Herzinsuffizienz, VAD, Herztransplantation - FINeST

2. Januar 2012 

Herzinsuffizienz, VAD, 

Herztransplantation 

Prof. Dr. med. Andres Beiras

2. Januar 2012

Ca. 2/3 der Fälle 

Meist erhaltene LVPF 

AHFS 

Auslöser: Ischämie (30-50%) 

Arrhythmie (20 %) 

Überleitungsstörungen 

Infektionen (20 %) 


Akut dekompensierte CHF 

Rechtsherzversagen j/n 

Akute Herzinsuffizienz 

Selten 

Prognose ↓ 

Pulmonale Vorerkrankungen 

Schnelle Diagnostik 

De Novo AHFS 

Ca. 1/3 der Fälle 

Meist ACS (70%) 

Kardiogener Schock j/n 

Nur ca. 2 % der Fälle 

Prognose ↓ 

Gandhi SK NEJM 2001


Myokardial: 

Akute Herzinsuffizienz: Ätiologie 

Ischämie 70-80 % aller KS-Patienten 

Infarkt 

Kardiomyopathie 

Kontusio cordis 

Myokarditis 

Pharmakotoxizität 

Arrhythmien!!! 




Mechanisch: 

Vitien 

Kunstklappenfehlfunktion 

Intrakavitäre Flußbehinderung 

Lungenembolie 

VSD 

Endokarditis

2. Januar 2012

Akute 

Herzinsuffizienz: 

Dekompensation 

Myokardinfarkt 

Herzoperation 


Akute Herzinsuffizienz & Niereninsuffizienz 

CO� 

Humorale 

Faktoren 

Perfusion� 

Diuretika 

ACE-Hemmer 

Kontrastmittel 

RAA Aktivierung: 

Na+H2O Retention 

Vasokonstriktion 

BNP Natriurese 

Zytokine� 

Venöser Druck� 

Akute 

Niereninsuffizienz: 

Perfusion� 

O2-Angebot� 

GFR� 

ANP/BNP Resistenz 

Ronco et al. Curr Opinion Crit Care 2009

2. Januar 2012


Jessup M et al. N Engl J Med 2003;348:2007


Jessup M et al. N Engl J Med 2003;348:2007

2. Januar 2012


Herzunterstützungssysteme 

Herzunterst tzungssysteme 

Intraaortale Ballonpumpe (IABP) 

VAD 

•ECMO 

•LVAD 

•BiVAD 

•TaH


Intraaortale Ballonpulsation (IABP) 

1. Herzunterstützungssystem 

Herzunterst tzungssystem 

2. Art. Punktion (A. femoralis) femoralis) 

3. Plazierung d. Ballons distal li. li. 

A. subclavia 

4. EKG-getriggerte 

EKG getriggerte Inflation/Deflation 

5. Spezifische Therapie

2. Januar 2012


Diastolische 

Augmentation 

Leersaugen 

des Ballons

40 

30 

20 

10 

0 


Perioperative Mortalität (Prozent) 

33,8 

19,6 

Cresswell 

1992, n=669 

31 

0 

Dziuban 

1994 

11,9 

intra-/postoperative IABP-Insertion 

präoperative IABP-Insertion 

2,7 

Dietl 1996 

n=163 

16,7 

0 

Christenson 

1997, n=52 

20 

3,3 

Christenson 

1999, n=60 

22 

5,7 

Kang 2001 

n=101

2. Januar 2012


Therapiekonzepte 

1. Ziel: Transplantation: 

„bridge to transplantion“ 

2. Ziel: Permanenter Herzersatz: 

„destination therapy“ 

3. Ziel: Myokarderholung und VAD-Explantation: 

„bridge to recovery“ 

4. Ziel: Überbrückung bis zur Langzeitassist- 

Implantation: 

„bridge to bridge“ - und langfristig HTx

Extrakorporale Pumpen 

(Mono-/ Biventrikulär) 

Pulsatil 

Abiomed 

Thoratec 

Excor 

2. Medos Januar 2012 

Nichtpulsatil 

ECMO 

MECC 

Lifebridge 

Unterstützungssysteme 

Pulsatil 

Novacor 

HeartMate I 

HeartMate I 

Thoratec 

IVAD 

Intrakorporale Pumpen 

(LVAD) 

