Trasplante cardiaco: viejos problemas con nuevos enfoques. Fallo precoz del injerto

1. Fallo precoz del injerto J. Segovia Hospital Puerta de Hierro – Madrid No conflictos de interés relativos a esta presentación Congreso SEC. Barcelona, 24 octubre 2009

3. ADULT HEART TRANSPLANT RECIPIENTS: Cause of Death (Deaths: January 1992 - June 2006) ISHLT Last updated based on data as of December 2006 2008 J Heart Lung Transplant 2008;27: 937 CAUSE OF DEATH 0-30 Days (N = 3,006) 31 Days – 1 Year (N = 2,722) >1 Year – 3 Years (N = 2,135) >3 Years – 5 Years (N = 1,857) >5 Years – 10 Years (N = 4,054) >10 Years (N = 2,107) TECHNICAL 233 (7.8%) 28 (1.0%) 17 (0.8%) 17 (0.9%) 36 (0.9%) 20 (0.9%) GRAFT FAILURE 1,257 (41.8%) 500 (18.4%) 499 (23.4%) 379 (20.4%) 765 (18.9%) 353 (16.8%) CARDIAC ALLOGRAFT VASCULOPATHY 52 (1.7%) 127 (4.7%) 298 (14.0%) 299 (16.1%) 581 (14.3%) 309 (14.7%) ACUTE REJECTION 193 (6.4%) 338 (12.4%) 220 (10.3%) 82 (4.4%) 69 (1.7%) 26 (1.2%) LYMPHOMA 2 (0.1%) 54 (2.0%) 85 (4.0%) 96 (5.2%) 195 (4.8%) 73 (3.5%) MALIGNANCY, OTHER 1 (0.0%) 57 (2.1%) 218 (10.2%) 340 (18.3%) 749 (18.5%) 392 (18.6%) CMV 4 (0.1%) 34 (1.2%) 16 (0.7%) 3 (0.2%) 5 (0.1%) 1 (0.0%) INFECTION, NON-CMV 393 (13.1%) 896 (32.9%) 276 (12.9%) 180 (9.7%) 442 (10.9%) 213 (10.1%) OTHER 162 (5.4%) 175 (6.4%) 187 (8.8%) 147 (7.9%) 339 (8.4%) 175 (8.3%) MULTIPLE ORGAN FAILURE 356 (11.8%) 268 (9.8%) 117 (5.5%) 102 (5.5%) 309 (7.6%) 190 (9.0%) RENAL FAILURE 20 (0.7%) 25 (0.9%) 36 (1.7%) 65 (3.5%) 225 (5.6%) 173 (8.2%) PULMONARY 133 (4.4%) 108 (4.0%) 96 (4.5%) 85 (4.6%) 172 (4.2%) 99 (4.7%) CEREBROVASCULAR 200 (6.7%) 112 (4.1%) 70 (3.3%) 62 (3.3%) 167 (4.1%) 83 (3.9%) 8%

4. Fallo Precoz del Injerto: Impacto A) Frecuente, poco previsible B) Alta mortalidad C) Consumo de recursos sin apenas beneficio D) Frustración para implicados E) Culpa

5. FPI ¿Qué sabemos? Publicación N Pacientes Epoca Definición Incidencia Soporte circulatorio Mortalidad a 30 días Karavana 2003 462 Adulto 1992-1999 Necesidad de asistencia mecánica en 30 días postrasplante. Se excluyen las causas secundarias. 2.8% 23%IABP 92% VAD 8%ECMO 61.5% Huang 2004 165 Pediátrico 1986-2001 Deterioro hemodinámico en las 24 hs tras el TxC que precisa asistencia circulatoria o 2 inotrópicos/presores que incluyen adrenalina 33% 44% 18.5% Leprince 2005 118 Adulto 2002-2004 Shock cardiogénico severo a pesar de soporte inotrópico máximo que requiere ECMO 11% 100% ECMO 50% Marasco 2005 214 Adulto 1996-2004 Hipotensión, bajo índice cardiaco y PCP elevada tras el TxC a pesar de dosis bajas de inotrópicos . Exclusión de causas secundarias 24% 92% IABP 21% VAD 8% ECMO 14% Aubert 2005 1095 Adulto 1987-2003 Asistencia circulatoria por insuficiencia cardiaca refractaria tras el TxC 1% 42% VAD 17%ECMO 42% TAH 66% Lima 2006 207 Adulto 2000-2005 Necesidad de inotrópicos en dosis altas (A≥ 0.07µg/kg/min) y/o asistencia circulatoria inmediatamente tras el TxC 23% 64%IABP 29% VAD 7% ECMO 14% Ibrahim 2007 385 Adulto 1984-2005 Disfunción significativa del injerto en el postrasplante precoz, en ausencia de causa secundaria 1.5% 33% IABP 33% VAD 16% TAH 83% Weis 2009 90 Adulto 2006-2008 FEVI <30%, necesidad de inotrópicos en dosis altas (A>0.1 µg/kg/min + milrinona >0.3 µg/kg/min 13% 17% IABP 8% ECMO 8% Santise 2009 36 Adulto 2006-2008 Necesidad de asistencia circulatoria para salir de CEC 16% 100% VAD 33%

