Atrial Fibrillation 21 Challengesvfustercourse.com/assets/pdfs/ponencia8.pdfGroup 3-D-adjusted vitamin K antagonist plus DAPT for 1, 6, or 12 months. Group 2 -VLD rivaroxaban (2.5

Molecular (M), Clinical (C) and Population (P)Bases of Cardiovascular Disease and Health

16 and 17 July 2018 / 16 y 17 de julio de 2018Cardona (Barcelona, Spain) – Auditori Valentí Fuster

Atrial Fibrillation 21 Challenges

MCP BASES OF MYOCARDIAL & STRUCTURAL DISEASE, 2019

Molecular (M), Clinical (C), Population (P)Bases of Cardiovascular Disease and Health, 2019

3. MCP of Rhythm, Myocardial & Structural Disorders

9. Atrial Fibrillation 21 Challenges

10. Genetics, Omics & Cardiomyopathies at Full Speed

11. Myocardial Tissue Regeneration in Controversy

12. Structural Valvular Heart Disease in Motion

4. Bases of My Academic (Creative) Future

13. A View of my Professional Life. Where I am Going?

Cardona, July 16, 2019 No Disclosures

AF - CLINICAL CHALLENGES (21) – 2019

1. Presentation: Simplified vs Insightfulness (3)

2. Pathogenesis: Myocardial vs Electrical (3)

3. AC Rx: When/How/Bridge vs NS-TE / SCI (3)

4. AF / Stent: Triple Rx vs Double Rx (3)

5. AC. / NOACs: Efficacy vs Safety (3)

6. Ablation Yes vs No (3)

7. Screening Screening vs No Screening (3)









1. EHJ 2016; 37:2893 - SimpleObesity is Complex

1). Acute Management of AF

2). Chronic Contributor & Management Epicardial Fat

CX Wong et. al. Eur Heart J. 2017;38:1294

3). Trigger - Post-Operative AF Thromboembolism Compared With Nonvalvular AF

JH Butt et. al. J Am Coll Cardiol 2018;72:2027 – Danish Reg. (15,000 vs 4000)









TJ Bunch et. al. Eur Heart J. 2016;37:2890BW Calenda, V Fuster, V Reddy et. al. Nat Rev Cardiol 2016;13:549

1). Myocardial Pathogenesis of AF

Alcohol

Genetics

Aging

TJ Bunch et. al. Eur Heart J. 2016;37:2890BW Calenda, V Fuster, V Reddy et. al. Nat Rev Cardiol 2016;13:549

Myocardial Pathogenesis of AF

Alcohol

Genetics

Aging

S Nattel et. al. Nat Rev Cardiol. 2016; 13: 575.

2) Electrical Pathogenesis of AF At The Pulmonary Veins

S Nattel et. al. Nat Rev Cardiol. 2016; 13: 575. – Also Re-entry

Molecular Mechanisms of Focal Ectopic Firing In Paroxysmal AF

3). Natural History of AF

JB Guichard et. al. J Am Coll Cardiol 2017;70:756

LA Tissue Fibrosis on 3D LGE CMR Scans

JB King, N Marrouche et. al. J Am Coll Cardiol 2017;70:1311

JAMA. 2014;311(5):498

Fibrosis of the LA Wall, Blinded To The Treating Physicians:

Stage 1 (<10% ), Stage 2 (≥10%-<20%),Stage 3 (≥20%-<30%), Stage 4 (≥30%).




3. AC Rx: How/When//Bridge vs NS-TE / SCI (3)





1a). Atherothrombotic and Atheroembolic Diseases

J Narula, V Fuster et. al. J Am Coll Cardiol 2019;73:1000

How?, Coagulation Cascade and Oral Anticoagulation

FWA Verheugt, CB Granger et. al. J Am Coll Cardiol 2019;74:699

Thrombin & Platelet Activation

FWA Verheugt, CB Granger et. al. J Am Coll Cardiol 2019;74:699

1b). AC When ?- The Prevention of Stroke .

V Fuster, JS Chinitz, Circ. 2012 ; 125: 2285Swedish AF Cohort Register (L Friberg, GYH Lip et al) Circ. 2012; 125: 2298CHA2DS2VASc: ESC Guidelines (P Kirchhof, AJ Camm et al ) 2013 - ACC / AHA / HRS 2014 A/C Prevention - Emboli >>> Bleeding, Thrombosis > Bleeding

?