Nichtpulsatil 

DeBakey 

HeartMate II 

Jarvik 2000 

Incor 

Mikroaxial 

Impella 

AMED 

Komplett implantierbare 

Systeme (LVAD) 

LionHeart 

Kunstherzen 

Abiocor 

Cardiowest 

Elektrisch 

Pneumatisch


Indikationsstellung zur VAD-Implantation 

Herzinsuffizienz NYHA IV trotz 

prolongierter inotroper i.v.-Therapie und 

Einsatz der IABP, sowie 

� syst. RR < 90 mmHg 

� Herzindex < 2 l/min/kg 

� ZVD > 16 -20 mmHg 

� PCWP > 20 -25 mmHg 

� SvO2 < 50 % 

� Oligurie < 20 ml/h

Antriebstechnik: 

- pneumatisch 

- elektromechanisch 

- elektromagnetisch 

- elektrohydraulisch 

Typ: Verdränger- oder Rotorpumpe 

Fluß: pulsativ oder nonpulsatil 


VAD: Welche Pumpe / Welche Patient?


P. B.


ECMO 

1. Zentrifugalpumpe 

2. Oxygenator 

3. Wärmetauscher

ECMO: Nur kurzzeitige Überbr berbrückung! ckung! 

�� „Bridging Bridging Concept“ Concept 

Dann Entscheidung: Explantation / VAD / HTx 


1. Kardial 

� Kardiogener Schock 

2. Pulmonal 

(Herzchirurgie, Myokardinfarkt) 

� ARDS 

� PPHT 

ECMO - Indikationen


ECMO - Komplikationen 

1. Blutung !!! 

2. Extremitätenischämie 

3. Infektion 

4. Malperfusion (ZNS, Abdominell) 

5. Hämolyse (ANV)


DeBakey LVAD 

Steuerungs - 

Gerät 

Fluß-Meßkopf 

Ausflußkonduit 

Einflußkonduit


Sackpumpen: 

- Pumpsack wird durch Membran / Druckplatten 

„ausgepreßt“ 

- pulsatil 

z. B. - Novacor 

- Berlin Heart Excor-System 

-TCI HeartMateI 

- Thoratec VAD 

- Medos VAD 

- Abiomed BVS 5000 

- Lionheart 

P. B.


Novacor Novacor Plus 

P. B.

TCI HeartMate IP 


TCI Heartmate I® 

Typ: Verdrängerpumpe 

Firma: Thoratec Inc., USA 

Dauer: mittel- bis langfristig 

Anwendung: LVAD, Bridge to Transplant 

Ort: Implantierbar 

Fluss: bis 10 l/min. 

Funktion: 

IP: Ein Blutsack wird mit Hilfe von Druckluft 

entleert. 

VE:Ein Blutsack wird von einer sog. Pusherplate 

entleert.


Zukunft ist da: HVAD-Heartware inc.


Zukunft ist da: HVAD-Heartware inc.

Berlin Heart Excor 

2. Januar 2012

Thoratec VAD-System 

Parakorporale Blutpumpe Dual Drive Konsole 

TLV II Portable Driver 

2. Januar 2012


AbioCor

VADs: Antikoagulation 

1. Stufe: - 12 h postoperativ Heparin i.v. 

(ACT 160-180 s) 

2. Stufe: - Tirofiban ( Aggrastat ) ~ 0,5 mg/h 

3. Stufe: - Ersatz von Heparin durch 

Marcumar (PI 20-30% ) 

- Aggrastat-Ersatz durch 

Clopidogrel 75 mg/d 

- ASS 100 mg/d 

4. Stufe: - Marcumar nach INR/Quick-Wert 

- ASS 300 mg/d 

2. Januar 2012

2. Januar 2012

Groote Schuur Hospital, 

University of Cape Town 


December 3, 1967 

First human-to-human 

cardiac allograft

ORGAN 


ISHLT 

ISHLT REGISTRY DATABASE: 

