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

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 (AF) and heart failure are well intertwined • Catheter ablation of AF in patients with heart failure has been shown feasible

CASTLE­AF Rationale and Objective • 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 Primary Endpoint Secondary Endpoints • All­cause mortality • • All-cause mortality Worsening of heart failure admissions • Cerebrovascular accidents • Cardiovascular mortality • Unplanned hospitalization due to cardiovascular reason • Worsening heart failure • All­cause hospitalization • Quality of Life: Minnesota Living with Heart Failure and admissions 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

CASTLE­AF Inclusion Criteria • 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

Study Design— CASTLE­AF • Investigator initiated, Prospective, Multicenter ( 31 sites, 9 countries), Randomized, Controlled 179 pts 3013 pts 153 pts (26 cross­overs) Eligibility Assessment Ablation 21 pts excluded ICD/CRT­D check 200 pts Adverse event documentation Echocardiography Run­in 5 weeks Enrolled/ 6­minute walk test Follow­up: 3, 6, 12, 24, 36, 48, 60 months Randomized Optimization of medication for HF ­Home Monitoring programming 197 pts NYHA, weight, BP, QoL Patients’ diary 397 pts 13 pts excluded Conventional 165 pts (18 cross­overs) 184 pts

CASTLE­AF Treatment Protocol - Conventional Arm • 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

CASTLE AF Ablation Protocol • Pulmonary Vein Isolation • Additional lesions Ø at discretion of operator • Repeat ablation after blanking period

Baseline Characteristics­CASTLE AF Ablation group Conventional group (179 patients) (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 Ablation group Conventional group (179 patients) (184 patients) 94 91 ACE­inhibitor or ARB – no. (%) 93 95 Beta­blocker – no. (%) 93 93 Diuretic – no. (%) 18 31 Digitalis – no. (%) 93 96 Oral anticoagulant – no. (%) 32 30 Antiarrhythmic drug – no. (%) 97 85 Amiodarone – no. (%)

Results­CASTLE AF Rate Versus Rhythm Control in Conventional Arm Rate control: Percent of Patients (%)  100 Beta-blocker  Digitalis 80  Calcium antagonist 60  Atrioventricular node 40 ablation (in 5 patients) 20 0 Rhythm control: 12/31/ 1/12/1 1/24/1 2/5/19 2/17/1  Antiarrhythmic drug  Atrial fibrillation ablation 1899 900 900 00 900 (18 crossover cases) 12:00: 12:00: 12:00: 12:00: 12:00: 00 AM 00 AM 00 AM 00 AM 00 AM Follow-Up Time (Months)

Results­CASTLE AF AF Burden Derived from Memory of Implanted Devices 70 60 Percent (%) in Time 50 40 30 20 10 0 Baseline 3M 6M 12M 24M 36M 48M 60M AF Burden Ablation Conventional

Results­CASTLE AF Absolute change in LVEF from baseline 20 p *=0.001 p *=0.005 p =0.055 LVEF Change from Baseline 15 10 [VALUE] [VALUE] [VALUE] 5 [VALUE] [VALUE] [VALUE] 0 -5 -10 12mo 36mo 60mo Ablation Conventional

Results­CASTLE AF Serious Adverse Events Ablation Group Conventional Group (n=179) (n=184) Event no. patients with event (%) no. patients with event (%) Pericardial effusion (acute) 3 (1.7) 0 Severe bleeding (acute) 3 (1.7) 0 Stroke or TIA 7 (3.9) 12 (6.7) Pulmonary vein stenosis 1 (0.6) 0 Pneumonia 3 (1.7) 1 (0.5) Groin infection 1 (0.6) 0 Worsening heart failure 1(0.6) 0

