Objectives: Co-existing HF and AF•Define the clinical significance and risk profile in this population•Recognize rate, rhythm and device considerations in HF and AF•Discuss the impact of recent clinical trial data relevant to these patients

In-Sync: Heart Failure and Atrial Fibrillation Guideline-Based ManagementM. McDonald, E. O’MearaHF Update, 2019 Disclosures•Michael McDonald –Honoraria: Novartis, Servier–Clinical Trials: None•Eileen O’Meara–Honoraria: Amgen, Novartis, Pfizer-BMS, Servier–Clinical Trials: Amgen, Bayer, Luitpold, National Institutes of Health, Novartis, Merck Objectives: Co-existing HF and AF•Define the clinical significance and risk profile in this population•Recognize rate, rhythm and device considerations in HF and AF•Discuss the impact of recent clinical trial data relevant to these patients Common Comorbidities Associated with HFCardiovascular Comorbidities•HTN 48%•A fib44%•MI26%•Valve disease24%•Stroke24% Non-cardiovascular comorbidities•COPD35%•Anemia30%•CKD27%•Diabetes25% Patients typically have multiple comorbidities: Mean 4.7 comorbidities per ptRuttanet al. Fam Prac2012 Does it matter?•Meta analysis of 7 RCTs in HF•30 248 patients–14% had AF–86% in sinus rhythm•Presence of AF in HF associated with increase risk of death–OR 1.40–Not influenced by LVEF Mamas et al, EurJ Heart Fail 2009 With AF Without AF Consider:70 F, ischemic CMPNYHA 3 EF 30% on optimal medical RxICD in situWhat is her predicted survival with and without atrial fibrillation?AF is associated with worse survival at all time points Alba et al, J Cardiac Fail, 2018 Prognostic Impact of AF in HF Same Patient:70 F, EF 30% on optimal medical Rx, ICD in situ, NYHA 3 sx, unknown duration of persistent AF What is the optimal strategy in this scenario?A.Target rate controlB.Rhythm controlC.Upgrade ICD to CRT-D AF CHF Trial Roy et al, N EnglJ Med 2008 1376 patients, persistent or paroxysmal AFLVEF <35%, NYHA II-IVRandomized to rate control (HR <80 at rest) vs rhythm control (cardioversion +/-antiarrhythmicsdrugs) Mean f/u 37 months –higher % of patients in sinus rhythm at all time points in rhytmcontrol groupNo significant difference in death due to CV causes or any secondary outcomes Rate control approach may be a reasonable first line strategy•Rate control is not associated with worse outcomes for most patients•Can assess clinical response•Avoids procedures, hospitalization and AAD What heart rate should be targeted?•RACE II Trial•614 patients, permanent AF•Randomized to one of two rate control strategies•Followed 2-3 years; approx. 10bpm difference between groups at all time points•No significant difference in cumulative incidence of CV death, HF, stroke/embolism, bleeding, serious arrhythmia HR <80 bpm HR <110 bpm p <0.001 for non-inferiority BUT… NOT a HF Trial~10%patients had a history of HFVan Gelderet al, NEJM 2010 Heart rate targets for AF in HF patients? Andrade et al, Heart Rhythm, 2016 Post hoc patient-level analysis of combined AF-CHF and AFFIRM trials5164 patients; 4848 AF and 2311 sinus rhythmMean f/u 40.8 months36% of patients had LVEF <40% Baseline HR predicts mortality in sinus rhythm patients but NOT in AF patients in*AF with HR> 114bpm was associated with more hospitalizations vs HR <114bpm Recommendations: Rate ControlWe recommend in patients with HF and AF that the ventricular rate be controlled at rest and during exercise (Strong Recommendation; Moderate-Quality Evidence)We recommend β-blockers for rate control particularly in those with HFrEF(Strong Recommendation; Moderate-Quality Evidence).We recommend rate-limiting CCBs be considered for rate control in HFpEF(Weak Recommendation; Low-Quality Evidence). Values and preferencesThese recommendations are on the basis of an understanding that the management of patients with HF with AF should be individualized with respect to the need to identify