When does enhanced monitoring for atrial fibrillation add value?

Transcription

1 When does enhanced monitoring for atrial fibrillation add value? Jonathan P. Piccini, MD, MHS, FHRS Associate Professor of Medicine Duke Clinical Research Institute Duke University Medical Center

2 Disclosures Research Grants AHRQ ARCA biopharma Boston Scientific German AFNet Gilead Johnson & Johnson ResMed St Jude Medical Consulting BMS/Pfizer GSK Johnson & Johnson Laguna Pharmaceuticals Medtronic Spectranetics Full disclosures available at

3 SF-36 Score AF Adversely Affects QoL AF 120 Post MI 100 * * Controls * * General Health Physical Function Social Function Mental Health Dorian P, et al. J Am Coll Cardiol. 2000;36: *P <.05 AF vs controls

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5 Natural History of Atrial Fibrillation Death Stroke Heart Failure CV Hospitalization TIA

6 The importance of outcomes beyond stroke Death Heart Failure Piccini J P et al. Eur Heart J 2014;35:

7 Rate of all-cause mortality Persistent AF is associated with worse survival Persistent AF Paroxysmal AF Adjusted HR paroxysmal = 0.79 ( ) p= Months since randomization No. at Risk Persistent Paroxysmal Steinberg, BS. Eur Heart J. 2014; In press.

8 AFB is associated increased risk of hospitalization in pacemaker patients: BRADYCARE Mittal S, et al. HRS Scientific Sessions. 2015

9 Pts <67 years HR 1.81 (95% CI ) Independent of clinical stroke. Strongly associated with duration of exposure to AF de Bruijn RF. JAMA Neurol. 2015;72: Alznet.org

10 Effectiveness Endpoints in Trials of Surgical Interventions for AF Primary Endpoints Secondary Endpoints Electrocardiographically documented AT/AF 30 seconds Antiarrhythmic therapy Cardioversion Repeat surgical/catheter ablation AF burden Symptom scores Quality of life Exercise tolerance LVEF Atrial transport function Left atrial size CDRH. Clinical Study Designs for Surgical Ablation Devices for Treatment of Atrial Fibrillation. February 15, 2013

11 Effectiveness Endpoints in Trials of Surgical Interventions for AF Primary Endpoints Secondary Endpoints Electrocardiographically documented AT/AF 30 seconds Antiarrhythmic therapy Cardioversion Repeat surgical/catheter ablation AF burden Symptom scores Quality of life Exercise tolerance LVEF Atrial transport function Left atrial size CDRH. Clinical Study Designs for Surgical Ablation Devices for Treatment of Atrial Fibrillation. February 15, 2013

12 24-Hour Continuous ECG Monitoring before TAVR Marina Urena et al. Circulation. 2015;131:

13 Cerebrovascular events within 30-days after TAVR Marina Urena et al. Circulation. 2015;131:

14 Effect of ranolazine on AF in NSTEMI (MERLIN TIMI 36): continuous ECG during the first 7 days Scirica BM, et al. Europace 2015;17:32-37

15 Clinical AF events in patients treated with ranolazine or placebo Scirica BM, et al. Europace 2015;17:32-37

16 Median Percent Change from Baseline PASCAL: Importance of AF burden in clinical trials ITT Population, % Change in AFB from Baseline Wilcoxon rank sum test vs Placebo 11.2 p=0.07 p=0.013 p= N= N= N=18 Dose Response: p=< Jonckheer-Terpstra test N=15 Placebo 200 mg bid 400 mg bid 600 mg bid Ezekowitz M et al; Abstract

17 Enhanced Late I Na Causes and/or contributes to EP Mechanisms of Arrhythmias Enhanced Late I na and Arrhythmogenesis EP Phenotype GS-6615 (eleclazine) GS967 Abnormal automaticity Late I Na [Na + ] i NCX [Ca 2+ ] i VT QTc EAD DADs Triggers Substrate Dispersion Endo APD Epi Belardinelli et al, Heart Rhythm 12: , 2015 Spatial Temporal Belardinelli et al, Heart Rhythm 12: ,

18 Changes in AF Burden Over 12 Weeks 70% Reduction in AFB Overall Changes in AFB Reiffel JA. Circ Arrhythm Electrophysiol. 2015;8:

19 CAT HF: Arrhythmia Substudy Design Overall CAT-HF Population R MV-triggered ASV Control Arm ~50 dual-chamber devices ~50 dual-chamber devices Arrhythmia Core Lab Adjudication 1 and 2 Events at 0, 3, 6 months

20 Probability of Event-Free Survival Probability of Event-Free Survival Genotype-Directed Therapy of AF in HF: Bucindolol b Arg/Arg (n = 441; 36 events) b Gly carriers (n = 484; 44 events) Interaction p = Risk reduction 74% No risk reduction Placebo Bucindolol Hazard Ratio = 0.26 ( ) P-value = Months After Randomization Placebo Bucindolol Hazard Ratio = 1.01 ( ) P-value = Months After Randomization Aleong R. JACC Heart Fail. 2013;1:338-34

21 Genetically Targeted Therapy for the Prevention of Symptomatic AF in Patients With Heart Failure (GENETIC-AF) LVEF <0.50, Class II-III HF w/in 90 days No contra-indications to b-blockers b Arg/Arg genotype n = 100 (310) Bucindolol Recent onset Sx AF, 1 wk 1 yr; Class I-III HF Toprol-XL n = 100 (310) Time 0 (chemical conversion to SR or ECV) 3 wks if still in AF AF free/event: from 24 hrs after ECV 1 Endpoint = Recurrent AF or ACM at 24 weeks Co-Primary for Phase 2b = AF Burden ClinicalTrials.gov Identifier: NCT

22 Overaccessorize much?

23 Patch-Based Holter Monitoring Smart Phone-Based Event Monitoring

24 Monitoring Dofetilide Antiarrhythmic Drug Therapy Chung EH. J Electrocardiol. 2015;48:8-9

25 Pill in Pocket Anticoagulation: react.com Slide courtesy of Rod Passman, Northwestern University.

26 Conclusions AF symptoms are the tip of the iceberg AF burden is an important biosignature Associated with a variety of important outcomes including stroke, hospitalization, and all-cause mortality AF burden can assist in trials, particularly in early clinical development

27 Summary Duke Center for Atrial Fibrillation Safety first. Be aggressive with your ACT targets Bridging therapy is associated with a higher risk of bleeding complications Emerging theme >> Anticoagulation transitions carry more risk than continued anticoagulation Once a diagnosis of AF is made, stroke prophylaxis should be guided by risk stratification alone (and not rhythm)