II, III, IV, V, VI, ASPECT, ELUTES + DE 200.000 PACIENTES

3 Zenith iliac leg graft

12mmmx122mm

2 Converter Renu
28mmmx108mm

4 Zenith iliac leg graft

14mmmx88mm

5 Amplatzer 18 1 3 Coils
8 mm

6 Fem-Fem by pass

IHSS

En 2009
EDWARDS Sapien COREVALVE

Balon-expandible

Auto-expandable

> 5 000 Pacientes tratados

RCA

LM

AVA: 1.7 cm2

Antegrade and Retrograde Approach

Evalve Mitral Repair System Severe MR reduced to Trace MR

Performed in Cath Lab, Quick Recovery, No Morbidity

Regurgitant Jet =Yellow

Evalve Healing Results

- edge-to-edge repair - explanted human heart - 4yrs post repair - Evalve repair - porcine heart - 6 mos post repair

Privitera et al. Circ 2002

SIGLO XXI NUEVAS FRONTERAS

Placa estable

Placa vulnerable
Remodelamiento + Inflamacin Gran core lipdico
MMP-3 MMP-3 Macrfagos

Deplecin de colgeno de la cpsula fibrosa degradacin de la matriz Afinamiento de la cpsula fibrosa MMP-3
mRNA Macrfagos

Apoptosis Macrfagos

Placa Vulnerable Placa estable Clnica=Asintomtico o ACE Clnica=Asintomtico o ACE

Adaptada de Davies MJ ndian Heart Journal 2000; Virmani R. 2000; Sha PK. ACC2002 Pasterkamp G et al. JACC. 1998; 32: 655 Galis ZS et al. J Clin Invest. 1994; 949: 2493 Mallat Z et al. Circulation. 1999; 99: 348

PREVENCIN

PREVENCIN ESTRATIFICACIN INTERVENCIN ?

ESTRATIFICACIN INTERVENCIN

Accidente de placa SIN oclusin Clinica = SIA ST

Placa estable Clnica=Asintomtico o ACE

Placa Vulnerable Clnica=Asintomtico o ACE

Accidente de placa CON oclusin Clnica = IAM ST

Adaptada de Davies MJ ndian Heart Journal 2000; Virmani R. 2000; Sha PK. ACC2002 Pasterkamp G et al. JACC. 1998; 32: 655 Galis ZS et al. J Clin Invest. 1994; 949: 2493 Mallat Z et al. Circulation. 1999; 99: 348

Active and inflamed plaque

Morphology Activity Chemistry
Virtual histology
Thermography

Inactive and non-inflamed plaque Physical properties

OCT Spectroscopy

IV MRI Endothelial shear stress

Drugs deposited in multi-layered degradable polymer inlays

Chondrityn 4-sulphate hydrogel

Aprotinin 1 Aprotinin 2
90 80 AMOUNT RELEASED (x 10 mmol) 70 60 50 40 30 20 10 0 0

Lysozime1 Lysozime2

Aprotinin spontaneous release Lysozime spontaneous release

-6

20 40 60 80

100 TIME (min)

120

140

160

180

Jensen et al. European Journal of Pharmacological Sciences. 15( 2002) 139-148

400 Release rate (ng min-1) 0 1 2 3 4 5 6 7

40

Mass released (ng)

300

30

200

20

100

10

0 Time (days) 50 40 30

0 0 1 2 3 4 Time (days) 5 6 7

Release rate (ng min-1)

Controlled-release microchip
Ca+

20

Na+

10 0 0 10 20 30 40 Time (days) 50 60 70
Santini TS et al. NATURE. Vol 397. 28 January 1999. www.nwture.com

Absorbable metallic Mg+ stent

BVS Bioabsorbable eVerolimus-eluting Stent; Abbott Vascular

6 Months (n = 26) In-Stent RVD, mm In-Stent MLD, mm In-Stent DS In-Stent Late Loss, mm Proximal Late Loss, mm Distal Late Loss, mm In-Stent Binary Restenosis In-Segment Binary Restenosis 2.64 1.89 27.0% 0.43 0.23 0.23 7.7% 7.7% 2 Years (n = 19) 2.43 1.76 27.0% 0.48 0.34 0.36 0% 0%

P Value
0.0058 0.23 0.81 0.233 0.0553 0.0091 1.00 1.00

34.5% struts reduction over 2 years

JA Ormiston, PW Serruys et al Lancet, 373, 9667: 887,.March 2009

Functional PET, f MRI

X-Ray fluoroscopic display Structural Echo Imaging

Clinical Records

X-Ray imaging system CT64, MRI Video Camera

Functional Echo Imaging

Table Advanced QCA 6 QSA Display of physician Motion Tracking Globes Dr. Mohammed Haroon Rashid

Robot Manipulator

Advanced Pathway Analysis

Holographic Fusion & 3D MULTI-IMAGE

Motion Tracking Globes

Summary of GNP per Capita and Probability of Mortality at age 15-59 years per 1000 in Several Countries
600

500

400

300

200

100

0
Sweeden Japan Israel Italy Canada UK Greece Switzer Spain DenmarkFrance Finland USA Portugal Czk R ArgentinaPoland Hungary Brasil South Africa

Gross National Product Mortality per 10000

Shibata et al. Am Heart J 2001;141:1019-24.

Human Resources in Cardiovascular Medicine*

Where is the difference?

