XIII Reunión anual de la sección de Insuficiencia Cardiaca de la SEC OVIEDO, 16-18 JUNIO 2016 HOSPITAL UNIVERSITARIO CENTRAL DE ASTURIAS (HUCA) http://secardiologia.es/insuficiencia/cientifico/ic-oviedo-2016 Utilidad de las técnicas de imagen de la insuficiencia cardiaca y trasplante ¿Qué técnica debemos utilizar y qué nos aporta en cada situación clínica? VIERNES, 17 DE JUNIO 10:30-12:15 SALÓN DE ACTOS Trasplante cardiaco. ¿Es posible la detección no invasiva del rechazo agudo? José Antonio Vázquez de Prada, Santander

1. TRASPLANTE CARDIACO:¿ES POSIBLE LA
DETECCIÓN NO INVASIVA DEL RECHAZO AGUDO?
José A Vázquez de Prada
HOSPITAL UNIVERSITARIO
VALDECILLA. SANTANDER

2. Chairmen: MA Farr, KK Dhital/Concurrent Session 11
The Heartbreak of Rejection: All Against the Graft
HEART TRANSPLANTATION WITHOUT ROUTINE
ENDOMYOCARDIAL BIOPSIES IS FEASIBLE: RESULTS
OF A CLINICAL-ECHOCARDIOGRAPHIC STRATEGY.
JOSÉ A VÁZQUEZ DE PRADA, MD,PHD, FRANCISCO GONZÁLEZ-VILCHEZ, MD,PHD,
FELIPE RODRIGUEZ-ENTEM MD,PHD, JAVIER RUANO, MD, MARIA ISABEL DEL
CAMPO, RN, AND RAFAEL MARTÍN DURÁN, MD.
WASHINGTON DC, APRIL 27, 2016
PROGRAMA DE TRASPLANTE CARDIACO.
HOSPITAL UNIVERSITARIO MARQUÉS DE VALDECILLA
SANTANDER, SPAIN.

3. • EMB
– Invasive, uncomfortable and expensive
– Small but definite incidence of severe
complications
– Sensitivity? Specificity? Unknown!
– Inter and intra-observer variability? Large!
– Yield? Low!
ENDOMYOCARDIAL BIOPSY
FOR REJECTION SURVEILLANCE
IN HEART TRANSPLANTATION

4. ….HAVE NEVER ACTUALLY REPLACED EMB
NON-INVASIVE TECHNIQUES…

5. Gene expression profiling
European Heart J, 2016
New Engl J Med, 2010
Circ Heart Fail, 2015
®

6. REJECTIONINTENSITY
time
3 96 12
ECHO-CLINICAL THRESHOLD
BIOPSY THRESHOLD
months
0

7. month 1
month 2
month 3
month 4
month 5
month 6
month 7
month 8
month 9
month 10
month 11
month 12
WEEKLY
BI-WEEKLY
MONTHLY
BI-MONTHLY
4
4
Total: 14 visits-1st year
FOLLOW-UP
SCHEDULE
4
3
4
Valdecilla Hospital clinical-echocardiographic
strategy of monitoring for rejection
NO MANDATORY BIOPSY
OPTIONAL
BIOPSY
Santander, Spain

8. Systolic dysfunction
LVEF <50%
LVEF>10 points
Clinical symptoms
consistent with rejection
Signs of heart failure
Hypotension
Unexplained sinus tachycardia
Arrythmias
+
LV wall thickness (IVS + PW > 4 mm)
Doppler based parameters were
NOT routinely considered

9. SAME PHYSICIAN
performing
• Clinical evaluation
• Echocardiogram
• Clinical decision:
…....biopsy?
Side by side comparison
of echo studies
DICOM
??

