EHRA/EUROPACE 2011 Madrid, Spain June 26.-29.2011 Implementing modern management in atrial fibrillation patients Proceedings from the 3rd AFNet/EHRA consensus conference EHRA Special Session Different types of atrial fibrillation: why they should receive different treatments (no conflict of interest to disclose) Prof. Dr. Stefan Kääb LMU-Klinikum Grosshadern Medizinische Klinik und Poliklinik skaab@med.lmu.de LMU
Types of Atrial Fibrillation Classification of types of AF by: duration AF related symptoms extent of atrial damage disease causing mechanisms
Types of Atrial Fibrillation at risk for AF? Camm AJ et al. Guidelines for the management of atrial fibrillation. Eur Heart J 2010
Types of Atrial Fibrillation Different types of atrial fibrillation paroxysmal Paroxysmal vagal induced Persistent Long-standing persistent (Post ablation/post operative) Permanent silent AF (asymptomatic) may manifest as an AF-related complication (ischemic stroke or tachycardiomyopathy) or may be an opportunistic ECG. silent AF may present as any of the temporal forms of AF Camm AJ et al. Guidelines for the management of atrial fibrillation. Eur Heart J 2010
Types of Atrial Fibrillation EHRA score of AF related symptoms
Types of Atrial Fibrillation Choice of rate and rhythm control strategies
Types of Atrial Fibrillation choice of ablation and antiarrhythmic drug therapy for patients w and w/o structural heart disease
Clinical Classification
Types of Atrial Fibrillation Pathophysiology (revisited) Kirchhof P, et al. Early and comprehensive management of AF: proceedings from the 2nd AFNET/EHRA consensus conference on atrial fibrillation entitled 'research perspectives in atrial fibrillation.eur Heart J 2009
A classification of AF types based on the underlying pathophysiology could help to better select therapies for specific AF patients based on underlying cause and / or degree of atrial damage Inheritable or genetic AF (monogenic, polygenic) Focal AF Complex AF Postoperative AF
Heritable Forms of AF: monogenic Wolff L. Familial auricular atrial fibrillation. N Engl J Med. 1943; 229:396-7 monogenic forms account for 5% of AF often in context of genetic cardiomyopathies (w or w/o structural heart disease) in familial forms of AF search for subtle ECG abnormalities (short / long QT interval, QRS amplitude, changes of right precordial ST-segment, and ) Lubitz SA, et al. Circ. Arrhythm Electrophysiol 2010;3:291-299
female, 33ys, presenting with paroxysmal AF, family history of AF and SCD pathognomic flat P waves prolonged PQ narrow QRS typical ECG for a Laminopathy! presenting with AF prior to any detectable myocardial disease 50 mm/s Beckmann BM, et al. Int J Cardiol 2010
4yr AF Risk/1,000 person yr Heritable Forms of AF: polygenic 100 AF 1 parent OR 1.9; (P=0.02) 80 Men Women <75yo, w/o h/o heart disease OR 3.2; (P< 0.001) 60 40 Fox Benjamin JAMA 2004;291:2851 20 0 HTN - - + + + + Diabetes - - - + + + Heart Disease - - - - + + Parent hx AF - + - - - +
Framingham Heart Study and Offspring-Study Heritable Forms of AF: polygenic Risk of AF by familial age of onset n=4421 participants ( 1 parent or sibling enrolled at baseline) 11.971 examinations over a 39 year follow up familial AF 1185 (26.8%) familial AF early onset ( 65 years) 351 (7.9 %) Lubitz SA, et al. JAMA 2010;304 (20):2263-2269
Heritable Forms of AF: polygenic Main signal for AF on Chr 4q25 PITX2 KCNN3 ZFHX3 Gudbjartsson DF, et al. Nature 2007 Benjamin EJ, et al. Nature Genetics 2009 Ellinor PT, et al. Nature Genetics 2010
Focal AF In the absence of severe cardiac disease, the initial event that triggers AF is often atrial ectopy from the pulmonary veins Many short episodes of AF are a good clinical indicator for this pathophysiology There is a continuum from atrial ectopy, atrial runs and short lasting atrial tachycardias to self-terminating AF. Long-lasting focal AF may lead to multiple wavelet complex AF
