The CASTLE-AF trial - Clinical Trial Results · Catheter Ablation versus Standard conventional...
Transcript of The CASTLE-AF trial - Clinical Trial Results · Catheter Ablation versus Standard conventional...
Catheter Ablation versus Standard conventional Treatment in patients with LEft ventricular dysfunction and Atrial Fibrillation
The CASTLE-AF trial
Nassir F. Marrouche MD on behalf the CASTLE AF Investigators
• Atrial fibrillation (AF) and heart failure are well intertwined
• Catheter ablation of AF in patients with heart failure has been shown feasible
Background
• Study the effectiveness of catheter ablation of
atrial fibrillation in patients with heart failure in
improving hard primary endpoints of mortality and
heart failure progression when compared to
conventional standard treatment
CASTLEAFRationale and Objective
CASTLEAF
Primary Endpoint
• All-cause mortality
• Worsening heart failure admissions
Secondary Endpoints • Allcause mortality • Worsening of heart failure admissions• Cerebrovascular accidents • Cardiovascular mortality • Unplanned hospitalization due to cardiovascular reason • Allcause hospitalization • Quality of Life: Minnesota Living with Heart Failure and
EuroQoL EQ5D • Exercise tolerance (6 minutes walk test) • Number of delivered ICD shocks, and ATPs
(appropriate/inappropriate) • LVEF• Time to first ICD shock, and time to first ATP • Number of device detected VT/VF • AF burden: cumulative duration of AF episodes • AF free interval: time to first AF recurrence after 3 months
blanking period post ablation
• Symptomatic paroxysmal or persistent AF• Failure or intolerance to ≥ 1 or unwillingness to take AAD• LVEF ≤ 35%• NYHA class ≥ II• ICD/CRTD with Home Monitoring capabilities already implanted due to primary or secondary prevention
CASTLEAFInclusion Criteria
Study Design— CASTLEAF
EligibilityAssessment
3013 pts
Enrolled/Randomized
397 pts
Runin 5 weeks
Ablation
13 pts excluded
21 pts excluded
179 pts
184 pts
200 pts
197 pts
153 pts (26 crossovers)
165 pts (18 crossovers)
Followup: 3, 6, 12, 24, 36, 48, 60 months
ICD/CRTD checkAdverse event documentationEchocardiography6minute walk testOptimization of medication for HFHome Monitoring programming NYHA, weight, BP, QoLPatients’ diary
Conventional
• Investigator initiated, Prospective, Multicenter ( 31 sites, 9 countries), Randomized, Controlled
• According to the ACC/AHA/ESC 2006 guidelines for treatment of AF in Heart Failure patients
• Efforts to maintain sinus rhythm in this study arm were recommended
• In case of rate control strategy:• 60 and 80 beats per minute at rest• 90 and 115 beats per minute during moderate exercise
• Anticoagulation was initiated, if not already started, and maintained throughout the study. The INR was maintained between 2.0 and 3.0
CASTLEAFTreatment Protocol - Conventional Arm
• Pulmonary Vein Isolation• Additional lesions
Øat discretion of operator
• Repeat ablation after blanking period
CASTLE AFAblation Protocol
Ablation group(179 patients)
Conventional group(184 patients)
Age – years 64 (5671) 64 (5673.5)New York Heart Association class I (%) 11 11 II (%) 58 61 III (%) 29 27 IV (%) 2 1Left ventricular ejection fraction – % 32.5 (25.038.0) 31.5 (27.037.0)Current type of atrial fibrillation Paroxysmal (%) 30 35 Persistent (%) 70 65CRTD implanted (%) 27 28
ICD implanted (%) 73 72
Baseline CharacteristicsCASTLE AF
Baseline CharacteristicsCASTLE AF
Ablation group
(179 patients)
Conventional group
(184 patients)
ACEinhibitor or ARB – no. (%) 94 91
Betablocker – no. (%) 93 95
Diuretic – no. (%) 93 93
Digitalis – no. (%) 18 31
Oral anticoagulant – no. (%) 93 96
Antiarrhythmic drug – no. (%) 32 30
Amiodarone – no. (%) 97 85
ResultsCASTLE AFRate Versus Rhythm Control in Conventional Arm
Rate control: Beta-blocker Digitalis Calcium antagonist Atrioventricular node
ablation (in 5 patients) Rhythm control: Antiarrhythmic drug Atrial fibrillation ablation
(18 crossover cases)
12/31/1899 12:00:00 AM
1/12/1900 12:00:00 AM
1/24/1900 12:00:00 AM
2/5/1900
12:00:00 AM
2/17/1900 12:00:00 AM
100806040200
Follow-Up Time (Months)
Perc
ent o
f Pat
ient
s (%
)
ResultsCASTLE AFAF Burden Derived from Memory of Implanted Devices
AF Burden
Percent (%) in Time
Baseline 3M 6M 12M 24M 36M 48M 60M0
10
20
30
40
50
60
70
Ablation Conventional
ResultsCASTLE AFAbsolute change in LVEF from baseline
LVEF
Change fro
m Baseline
12mo 36mo 60mo
0
5
10
15