1c). To Bridge & How to Bridge for DOACs/VKAs

JU Doherty, JL Januzzi et. al. J Am Coll Cardiol 2017;69:872 - Exeptions OnlyORBIT=AF (BA Steinberg et al.), Circulation 2015; 131:488 –

2). LAA Structure / Function – Stroke in NSRCardiac Imaging For Assessment

J Romero et. al. Nat Rev Cardiol. 2014;11:470ENGAGE AF (DK Gupta et al.) EHJ 2014; 35:1457 – LA Function / NSR ?ASSERT (M Brambatti, et al.) Circ. 2014; 129:2094- LV Function / NSR ?IMPACT (DT Martin et al.) EHJ; 2015; 36:1660- LV Function / NSR ?

3). Silent Cerebral Infarcts (SCI) Cardiac Disease And Procedures

ME Hassell et. al. Nat. Rev. Cardiol. 2013;10:696F Gaita et. al. J Am Coll Cardiol 2013;62:1990 (Italy)S Kalantarian et. al. Ann Intern Med. 2014;161:650 – 15 Studies, SCI

Decline In The Global Cognitive Score Function of AF

A Singh-Manoux et. al. Eur Heart J. 2017;38:2612F Gaita et. al. J Am Coll Cardiol 2013;62:1990 (Italy)S Kalantarian et. al. Ann Intern Med. 2014;161:650

AF, Cognitive Decline, and DementiaVia Different Mechanisms

HC Diener, GYH Lip et. al. J Am Coll Cardiol 2019;73:612









1). AF & PCI in the Era of Vitamin K Antagonists:WOEST & ISAR-TRIPLE

D Capodanno, DJ Angiolillo et. al. J Am Coll Cardiol 2019;74:83

2). AF & PCI in the Era of DOACs: PIONEER AF, RE-DUAL PCI, and AUGUSTUS


PIONEER AF-PCI (CM Gibson et. al. ) NEJM 2016;375:2423

Preventing Bleeding in Pts with AF-PCI

Group 3 - D-adjusted vitamin K antagonist plus DAPT for 1, 6, or 12 months.Group 2 - VLD rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, 12 MoGroup 1 - LD rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 Mo

PIONEER AF-PCI (CM Gibson et. al. ) NEJM 2016;375:2423

Group 3 - D-adjusted vitamin K antagonist plus DAPT for 1, 6, or 12 months.Group 2 - VLD Rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, 12 MoGroup 1 - LD Rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 Mo

CV Events in Pts with AF-PCI

3). AF & PCI in the Era of DOACs: Consensus Recommendations on Management







5. AC. / NOACs1: Efficacy vs Safety (3)


7. Screening Screening vs No Screening (3) 1LAAC

1). Annual Stroke Risk and Risk Reduction With Various Preventative Strategies in AF

M Alkhouli, DR Holmes et. al. J Am Coll Cardiol 2018;71:2790

Relative Differences In Efficacy And Safety Outcomes Between NOACSs And Warfarin

D Lakkireddy et. al. J Am Coll Cardiol 2019 (Submitted)

Doses Of The Different NOACsIn The 4 Large Trials In AF Patients

HC Diener et. al. Eur Heart J. 2017;38:860

Annual Stroke Risk and Risk Reduction With Various Preventative Strategies in AF


Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation


Stroke Prevention in AF With LAA Closure

PREVAIL and PROTECT AF (VY Reddy et. al.) J Am Coll Cardiol 2017;70:2964

KE Chan et. al. J Am Coll Cardiol 2016;67:2888YC Lau et. al. J Am Coll Cardiol 2016;68:1452 – Apixaban 2.5mg BID

2). Renal Function - Warfarin & NOACs

Pharmacokinetic and Primary Routes of Clearance of Oral Anticoagulant Agents in Liver

A Qamar et. al. J Am Coll Cardiol 2018;71:2162

VHD-AF, Patients on Edoxaban or Warfarin in the ENGAGE AF-TIMI 48 Trial

VHD was defined as history or baseline echo evidence of at least moderate aortic/mitral regurgitation, aortic stenosis, or prior valve surgery -bioprosthesis replacement, valve repair, valvuloplasty. Excluded from the trial, patients with moderate to severe mitral stenosis or mechanical heart valves. Comparisons were made of rates of stroke/systemic embolic event (SSEE) & major bleeding.VHDincreased the risk of death, major adverse CV events, and major bleeding but did not affect the relative efficacy or safety of higher-dose edoxaban versus warfarin in AF.

R De Caterina et al., J Am Coll Cardiol 2017; 69:1372CT January et. al. J. Am. Coll. Card. 2014;64:e1 – No Dabigatran in Mechanical HV

Mitral Stenosis and AF, DOACs vs Warfarin

JY Kim, TH Rho et. al. J Am Coll Cardiol 2019;73:1123

The study population was enrolled from the Health Insurance Review and Assessment Service (HIRA) database in the Republic of Korea. A total of 2,230 patients (mean age 69.7) were included in the present study. Thromboembolic events occurred at a rate of 2.22%/year in the DOAC group, and 4.19%/year in the warfarin group.

