The CASTLE-AF trial Nassir F. Marrouche MD on behalf the CASTLE AF - - PowerPoint PPT Presentation

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The CASTLE-AF trial Nassir F. Marrouche MD on behalf the CASTLE AF - - PowerPoint PPT Presentation

Jun 23, 2023 125 likes •375 views

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 Background Atrial fibrillation

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Catheter Ablation versus Standard conventional Treatment in patients with LEft ventricular dysfunction and Atrial Fibrillation

The CASTLE-AF trial

Nassir F. Marrouche MD

  • n behalf the CASTLE AF Investigators
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SLIDE 2
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SLIDE 3
  • Atrial fibrillation (AF) and heart failure

are well intertwined

  • Catheter ablation of AF in patients with

heart failure has been shown feasible

Background

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SLIDE 4
  • 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

CASTLE­AF

Rationale and Objective

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SLIDE 5

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

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SLIDE 6
  • 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

CASTLE­AF

Inclusion Criteria

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SLIDE 7

Study Design— CASTLE­AF

Eligibility Assessment

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 check Adverse event documentation Echocardiography 6­minute walk test Optimization of medication for HF ­Home Monitoring programming NYHA, weight, BP, QoL Patients’ diary

Conventional

  • Investigator initiated, Prospective, Multicenter ( 31 sites, 9 countries),

Randomized, Controlled

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  • 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

CASTLE­AF

Treatment Protocol - Conventional Arm

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SLIDE 9
  • Pulmonary Vein Isolation
  • Additional lesions

Øat discretion of operator

  • Repeat ablation after blanking period

CASTLE AF Ablation Protocol

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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 1 Left ventricular ejection fraction – % 32.5 (25.0­38.0) 31.5 (27.0­37.0) Current type of atrial fibrillation Paroxysmal (%) 30 35 Persistent (%) 70 65

CRT­D implanted (%) 27 28 ICD implanted (%) 73 72

Baseline Characteristics­CASTLE AF

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SLIDE 11

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

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Results­CASTLE AF

Rate 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 1/12/1 900 12:00: 00 AM 1/24/1 900 12:00: 00 AM 2/5/19 00 12:00: 00 AM 2/17/1 900 12:00: 00 AM

100 80 60 40 20 Follow-Up Time (Months) Percent of Patients (%)

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Results­CASTLE AF

AF Burden Derived from Memory of Implanted Devices

AF Burden Percent (%) in Time Baseline 3M 6M 12M 24M 36M 48M 60M 10 20 30 40 50 60 70 Ablation Conventional

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Results­CASTLE AF

Absolute change in LVEF from baseline

LVEF Change from Baseline 12mo 36mo 60mo 5 10 15 20

  • 5
  • 10

[VALUE] [VALUE] [VALUE] [VALUE] [VALUE] [VALUE] Ablation Conventional

p*=0.001 p=0.055 p*=0.005

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SLIDE 15

Event Ablation Group (n=179) Conventional Group (n=184)

  • no. patients with event (%)
  • no. patients with event (%)

Pericardial effusion (acute) 3 (1.7) Severe bleeding (acute) 3 (1.7) Stroke or TIA 7 (3.9) 12 (6.7) Pulmonary vein stenosis 1 (0.6) Pneumonia 3 (1.7) 1 (0.5) Groin infection 1 (0.6) Worsening heart failure 1(0.6)

Results­CASTLE AF

Serious Adverse Events

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SLIDE 16

Results­CASTLE AF

Primary Composite Endpoint

12/31/1 899 12:00:0 0 AM 1/12/19 00 12:00:0 0 AM 1/24/19 00 12:00:0 0 AM 2/5/190 12:00:0 0 AM 2/17/19 00 12:00:0 0 AM

1 0.8 0.6 0.4 0.2

Risk Reduction: 38% Risk Reduction: 38%

Follow-Up Time (Months) Survival Probability

Patients at Risk Patients at Risk Ablation Ablation 179 179 141 141 114 114 76 76 58 58 22 22 Conventional Conventional 184 184 145 145 111 111 70 70 48 12 48 12