precipitating factors, to assess the risk of therapy such as the development of bradycardia and pro-arrhythmia with antiarrhythmic agents, and the bleeding risk of systemic anticoagulation.In patients with HF with AF , for whom a rate control strategy is used, the heart rate treatment target remains unclear. Retrospective analyses of large RCTs suggest that rates > 110-115 bpm might be associated with worse outcomes. Back to the case•Still symptomatic, HR 110-120 on max beta blocker•Is there a role for digoxin? Dig Trial:6800 patients, history of HF, EF <45%Digoxin (med. dose 0.25mg/d) vsplaceboNB: pre beta blocker, MRA era Overall mortalityDeath or HF Hospitalization Digoxin: friend or foe? Digitalis Investigators Group, N EnglJ Med 1997 Adams et al, JACC 2005 Digoxin: friend or foe? •Dig Trial: post hoc analysis•Mortality with digoxin relates to serum dig levels rather than sex•Low dig levels (<1.0 ng/mL) associated with lower risk of HF hospitalization Mortality in women according to dig levelsDeath/HF hospitalization in menand women according to dig levels Wyse, George. In DIG, patients did NOT have Afib! JACC 2015 Digoxin: safety in AF?Ongoing controversy Lancet 2015 Am J Cardiol2015 JACC 2014 CircArrhythmElectrophysiol2015 Digoxin for Rate Control of AF We recommend the additional use of digoxin in patients with HFrEFand chronic AF and poor control of ventricular rate and/or persistent symptoms despite optimally tolerated β-blocker therapy, or when β-blockers cannot be used (Strong Recommendation; Low-Quality Evidence). We suggest that digoxin can be considered as a therapeutic option to achieve rate control in patients with AF and symptoms caused by rapid ventricular rates whose response to β-blockers and/or calcium channel blockers is inadequate, or in whom such rate-controlling drugs are contraindicated or not tolerated (Conditional Recommendation, Moderate-Quality Evidence). HF Guidelines AF Guidelines No specific recommendation for digoxin in HF population Digoxin for Rate Control of AF Values and preferences.Digoxin is considered a second-line agent because although some published cohort, retrospective, and subgroup studies show no harm, there are others that suggest possible harm.Practical tips.•Dosing should be adjusted according to renal function and potential drug interactions•Maximum trough digoxin serum concentration of 1.2 ng/mL would be prudent •In the setting of reduced EF, digoxin use should be dictated by the recommendations of the CCS Heart Failure Clinical Guidelines Back to the case•HR 70-80bpm, persistent AF, now NYHA II-III symptoms•One hospitalization in past 6 months•Meds:–Bisoprolol10mg q am, 5mg qpm–Sacubitril-Valsartan 100mg bid–Eplerenone25mg/d–Digoxin 0.125mg/d•Next Move?•Rhythm control?•CRT upgrade? CRT is recommended for patients in sinus rhythm with NYHA II-IV symptoms, and:‒LVEF < 35%‒QRS duration > 130ms due to LBBBStrong recommendation, good quality of evidence Weak recommendations for:‒Patients with atrial fibrillation who are otherwise suitable candidates for CRT ‒Patients with QRS >150ms and non-LBBB who are otherwise suitable candidates for CRT CRT: CCS Recommendations Case: CRT-ICD follow-up•After reviewing options with the patient, a decision is made to proceed with CRT-D implant‒Uncomplicated procedure•6 month follow up:‒Feels about the same but struggling with intermittent fluid retention ‒No ICD shocks‒Lead thresholds all fine‒BiVpaced 75% What would you like to do next?A)Increase digoxin 0.25mg/dB)Ablate AV nodeC)Cardioversion +/-add amiodaroneD)AF ablation Hayes et al, Heart Rhythm 2011 Opportunities for optimizationTargeting 100% BiVpacing in AF ALTITUDE Study>36,000 patient databaseGreatest difference in survival observed with BiVpacing >98%Worsening HF associated with BiVpacing <98%Dichotomy seen for both sinus rhythm and AF patients Systematic Review:Effects