Linee guida ACC/AHA/HRS 2008 - Tigullio Cardiotigulliocardio.com/slide/Lunati.pdf · 2015-07-28 ·...

I risultati dei recenti trial suggeriscono un’estensione delle indicazioni della CRT dalla terapia dello scompenso conclamato alla sua prevenzione; suggerimenti per un approccio appropriato

Maurizio Lunati MDS.C. Elettrofisiologia‐Dipartimento Cardiologico “De Gasperis”

AO Niguarda Cà GrandaMilano

Key points:• 1‐L’evidenza che la “CRT profilattica” migliori outcome clinico e struttura ventricolare e’ convincente e solida• 2‐Le evidenze che la CRT nella FA e in funzione “anti pacemaker‐cardiomiopatia” migliori outcome clinico e struttura ventricolare sono convincenti • 3‐Sulla base dell’EBM e del “real world” è opportuno aggiornare la LG

Linee guida ACC/AHA/HRS 2008

Linee guida AIAC 2006

Cardiac Resynchronisation Therapy

Class I Indication Synus Rhythm, Reduced EF (≤ 35%)Ventricular Dyssynchrony (QRS > 120ms)

NYHA III-IV despite Optimal Medical Therapy

Class II IndicationsSynus Rhythm, Reduced EF (≤ 35%)Ventricular Dyssynchrony (QRS > 120ms)

Symptomatic (NYHA II) and with pacing indication or Primary Prevention ICD indication

Chronic Right Ventricular Stimulation, Reduced EF (≤ 35%)Severe Ventricular DyssynchronyNYHA III-IV despite Optimal Medical Therapy

Pts In Atrial Fibrillation, Reduced EF (≤ 35%)Ventricular Dyssynchrony (QRS > 120ms)

NYHA III-IV despite Optimal Medical Therapy

Reduced EF (≤ 35%), QRS ≤ 120 msVentricular Dyssynchrony (Echo assessment)

NYHA III-IV despite Optimal Medical Therapy

CRT nei pts in Classe NYHA I/II

Pazienti con indicazione convenzionale al pacing

Pazienti in fibrillazione atriale

CRT nei pts con dissincronia meccanica con o

senza dissincronia elettrica

Questioni aperte

CRT nei pts in Classe NYHA I/II

Pazienti con indicazione convenzionale al pacing

Pazienti in fibrillazione atriale

CRT nei pts con dissincronia meccanica con o

senza dissincronia elettrica

Questioni aperte

CRT in NYHA II

Abraham et al., MIRACLE ICD II, Circulation 2004

36% 34% 31%

58%

22% 20%

0%

20%

40%

60%

Improved No Change Worsened

Prop

ortio

n

CRT OFF (n=101) CRT ON (n=85)

Clinical Composite Score

186 pts in NYHA II, FE < 35% and QRS > 130ms randomized CRT ON vs CRT OFF

End Point CRT OFF CRT ON P

Change in peak VO2 0.2±3.2 0.5±3.2 0.87

Change in exercise duration, s

37±186 42±167 0.56

Change in NYHA 0.01±0.63) 0.18±0.61 0.05

Change in QOL 10.7±21.7 13.3±25.1 0.49

Change in 6MHWT, m 33±98 38±109 0.59

Left Ventricular End Diastolic Volume

200

250

300

350

400cm3

Base 6 Mo

P=0.04

Left Ventricular Ejection Fraction

20

22

24

26

28

30%

Base 6 Mo

P=0.02

Left Ventricular Ejection Fraction

20

22

24

26

28

30%

Base 6 Mo

P=0.02

Left Ventricular End Systolic Volume

200

250

300

350

400cm3

Base 6 Mo

P=0.01

Left Ventricular End Systolic Volume

200

250

300

350

400cm3

Base 6 Mo

P=0.01

•CRT (n=69)

Landolina et al.; AJC 2007

CRT in NYHA II952 pts analyzed: NYHA II (188 pts) vs NYHA III-IV (764)

Un minor numero di eventi CV maggiori Classe NYHA che migliora, ma in

una percentuale minore di soggetti

Simile grado di rimodellamento inverso

CRT in NYHA II: REVERSE & MADIT CRT

CRT in NYHA II: REVERSE & MADIT CRT

presentedat ESC 09

presentedat ACC09

Age (mean) yrs 61.3 ± 10.4

Ischemic 44%

NYHA II 83%

EF 27.1 ± 6.8

LVEDD (mm) 68.8 ± 9.2

QRS (ms)ICD therapy optional

156 ± 2368%

REVERSE262 patients (Europe) followed for 24 months

CRT OFF 82 Patients CRT ON 180 Patients

MADIT-CRT1820 patients (US&Europe) >30 months

Age (mean) yrs N.A.

Ischemic N.A.

