Herzinsuffizienz Register (HIR)Herzinsuffizienz Register (HIR)Austria 2006-2009Austria 2006-2009

1648 Patienten wurden von 5/06-3/09 1648 Patienten wurden von 5/06-3/09 eingeschlosseneingeschlossenBei 1246 Patienten war 1 Jahres FU Bei 1246 Patienten war 1 Jahres FU möglichmöglichBei 768 Patienten (62%) wurde das 1 J FUBei 768 Patienten (62%) wurde das 1 J FU

tatsächlich durchgeführt: tatsächlich durchgeführt: HospitalisierungHospitalisierung wegen kardialer wegen kardialer Dekompensation Dekompensation 9.6%9.6%1 Jahresmortalität1 Jahresmortalität 10.3%10.3%

Kandidaten für Gerätetherapie im Kandidaten für Gerätetherapie im Österrreichischen HIRÖsterrreichischen HIR

NYHA III/IV NYHA III/IV 30% / 1.7%30% / 1.7%

LSBLSB 27%27%

LVEF <35% (HIR < 40%)LVEF <35% (HIR < 40%)66%66%

Optimized Medical Therapy Optimized Medical Therapy ??

Richtliniengetreue HI Therapie Richtliniengetreue HI Therapie bei Erstvorstellungbei Erstvorstellung

0102030405060708090

ACEI/ARB %

Betablocker %

Diuretika %

AA %Am

iodaron %

Med. Klasse

>50% Zieldosis

100% Zieldosis

Optimierung der HI Therapie im Optimierung der HI Therapie im HIRHIR

02468

101214161820

ACEI

ARBBetabocker

Delta >50%

Delta 100%

„Nahezu drei Viertel der Patienten erhielten nach 1 Jahr mehr als 50% der Zieldosis“

Geräte Therapie im HIRGeräte Therapie im HIR

0,00

1,00

2,00

3,00

4,00

5,00

6,00

7,00

AICD %

CRT %

AICD+CRT %Erstvorstellung

1 Jahr

Offene Fragen:Offene Fragen:

AuswahlAuswahl der geeigneten der geeigneten PatientenPatienten mit mit Herzinsuffizienz zur GerätetherapieHerzinsuffizienz zur Gerätetherapie

Auswahl des geeigneten des geeigneten GerätesGerätes bei bei Herzinsuffizienz: AICD oder CRT oder CRT+AICDHerzinsuffizienz: AICD oder CRT oder CRT+AICD

ÜberweisungÜberweisung an Rhythmologen oder HI an Rhythmologen oder HI AmbulanzAmbulanz

NachsorgeNachsorge nach Implantation: nach Implantation:Niedergelassener BereichNiedergelassener Bereich

HerzinsuffizienzambulanzHerzinsuffizienzambulanzCRT Ambulanz / PM AmbulanzCRT Ambulanz / PM AmbulanzAICD AmbulanzAICD AmbulanzEchokardiographielaborEchokardiographielabor

Herzinsuffizienz vor/bei AICD Herzinsuffizienz vor/bei AICD ImplantationImplantation

HF %

No HF %

40% 60%

AICD 10 Jahres Überlebensrate in Abhängigkeit von Herzinsuffizienz (n=633)

n=..P<0.001

No HF; n=251

HF; n=382P<0.0001

AICD 10 Jahres Überlebensrate in Abhängigkeit von Herzinsuffizienz und LSB

P<0.001P<0.001

COMPANIONCOMPANION (3): (3):All-cause death: reduced only for CRT/ICDAll-cause death: reduced only for CRT/ICD

(4) Bristow MR, N Engl J Med 2004;350:2140-50.

(4) Bristow MR, N Engl J Med 2004;350:2140-50

It is important to note that the study was not designed or powered to evaluate effects on total mortality nor to compare CRT-P and CRT-D, and conclusive data comparing the effect of CRT-P to CRT-D are not available (1).Furthermore, COMPANION was prematurely terminated (median follow-up of only 16 months)

(1) ESC guidelines 2008

Recommendations for cardiac Recommendations for cardiac resynchronization therapy (1)resynchronization therapy (1)

NYHA III/IV and QRS>120ms and LVEF<35% NYHA III/IV and QRS>120ms and LVEF<35% under optimized medical therapy: under optimized medical therapy: Class I Level AClass I Level A

To improve symptoms/reduce hospitalization: To improve symptoms/reduce hospitalization: Class I Level AClass I Level A

To reduce mortality: To reduce mortality: Class I Level AClass I Level A

(1) ESC guidelines 2008

(3) Bardy GH, N Engl J Med. 2005 Jan 20;352(3):225-37.

