'Understanding Atrial Fibrillation: New Insights in Pathophysiology

Transcription

1 82 nd Annual Scientific Meeting of the Japanese Circulation Society Osaka 2018 'Understanding Atrial Fibrillation: New Insights in Pathophysiology Barbara Casadei, MD DPhil FMedSci FESC British Heart Foundation Professor of Cardiovascular Medicine & Consultant Cardiologist Division of Cardiovascular Medicine, John Radcliffe Hospital BHF Centre of Research Excellence University of Oxford United Kingdom

2 COI Disclosure I have no conflicts of interests to disclose concerning this presentation

3 The Problem with Atrial Fibrillation (AF) AF is common and its prevalence is predicted to double by 2060 AF is associated with a significantly higher risk of stroke, MI, heart failure and premature death Anticoagulation is the only treatment that has been consistently demonstrated to have a favourable impact on AF prognosis. Chug et al. Circulation 2014

4 Incident AF is associated with an increased risk for death and HF hospitalisation in patients with LV dysfunction (from the SOLVD trial) Death or Hospitalisation for HF All-cause Mortality Dries et al. JACC 1998

5 Working Hypothesis If AF were a significant cause of HF hospitalisation and death, recovering sinus rhythm should be beneficial. Restoration of sinus rhythm is associated with a modest but significant increase in LVEF

6 Rate vs. rhythm control in heart failure The Atrial Fibrillation and Congestive Heart Failure trial Roy et al. NEJM 2008

7 CASTLE-AF: death or hospitalization for worsening heart failure Adverse events: 12% vs. 19% (ablation), P=0.17 Complications rate: 6.5% Al Halabi et al JACC Clin Electrophysiol Median follow-up: 39 months Freedom from AF: 63% vs 22% LVEF: +8% Complications rate (ablation): 9% Marrouche et al New Engl J Med 2018

8 OK, but anticoagulants prevent stroke in AF, so AF must be causing embolic stroke right?

9 Relationship between atrial high rate episodes (AHRE) detected by an implanted device and thromboembolic events (TBE) The ASSERT I Study patients >65 yrs. without a history of AF and carrying a pacemaker or defibrillator. N of events 16 AHRE and time of stroke 54% % 4 15% Healey et al. NEJM 2012 Brambatti et al. Circulation >30 d before the <30 stroke d before the stroke after the stroke

10 DOAC therapy (alone or together with ASA) prevents ischaemic stroke in high-risk patients in sinus rhythm 10

11 Mean age of AF onset: 30 y High stroke risk (age 43 y) Atrial cardiomyopathy/ altered energetics 11

12 What about the relationship between AF and LV dysfunction?

13 Atrial Fibrillation and Cardiomyopathy: Causation or Association? CAUSATION ASSOCIATION Atrial Sinus fibrillation rhythm Cardiomyopathy LV dysfunction LV dysfunction Atrial Sinus fibrillation rhythm

14 Multi-Parametric Cardiac Magnetic Resonance Cardiac Volumes & Function Tissue Characterisation Myocardial Energetics

15 Pre-Ablation: Patients vs. Controls

16 Cardiac MR: AF patients vs. SR Controls Wijesurendra et al. Circulation 2016

17 Cardiac 31 P MRS : AF patients vs. SR Controls AF is associated with impaired myocardial energetics

18 After Ablation

19 Intra-scan rhythms EARLY 20±4 hours LATE 7±1 months Visit 1 Ablation Visit 2 Visit 3 SR 45% AF 55% SR 94% AF 6% SR 87% AF 13% 7-day Holter AF Burden 53% [IQR 1.5% - 100%] AF Burden 0% [IQR 0 0.1%]

20 Wijesurendra et al. Circulation 2016 Following ablation, LV function improves modestly, but does not normalise

21 Myocardial energetics is unchanged by ablation and still impaired compared to controls Wijesurendra et al. Circulation 2016

22 Conclusions & Clinical Implications 1. Lone AF is associated with mildly impaired LV function and myocardial energetics, which fail to normalise after successful ablation. 2. Lone AF appears to be the consequence (rather than the cause) of an underlying cardiomyopathy. 3. Impaired myocardial energetics may be important pathophysiological mechanisms and potential therapeutic targets in AF.

23 After plaque stenting, statins and life-style modifications are used to target the underlying pathobiology of CAD. We may also find that adjunctive therapies are needed in AF to target the ongoing drivers of the disease process.

24 Dr Rohan Wijesurendra Dr Francesco Notaristefano Dr Marco Spartera Prof Stefan Neubauer Dr Vanessa Ferreira Mr Christian Eichhorn Dr Tim Betts Dr Matthew Ginks Dr Kim Rajappan Dr Yaver Bashir