10. NO EMB TREATMENT
REJECTION
????
CLINICAL &
ECHO data
NORMAL ABNORMAL
(re-schedule)
Biopsy
NO REJECTION
Valdecilla Hospital clinical-echocardiographic strategy for rejection monitoring

11. 488 pts
536 HTx (1992-2014)
44 deaths <1st week 4 lost fw/up
Age 52.7+11years
Male gender 83.6%
Elective HTx 73.4%
Retransplantation 3.7%
V Assist Device 6.7%
Mech. ventilation 7.6%
Serum Cr 1.38+0.7 mg/dl
Pulm Vasc Resist 2.4+1.7 Wood/u
Donor age 34.5+13years
Induction therapy 18.9%
Cyclosporine 66.9%
Tacrolimus 26.6%
Azathioprine 64.5%
Mycophenolate 33.5%
Mycophenolic acid 1.2%
Prednisone 99.6%
Sirolimus 2.7%
Everolimus 4.3%
Strategy applied to

12. 5,6
4,4
3,2
1,8
1,3 1,3
0,8
0,3 0,3
0,1
0,4
0,5
0,2
0
1
2
3
4
5
6
92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14
avg biopsies per pt/1st-year, 1992-2014
730 Bx in 488 pts
1.49
years
Bx/pt/1styear
2001-2014
Bx/pt/1st year
0.43 Bx/pt/1st year

13. 157
143
84 78
26
NO
BIOPSIES
1
BIOPSY
2
BIOPSIES
3-5
BIOPSIES
> 5
BIOPSIES
0
20
40
60
80
100
120
140
160
180
TOTAL NUMBER OF BIOPSIES
PERFORMED TO EACH PATIENT
NO
BIOPSIES;
157; 32%
1 BIOPSY;
29%
2 BIOPSIES; 84;
17%
3-5 BIOPSIES;
78; 16%
>5 BIOPSIES
5%
32% of the pts. managed biopsy-free
79% of the pts. with 0 or only 1-2 biopsies
Only 5% pts. with >5 biopsies
No.ofPatients
No. of Biopsies
%

14. 327 treated
rejection episodes
Echo (-)
&
Biopsy (+)
Echo (+)
130 episodes
Echo (+)
&
Biopsy (+)
52 episodes
95 episodes
40% 16%
29%
Echo (+)
&
Biopsy (-)
50 episodes
15%
327/488 0.67
Rx/pt/1st year

15. 1,54 1,54
1,27
0,77
0,58
0,67
0,33
0,20
0,13
0,32
0,08
92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14
0,00
0,50
1,00
1,50
2,00
199-201
Treated rejection episodes per pt/1st-year, 1992-2014
327 Rx in 488 pts0.67 Rx/pt/1st year

16. 14,8
9,6
8,8
5,35
8,7
1,6
1992-95 1996-99 2000-03 2004-07 2008-11 2012-14
0
5
10
15
20
25
Percentage of Rejection
with hemodynamic compromise
199-201
43 Rx HC in 488 pts Avg = 8,8%

17. 0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Hospital Valdecilla
Registro Español
de Tx Cardiaco
Kaplan-Meier survival, HTx 1992-2014
85%
84,5% 73,1%
72,8% 59,6%
58,7%
YEARS
% n=5100
n=488
Log rank test p= 0.85
Patientssurviving
Hazard Ratio = 0,987 (0,86-1,12)

18. Kaplan-Meier estimate of the time to
death from Rejection or Graft failure, or ReTx
MONTHS
%
Patientswithevent
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10 11 12
Spanish registry
Valdecilla Hospital
Log rank test p= 0.11
Hazard Ratio = 1,41 (0,92-2,16)
0
2
4
6
8
10
0 1 2 3 4 5 6 7 8 9 10 11 12
1-Yr event rate 3,7%
1-Yr event rate 5,3%

19. CONCLUSIONS
• Heart transplantation without routine endomyocardial
biopsies is possible with a clinical-echocardiographic strategy
• The total number of biospsies can be reduced to a minimum
• Our strategy was not associated with an increased risk of
adverse outcomes