Number of Transplants Reported 

Transplants Reported from 7/1/2009 

through 6/30/2010 

Total Transplants Reported 

through 6/30/2010 

Heart 3,608 100,210 

Heart-Lung 69 4,248 

Lung 3,168 38,119 

ISHLT 

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132

Number of Transplants 

5000 

4500 

4000 

3500 

3000 

2500 

2000 

1500 

1000 

500 

0 

187 


NUMBER OF HEART TRANSPLANTS REPORTED BY YEAR 

322 

670 

1.254 

ISHLT 

2.349 

2.989 

3.504 

3.796 

4.456 

4.669 

4.639 

4.841 

4.747 

4.741 

4.614 

4.516 

4.258 

ISHLT 

3.992 

3.855 

3.830 

J Heart Lung Transplant. 2011 Oct; 30 (10): 1071-1132 

3.725 

3.650 

3.608 

3.708 

3.764 

3.765 

3.720 

3.742


% of Cases 

ReTX 

2% 

Congenital 

2% 

70 

60 

50 

40 

30 

20 

CAD 

46% 

1982 

1983 

DIAGNOSIS IN ADULT HEART 

TRANSPLANTS 

1982-1999 

ISHLT 

Misc. 

1% 

Valvular 

4% 

Myopathy 

45% 

2004 

ReTX 

2% 

J Heart Lung Transplant 2004; 23: 796-803 

CAD 

45% 

Congenital 

2% 

1/2000-6/2003 

Misc. 

2% 

Myopathy 

46% 

Myopathy CAD 

1984 

1985 

1986 

1987 

1988 

1989 

1990 

1991 

1992 

1993 

1994 

1995 

1996 

1997 

1998 

1999 

2000 

2001 

2002 

Valvular 

3%

ReTX 

2% 

Congenital 

2% 


CAD 

44% 

1/1982-6/2010 

DIAGNOSIS IN ADULT HEART TRANSPLANTS 

Misc. 

0% 

Myopathy 

48% 

Valvular 

4% 

ReTX 

3% 

Congenital 

3% 

ISHLT 

CAD 

38% 

1/2005-6/2010 

Misc. 

1% 

Valvular 

3% 

Myopathy 

53% 


�EF < 20% 

� CI < 2 l/min/m2 


Indikation zur HTx 

Hämodynamik + Klinik 

� LVEDP > 20 mmHg 

� ZVD > 15 mmHg 

� Maximale O2-Aufnahme < 10-14 ml/kg/min


Kontraindikationen zur (solitären) (solit ren) HTx 

� Fixierter pulmonaler Hypertonus (Ilomedin-Test) 

� PVR > 4 Wood (=320 dyn), TPG > 15 mmHG 

� Manifeste Infektionen + HIV 

� Akute Lungenembolie 

� Fortgeschr. Leber- o. Niereninsuffizienz 

� Nicht kurativ behandelte Malignome 

� Schwerer Nikotin-, Alkohol-,Drogenabusus 

� Mangelndes soziales Umfeld/Compliance


P. B.


P. B.


P. B.


P. B.


P. B.


P. B.


P. B.

Survival (%) 

100 

80 

60 

40 

20 

0 


N=89,006 

HEART TRANSPLANTATION 

Kaplan-Meier Survival (1/1982-6/2009) 

Half-life = 11.0 years 

Conditional Half-life = 14.0 years 

HEART TRANSPLANTATION 

Kaplan-Meier Survival (1/1982-6/2005) 

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 

ISHLT 

Years 


N at risk at 25 years = 98


P. B.


When the heart does not start (up)… 

… after Transplantation

CAUSE OF DEATH 

Cardiac Allograft 

Vasculopathy 


0-30 Days 

(N = 3,771) 

Does it really happen? 

