Atrial Cardiomyopathy is it relevant?

Transcription

1 Atrial Cardiomyopathy is it relevant? Dr Carl Shakespeare MD FRCP FACC FESC Consultant Cardiologist

2 Relevance Progressive nature of AF Implications for RF Targeting Risk Factors CHADS vasc scoring? Could it be an independent predictor of stroke?

3 Atrial Fibrillation A marker of Atrial disease AF affects 1-2 % of population Affect 10% of population >75yrs Both AF and HF are common AF is symptomatic in 50% of patients

4 Heart failure caused by AF Rate related Ischaemia Ca handling Inflammatory Neuroendocrine Sympathetic stimulation Pro-inflammatory state Mechanical LVED filling Beat to beat variation Abnormal ventricular function

5 Traditional model of AF Progression AF begets AF: may be not just fibrosis Overlap in fibrosis in the different phenotypes of AF AF duration predicts progression AF electrical and structural remodelling initially reversible Success of RF relates to fibrosis

6 Stroke Risk in Atrial Disease All stroke predictors cause atrial disease: It s all about the atrium... Stroke risk rises with comorbidities

7 Causes of Stroke in AF Patients Aortic and carotid vascular disease Left atrial appendage contractility and clot : co-morbidities are additive (including LVH) Endothelial dysfunction AF LV systolic dysfunction Disproportionate risk of stroke in amyloidosis with no evidence of AF Maybe AF is just a marker Maybe not just the CHADS vasc Score

8 Risk Factors for Stroke in AF Biomarkers: BNP and Troponin LA size Duration of AF (versus CHADS Vasc) 1 min, 6 mins, 5.5 hours, 24 hours Type of AF: PAF Persistent AF Permanent AF Sleep Apnoea

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10 .maybe aspirin has a role in preventing stroke in AF

11 ASSERT and IMPACT Trials Challenge to the concept of stasis and LA clot embolization Lack of a temporal relationship between onset of stroke and onset of AF Concept that impaired atrial endothelial function and atrial mechanics causes the stroke and not the AF JB Guichard JACC

12 ASSERT Trial Asymptomatic AF and Stroke Evaluation in Pacemaker Patients Examined temporal relationship between AF and subsequent strokes Prior to stroke, preceding AF seen in only 8% of patients First episodes of AF seen in patients in 16% after the stroke Does AHRE constitute AF? CHADS Vasc >2 with AHRE Brambatti Circulation ; 2094 Europace

13 Myocytes Fibroblasts Endothelium Neurones Pathological stimuli Genetic influences Architectural / structural changes Electrophysiological changes Myocyte Hypertophy Contractile Dysfunction Arrhythmogenic Changes Fibroblast Proliferation Hyperinnervation Thrombogenic Changes A Goette EHRA Heart Rhythm

14 Atrial Structural Remodelling Interstitial fibrosis leads to changes in cellular coupling connexin 43 down regulation Non-uniform anisotropic impulse propagation Atrial activation Abnormalities

15 Structural Remodeling Alteration in atrial tissue composition (primarily by fibrosis) generally heralding irreversible microscopic (and often macroscopic) changes and a more severe disease phenotype. Prabhu et al Prog Cardiov Dis 2015;58:

16 Reverse Remodelling During AF, remodelling occurs Termination results in Quick early electrical reversion Slower reversion of fibrosis or none

17 Fibrotic Atrial Cardiomyopathy (FACM) Preoperative elevation in markers of collagen synthesis associated with post surgical AF Possible role of familial genes Chronic inflammation; CRP? Role of steroids Progressive remodelling after ablation may be the cause of recurrences and new arrhythmia hence need to treat risk factors

18 FACM continued May be expressed from mild to severe fibrosis Wide clinical variation: Asymptomatic Multiple arrhythmias: sick sinus, tach-brady Thrombo-embolism Atrio-mechanical dysfunction RF ablation may not be curative in FACM Treat earlier?

19 Classification of ACM Jean-Baptiste Guichard, and Stanley Nattel JACC 2017;70: American College of Cardiology Foundation

20 Clinical Determinants in ACM

21 Fibrotic Atrial Cardiomyopathy: Relationship to AF and Links to Thromboembolism Benjamin J. Hirsh et al. JACC 2015;65:

22 Predisposition to Remodelling Heart failure Atrial size Age Obesity Hypertension Mitral Stenosis Autoimmune disease From MRI atrial studies the degree of left atrial structural remodelling was independent of co-morbidities.