Results­CASTLE AF Primary Composite Endpoint 1 0.8 Survival Probability 0.6 Ablation Ablation 0.4 0.2 HR, 0.62 (95% CI, 0.43-0.87); 0 P=0.007 Conventional Conventional Log-rank test: P=0.006 12/31/1 1/12/19 1/24/19 2/5/190 2/17/19 Risk Reduction: 38% Risk Reduction: 38% 899 00 00 0 00 12:00:0 12:00:0 12:00:0 12:00:0 12:00:0 0 AM 0 AM 0 AM 0 AM 0 AM Follow-Up Time (Months) Patients at Risk Patients at Risk Ablation 179 141 141 114 76 76 58 58 22 Ablation 179 114 22 Conventional 184 145 145 111 70 70 48 12 48 12 Conventional 184 111

Results­CASTLE AF All-Cause Mortality 1 0.8 Ablation Ablation Survival Probability 0.6 0.4 0.2 HR, 0.53 (95% CI, 0.32-0.86); Conventional Conventional 0 P=0.011 Log-rank test: P=0.009 12/31/1 1/12/19 1/24/19 2/5/190 2/17/19 Risk Reduction: 47% Risk Reduction: 47% 899 00 00 0 00 12:00:0 12:00:0 12:00:0 12:00:0 12:00:0 0 AM 0 AM 0 AM 0 AM 0 AM Follow-Up Time (Months) Patients at Risk Patients at Risk Ablation 179 154 154 130 94 94 71 71 27 Ablation 179 130 27 Conventional 184 168 168 138 97 97 63 19 63 19 Conventional 184 138

Results­CASTLE AF Worsening Heart Failure Admissions 1 0.8 Survival Probability Ablation Ablation 0.6 0.4 0.2 HR, 0.56 (95% CI, 0.37-0.83); 0 P=0.004 Conventional Conventional Log-rank test: P=0.004 12/31/1 1/12/19 1/24/19 2/5/190 2/17/19 Risk Reduction: 44% Risk Reduction: 44% 899 00 00 0 00 12:00:0 12:00:0 12:00:0 12:00:0 12:00:0 0 AM 0 AM 0 AM 0 AM 0 AM Follow-Up Time (Months) Patients at Risk Patients at Risk Ablation 179 141 141 114 76 76 58 58 22 Ablation 179 114 22 Conventional 184 145 145 111 70 70 48 12 48 12 Conventional 184 111

Results­CASTLE AF Cardiovascular Mortality 1 Ablation Ablation 0.8 Survival Probability 0.6 0.4 HR, 0.49 (95% CI, 0.29- 0.84); P=0.009 0.2 Conventional Conventional Log-rank test: P=0.008 0 12/31/1 1/12/19 1/24/19 2/5/190 2/17/19 Risk Reduction: 51% Risk Reduction: 51% 899 00 00 0 00 12:00:0 12:00:0 12:00:0 12:00:0 12:00:0 0 AM 0 AM 0 AM 0 AM 0 AM Follow-Up Time (Months) Patients at Risk Patients at Risk Ablation 179 154 154 130 94 94 71 71 27 Ablation 179 130 27 Conventional 184 168 168 138 97 97 63 19 63 19 Conventional 184 138

Results­CASTLE AF Cardiovascular Hospitalization 1 0.8 Survival Probability 0.6 0.4 Ablation Ablation 0.2 0 HR, 0.72 (95% CI, 0.52-0.99); P=0.041 12/31/1 1/12/19 1/24/19 2/5/190 2/17/19 Conventional Conventional Log-rank test: P=0.050 899 00 00 0 00 Risk Reduction: 28% Risk Reduction: 28% 12:00:0 12:00:0 12:00:0 12:00:0 12:00:0 0 AM 0 AM 0 AM 0 AM 0 AM Follow-Up Time (Months) Patients at Risk Patients at Risk Ablation 179 127 127 95 60 42 42 17 Ablation 179 95 60 17 Conventional 184 131 131 91 52 33 8 33 8 Conventional 184 91 52

Results­CASTLE AF Primary Endpoint-Subgroups Ablation Conventional better better

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