(2) Cleland JG, N Engl J Med 2005;352:1539-49.

(2) Cleland JG, N Engl J Med 2005;352:1539-49.

(6) J Card Fail. 2008 Oct;14(8):670-5.

SCD in CARE-HFSCD in CARE-HF

ConclusionConclusionCRT monotherapy is an effective treatment (2)CRT monotherapy is an effective treatment (2)

No effect of an ICD in SCD-HEFT in patients No effect of an ICD in SCD-HEFT in patients with NYHA III (3)with NYHA III (3)

No difference between CRT and CRT/ICD (4)No difference between CRT and CRT/ICD (4)

Stating that CRT/ICD is superior to CRT based Stating that CRT/ICD is superior to CRT based on COMPANION is in contradiction to the on COMPANION is in contradiction to the NYHA III population of SCD-HEFT.NYHA III population of SCD-HEFT.

(2) Cleland JG, N Engl J Med 2005;352:1539-49.(3) Bardy GH, N Engl J Med. 2005 Jan 20;352(3):225-37. (4) Bristow MR, N Engl J Med 2004;350:2140-50

No.at risk

CRT 95 68 44 34 3CRT/ICD 110 56 31 8 1

p<0.001

CRT/ICD n=110

CRT n=95

Adlbrecht C, et al. Eur J Clin Invest. 2009

CRT vs CRT+ICD GesamtmortalitätCRT vs CRT+ICD Gesamtmortalität

0. 00

0. 25

0. 50

0. 75

1. 00

Dauer

0 10 20 30 40 50 60

STRATA: CRT_MONO_CRTDEFI =1 Censor ed CRT_MONO_CRTDEFI =1CRT_MONO_CRTDEFI =2 Censor ed CRT_MONO_CRTDEFI =2

P=0.7

CRT-Mono; n=95

CRT/ICD; n=110

The survival advantage of CRT/ICD vs. CRT The survival advantage of CRT/ICD vs. CRT has has never been adequately addressednever been adequately addressed. . Due to the documented effectiveness of ICD Due to the documented effectiveness of ICD therapy in the prevention of sudden cardiac therapy in the prevention of sudden cardiac death, the use of a CRT/ICD device is death, the use of a CRT/ICD device is commonly preferred in clinical practice in commonly preferred in clinical practice in patients satisfying CRT criteria including an patients satisfying CRT criteria including an expectation of survival with good functional expectation of survival with good functional status for >1 year (1).status for >1 year (1).

(1) HF guidelines ESC (1) HF guidelines ESC 20082008

Geräte Therapie im HIRGeräte Therapie im HIR

0,00

1,00

2,00

3,00

4,00

5,00

6,00

7,00

AICD %

CRT %

AICD+CRT %Erstvorstellung

1 Jahr

Offene Fragen:Offene Fragen:

NachsorgeNachsorge nach Implantation: nach Implantation:

Niedergelassener BereichNiedergelassener Bereich

HerzinsuffizienzambulanzHerzinsuffizienzambulanz

CRT/PM AmbulanzCRT/PM Ambulanz

AICD AmbulanzAICD Ambulanz

EchokardiographielaborEchokardiographielabor

(8) Adlbrecht C, et al. Eur J Clin Invest. 2009,

As in “the real world”, medical therapy is not always up-titrated to the desirable dosages, this provides the opportunity to evaluate the impact of optimizing medical therapy in patients who had received a device therapy Although recommended, the need for optimization of medical

therapy following device implantation has never been proven.

We hypothesized that failure to optimize medical therapy We hypothesized that failure to optimize medical therapy impacts on outcome of patients with CRT or CRT/ICD although impacts on outcome of patients with CRT or CRT/ICD although device therapy itself has been demonstrated to affect outcome.device therapy itself has been demonstrated to affect outcome.

