9/14/2019 Disclosures AF and CHF Should ablation be the first line therapy? Research grants • NIH, Abbott, Sanofi, Biosense, BI, Biotronik, MARREK Inc., Medtronic, Boston Scientific, Catheter Robotics, Nassir F. Marrouche, MD VytronUs @nmarrouche Consulting, honoraria, stock options Director Cardiac Electrophysiology • Biosense Webster, Sanofi-Aventis, MRI Interv, BMS, Heart and Vascular Institute Tulane University School of Medicine Boehringer-Ingelheim, Biotronik , Ecardio, St Jude, Medtronic, Arapeen Med, MARREK Inc, Daiishi Sayko, Cardiac Designs, Arapeen Med, VytronUs Patient 1 • History of Atrial fibrillation for the last 2 years • 62 yo male • Paroxysmal AF for 9 months • Hx of CAD (MI) • Persistent AF with multiple DCC for the last 15 m • Hx of Atrial fibrillation for the last 2 years • Rate controlled with beta blockers • LV dysfunction (EF 24%) • S/P ICD implantation • Multiple hospitalization for CHF decomposition despite optimized HF treatment 1
9/14/2019 Patient 2 Twitter poll • 73 yo female • 69 yo female with symptomatic (NYHA II-III) • LV dysfunction (EF 30%) persistent #AFib and 29% ejection fraction, ischemic cardiomyopathy Never used • S/P ICD implantation #antiarrhythmics or had #DCCV. Left atrial size • Dilated Cardiomyopathy 5.5 cm. What is next assuming optimal heart • Persistent AF for failure tx! • 3 monthsShortness of breath on exertion Recommendation for Catheter Ablation of AF Twitter Poll Results in Heart Failure (IIa) 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation 2
9/14/2019 Ablation of atrial fibrillation in patients with heart failure Recommendation for Catheter Ablation deserves more than a IIb guidelines recommendation of AF in Heart Failure (2018 ACC/AHA updated recommendation) Chelu et al JCE 2019 Sep;30(9):1412-1415 The Challenges of the Antiarrhythmic Drugs in Outline the Heart Failure Population • Challenges of Antiarrhythmics in Heart Failure • Atrial Fibrillation Ablation in Heart Failure • Selecting the Right Patient for Ablation 3
9/14/2019 Dofetilide Has No Effect on Mortality in Patients with Atrial Fibrillation and Heart Failure 4
9/14/2019 PVI vs. AV node Ablation and Biventricular ICD: Outline PABA-CHF Trial • Challenges of Antiarrhythmics in Heart Failure • 41 Patients with symptomatic drug-resistant AF • Atrial Fibrillation Ablation in Heart Failure • Randomized control trial of patients EF <40%, NYH II, III • PVI vs. AV node ablation and Biventricular ICD • Selecting the Right Patient for Ablation • Primary end points: EF, 6-min walk, HF questionnaire Khan M et al. N Engl J Med 2008;359:1778-1785 PVI vs. AV node Ablation and Biventricular ICD: Ablation vs Amiodarone for Treatment of Atrial PABA-CHF Trial Fibrillation in Heart Failure (AATAC-Study) • EF improved in 76% of pts with PVI vs. 25% in AVNA • Mean EF increase of 8.8% in PVI vs. 1.1% in AVNA • Increased distance in 6 min walk with PVI • improved Quality of Life with PVI Khan M et al. N Engl J Med 2008;359:1778-1785 Di Biase et al. Circulation 2017 5
9/14/2019 Change in LVEF, 6MWD and MLHFQ Unplanned Hospitalization and Death AATAC-Trial AATAC-Trial 57 p -value = 0.04 p -value = 0.02 Relative Risk Reduction = 45% Relative Risk Reduction = 56% p -value < 0.001 31 p -value = 0.02 p -value = 0.037 18 22 8 11 10 8.1 6.2 6 Death Hospitalization LVEF 6MWD MLFHQ score reduction Ablation Amiodarone Ablation Amiodarone Change in LVEF (MRI) at Baseline and 6 Months Catheter ABlation vs ANtiarrhythmic Drug Therapy in Atrial Fibrillation (CABANA) Trial Packer et al. JAMA 2019 6