NYHA I+II

EF <30%

LVEDD (mm) >55

QRS (ms)ICD therapy mandatory

>130100%

CRT ON ~1092 PatientsCRT OFF ~728 Patients

Daubert et al.; JACC 2009 Moss et al 2009. NEJM 361; epub Sept 1

CRT in NYHA II: REVERSE

Daubert et al.; JACC 2009

Primary End Point:Clinical Composite Response at 24-month

% worsened

Entire distribution analysis of worsened, unchanged and improved: P=0.0006

CRT in NYHA II: REVERSE

Daubert et al.; JACC 2009

Powered Secondary End Point: LVESVi

91.688.8

94.5

76.873.6

69.2 69.7

92.5

93.9

96.6

60

70

80

90

100

110

0 6 12 18 24

Months Since Randomization

LVES

Vi (m

l/m2 )

CRT OFF

CRT ON P<0.0001

P-value compares 24-month changes.

CRT in NYHA II: REVERSE

Daubert et al.; JACC 2009

Other Remodeling ParametersLVEDVi (ml/m2) LVEF (%)

129 128124

132

112108

103 103

129

133

90

100

110

120

130

140

150

0 6 12 18 24

Months

LVE

DV

i (m

l/m2 )

CRT OFF

CRT ON

P<0.0001

29.0 29.1 29.5 29.9

32.733.4

34.9 34.8

27.8

28.1

25

30

35

40

0 6 12 18 24

Months

LVE

F (%

)CRT OFF

CRT ON

P<0.0001

P-value compares 24-month changes.

129 128124

132

112108

103 103

129

133

90

100

110

120

130

140

150

0 6 12 18 24

Months

LVE

DV

i (m

l/m2 )

CRT OFF

CRT ON

P<0.0001

29.0 29.1 29.5 29.9

32.733.4

34.9 34.8

27.8

28.1

25

30

35

40

0 6 12 18 24

Months

LVE

F (%

)CRT OFF

CRT ON

P<0.0001

CRT in NYHA II: MADIT CRT confirms REVERSE

Moss et al 2009. NEJM 361; epub Sept 1

Improvements in LV function with CRT-DChanges from baseline to 1-year follow-up

Time to First HF Hospitalization or Death

0%

5%

10%

15%

20%

25%

30%

0 6 12 18 24Months Since Randomization

Perc

enta

ge H

ospi

taliz

ed fo

r HF

or

Die

d

CRT ON

CRT OFF

24.0%

11.7%

HR (95%CI): 0.38 (0.20-0.73)P=0.003

Number at RiskCRT OFF 82 79 76 70 39CRT ON 180 176 173 168 77

CRT in NYHA II: REVERSE

Daubert et al.; JACC 2009

CRT in NYHA II: MADIT CRT confirms REVERSE

Moss et al 2009. NEJM 361; epub Sept 1

Primary endpoint:Heart Failure or Death

Predictive value of QRS: MADIT CRT-REVERSEMADIT CRT

REVERSE 24-months

P for interaction: 0.001

REVERSEPresented at ACC09

Presented results show that CRT

Significanty reduces time to first HF hospitalization or

death1 by 62 percent(HR 0.38 (0.20-0.73) p=0.003

within 24 months

When compared to OMT, ICD optional

CRT in NYHA II: REVERSE & MADIT CRT

Daubert et al.; JACC 2009 Moss et al 2009. NEJM 361; epub Sept 1

CRT reduces Morbidity and Mortality in asymptomatic HF Patients with LVD and wide QRS

MADIT-CRTPresented at ESC

Presented results show that CRT is associated with a

Significant 34 percent reduction (p<0.001) in death or heart failure interventions within 33 months

When compared to OMT, ICD mandatory1 Note:ime to First HF hospitalization or death“ was not the primary endpoint

L’evidenza che la “CRT profilattica” 

migliori outcome clinico e struttura ventricolare e’ convincente e solida 

CRT nei pts in Classe NYHA I/II

Pazienti con indicazione convenzionale al pacing

Pazienti in fibrillazione atriale

CRT nei pts con dissincronia meccanica con o

senza dissincronia elettrica

Questioni aperte

CRT in pts con indicazioni convenzionali al pacing

•50 pts with complete A-V block and normal pump function

•randomized single site RV pacing or BIV pacing

Conclusions:

BIV pacing preserved LV pump function and minimized LV dyssynchrony as compared to conventional RV pacing;

LV pump function decreased significantly and LV dyssynchrony was more pronounced in the RV pacing group

Albertsen AE et al, Europace 2008

BioPace studyRandomized, multicentric, prospective, single-blind, parallel-group-

designInternational (EMEAC + Australia)

– 1st large scaled randomized study looking at the prevention of mechanical desynchronization

– Extend the benefit of BiV pacing to a broader patient population

Enrollment Goal– 1800 patients @ 94 centers– Follow-up phase

Evaluate whether patients with standard pacing indication (pacemaker or ICD)