Cellular mechanisms underlying focal-ectopic activity Wakili R, Voigt N, et al. J Clin Invest 2011, in press
Vagal paroxysmal atrial fibrillation: prevalance and ablation outcome in patients without structural heart diseases n= 209 pts.; undergoing first PVI vagal or adrenergic AF if >90% of AF episodes were related to vagal or adrenergic triggers; otherwise, a diagnosis of random AF was made. Rosso R et al.j Cardiovasc Electrophysiol. 2010 May;21(5):489-93
Heritable Forms of AF: polygenic Main signal for AF on Chr 4q25 PITX2 KCNN3 ZFHX3 Gudbjartsson DF, et al. Nature 2007 Benjamin EJ, et al. Nature Genetics 2009 Ellinor PT, et al. Nature Genetics 2010
Genetic variants as potential biomarkers to guide therapy n=195 Husser D, et al. JACC 2010; 55(8):747-753 Editorial by Hall JL, et al. JACC 2010; 55(8):754-757
Is PTX2 a suitable biomarker for selecting patients for PVI for AF therapy? Multimarker risk score 4q25 Lubitz S, Sinner MF et al. Circulation 2010
Complex AF AF in advanced structural heart disease, old age and comorbidities Several pathophysiological processes such as electrical, structural and contractile remodelling involved Degree of complexity highly variable Need for quantification and specification of the complexity to guide safe and (cost) effective therapy
ATRIAL FIBRILLATION AS CAUSE OF HEART FAILURE MECHANISMS irregular ventricular response loss of atrial contraction rapid heart rate impaired coronary blood flow mitral regurgitation ventricular dilatation AF HF
HEART FAILURE AS CAUSE OF ATRIAL FIBRILLATION MECHANISMS AF HF dispersion of refractory period slowing of conduction fibrosis loss of myocardial mass atrial dilatation
ATRIAL FIBRILLATION AND HEART FAILURE AS VICIOUS CIRCLE AF HF
Molecular mechanisms leading to atrial fibrosis Wakili R, Voigt N, et al. J Clin Invest 2011, in press
Genetic contribution to AF Wakili R, Voigt N, et al. J Clin Invest 2011, in press
Benefit of additional CFAE Ablation in complex AF Non-paroxysmal AF Paroxysmal AF Randomized controlled trials Hayward RM et al. Heart Rhythm, 2011 in press
Non-invasive Assessment of the AF Substrate Low Substrate Complexity Direct Contact Mapping (Right Atrium) High Body Surface Potential Maps courtesy to U. Schotten, Maastricht 2011
Postoperative AF 20-30% undergoing cardiac surgery suffer from post-operative AF Many pre-existing aswell as transient factors contribute to the occurence of post-operative AF (fluid and electrolyte changes, hemodynamic changes, inflammation; enhanced sympathetic tone, surgical trauma) beta-blockers and anti-inflammatory agents seem In any case tarnsient nature of the pathogenesis of AF needs to be considered (quantification of complexity of AF in post-operative AF desireable)
Different types of atrial fibrillation: why they should receive different treatments Summary Different types of AF based on pathophysiological considerations include: Inheritable or genetic AF (both monogenic and polygenic) Focal AF Complex AF Post-operative AF These classification will trigger more basic and translational research on specific forms of AF and will improve pathophysiology guided therapeutic decisions The benefit of this classification needs to be tested prospectively
Atrial Fibrillation in the Context of The Cardiovascular Continuum Identify different types of atrial fibrillation! Coronary Myocardial Infarction Myocardial Ischemia Thrombosis Myocardial Arrhythmias CAD Atrial Fibrillation Remodeling LV Dysfunction Atherosclerosis LVH Risk Factors such as: Hypertension Diabetes Family history Death Chronic CHF