9/14/2019 CABANA-Trial CABANA-Trial Primary Endpoint (Death, Disabling All-Cause mortality, stroke, serious bleeding Stroke, Serious Bleeding, or Cardiac Arrest) (ITT) or cardiac arrest: Impact of Heart Failure Hazard ratio 0.64 CASTLE-AF Catheter Ablation versus Standard conventional Treatment in patients with LEft ventricular dysfunction and Atrial Fibrillation The CASTLE-AF trial Marrouche et al. N Engl J Med. 2018 Feb 1;378(5):417-427 7
9/14/2019 CASTLE AF CASTLE AF Primary Composite Endpoint All-Cause Mortality 1 1 Ablation Survival Probability Survival Probability 0.8 0.8 Ablation 0.6 0.6 HR, 0.62 (95% CI, 0.43-0.87); HR, 0.53 (95% CI, 0.32-0.86); Conventional 0.4 P=0.007 0.4 P=0.011 Conventional Log-rank test: P=0.006 Log-rank test: P=0.009 0.2 0.2 Risk Reduction: 38% Risk Reduction: 47% 0 0 0 12 24 36 48 60 0 12 24 36 48 60 Follow-Up Time (Months) Follow-Up Time (Months) Patients at Risk Patients at Risk Ablation 179 141 114 76 58 22 Ablation 179 154 130 94 71 27 Conventional 184 145 111 70 48 12 Conventional 184 168 138 97 63 19 N Engl J Med. 2018 Feb 1;378(5):417-427 CASTLE AF Intention-to-treat, per-protocol, as-treated Worsening Heart Failure Admissions 1 Survival Probability Ablation 0.8 0.6 HR, 0.56 (95% CI, 0.37-0.83); 0.4 P=0.004 Conventional Log-rank test: P=0.004 0.2 Risk Reduction: 44% 0 0 12 24 36 48 60 Follow-Up Time (Months) Patients at Risk Ablation 179 141 114 76 58 22 Conventional 184 145 111 70 48 12 8
9/14/2019 AF recurrence (30 sec) was not CASTLE-AF: Time to first 30 sec recurrence associated with outcome HR 95% CI P-value 0.87 – 5.18 Ablated patients 2.13 0.097 Non-ablated patients 0.96 0.44 – 2.09 0.914 AF Burden <50% at follow up a strong predictor for AF Burden <50% at follow up a strong Composite of Mortality + Hospitalization predictor for mortality HR, 2.52 (95% CI, 1.15-5.50); P=0.021 9
9/14/2019 CASTLE-AF CASTLE-AF Ablation and incidence of VT Ablation and incidence of VF AF recurrence 0.09 [0.03- 0.18 [0.05-0.63] AF recurrence Yes Yes 0.28] AF recurrence 0.8 [0.54-1.18] No AF recurrence No 1.04 [0.68-1.61] -0.5 0 0.5 1 1.5 -0.5 0 0.5 1 1.5 2 Ablation better Pharmacological treatment better Ablation better Pharmacological treatment better CASTLE AF CASTLE-AF Absolute change in LVEF from baseline Ablation led to better QoL 20 p *=0.001 p *=0.005 p =0.055 LVEF Change from Baseline 15 10 8 7 4.5 5 2 1 0 0 -5 -10 12mo 36mo 60mo Ablation Conventional Sanders et al HRS 2019 10
9/14/2019 CASTLE-AF CASTLE-AF Outcome in EF<20% improvement to >35% OR=2.17,p<0.001 Marrouche et al HRS 2019 CASTLE-AF Ablation of AF in Heart Failure Outcome in EF>20% Patient Selection Marrouche et al HRS 2019 11
9/14/2019 CASTLE-AF Correlation between % of ventricular Impact of NYHA functional class scar and ΔLVEF following catheter ablation Late gadolinium enhancement demonstrating regional mid-wall fibrosis in dilated cardiomyopathy B. A. LGE Positive LGE Negative Marrouche et al HRS 2019 Prabhu et al J Am Coll Cardiol. 2017 Oct 17;70(16):1949-1961. Classification of AF based on degree Higher degree of left atrial fibrosis in patients of atrial fibrosis/myopathy with AF and left ventricular systolic dysfunction Left atrium fibrosis � Marrouche et al. JAMA. 2014 Feb 5;311(5):498-506 Akkaya et al. JCE 2013 12
9/14/2019 Degree of atrial disease affects LVEF improvement What we know today! post AF ablation • ABLATION CONTROLL of atrial fibrillation in heart failure • Improves AF Burden • Improves QoL • Improves incidence of Ventricular Arrhythmias • Improves LVEF • Improves Hospitalization • Improves Mortality • Patient selection is important � Akkaya et al. JCE 2013 Personalized Management of Ablation of Atrial Fibrillation Heart Failure Patient Thank You! LGE-MRI NYHA I-II NYHA III-IV Medical <15% ventricular LGE Scar management Fibrosis ≥30% Fibrosis <10% Fibrosis ≥10% -<20% Fibrosis ≥20% -<30% NYHA II Healthy Fibrotic tissue 13
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