No.at risk

Optimized 56 46 24 16 0Non-optimized 147 78 51 26 4

p=0.003

Optimized patients n=56

Non-optimized patients n=148

Optimierung der HI Therapie im Optimierung der HI Therapie im HIRHIR

02468

101214161820

ACEI

ARBBetabocker

Delta >50%

Delta 100%

„Nahezu drei Viertel der Patienten erhielten nach 1 Jahr mehr als 50% der Zieldosis“

ConclusionConclusionOur data showing worse outcome for CRT/ICD Our data showing worse outcome for CRT/ICD patients should be interpreted with caution, but patients should be interpreted with caution, but underscore the fact, that combined systems should underscore the fact, that combined systems should not be implanted routinely. not be implanted routinely. The impact of quality of baseline pharmacotherapy The impact of quality of baseline pharmacotherapy exceeds the effect of the device implanted.exceeds the effect of the device implanted.Pharmacotherapy must be optimized before device Pharmacotherapy must be optimized before device and re-evaluated after implantation.and re-evaluated after implantation.At present no general advise for the selection of At present no general advise for the selection of patients who will profit most of CRT/ICD can be made.patients who will profit most of CRT/ICD can be made.Finally, the higher costs of a CRT/ICD compared to a Finally, the higher costs of a CRT/ICD compared to a CRT device have to be kept in mind.CRT device have to be kept in mind.

Die Bedeutung der Die Bedeutung der Echokardiographie zur Echokardiographie zur

AV Optimierung nach CRT AV Optimierung nach CRT ImplantationImplantation

A B

p<0.001 p<0.001

Patients at risk:

“Evaluated”: 133 99 79 56 30 6“Not scheduled”: 72 34 23 11 6 2

Patients at risk:

“Evaluated”: 133 128 122 91 52 14 “Not scheduled”: 72 53 43 24 15 3

„evaluated“

„not scheduled“

„evaluated“

„not scheduled“

„optimized“

„judged fine“

„not scheduled“

„impossible“

p<0.001

Patients at risk:

“Optimized”: 58 48 43 30 16 3“Judged fine”: 46 35 28 21 12 3“Not scheduled”: 72 34 23 11 6 2 “Impossible: 29 16 8 4 2 0

Zusammenfassung 1:Zusammenfassung 1:

Obwohl 27% der Patienten im HIR einen LSB Obwohl 27% der Patienten im HIR einen LSB aufweisen, ist die Zahl der CRT Kandidaten nicht aufweisen, ist die Zahl der CRT Kandidaten nicht bekanntbekanntBei Erstvorstellung ist eine leitliniengestützte Bei Erstvorstellung ist eine leitliniengestützte Pharmakotherapie selbst bei einem positiv Pharmakotherapie selbst bei einem positiv selektionierten Krankengut vebesserungswürdigselektionierten Krankengut vebesserungswürdigFür die vermehrte Implantation von Für die vermehrte Implantation von Kombinationsgeräten mangelt es an EvidenzKombinationsgeräten mangelt es an EvidenzAuswahl und Nachsorge der Patienten sollte in erster Auswahl und Nachsorge der Patienten sollte in erster Linie über Herzinsuffizienz- und CRT Ambulanz Linie über Herzinsuffizienz- und CRT Ambulanz erfolgen.erfolgen.

Zusammenfassung 2:Zusammenfassung 2:

Morbidität und Mortalität wird durchMorbidität und Mortalität wird durch

AV-Optimierung undAV-Optimierung und

Pharmakologische Optimierung verbessertPharmakologische Optimierung verbessert

ABER NICHT DURCH vermehrte Implantation von ABER NICHT DURCH vermehrte Implantation von KombinationsgerätenKombinationsgeräten

DankeDankeProf. Pölzl und Prof. Fruhwald für die HIR Prof. Pölzl und Prof. Fruhwald für die HIR DatenDatenProf. Graf und Prof. Binder für die Prof. Graf und Prof. Binder für die EchokardiographiedatenEchokardiographiedatenProf. Gwechenberger für die Daten der Prof. Gwechenberger für die Daten der AV-OptimierungAV-OptimierungDr. Adlbrecht für die Daten der Dr. Adlbrecht für die Daten der medikamentösen Optimierungmedikamentösen OptimierungFa. Guidant/Boston Scientific und Fa. Fa. Guidant/Boston Scientific und Fa. Medtronic für die Stiftung des Medtronic für die Stiftung des EchocardiographiegerätesEchocardiographiegerätes

(6) Auricchio A, Am J Cardiol 2007;99:232–238

REVERSE (REsynchronization REVERSE (REsynchronization reVErses Remodeling in Systolic reVErses Remodeling in Systolic

left vEntricular dysfunction) trial (4)left vEntricular dysfunction) trial (4)

CRT, in combination with optimal medical CRT, in combination with optimal medical therapy, reduces the risk for heart failure therapy, reduces the risk for heart failure hospitalization and improves ventricular hospitalization and improves ventricular structure and function in NYHA functional structure and function in NYHA functional class I and II patients with previous HF class I and II patients with previous HF symptoms. symptoms.