of AV nodal ablation on permanent AF patients with CRT Yin et al, Clin Cardiol2014 Meta-analysis of observational studies•>1200 patients with permanent (mostly) AF and CRT•Comparison: AVN ablation versus no AVN ablation strategy•BiVpacing: 100% AVN ablation group 82-95% no-AVN ablation group•Signal toward reduced all-cause(A) and cardiovascular(B) mortality Back to the case•Continues to have NYHA III symptoms; low output and congestive features•Persistent AF–Avg. HR 70-80 bpm–Cardiovertedx 2, unsuccessful–BiVpacing 80%–Not happy with his quality of life–Referred for AV node ablation… Another Case: 59 F•Presented with acute pulmonary edema and atrial fibrillation•LVEF 35-40%, normal valves•Normal coronaries•Started on HF medical therapy, improvedbut still NYHA II-III sx 59 F•Outpatient monitoring–Rhythm alternated between sinus and AF•Meds–Perindopril, metoprolol, spironolatone–Started amiodarone•Initially long periods of sinus rhythm (months)–Improved LVEF (>50%)•After 2 years, increasing frequency of paroxysmal/persistent AF, worsened HF symptoms and drop in LVEF (~40%)•Wished to pursue rhythm control Rate vs Rhythm Control in AF Recommendations: Rhythm ControlWe recommend the use of antiarrhythmic therapy to achieve and maintain sinus rhythm; if rhythm control is indicated, it should be restricted to amiodarone (Strong Recommendation; Moderate-Quality Evidence).We recommend that restoration and maintenance of sinus rhythm in chronic HF not be performed routinely, but individualized on the basis of patient characteristics and clinical status (Strong Recommendation; High-Quality Evidence). AF Ablation: Contemporary Evidence in HF •Multicentre, open label RCT•363 patients with paroxysmal/persistent AF•LVEF <35%, NYHA II-IV, ICD in situ•Failed antiarrhythmic drugs•Randomized to catheter ablation vs medical management (rate or rhythm control)•Primary endpoint: death or HF hospitalization Marroucheet al, N EnglJ Med 2018 Marroucheet al, N EnglJ Med 2018 3013 patients screenedMean f/u 38 months84% of ablation group received an ablation (1.3 +/-0.5 procedures per pt)10% of medical therapy group crossed over to receive ablation50% of patients in ablation group had recurrence of AF Catheter ablation improved primary endpoint, LVEF, HF symptoms We suggest catheter ablation of AF be considered as a therapeutic strategy to achieve and maintain sinus rhythm if rhythm control is indicated and antiarrhythmic therapy has failed or the patient is unable to tolerate antiarrhythmic therapy (Weak Recommendation; Low-Quality Evidence). Recommendations: Rhythm Control CABANA Trial and Generalizability CABANA Trial and Generalizability Back to our case….•Patient amenable to catheter ablation•Underwent uncomplicated PVI–2 procedures over 18 months•Sinus rhythm documented in follow up at all time points after 2ndablation (2 year f/u)•Rare palpitations, NYHA 1•LVEF 55% Catheter ablation of AF in HF «The considerationof patients withstructural heartdiseaseas an appropriateablation candidate doesrepresenta philosophicalshift in practice becausethesepatients werepreviouslydiscouragedfromablation becauseof concernsregardingpotentialinefficacyand harm.» §Lower HF hospitalization rates§Reduced all-cause mortality§Improved LV function§Increased 6-min walk test§Improved peak VO2§No difference in adverse events Finally, don’t forget the basics We suggest that non-vitamin K antagonist oral anticoagulants should be the agent of choice for stroke prophylaxis in patients with HF and nonvalvularAF, and that the treatment dose be guided by patient-specific characteristics including age, weight, and renal function (Weak Recommendation; Moderate-Quality Evidence).We suggest the application of evidence-based therapies for HFrEF, per CCS HF guidelines, for primary prevention of AF (Weak Recommendation; Moderate-Quality Evidence). Thank you!