Atrial Fibrillation and Heart Failure: Rate vs. Rhythm Control Time for Re-evaluation ANIL K. BHANDARI, M.D, Director, Electrophysiology and EPS Fellowship Program Good Samaritan Hospital/ Harbor UCLA Medical Center, Los Angeles
AF and HF: Background and Status of the Problem Closely related and common conditions AF: 3-5 million in U.S. HF: 5-7 million in U.S. Share common etiologies: age, HTN, CAD, DM, sleep apnea, valvular disease, CKD Significant overlap in pathophysiology: each predispose to other Combination of both lead to deleterious hemodynamics ñ morbidity/mortality
Prevalence of AF in CHF Trials 50 Class IV 40 AF (%) 30 20 10 Class I Class II-III Class II-III Class III 0 SOLVD-P SOLVD-T US CARVD ATLAS CONSENSUS CP1033396-2
Interaction Between AF and HF Trulock et al., JACC 2014; 64:710-721 Action potential duration heterogeneity includes spatial and temporal non-uniformities ** This mechanistic hypothesis has fallen out of favor with recent evidence
Time to All-Cause Mortality in CHARM Based Upon EF and AF at Baseline Source: Olsson LG et al., Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM) program. JACC 47;1997-2004, 2006
Prognostic Significance of Afib in Patients with HF Independent Predictor of Mortality Yes No 60 p=0.001 p=0.001 p=0.001 p=0.001 p=0.18 Sinus 50 AFib Mortality (%) 40 30 20 10 0 Middlekauf (1991) Dries (1993) Crijns (2000) Mathew (2000) Carson (1993) Mahoney (1999) # Pts F/U (mos) 315 75 19 6498 419 30 443 84 40 922 866 37 688 107 24 172 62 13
AF and HF: Restoration of Sinus will be Expected to Lead to: Improved hemodynamics and LVEF HF-related hospitalizations Stroke risk Improved survival Reversibility of HF in a select subset
Overview of Randomized Trials: Rate Control vs. Rhythm Control in A Fib Mortality Risk Thrombotic Stroke Risk Rate Control Rhythm Control Rate Control Rhythm Control
AF-CHF Trial 100 A. Death from Any Cause 100 B. Stroke NEJM 358:2667, 2009 80 60 40 20 0 No. at Risk Rhythm Control Rate Control 100 Hazard ratio, 0.97 (95% CI, 0.80-1.17) P = 0.73 Rhythm Control Rate Control 0 12 24 36 48 60 Months 593 604 514 521 378 381 228 219 82 69 C. Worsening Heart Failure D. Composite Outcome 100 80 60 40 20 0 No. at Risk Rhythm Control Rate Control Hazard ratio, 0.74 (95% CI, 0.40-1.35) P = 0.32 Rhythm Control Rate Control 0 12 24 36 48 60 Months 589 596 507 512 367 373 221 216 79 68 80 60 40 20 0 No. at Risk Rhythm Control Rate Control Hazard ratio, 0.87 (95% CI, 0.72-1.06) P = 0.17 Rhythm Control Rate Control 0 12 24 36 48 60 523 509 436 419 Months 311 289 174 165 63 54 80 60 40 20 0 No. at Risk Rhythm Control Rate Control Hazard ratio, 0.90 (95% CI, 0.77-1.06) P = 0.20 Rhythm Control Rate Control 0 12 24 36 48 60 Months 518 502 432 412 303 281 169 162 60 53
RF Catheter Ablation of AF First introduced in late 1990 Cures AF by eliminating and/or modifying AF sources in one or both atria Guidelines endorsed 1 st or 2 nd line Rx in symptomatic AF Success 3-4 fold higher in sinus restoration vs AADS: 80-90% paroxysmal 70-80% recent persistent AF 50-70% long lasting persistent AF Serious complications infrequent (1-2%) Not associated with adverse effects of AADs
Catheter Ablation of HF: Metanalysis Circ. Arrhythm Electrophysiol. 2014;7:1011-1018