23 Obesity and the AF substrate Nalliah et al. EHJ 2015; epub ahead of print

24 Mitral Stenosis Electrical remodelling in MS patients without known atrial arrhythmia Left atrial enlargemant Significantly reduced bi-atrial voltages Reduced conduction velocity Prolonged effective refractory periods Reverse remodelling after commissurotomy with increased voltages late reversal of chronic stretch Also occurs in ASD MR? John B EHJ

25 Remodelling in HT 20% of all AF cases Commonly associated with AF Electrical slowing of conduction velocity Sustained AF induced in 30% of HT pts Increased AF risk in pre-ht Short term HT shows reversible electrical substrate with Renin Angiotensin System

26 Age Age associated with increased likelihood of AF.. Conventional wisdom No correlation between age and degree of fibrosis Age equally distributed in all Utah Fibrosis groups No difference in atrial voltages in older compared to middle aged autopsies.

27 Phenotype Paroxysmal, Persistent, Permanent AF Significant fibrosis overlap in patients with phenotypes No reversal of fibrosis after ablation? No evidence that AF causes fibrosis Eur Heart J. 2013;34(35): doi: /eurheartj/eht194

28 Lone AF Collagen I is increased in lone AF Chronic structural bi-atrial electrical substrate persists No clear correlation between extent of fibrosis and duration of AF

29 Lone AF (LAF) isn t lone. Frequency M:F 3:1 LA enlargement may be the consequence of PAF Low end of thrombo-embolic risk (1-2% risk after 15 years) Risk rises with co-morbidities Course of LAF predicted by LA volume Atrial histology suggests ACM class II There my be bi-atrial changes, perfusion abnormalities and sinus node dysfunction

30 Atrial Amyloidosis The commonest form of senile amyloidosis is limited to the atrium (90% in 90 yrs old) Common in rheumatic patients Can be associated with conduction problems Amyloid fibrillary proteins are related to ANP

31 Gene related abnormal ANP Abnormal ANP associated with atrial tachyarrhythmia Associated with young onset AF Can lead to Ika defect and shortened AP Specific autosomally recesive ACM Bi-atrial enlargement can be as a result in a loss of anti-hypertrophic ANP

32 Atrial Function 3D or 2D-volumes P wave onset to A wave 2D speckle tracking measures remodelling Measurement of strain and strain rate RA is the dark side of the moon

33 MRI Reconstruction of LA Fibrosis Benjamin J. Hirsh et al. JACC 2015;65: American College of Cardiology Foundation

34 Other Atrial diseases Muscular dystrophy Obstructive sleep apnoea AF begets AF Due to increased Ca++ loading and Ica Myocarditis (AF in 30%) Autoimmune disease Atrial standstill related to repolarization abnormalities and channelopathies causing AF

35 RF Ablation: who? Reduce recurrence LA strain and strain rate are predictors of successful ablation (mechanical) Success of RFA relates to the extent of fibrosis (fibrotic) Atrial (structure) and function may also predict progression of AF and success (Electrical): PR interval and voltages Risk Factor modification: recurrence

36 DECAFF study data McGann et al. Circ Arrhythm Electrophysiol 2014;7:23-30

37 Summary The degree of left atrial structural remodelling is independent of co-morbidities: Rx Risk Significant overlap in the degree of fibrosis and clinical phenotype of AF Chronic bi-atrial substrate for AF is the result of FACM isolated atrial enlargement an indicator? Atrial CM is an independent risk of stroke Implication of left atrial fibrosis and risk of stroke Anticoagulation?

38 Summary 2 Atrial CM may be an independent risk factor for stroke, AF is surrogate? Although the length of AF episodes may predict the risk of stroke, it is the presence of CHADS vasc factors that carry weight Don t treat High Rate Atrial Episodes seen on devices without corroboration Echocardiography and MRI may provide better selection for succesful RF ablation Maybe, never stop anticoagulation. Aspirin may still have a role

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