31 Days – 

1 Year 

(N = 3,675) 

>1 Year – 

3 Years 

(N = 2,848) 

>3 Years – 

5 Years 

(N = 2,448) 

>5 Years – 

10 Years 

(N = 5,592 ) 

>10 Years 

– 15 Years 

(N =3,070) 

>15 Years 

(N =1,075) 

63 (1.7%) 173 (4.7%) 394 (13.8%) 386 (15.8%) 806 (14.4%) 455 (14.8%) 134 (12.5%) 

Acute Rejection 242 (6.4%) 442 (12.0%) 292 (10.3%) 110 (4.5%) 100 (1.8%) 28 (0.9%) 8 (0.7%) 

Lymphoma 2 (0.1%) 69 (1.9%) 93 (3.3%) 106 (4.3%) 254 (4.5%) 119 (3.9%) 43 (4.0%) 

1992-2009: 58600 Htx 

„Graft Failure“� n=5000 

(8,6 %) 

0-30 days „Graft Failure“� n=1550 

(2,7 %) 

Malignancy, Other 4 (0.1%) 82 (2.2%) 311 (10.9%) 448 (18.3%) 1,064 (19.0%) 599 (19.5%) 188 (17.5%) 

CMV 4 (0.1%) 44 (1.2%) 18 (0.6%) 5 (0.2%) 6 (0.1%) 1 (0.0%) 0 

Infection, Non-CMV 484 (12.8%) 1,116 (30.4%) 365 (12.8%) 245 (10.0%) 601 (10.7%) 313 (10.2%) 131 (12.2%) 

Graft Failure 1,553 (41.2%) 651 (17.7%) 681 (23.9%) 495 (20.2%) 1,015 (18.2%) 499 (16.3%) 153 (14.2%) 

Technical 270 (7.2%) 42 (1.1%) 19 (0.7%) 19 (0.8%) 41 (0.7%) 27 (0.9%) 11 (1.0%) 

Other 201 (5.3%) 303 (8.2%) 272 (9.6%) 211 (8.6%) 518 (9.3%) 275 (9.0%) 104 (9.7%) 

Multiple Organ Failure 508 (13.5%) 419 (11.4%) 144 (5.1%) 132 (5.4%) 382 (6.8%) 236 (7.7%) 90 (8.4%) 

Renal Failure 24 (0.6%) 36 (1.0%) 46 (1.6%) 88 (3.6%) 332 (5.9%) 254 (8.3%) 105 (9.8%) 

Pulmonary 154 (4.1%) 147 (4.0%) 111 (3.9%) 120 (4.9%) 235 (4.2%) 134 (4.4%) 59 (5.5%) 

Cerebrovascular 262 (6.9%) 151 (4.1%) 102 (3.6%) 83 (3.4%) 238 (4.3%) 130 (4.2%) 49 (4.6%) 


2. Januar 2012

2. Januar 2012

2. Januar 2012


Immunsuppression 

Slide 27- Core

% of patients 

80 

70 

60 

50 

40 

30 

20 

10 

0 


ADULT HEART RECIPIENTS 

Induction Immunosuppression by Location 

Transplants: January 2002 – June 2010 

Europe North America 

ISHLT 

Any Induction IL-2R Antagonist Polyclonal ALG/ATG 

Analysis is limited to patients who were 

alive at the time of the discharge

% of Patients 

100 

80 

60 

40 

20 

0 



Maintenance Immunosuppression at Time of 1 Year Follow-up 

2000 (N = 1,538) 2003 (N = 1,668) July 2009 - June 2010 (N = 1,616) 

Cyclosporine Tacrolimus Sirolimus/ 

Everolimus 

MMF/MPA Azathioprine Prednisone 

Analysis is limited to patients who were 

alive at the time of the follow-up

2. Januar 2012

2. Januar 2012

POST-HEART TRANSPLANT MORBIDITY FOR ADULTS Cumulative Prevalence 

in Survivors within 1 and 5 Years 

Post-Transplant (Transplants: 2000 - June 2005) 

Outcome 


Within 1 

Year 

Total N with 

known response 

Within 5 

Years 

Total N with known 

response 

Hypertension 75.1% (N = 3,273) 89.5% (N = 3,273) 

Renal Dysfunction 26.3% (N = 3,273) 28.9% (N = 3,273) 

Abnormal Creatinine < 2.5 mg/dl 20.7% 22.1% 

Creatinine > 2.5 mg/dl 4.8% 5.0% 

Chronic Dialysis 0.5% 1.5% 

Renal Transplant 0.3% 0.3% 

Hyperlipidemia 73.4% (N = 3,273) 90.7% (N = 3,273) 

Diabetes 28.0% (N = 3,273) 40.0% (N = 3,273) 