AF Catheter Ablation in Heart Failure: Meta Analysis 26 studies (mostly observational and small population) involving a total of 1838 patients Average F/U: 23 months (18-40 months) Efficacy for sinus maintenance: 60% (54-67%) Complication rate 4.2% Majority of the studies reported improvement in LVEF from 40% to 53% No meaningful data on morbidity or mortality benefit Anselmino et al., Circ. Arrhythm Electrolphysiol 2014;7:1011-10158
Meta Analysis of AF Catheter Ablation in HF Anselmino et al., Circ. Arrhythm Electrolphysiol 2014;7:1011-1018
2014 Guidelines-based Approach to AF in Heart Failure No evidence that rhythm control by AADs improves survival or LV dysfunction Routine use of rhythm-control strategy not recommended and rate control with anticoagulation preferred strategy Rhythm control indicated when: - symptoms persist despite rate control - rate control difficult to achieve - tachycardia-related CM suspected Catheter ablation role not adequately defined or studied
Recent Randomized Controlled Trials (RCTs) of Afib Catheter Ablation in Heart Failure RCT Year Published Addressed Question AATAC 2016 Is RF ablation superior to amiodarone for sinus maintenance in HF with AF? CAMERA-MRI 2017 Does AF catheter ablation improve LV dysfunction in patients with unexplained HF? CASTLE-AF 2018 Does catheter ablation improve mortality and morbidity in HF?
Patient Population in AATAC DiBiase et al., Circ. 2016;133:1637-1644
Ablation vs. Amiodarone for Treatment of Persistent AF in CHF and Implanted ICD-AATACH Baseline Characteristic Catheter Ablation n=102 Amiodarone n=101 Age, yr 62 ± 10 60 ± 11 AF duration, mo 9 ± 3 8 ± 4 LVEF, % 29 ± 5 30 ± 8 CAD, % 62 65 ACE/ARB, % 92 88 Beta blockers, % 76 80 Left atrium, mm 47 ± 4 48 ± 5 DiBiase et al., Circ. 2016;133:1637-1644
Freedom from AF (ICD documented) in AATACH DiBiase et al., Circ. 2016;133:1637-1644
Other Outcome Analysis in AATACH Outcome Catheter Ablation Amiodarone P-value 2-yr Mortalaity, % 8 18 0.037 All-cause Hospitalization, % 31 57 0.001 LVEF, Δ, % 8 6 0.02 QoL (MLFHQ score) 11 6 0.04 DiBiase et al., Circ. 2016;133:1637-1644
Catheter Ablation vs Medical Rate Control in AF and Systolic Dysfunction The CAMERA-MRI Study Prospective, multi-center, parallel group. Open label randomized trial (2013-2016) Inclusion Criteria: Unexplained HF with persistent AF and EF <45% (Ischemic/valvular etiologies excluded) 4-week phase-in to control rate and optimize Rx Cardiac MRI (Gadolinium) at baseline and 6 months Primary endpoint: ΔLVEF at 6 months Secondary endpoints: MRI detected scar, BNP, 6 min walk, AF burden Prabhu et al., JACC 2017; 70:1949-1961
AF Catheter Ablation in HF CAMERA-MRI Prabhu et al., JACC 2017; 70:1949-1961
CAMERA-MRI Patient Characteristics Variable Prabhu et al., JACC 2017;70:1949 Catheter Ablation N = 33 Med Rx n=33 Age, yr. 59 62 AF History Duration, mo Previous Cardioversion, % Amiodarone failure, % HF History and AF Co-diagnosis, % AF preceded, % HF preceded, % Cardiac MRI LVEF, % Scar % 23 97 91 70 24 6 32 ± 9 36 21 94 82 67 27 6 34 ± 8 36 Echo LVEF, % 35 ± 10 35 ± 9 Med Rx BB, % ACE/ARB, % 97 94 97 94
AF Catheter Ablation in HF CAMERA-MRI Prabhu et al., JACC 2017; 70:1949-1961
CAMERA-MRI Outcomes at 6 Months Outcome Catheter Ablation N = 33 Med Rx n=33 P value Primary Endpoint Δ MRI-LVEF, % 18 4 0.0001 Secondary Endpoints Δ Echo-LVEF, % Δ Functional class Δ BNP 18 1.2 168 Normal LVEF at 6 months, % 58 9 9 0.4 9 0.01 0.0001 0.0006 Prabhu et al., JACC 2-17;70:1949-61