(5) Linde C, JACC, 2008(5) Linde C, JACC, 2008

Predictors of mortality from pump failure Predictors of mortality from pump failure and sudden cardiac death in patients with and sudden cardiac death in patients with

systolic heart failure and left ventricular systolic heart failure and left ventricular dyssynchrony: results of the CARE-HF trial. dyssynchrony: results of the CARE-HF trial.

There was a risk reduction for SCD There was a risk reduction for SCD by CRT of 0.47 (95% confidence by CRT of 0.47 (95% confidence

interval 0.29-0.76; P =0.002) interval 0.29-0.76; P =0.002)

(7) Uretsky BF, J Card Fail. 2008 Oct;14(8):670-5.

MethodsMethods

This observational cohort study (n=205) retrospectively This observational cohort study (n=205) retrospectively assessed the “real life“- impact of concomitant assessed the “real life“- impact of concomitant pharmacotherapy and the effect of CRT compared to CRT/ICD pharmacotherapy and the effect of CRT compared to CRT/ICD therapy on outcome. therapy on outcome.

Outcome of patients with guideline recommended renin-Outcome of patients with guideline recommended renin-

angiotensin system inhibitor and ß-blocker dosages were angiotensin system inhibitor and ß-blocker dosages were compared to patients who did not receive the desired dosages. compared to patients who did not receive the desired dosages.

Co-morbidities were accounted for by application of a Co-morbidities were accounted for by application of a risk stratification score which included age, NYHA functional risk stratification score which included age, NYHA functional class, renal function, atrial fibrillation, and QRS duration. The class, renal function, atrial fibrillation, and QRS duration. The validity of this score has already been proven for device validity of this score has already been proven for device patients (9).patients (9).

(9) Goldenberg I, et al. JACC 2008;51:288-96.

non-optimized optimized p-value(n=148) (n=56)

Age (years) 67.1±11.1 61.8±11.3 p=0.003 Male sex n (%) 112 (76) 46 (82) p=0.324Failed RAAS_BL_100% BL 137 (93) 17 (30) p<0.001HF unit follow-up n (%) 34 (23) 41 (73) p<0.001Diuretics n (%) 109 (74) 41 (73) p=0.950Aldosterone antagonist n (%) 87 (59) 34 (61) p=0.843Digitalis n (%) 43 (29) 13 (23) p=0.404Ischemic heart disease 75 (51) 19 (34) p=0.032Hypertension n (%) 102 (69) 42 (75) p=0.395Diabetes n (%) 30 (21) 17 (30) p=0.177Sodium (mmol/L) 138.0±3.6 138.7±2.6 p=0.172Hemoglobin (mg/dL) 12.9±1.8 13.1±1.8 p=0.526GFR_MDRD (mL/min/1.73 m2) 54.2±20.8 58.9±24.0 p=0.191NT-proBNP (pg/mL) 3861.9±5065.0 4863.4±6848.4 p=0.513QRS duration (ms) 155±34 156±30 p=0.993NYHA p=0.759 NYHA II n (%) 3 (2) 2 (4) NYHA III n (%) 124 (84) 45 (80) NYHA IV n (%) 21 (14) 9 (16)LVEF (%) 27.2±10.0 27.8±8.5 p=0.722Risk stratification score (3) p=0.132

0 0 (0) 1 (2)I 13 (9) 5 (9)II 65 (44) 28 (50)III 45 (30) 19 (34)IV 25 (17) 3 (5)

No.at risk

Optimized 56 56 56 14 2Non-optimized 147 117 86 38 7

p=0.004

Optimized patients n=56

Non-optimized patients n=148

Stepwise multivariate Cox Stepwise multivariate Cox regression: All cause deathregression: All cause death

Including failed pharmacotherapy Including failed pharmacotherapy optimization at follow-up, the co-morbidity optimization at follow-up, the co-morbidity score and CRT/ICD vs. CRT score and CRT/ICD vs. CRT

WaldWald HRHR CICIsignificancesignificance

Failed RAAS_BB_FUFailed RAAS_BB_FU 5.296 5.296 10.410.4 1.416-76.9231.416-76.923 0.0210.021

Stepwise multivariate Cox Stepwise multivariate Cox regression: All cause deathregression: All cause deathand cardiac hospitalisationand cardiac hospitalisation

BB SESE WaldWald Sig.Sig. HRHR 95% CI95% CI

Failed RAAS_BL_100% FUFailed RAAS_BL_100% FU 0.7320.732 0.2950.295 6.1546.154 0.0130.013 2.0802.080 1.166-3.7101.166-3.710