– any standard-indication for permanent ventricular pacing– LVEF without any limitation– any QRS-width– benefit from the prevention of ventricular remodeling (induced by RV

pacing) with the implantation of a BiV pacing systemA landmark study which results will impact the future of pacemaker therapy

CRT in pts con indicazioni convenzionali al pacing

Yu et al., NEJM Nov 2009

177 pts with bradycardia and normal EF implanted with a CRT deviceRandomization 1:1 Biventricular pacing versus Right Ventricular Apical pacing

Primary end-point: LVEF and LVESV at 12 mos FU

CRT in pts con indicazioni convenzionali al pacing

Yu et al., NEJM Nov 2009

177 pts with bradycardia and normal EF implanted with a CRT deviceRandomization 1:1 Biventricular pacing versus Right Ventricular Apical pacing

Subgroup analysis of LVEF and LVESV

Pazienti con funzione sistolica preservata e indicazione convenzionale al pacing

beneficiano della terapia di resincronizzazione cardiaca in termini di

rimodellamento venrticolare inverso e miglioramento della frazione di eiezione.

CRT nei pts in Classe NYHA I/II

Pazienti con indicazione convenzionale al pacing

Pazienti in fibrillazione atriale

CRT nei pts con dissincronia meccanica con o

senza dissincronia elettrica

Questioni aperte

CRT e FA

Evaluation of CRT in 263 consecutive pts, 96 with chronic AF and 167 in sinus rhythm

Delnoy et al., Am J Cardiol 2007

NYHA QOL

LVEF

CRT e FA

Gasparini et al., JACC 2006

In 162 pts with permanent AF vs 511 pts in SR162 pts with permanent AF where: 48 pts with rhythm control by drugs; 114 pts with AVJ ablation

CRT e FA

Khadjooi et al., Heart 2008

In 86 pts with AF vs 209 pts in SR86 pts with AF where: 66 permanent AF, 20 paroxismal AF

I dati delle casistiche pubblicate mostrano come i pazienti in FA

beneficino della CRT almeno quanto i pazienti in ritmo sinusale

CRT nei pts in Classe NYHA I/II

Pazienti con indicazione convenzionale al pacing

Pazienti in fibrillazione atriale

CRT nei pts con dissincronia meccanica con o

senza dissincronia elettrica

Questioni aperte

68%

32%

≥ 40IVMD < 40≥ 40IVMD < 40

74%

26%

≥ 40IVMD < 40

77%

23%

QRS < 110 ms(46%)

110 ms ≤ QRS < 150 ms(22%)

QRS ≥ 150 ms(32%)

QRS Duration and IVMD

Ghio et al;European Heart Journal(2004) 25,571-578

Ampiezza del QRS e IVMD

CRT e QRS stretto

Beshai et al., RETHIN Q; NEJM 2007

172 pts with narrow QRS (<130ms), EF<35% and NYHA IIIRandomization 1:1 CRT ON vs CRT OFF

I dati disponibili non consentono di affermare che i pazienti con sola

dissincronia meccanica beneficiano della CRT quanto i pazienti con QRS

largo.

EHJ; 31 Aug 2009

EHJ; 31 Aug 2009

...e noi....

Clinical Service data

560 pazienti

Età media: 63,7 + 10,9 anni

21%

79%femmine maschi

Conclusioni

Cardiac Resynchronisation Therapy

Class I Indication Synus Rhythm, Reduced EF (≤ 35%)Ventricular Dyssynchrony (QRS > 120ms)

NYHA III-IV despite Optimal Medical Therapy

Class II IndicationsSynus Rhythm, Reduced EF (≤ 35%)Ventricular Dyssynchrony (QRS > 120ms)

Symptomatic (NYHA II) and with pacing indication or Primary Prevention ICD indication

Chronic Right Ventricular Stimulation, Reduced EF (≤ 35%)Severe Ventricular DyssynchronyNYHA III-IV despite Optimal Medical Therapy

Pts In Atrial Fibrillation, Reduced EF (≤ 35%)Ventricular Dyssynchrony (QRS > 120ms)

NYHA III-IV despite Optimal Medical Therapy

Reduced EF (≤ 35%), QRS ≤ 120 msVentricular Dyssynchrony (Echo assessment)

NYHA III-IV despite Optimal Medical TherapyNecessità di altri studi

Come negare l’evidenza?

Come negare l’evidenza?

Evidenze molto forti

Il futuro...Babec's Story

“On September 25th, 2004, the Birmingham Zoo successfully implanted the first cardiac resynchronization therapy device, or CRT, in a gorilla. One year later Babec is still alive, an unlikely scenario without the device, and his quality of life is significantly improved from that prior to surgery.”

Babec died in 2009...5 years after CRT!!!

http://www.birminghamzoo.com/babec%20story.asp