Ablation Ablation Conventional Conventional

HR, 0.62 (95% CI, 0.43-0.87); P=0.007 Log-rank test: P=0.006

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SLIDE 17

Results­CASTLE AF

All-Cause Mortality

12/31/1 899 12:00:0 0 AM 1/12/19 00 12:00:0 0 AM 1/24/19 00 12:00:0 0 AM 2/5/190 12:00:0 0 AM 2/17/19 00 12:00:0 0 AM

1 0.8 0.6 0.4 0.2

Patients at Risk Patients at Risk Ablation Ablation 179 179 154 154 130 130 94 94 71 71 27 27 Conventional Conventional 184 184 168 168 138 138 97 97 63 19 63 19 HR, 0.53 (95% CI, 0.32-0.86); P=0.011 Log-rank test: P=0.009

Ablation Ablation Conventional Conventional

Survival Probability Follow-Up Time (Months)

Risk Reduction: 47% Risk Reduction: 47%

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SLIDE 18

Results­CASTLE AF

Worsening Heart Failure Admissions

12/31/1 899 12:00:0 0 AM 1/12/19 00 12:00:0 0 AM 1/24/19 00 12:00:0 0 AM 2/5/190 12:00:0 0 AM 2/17/19 00 12:00:0 0 AM

1 0.8 0.6 0.4 0.2

Patients at Risk Patients at Risk Ablation Ablation 179 179 141 141 114 114 76 76 58 58 22 22 Conventional Conventional 184 184 145 145 111 111 70 70 48 12 48 12 HR, 0.56 (95% CI, 0.37-0.83); P=0.004 Log-rank test: P=0.004

Ablation Ablation Conventional Conventional

Survival Probability Follow-Up Time (Months)

Risk Reduction: 44% Risk Reduction: 44%

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Results­CASTLE AF

Cardiovascular Mortality

12/31/1 899 12:00:0 0 AM 1/12/19 00 12:00:0 0 AM 1/24/19 00 12:00:0 0 AM 2/5/190 12:00:0 0 AM 2/17/19 00 12:00:0 0 AM

1 0.8 0.6 0.4 0.2

Patients at Risk Patients at Risk Ablation Ablation 179 179 154 154 130 130 94 94 71 71 27 27 Conventional Conventional 184 184 168 168 138 138 97 97 63 19 63 19 HR, 0.49 (95% CI, 0.29- 0.84); P=0.009 Log-rank test: P=0.008

Ablation Ablation Conventional Conventional

Survival Probability Follow-Up Time (Months)

Risk Reduction: 51% Risk Reduction: 51%

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Results­CASTLE AF

Cardiovascular Hospitalization

12/31/1 899 12:00:0 0 AM 1/12/19 00 12:00:0 0 AM 1/24/19 00 12:00:0 0 AM 2/5/190 12:00:0 0 AM 2/17/19 00 12:00:0 0 AM

1 0.8 0.6 0.4 0.2

Patients at Risk Patients at Risk Ablation Ablation 179 179 127 127 95 95 60 60 42 42 17 17 Conventional Conventional 184 184 131 131 91 91 52 52 33 8 33 8 HR, 0.72 (95% CI, 0.52-0.99); P=0.041 Log-rank test: P=0.050

Ablation Ablation Conventional Conventional

Survival Probability Follow-Up Time (Months)

Risk Reduction: 28% Risk Reduction: 28%

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SLIDE 21

Results­CASTLE AF

Primary Endpoint-Subgroups

Ablation better Conventional better

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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

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SLIDE 23

Steering Committee

Nassir Marrouche Johannes Brachmann Dietrich Andresen Dietmar Bänsch Lucas Boresma Luc Jordaens Heribert Schunkert Jürgen Siebels Juergen Vogt

The study was funded by BIOTRONIK

Endpoint Adverse Event Committee Heinrich Wieneke Frieder Braunschweig, Harriette F. Verwey

Data and Safety Monitoring Board

John Camm Etienne Aliot Walter Lehmacher

Hüseyin Ince, Béla Merkely, Hüseyin Ince, Evgeny Pokushalov, Georg Nölker, Sergey Popov Prashanthan Sanders Lukasz Szumowski Dimitry Lebedev Tamàs Szili­Török Paul Martin Eduard Ivanitskiy Bernhard Zrenner Anthony Chow Arif Elvan, MD Ivan Diaz Remirez Thomas Pezawas Mathias Busch Zoltán Csanádi Wilhelm Haverkamp Helmut Pürerfellner Andreas Schärtl Bernd Lemke Stefan Schlüter Isabel Deisenhofer Jens Günther Thorsten Lawrenz Ernst Günter Vester Michael Wiedemann

Co­Investigators