CRT/ICD versus CRTCRT/ICD versus CRT 0.9180.918 0.2450.245 14.07814.078 <0.001<0.001 2.5042.504 1.550-4.0451.550-4.045

Stepwise Cox regression model including the co-morbidity risk stratification score, failure to Stepwise Cox regression model including the co-morbidity risk stratification score, failure to

reach 100% of the recommended ß-blocker and RAAS antagonist dosages at follow-up and reach 100% of the recommended ß-blocker and RAAS antagonist dosages at follow-up and

the device mode (CRT vs. CRT/ICD).the device mode (CRT vs. CRT/ICD).

Goldenberg Score IGoldenberg Score I

Goldenberg Score IIGoldenberg Score II

To test the validity of the Goldenberg To test the validity of the Goldenberg score in our population at baseline we score in our population at baseline we assessed the prognostic value of this assessed the prognostic value of this score (0-4) on mortality, receiving a proof score (0-4) on mortality, receiving a proof for generalizability of the score for our for generalizability of the score for our patients (HR=1.728 [1.114-2.679], patients (HR=1.728 [1.114-2.679], p=0.015). p=0.015).

ESC guidelines 2008ESC guidelines 2008

In COMPANION, CRT-P and CRT-D were both associated with a 20% reduction in the primary combined end-point of all-cause mortality and all-cause hospitalization (P , 0.01). CRT-D was associated with a significant decrease in total mortality (P=0.003), whereas reduction in mortality associated with CRT-P was not statistically significant (P=0.059). It is important to note that the study was not designed or powered to evaluate effects on total mortality nor to compare CRT-P and CRT-D, and conclusive data comparing the effect of CRT-P to CRT-D are not available. In the CARE-HF trial, CRT-P was associated with a significant reduction of 37% in the composite end-point of total death and hospitalization for major cardiovascular events (P=0.001) and of 36% in total mortality (P=0.002).

(5) Moss A et al. N Engl J Med 2009;10.1056/NEJMoa0906431

MADIT CRT (5): NYHA I & II ischemics, NYHA II non-ischemics, QRS≥

130 ms, LVEF≤ 30%

ESC CRT guidelines 2007ESC CRT guidelines 2007

Class I, level of evidence A: For CRT to Class I, level of evidence A: For CRT to reduce morbidity and mortalityreduce morbidity and mortality

Class I, level of eviddence B: CRT/ICD Class I, level of eviddence B: CRT/ICD is is an acceptable optionan acceptable option for patients who for patients who have expectancy of survival with a good have expectancy of survival with a good functional status for more than 1 year.functional status for more than 1 year.

(6) Auricchio A, Am J Cardiol 2007;99:232–238

(6) J Card Fail. 2008 Oct;14(8):670-5.

Macht der ICD als Add-on zum Macht der ICD als Add-on zum CRT Sinn? – CRT Sinn? –

Risiko versus EffektRisiko versus Effekt

Christopher Adlbrecht

Medical University of Vienna, Department of Medical University of Vienna, Department of Internal Medicine II, Division of Cardiology,Internal Medicine II, Division of Cardiology,

Vienna, AustriaVienna, Austria

No.at risk

CRT 95 84 61 43 6CRT/ICD 110 84 55 14 2

p=0.031

CRT/ICD n=110

CRT n=95

Adlbrecht C, et al. Eur J Clin Invest. 2009, in press

No.at risk

CRT 95 68 44 34 3CRT/ICD 110 56 31 8 1

p<0.001

CRT/ICD n=110

CRT n=95

No.at risk

CRT 95 84 61 43 6CRT/ICD 110 84 55 14 2

p=0.031

CRT/ICD n=110

CRT n=95

(3) Bardy GH, N Engl J Med. 2005 Jan 20;352(3):225-37.

(3) Bardy GH, N Engl J Med. 2005 Jan 20;352(3):225-37.

AuswahlAuswahl der geeigneten der geeigneten PatientenPatienten mit mit Herzinsuffizienz zur GerätetherapieHerzinsuffizienz zur Gerätetherapie

Auswahl des geeigneten des geeigneten GerätesGerätes bei bei Herzinsuffizienz: AICD oder CRT oder Herzinsuffizienz: AICD oder CRT oder CRT+AICDCRT+AICD

ÜberweisungÜberweisung an Rhythmologen oder HI an Rhythmologen oder HI AmbulanzAmbulanz