20
-5
-10
[VALUE][VALUE]
[VALUE]
[VALUE] [VALUE] [VALUE]
Ablation Conventional
p*=0.001 p=0.055 p*=0.005
Event
Ablation Group(n=179)
Conventional Group(n=184)
no. patients with event (%) no. patients with event (%)
Pericardial effusion (acute) 3 (1.7) 0 Severe bleeding (acute) 3 (1.7) 0Stroke or TIA 7 (3.9) 12 (6.7)Pulmonary vein stenosis 1 (0.6) 0Pneumonia 3 (1.7) 1 (0.5)Groin infection 1 (0.6) 0Worsening heart failure 1(0.6) 0
ResultsCASTLE AFSerious Adverse Events
ResultsCASTLE AFPrimary Composite Endpoint
12/31/1899
12:00:00 AM
1/12/1900
12:00:00 AM
1/24/1900
12:00:00 AM
2/5/1900
12:00:00 AM
2/17/1900
12:00:00 AM
10.80.60.40.20
Risk Reduction: 38% Risk Reduction: 38%
Follow-Up Time (Months)
Surv
ival
Pro
babi
lity
Patients at RiskPatients at RiskAblationAblation 179179 141 141 114 114 76 76 58 58 22 22ConventionalConventional 184184 145 145 111 111 70 70 48 12 48 12
AblationAblation
ConventionalConventionalHR, 0.62 (95% CI, 0.43-0.87); P=0.007Log-rank test: P=0.006
ResultsCASTLE AFAll-Cause Mortality
12/31/1899
12:00:00 AM
1/12/1900
12:00:00 AM
1/24/1900
12:00:00 AM
2/5/1900
12:00:00 AM
2/17/1900
12:00:00 AM
10.80.60.40.20
Patients at RiskPatients at RiskAblationAblation 179179 154 154 130 130 94 94 71 71 27 27ConventionalConventional 184184 168 168 138 138 97 97 63 19 63 19
HR, 0.53 (95% CI, 0.32-0.86); P=0.011Log-rank test: P=0.009
AblationAblation
ConventionalConventional
Surv
ival
Pro
babi
lity
Follow-Up Time (Months)
Risk Reduction: 47% Risk Reduction: 47%
ResultsCASTLE AFWorsening Heart Failure Admissions
12/31/1899
12:00:00 AM
1/12/1900
12:00:00 AM
1/24/1900
12:00:00 AM
2/5/1900
12:00:00 AM
2/17/1900
12:00:00 AM
10.80.60.40.20
Patients at RiskPatients at RiskAblationAblation 179179 141 141 114 114 76 76 58 58 22 22ConventionalConventional 184184 145 145 111 111 70 70 48 12 48 12
HR, 0.56 (95% CI, 0.37-0.83); P=0.004Log-rank test: P=0.004
AblationAblation
ConventionalConventional
Surv
ival
Pro
babi
lity
Follow-Up Time (Months)
Risk Reduction: 44% Risk Reduction: 44%
ResultsCASTLE AFCardiovascular Mortality
12/31/1899
12:00:00 AM
1/12/1900
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1/24/1900
12:00:00 AM
2/5/1900
12:00:00 AM
2/17/1900
12:00:00 AM
10.80.60.40.20
Patients at RiskPatients at RiskAblationAblation 179179 154 154 130 130 94 94 71 71 27 27ConventionalConventional 184184 168 168 138 138 97 97 63 19 63 19
HR, 0.49 (95% CI, 0.29- 0.84); P=0.009Log-rank test: P=0.008
AblationAblation
ConventionalConventional
Surv
ival
Pro
babi
lity
Follow-Up Time (Months)
Risk Reduction: 51% Risk Reduction: 51%
ResultsCASTLE AFCardiovascular Hospitalization
12/31/1899
12:00:00 AM
1/12/1900
12:00:00 AM
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12:00:00 AM
2/5/1900
12:00:00 AM
2/17/1900
12:00:00 AM
10.80.60.40.20
Patients at RiskPatients at RiskAblationAblation 179179 127 127 95 95 60 60 42 42 17 17ConventionalConventional 184184 131 131 91 91 52 52 33 8 33 8
HR, 0.72 (95% CI, 0.52-0.99); P=0.041Log-rank test: P=0.050
AblationAblation
ConventionalConventional
Surv
ival
Pro
babi
lity
Follow-Up Time (Months)
Risk Reduction: 28% Risk Reduction: 28%
ConclusionCASTLE AF
• Catheter ablation of atrial fibrillation in patients with heart failure is associated with improved all-cause mortality and fewer admissions for worsening heart failure when compared to conventional standard of care treatment
• Catheter ablation of atrial fibrillation in patients with heart failure is also associated with improved cardiovascular mortality and hospitalization when compared to conventional standard of care treatment
Steering Committee
Nassir MarroucheJohannes BrachmannDietrich AndresenDietmar BänschLucas BoresmaLuc JordaensHeribert SchunkertJürgen SiebelsJuergen Vogt
The study was funded by BIOTRONIK
Endpoint Adverse Event Committee
Heinrich Wieneke Frieder Braunschweig, Harriette F. Verwey
Data and Safety Monitoring Board
John CammEtienne AliotWalter Lehmacher
Hüseyin Ince, Béla Merkely, Hüseyin Ince, Evgeny Pokushalov, Georg Nölker, Sergey PopovPrashanthan Sanders Lukasz Szumowski Dimitry Lebedev Tamàs SziliTörök Paul Martin Eduard IvanitskiyBernhard Zrenner Anthony ChowArif Elvan, MD Ivan Diaz Remirez Thomas Pezawas Mathias Busch Zoltán CsanádiWilhelm Haverkamp Helmut Pürerfellner Andreas SchärtlBernd Lemke Stefan Schlüter Isabel Deisenhofer Jens Günther Thorsten Lawrenz Ernst Günter Vester Michael Wiedemann
CoInvestigators