10. FPI: variables del receptor Recipient Non PGF n=578 PGF n=65 p Age (years) 48.3±12.9 51.3±16.5 0.05 Male Gender 83.4% 76.9% 0.19 Body mass index (kg/m 2 ) 24.7±4 24.3±3 0.4 Diabetes mellitus 10.6% 24.6% 0.001 Ischemic cardiomyopathy 37% 29.2% 0.8 Valve heart disease 11% 13.8% 0.9 Renal dysfunction (Cr>2 mg/dl) 16.5% 22.6% 0.22 Previous cardiac surgery 25.8% 32.8% 0.22 Amiodarone treatment 13.2% 18.3% 0.27 Pre operative inotrope requirement 37% 56.9% 0.002 Pre operative IABC 7.8% 9.5% 0.9 Pre operative ventricular assist device 2.6% 3.2% 0.9 Ventilatory support at the time of HT 10.8% 11.1% 0.9 Right atrial pressure (mmHg) 8.26±6.6 12.3±7.7 0.001 Pulmonary systolic pressure (mmHg) 47.2±15.6 53.9±15.6 0.001 Pulmonary mean pressure (mmHg) 32.8±11.5 38.5±12.2 0.001 Cardiac index (l/min/m2) 2.3±0.66 2.2±0.78 0.15 Pulmonary vascular resistance 2.4±1.25 2.99±1.43 0.003 Transpulmonary gradient (mmHg) 8.4±5.9 10±7.3 0.05 Left ventricular ejection fraction 0.16±0.14 0.17±0.15 0.67

11. FPI: variables del donante Donor Non PGF n=578 PGF n=65 p Age years 28.6±11.5 31.1±11.4 0.04 Female gender 23.5% 34.9% 0.04 BMI (kg/m 2 ) 24.1±3.9 23.9±3.8 0.7 Inotropic requirement 76.5% 81.3% 0.45 Time in ICU (days) 3.2±3.3 3±3.1 0.7 CNS Hemorrhage 27% 40% 0.2 Trauma 59% 43% 0.3 Other 14% 17% 0.3

12. FPI: variables quirúrgicas Operative Non PGF n=578 PGF n=65 p Ischemic time 199.1±59.2 217±67.9 0.02 Cardiopulmonary by-pass time 122.2±48.6 176.7±76.4 0.001 Urgent transplant (%) 25.8% 29.7% 0.5 Body mass index mismatch >20% 14.2% 13.7% 0.9

13. FPI: análisis multivariado de regresión logística R ight atrial pres > 10 A ge Rec> 60 D iabetes mellitus I notrope dependence A ge Donor > 30 L ength of ischemia Individual score: each factor adds 1 point, range 0-6 Risk factors Prevalence Relative risk CI (95%) p Recipient RAP >10 mmHg 40.9% 2.2 1.2-4.0 0.009 Recipient age >60 years 20.2% 1.9 1.1-3.7 0.047 Recipient diabetes mellitus 12.1% 2.5 1.2-5.1 0.008 Recipient inotrope therapy 38.3% 2.1 1.1-3.7 0.016 Donor age > 30 years 39.3% 1.7 1.1-3.1 0.04 Ischemic time > 240 minutes 20.6% 1.9 1.1-3.5 0.04

14. Clasificación de TxC con RADIAL Risk score Nº of patients

15. Tendencia secular en el FPI * Somers d test Period 1 1984-1989 (n=78) Period 2 1990-1994 (n=180) Period 3 1995-1999 (n=194) Period 4 2000-2007 (n=169) p for trend* PGF Incidence 7 (9%) 9 (5%) 19 (9.8%) 21 (12.4%) 0.05 Recipient age>60 years 2 (2.5%) 21 (11.6%) 57 (29.3%) 46 (27.2%) 0.001 Recipient diabetes 4 (5.1%) 13 (7.2%) 26 (13.4%) 32 (18.9%) 0.001 Rec. inotrope dependence 22 (28.2%) 61 (33.9%) 70 (36.1%) 85 (50.3%) 0.001 Recipient RAP>10 mmHg 25 (32%) 58 (32.2%) 83 (42.8%) 88 (52.1%) 0.001 Donor age>30 years 12 (15.4%) 52 (28.9%) 90 (46.4%) 90 (53.3%) 0.001 Ischemic time >240min 4 (5.1%) 36 (20%) 52 (26.8%) 36 (21.3%) 0.007 PGF 30-Day Mortality 7 (100%) 8 (88.9%) 16 (84%) 14 (66.7%) 0.03 VAD or IABP 3 (42.9%) 5 (55.6%) 11 (57.9%) 18 (85.7%) 0.004

16. * Somers d test Tendencia secular en el FPI Period 1 1984-1989 (n=78) Period 2 1990-1994 (n=180) Period 3 1995-1999 (n=194) Period 4 2000-2007 (n=169) p for trend* PGF Incidence 7 (9%) 9 (5%) 19 (9.8%) 21 (12.4%) 0.05 Recipient age>60 years 2 (2.5%) 21 (11.6%) 57 (29.3%) 46 (27.2%) 0.001 Recipient diabetes 4 (5.1%) 13 (7.2%) 26 (13.4%) 32 (18.9%) 0.001 Rec. inotrope dependence 22 (28.2%) 61 (33.9%) 70 (36.1%) 85 (50.3%) 0.001 Recipient RAP>10 mmHg 25 (32%) 58 (32.2%) 83 (42.8%) 88 (52.1%) 0.001 Donor age>30 years 12 (15.4%) 52 (28.9%) 90 (46.4%) 90 (53.3%) 0.001 Ischemic time >240min 4 (5.1%) 36 (20%) 52 (26.8%) 36 (21.3%) 0.007 PGF 30-Day Mortality 7 (100%) 8 (88.9%) 16 (84%) 14 (66.7%) 0.03 VAD or IABP 3 (43%) 5 (55%) 11 (58%) 18 (86%) 0.004

17. Predicción del riesgo de FPI con RADIAL Nº. patients 103 189 165 119 36 9 PGF actual 2,9% 3,7% 8,5% 15,1% 30,6% 33,3% FPI predicted (CI 95%) 2.1% (0-5,3) 4,1% (3-4.7) 8,1% (4-12) 15,2% (13-17) 27,4% (15-39) 44,2% (17-68)