Region Spain Germany USA

Cardiologists 51.2 22.6 69.4

Surgeons 6.4 1.5 9.4 5.0 0.93

Residents 7.5 ... ... 6.99 0.46

Nurses 12.5 ... ... 5.06 1.67

Latin 65.0 America Africa and Asia 2.1

*per million in habitants

White Book Impending Global Pandemic of Cardiovascular Diseases

From practice

From evidence

From evidence

Evidence

Practice
Market share of GRANTS

Practice

Participation in research founding %

70 60 50 40 30 20 10 0 86 88 90 92 94 96 Industry NIH 98
40% 60%

Real world 60% (including $)

40%

2000
Modified from Holmes D et al. Am Heart J. 2004; 147: 228-237

Docencia Investigacin Destrezas Imgenes Coag. y tromb. Diabetes Cardilogo Intervencionista Salud Pblica

Reparacin
Berrocal D et al.

Biologa Molecular
Inflamacin

Hemorragia
Farb A et al.

Cardiopatas estructurales
Berrocal D et al.

Necrosis
Farb A et al.

Insuficiencia Cardaca

Valvulopatias Cardiopatas congnitas el adulto

Berrocal D et al.

Berrocal D et al.

Berrocal D et al.

Courtesy A. Aizaid

TECNOLOGIA
CONOCIMIENTO de la tcnica

Las especialidades no son estticas, sino dinmicas, fluctuantes e interactan unas con otras. Los conocimientos se cruzan de reas
Michael Mack. President of the STS (Society of Thoracic Surgery) Bruce Lytle Director of CCF (Cleveland Clinic Foundation) 2005

Cardiovascular Invaders
1. Cirujanos cardiovasculares 2. Cardilogos Intervencionistas 3. Radilogos Intervencionistas

QUIEN ESTA CAPACITADO PARA? 1. 2. 3. 4. Diagnosticar mejor Resolver mejor Acertar mas en su visin a futuro Administrar mejor los recursos

QUIEN REPRESENTA LA MEJOR OPCION PARA LA GENTE?

Obstculos
1. 2. 3. 4. 5. Mentalidad Nadie puede saber y hacer todo Programas de formacin Acreditacin Afrontar casos muy difciles quirrgicos o endoluminales en el futuro ESTRATEGIAS 1. Unificar residencias 2. Training post residencia 3. Training ad hoc para determinadas practicas (TAVI, AAA)

Formacin BASICA para el futuro especialista en intervenciones cardiovasculares Medicina Interna Cardiologa Clnica Cardiologa Intervencionista Ciruga General Ciruga Cardiovascular 1 ao 3 aos 3 aos 4 aos 3 aos

TOTAL

14 aos

Numero mnimo de procedimientos anuales para mantener expertise

Cateterismos Diagnsticos Angioplastias coronarias Angioplastias perifricas Angioplastias carotideas Teraputica de estructurales TAVI Endoprtesis articas Cirugas coronarias Cirugas valvulares Cirugas articas Cirugas carotideas Cirugas perifricas 500/ao 75/ao 50/ao 35/ao 25/ao 10/ao 25/ao 75/ao 40/ao 50/ao 30/ao 50/ao 965/ao 45 120 180 90 90 210 180 210 180 150 90 120 22500 9000 9000 3150 2250 2100 4500 15750 7200 7500 2700 6000

TOTAL

91.650 (1527,5 horas)

 Vacaciones
1 ao

248 das laborables 20 das

1527,5 horas

+
2hs. Intervalo entre casos da x 228 das laborables (456hs)

1983,5 horas

8.7 horas diarias

The new Cardiovascular invader!!!!!

*!!!!#

Tiene cerca de 40 aos Su cabeza no da mas!! No es experto en NADA!! No consigue trabajo!!!!!!

INTEGRAR A TRAVES DE PROYECTOS 1. TAVI 2. AAA 3. Diseccin artica 4. Isquemia aguda de MMII 5. Hibridos PATIENT CENTERED CARE INTEGRACION Geogrfica

Asistencial Cientfica

Research the best way to integrate, ever

INTEGRAR A TRAVES DE PROYECTOS PATIENT CENTERED CARE

DISEASE CENTERED

PROCEDURE CENTERED

NAVY SEALS Expertise and strength Resides in TEAM

TECH & DEVICES CENTERED

Definir y entrenar diferentes roles y funciones en el TEAM NO TODOS pueden hacer TODO!

CLAVES PARA EL EXITO 1. Co-Liderazgo 2. Comunicacin continua y fluida 3. Resolucin precoz de los conflictos 4. Compartir economa 5. Cajas separadas (SIC) 6. Evaluacin pre 7. Evolucin compartida 8. Consensuar todo DEJAR DE DISCUTIR QUIEN ES EL MEJOR PARA QUE Y CONSTRUIR CON EL APORTE DE LO MEJOR DE CADA UNO

DESAFIOS 1. Cambio de mentalidad 2. Programas educativos dinmicos 3. Adaptabilidad de los nuevos especialistas a otras instituciones 4. Adaptabilidad de los nuevos especialistas a otras realidades geogrficas, sociales, culturales y econmicas 5. Perdida de los EXPERTOS? 6. Certificacin y acreditacin 7. Racionalizacin de las prcticas

Crisis (del latn crisis, a su vez del griego ) es un conjunto de cambios en qualquier parte de una realidad organizada pero inestable y sujeta a evolucin que genera conflictos y oportunidades

En la realidad actual la crisis es un estado permanente

Solamente en las pocas de crisis, la imaginacin es mas importante que el conocimiento

DESAFIOS PARA EL FUTURO DE LA CARDIOLOGIA INTERVENCIONISTA Integracin de los conocimientos Programas de educacin mdica dinmicos Reformular exigencias y costos de la investigacin Financiacin de la salud Lograr sinergias entre especialistas

PACIENTE
Daniel Berrocal, MD, FACC
Jefe de Cardiologia Intervencionista

daniel.berrocal@hiba.org.ar