Cardiac Allograft Vasculopathy 5.4% (N = 3,273) 27.1% (N = 3,273) 

ISHLT 


Incidence of Cause-Specific Deaths 

14% 

12% 

10% 

8% 

6% 

4% 

2% 

0% 


ADULT HEART TRANSPLANT RECIPIENTS: 

Cumulative Incidence of Leading Causes of Death 

(Transplants: January 1992 - June 2009) 

CAV Acute Rejection 

Malignancy (non-Lymph/PTLD) Graft Failure 

CMV Infection (non-CMV) 

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 

Time (years)

Incidence of Cause-Specific Deaths 

10% 

8% 

6% 

4% 

2% 

0% 


ADULT HEART TRANSPLANT RECIPIENTS: 

Cumulative Incidence of Leading Causes of Death 


CAV Acute Rejection 

Malignancy (non-Lymph/PTLD) Graft Failure 

CMV Infection (non-CMV) 

0 1 2 3 4 5 

Time (years)

Recipient age 

Donor age 

Recipient height 

BMI difference 

Bilirubin 


ADULT HEART TRANSPLANTS (1/2000-6/2005) 

Risk Factors for 5 Year Mortality 

Continuous Factors (see figures) 

Ischemia time 

Serum creatinine 

Transplant center volume 

TPG 

ISHLT 


Recipient age 

Recipient weight 

Recipient height 

Donor age 


ADULT HEART TRANSPLANTS (1995-6/2000) 

Risk Factors for 10 Year Mortality 

Continuous Factors (see figures) 

ISHLT 

Creatinine 

Bilirubin 

Ischemia time 

Volume 


% Freedom from OB 

Freedom from Bronchiolitis Obliterans 

For Adult Lung Recipients (Follow-ups: April 1994-June 2003) 

100 

80 

60 

40 

20 

0 

0 1 2 3 4 5 

Years 

ISHLT 


2004 


Chronische Abstoßung: BOS/TVP 

% Free from CAV 

Transplantatsvaskulopathie 

ISHLT 

FREEDOM FROM CAV 

Stratified by Diagnosis 

For Adult Heart Recipients (Follow-ups: January 1996-June 2003) 

100 

90 

80 

70 

60 

50 

40 

30 

20 

10 

0 

Coronary Artery Disease (N = 8,195) 

Cardiomyopathy (N = 7,924) 

0 1 2 3 4 5 6 7 

Years 

2004 


p = 0.005

24% 


ADULT LUNG TRANSPLANTATION: Indications 


Alpha-1 Bronchiectasis Congenital Heart Disease 

COPD CF IP F 

LAM OB (Non-ReTX) Other 

PPH Re-TX Sarcoidosis 

1% 5% 

1% 

2% 

1% 

IPF 

2% 

ISHLT 

2% 

9% 

COPD 

Single Lung 

Transplants 

0% 

0% 

53% 

2004 

10% 


1% 

1% 

5% 

8% 

IPF 

30% 

2% 3% 

CF 

Bilateral/Double Lung 

Transplants 

10% 

COPD 

5% 

2% 

23%


Idiopathische Lungenfibrose 

�Symptomatische zunehmende 

Verschlechterung 

�bereits bei geringer Symptomatik 

Evaluation der LTx, da bereits bei VC < 

60% fortgeschrittene Erkrankung mit 

sehr ungewisser Prognose vorliegt

�FEV1 < 25 % 


Chronisch obstruktive 

Lungenerkrankung 

�pCO2 > 55 mmHg (7,3 kPa) 

�erhöhter PAP +/- Cor pulmonale


DIAGNOSIS IN ADULT HEART-LUNG TRANSPLANTS BY ERA 

COPD/Alpha-1 Congenital Heart Disease Acquired Heart Disease 

Alpha-1 CF IPF 

PPH Re-TX Other 

15% 

4% 

Indikationen zur HLTx 

29% 

3% 26% 

CHD 

ISHLT 

PPH 

8% 

3% 

12% 

2004 


3% 

6% 

17% 

36% 

CHD 

1982-1995 1/1996-6/2003 

2% 

PPH 

3% 

“Other” includes OB (non-ReTX), Bronchiectasis, Sarcoidosis 

1% 

19% 

13%

2. Januar 2012


Herz-Lungen-Transplantation


HLtx: Late Mortality (>30 days) 