3). Reversal Agents For NOACS

JH Levy et. al. Nat Rev Cardiol. 2018;15:273









1). Types of Catheter Ablations In Sweden Between 2006 And 2015

F Holmqvist, P insulander et. al. Eur Heart J. 2019;40:820

Probability of Repeat Ablation (Same Arrhythmia) After A De Novo Ablation

F Holmqvist, P insulander et. al. Eur Heart J. 2019;40:820

Atrial Fibrillation BurdenFrom Implantable Cardiac Monitor

C Blomström-Lundqvis, D Mörtsell et. al. JAMA. 2019;321:1059

CHA2DS2-VASc (Recurrent AF) in Predicting Clinical Outcomes in AF After Catheter Ablation

T-F Chao et al., JACC 2011; 58:2380 (Japan) – 565 Pts

AF Burden - After Catheter AblationSeveral Strategies (Linq Recorder etc)

EI Charitos et. al. Circulation. 2012;126:806 (Luebeck, Germ.)

Cumulative Hazard Rates Of Embolic Events According To The Pattern Of AF Occurrence

T Vanassche, SJ Connolly et. al. Eur Heart J. 2015;36:281

2). AF - Catheter Ablation vs AntiarrhythmicTherapyon Mortality, Stroke, Bleeding, & Cardiac Arrest

This is an investigator-initiated, open-label, multicenter, randomized trial involving 126 centers in 10 countries. A total of 2204 symptomatic patients with AF aged 65 years and older or younger than 65 years with 1 or more risk factors for stroke were enrolled from November 2009 to April 2016, with follow-up through December 31, 2017. Among patients with AF, the strategy of catheter ablation vs medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest.However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers

CABANA (DL Packer, KL Lee et al., JAMA 2019; 321:1261)

CABANA AF Incidence Primary End Point by ITT

DL Packer, KL Lee et. al.) JAMA 2019;321:1261

CABANA AF1ary End Point by Per-Protocol Analysis (AT)


CABANA AFAll-Cause Mortality & Mortality / CV Hosp by ITT


CABANA AFRecurrent AF Post Blanking by ITT (AT)


Effect of Catheter Ablation vs Medical Therapy on Quality of Life Among Patients With AF

In this randomized trial of 2204 patients with AF, catheter ablation vs conventional medical therapy, significantly improved quality of life at 1 year as measured by the AF Effect on Quality of Life score and the Mayo AF-Specific Symptom Inventory frequency score, and severity score.

DB Mark, DL Packer, et al., JAMA 2019; 321:1275

AF Effect on Quality of Life (AFEQT) Summary Scores

CABANA (DB Mark, DL Packer et. al.) JAMA 2019;321:1275

Mayo AF–Specific Symptom Inventory (MAFSI) Frequency Scores

CABANA (DB Mark, DL Packer et. al.) JAMA 2019;321:1275

Effect of Catheter Ablation vs Antiarrhythmics on Quality of Life in AF

Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of AF and treatment failure with 1 antiarrhythmic drug or β-blocker, with 4-year follow-up. Pulmonary vein isolation ablation (n=79) or previously untested antiarrhythmic drugs (n=76). Among patients with symptomatic AF despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication.

The CAPTAF (C Blomström-Lundqvist, D Mörtsell et al), JAMA 2019; 321:1059

Observational Study of CABANA-eligible Patients In Both, ITT & As Treated (AT)

AJ Camm. Eur Heart J. 2019;40:1265

3). Pulmonary Vein Isolation for AFby Pulsed Field Ablation

VY Reddy, P Jais et. al. J Am Coll Cardiol 2019;74:315

In first-in-human trials, PFA preferentially affected myocardial tissue, allowing facile ultra-rapid PV isolation with excellent durability & safety.









7). Screening for Atrial Fibrillation

B Freedman et. al. Circulation. 2017;135:1851

Molecular (M), Clinical (C), Population (P)Bases of Cardiovascular Disease and Health, 2019

3. MCP of Rhythm, Myocardial & Structural Disorders

9. Atrial Fibrillation 21 Challenges

10. Genetics, Omics & Cardiomyopathies at Full Speed

11. Myocardial Tissue Regeneration in Controversy

12. Structural Valvular Heart Disease in Motion

4. Bases of My Academic (Creative) Future

13. A View of my Professional Life. Where I am Going?

Cardona, July 16, 2019 No Disclosures

Documents

Atrial Fibrillation 21 Challengesvfustercourse.com/assets/pdfs/ponencia8.pdfGroup 3-D-adjusted vitamin K antagonist plus DAPT for 1, 6, or 12 months. Group 2 -VLD rivaroxaban (2.5