AF Catheter Ablation in HF CAMERA-MRI Prabhu et al., JACC 2017; 70:1949-1961
Summary Statements of the CAMERA- MRI Study n Persistent AF is an under-recognized cause of otherwise unexplained sys HF (AF mediated CM) in a significant proportion of such pts n Sinus restoration with Catheter Ablation is associated with an improved LVEF, cardiac remodeling and functional capacity n Absence of MRI detected fibrosis identifies Super Responders to Catheter ablation
Catheter Ablation vs. Standard Therapy in Patients with LV Dysfunction and Atrial Fibrillation CASTLE-AF Multi-center, open-label, randomized trial (2008-2016) Inclusion Criteria: - HF patients, with symptomatic paroxysmal/persistent AF - LVEF 35%, HF class II-IV - Implanted ICD/CRT (Biotronic) 5 weeks of phase-in period to adjust HF meds before randomizing 1:1 to catheter ablation vs med Rx Primary endpoint: Composite of all-cause mortality and HF-related hospitalizations Secondary endpoints: CVA, AF freedom, all-cause hospitalization Median F/U: 38 months Morrouche et al., NEJM 2018;378:417-427
Patient Characteristics in CASTLE-AF Characteristic Ablation Treatment Type Medical Rx Number of patients 179 184 Age, year 64 64 HF Class II-III, % 87 88 Etiology of HF Ischemic, % Non-ischemic, % Type of AF Paroxysmal, % Persistent, % Type of AF Median Range 40 60 30 70 32 25-38 52 48 35 65 32 27-37 Amiodarone failure, % 57 61 Morrouche et al., NEJM 2018;378:417-427
Survival Curve for Primary Endpoint in CASTLE-AF Morrouche et al., NEJM 2018;378:417-427
Survival Curve for Primary Endpoint in CASTLE-AF Morrouche et al., NEJM 2018;378:417-427
Primary and Secondary Endpoints In CASTLE-AF Endpoint Ablation Treatment Type Medical Rx Hazard Ratio P value Primary 28% 45% 0.62 0.007 Secondary Mortality HF hospital CV deaths CVA Other outcomes LVEF Δ over 5 yrs AF freedom 13% 21% 11% 3% 8% (2-19%) 63% 25% 36% 22% 6% 0.2% (-3 16%) 22% 0.53 0.56 0.49 0.46 0.01 0.004 0.009 0.15 0.005 0.001 Morrouche et al., NEJM 2018;378:417-427
Sub group Anaysis for Primary Endpoint In CASTLE-AF Morrouche et al., NEJM 2018;378:417-427
AF and HF: Summary Statements and Implications RF catheter ablation restores sinus with 60-70% success rate Efficacy superior than amiodarone and maintained over longterm follow up Sinus restoration associated with total mortality, LVEF, HFrelated hospitalizations Non-ischemic etiology of HF, absence of MRI-detected scar and shorter AF duration predicts greater improvement in LVF and normalization of LV dysfunction in a select subset
Management of AF and HF in 2018 Guidelines endorsed Rate alone Rx (along with anticoagulation) likely to be an insufficient strategy AF catheter ablation approach should be considered earlier in the management It may prevent AF mediated CM in a subset and avoid the need for prophylactic ICD More prospective data ( e.g., CABANA) and Guidelines endorsement awaited
CABANA Trial Design Recent Onset AF Eligible for ablation and drug Rx 65 yr of age < 65 yr w / 1 CVA risk factor R Drug Rx Rate Rhythm w/ anticoagulation 1 ablation PVI WACA CFEGM GP Secondary analysis 1) NSR vs AF 2) ± underlying heart disease 3) AF type (parox, pers, perw) 4) DVC anticoagulation Discontinued AC R Continued AC