� Bronchiolitis obliterans: 64% 

� Infection : 24% 

� Bronchiolitis obliterans 

in combination with 

graft vasculopathy : 12%

100% 

90% 

80% 

70% 

60% 

50% 

40% 

30% 

20% 

10% 


0% 

Cumulative Survival 

6m 1y 2y 

1996-9/2000 

1983-1995 

ISHLT-registry

Survival (%) 


HEART-LUNG TRANSPLANTATION 

Kaplan-Meier Survival for Adult Recipients 

100 

80 

60 

40 

20 

0 

ISHLT 


0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 

2004 

Years 


Half-life = 3.1 years 

N=2,389


NUMBER OF HEART TRANSPLANTS 

REPORTED BY YEAR 

4500 

4000 

3500 

3000 

2500 

2000 

1500 

1000 

500 

0 

189 

1982 

1983 

1185 

669 

318 

ISHLT 

1984 

1985 

2165 

1986 

1987 

3156 

2720 

3380 

1988 

1989 

2004 



Spannungsfeld: Organmangel… 

4024 4186 4219 4382 4438 4356 4206 4087 3769 3436 3314 3219 3107 

1990 

1991 


1992 

1993 

NUMBER OF LUNG TRANSPLANTS REPORTED 

BY YEAR AND PROCEDURE TYPE 

1800 

1600 

1400 

1200 

1000 

800 

600 

400 

200 

0 

1994 

1995 

13 

1996 

1997 

Bilateral/Double Lung 

Single Lung 

188 

15 46 83 

1985 

1986 

1987 

1988 

1989 

1990 

1991 

1992 

1993 

1994 

1995 

1996 

1997 

1998 

1999 

2000 

2001 

2002 

ISHLT 

1998 

1999 

2000 

2001 

418 

706 

2002 

922 

1086 

2004 


1365 

1370 

1229 

1443 1497 

14361412 

15631655 

NUMBER OF HEART-LUNG 

TRANSPLANTS REPORTED BY YEAR 


250 

200 

150 

100 

50 

0 

1982 

1983 

1984 

1985 

ISHLT 

1986 

1987 

1988 

1989 

1990 

1991 

1992 

1993 

2004 


1994 

1995 

1996 

1997 

1998 

1999 

2000 

2001 

2002

2. Januar 2012

ADULT HEART TRANSPLANTATION 

% OF PATIENTS BRIDGED WITH MECHANICAL CIRCULATORY SUPPORT* (Transplants: 1/2000 – 12/2009) 

50 

% of patients 

40 

30 

20 

10 

0 


2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 

ISHLT 

Year 


* LVAD, RVAD, TAH

100% 

80% 

60% 

40% 

20% 

0% 



Employment Status of Surviving Recipients 

(Follow-ups: 1995 - June 2010) 

1 Year (N = 20,930) 3 Year (N = 18,213) 5 Year (N = 15,627) 

Retired 

Not Working 

Working Part Time 

Working Full Time 

Working (FT/PT 

status unknown)

% of transplants 

40 

35 

30 

25 

20 

15 

10 

5 

0 


AGE DISTRIBUTION OF HEART TRANSPLANT RECIPIENTS BY ERA 

1982-1991 (N = 23,929) 

1992-2001 (N =43,912) 

2002-6/2010 (N = 31,398) 

p < 0.0001 

0-9 10-19 20-29 30-39 40-49 50-59 60-69 70+ 

Recipient Age 



Die Schattenseite der Warteliste… 

Warteliste


Lebensqualität 10 Jahre nach HTx 

Sind Sie mit Ihrem Leben zufrieden? 

absolut 

ziemlich 

mehr oder weniger 

eher unzufrieden 

absolut unzufrieden 

20% 

20% 

24% 

4% 

32%

Lebensqualität 10 Jahre nach HTx 

Würden Sie sich wieder für HTx entscheiden ? 


ja 

weiß nicht 

nein 

76% 

8% 

16%

Herzinsuffizienz, VAD, Herztransplantation - FINeST

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