Atrial fibrillation from prevention to treatment

Transcription

1 State of the Art Atrial fibrillation from prevention to treatment Carina Blomström Lundqvist Dept Cardiology, Uppsala University, Sweden

2 AF - from prevention to treatment 1. Upstream preventive therapy and risks in AF 1. ACE inhibit, ARB, statins and steroids 2. including Postoperative AF 2. Long Term Reliability of AF ablation. Statin Therapy did not Prevent Atrial Fibrillation in the (SToP AF trial) Troponin I elevation increased the risk of death and stroke in patients with AF in the RE-LY substudy Duration of New-onset Postop. AF following Cardiac Surgery Predicted the Development of Late AF. Long Term Reliability And Impact Of Balloon Size In Antral Cryo Isolation Of Pulmonary Veins

3 Inflammatory markers Risk unclear Factors whether primary for AFor secondary Obesity- metabolic syndrome, Insulin resistance, Thrombogenic tendencies, Sleep apnea, Decreased arterial compliance, LA volume and diastolic dysfunction. Diabetes HT VOC MI LA CMP CHF LAd h LV fs i LVH Atrial remodelling pathways promoting AF: Inflammation RAAS activation Sympath. NS Ca overload Oxid stress AF begets AF Upstream therapy

4 Angiotensin II - potential mechanism for AF occurrence. Potentiates I Ks via AT-1 stimulation in atrial myocytes - shortens AP duration; Increases rate of atrial ectopy (from PV s and posterior LA). Zankov DP, Circulation 2006 Kumagai K, JACC 2003

5 Meta-analysis of trials evaluating ACEi/ARB for AF prevention Included trials 1. Madrid, PACE Healey, JACC Kalus, J Clin Pharm Anand, Am Heart J Salehian (HOPE), Am Heart J Jibrini, Am J Therap Pats included: CHF, HT, Diab, post.mi, Cardiovasc diseases, AF. Primary preventive (new onset AF ) vs secondary preventive trials post CV/ablation.

6 Meta-analysis of studies of ACEi/ARB for prevention of AF Overall, ACEi and ARB reduced the relative risk (RR) for AF by 19% (RR 0.810, P <0.001, 95% CI ). Jibrini MB, American Journal of Therapeutics. 15(1):36-43, 2008 But, primary preventive studies, Designed for other CV disease studies than AF.

7 ACEi/ARB for primary prevention of AF Majority are retrospective studies from large randomized trials designed to assess outcomes in cardiovascular conditions other than AF, collecting data on new onset AF. 4 heart failure trials, 3 post hoc analysis CHARM study; AF prespecified as secondary endpoint 5 trials in hypertension popul. 4 planned secondary analysis (2 based on AE reports) 1 post hoc analysis 1 retrospective cohort 2 in post MI pats post hoc analysis Healey JS, J Am Coll Cardiol Jun 7;45(11):

8 Meta-analysis of randomized studies examining AF prevention with ACEi/ ARBs in various pat populations. Salehian,HOPE, Am Heart J 2007 Reduction in AF seen in trials done in pats with LV dysfunction (RR, 0.55) and for AF treatment (RR, 0.52). AF reduction by ACEi and ARBs - may not be applicable in pats with preserved LV systolic function.

9 Prevent AF: meta-analysis of RCT 11 studies 47,457 pats CHF: 4 studies; 10,314 pts MI: 2 studies; 10,441 pts HTN: 3 studies; 26,403 pts AF: 2 studies; 299 pts AF relative risk reduction 20-30%. CHF: 0.56 ( ) HTN: 0.88 ( ) MI: 0.73 ( ) AF: 0.52 ( ) ACEI: 0.72 ( ) ARB: 0.71 ( ) Total: 0.71 ( ) Adapted from Healey JS et al. J Am Coll Cardiol 2005;45: ACEI/ARB better Control better

10 Secondary preventive trials Meta-analysis: ACEi and ARB before electrical CV Randomised open label studies amio/placebo + RAAS inh RAAS inhib. reduced AF recurrence in AF popul. by 51%. Jibrini MB, American Journal of Therapeutics. 15(1):36-43, 2008

11 ARB in lone AF pats N AF recurrence post CV Tveit, RCT % vs 65%, ns Candesartan vs placebo Madrid, R,open 90 77% vs 52%, Amio +Irbesartan p=0,001 PAF Yin, R,open % vs 19% Amio +Losartan p=0,006 Tveit (CAPRAF study), Intern J Cardiol 2008 Madrid, J Renin Ang.Ald Syst 2004 Yin, EHJ 2006

12 Limitations: How AF was diagnosed Primary preventive trials ECG yearly ECG at 1,2 and every 3 mo ECG in hospital All available ECG, not routine If symptoms Not stated Secondary preventive trials Daily Event recorder for 3 mo Holter at 1,6,12 mo Weekly ECG 1 mo ECG 2,3,6,12 mo Holter at 1,6,12 mo ECG 1w, 6w, 3+6 mo

13 Steroids for prevention of AF 3 RCT on postop. AF 2/3 trials significantly lower rates of postop AF after steroids vs placebo: 21% vs 51%, and 30% vs 48% RCT. Methylprednisolone reduced recurrence of AF after cardioversion from 50% to 9.6%, p< Halvorsen, Anest Analg -03 Prasongsukarn, J Th Card Surg -05 Halonen, JAMA -07 Dernellis, EHJ 2004

14 Meta-analysis of preop. statin therapy on adverse postop outcomes (cardiac surgery) 7643 patients from seven analysed studies 19 studies; (3 RCT, 16 observational); pats 4.3% absolute risk reduction for AF in statin pretreated pats (24.9 vs. 29.2%; P = ) Liakopoulos, EHJ 2008

15 Meta-Analysis of RCT evaluating statins for AF prevention 6 studies; 3,557 pats; PAF (1), persistent AF after electrical CV (2), postop AF/acute coronary syndrome (3). Statins significantly decreased risk of AF versus controls. (odds ratio 0.33, 95% CI 0.18 to 0.85, p 0.02). Fauchier, JACC 2008

16 Statins for prevention of AF Observational cohort study post PM impl. N=157 pats. At 1 year: pats on statin less likely to experience AT/AF vs pats not on statin, p = Gillis, European Heart Journal 2008

17 Upstream therapy: statins, RAAS inhib., and steroids ESC guidelines 2010 Camm et al, ESC Guidelines on Atrial Fibrillation, EHJ 2010.

18 AA drugs Risk Factors for AF Diabetes HT VOC MI LA CMP CHF LAd h LV fs i LVH Inflammatory markers unclear whether primary or secondary Obesity- metabolic syndrome, Insulin resistance, Thrombogenic tendencies, Sleep apnea, Decreased arterial compliance, LA volume and diastolic dysfunction. Atrial remodelling pathways promoting AF: Inflammation RAAS activation Sympath. NS Ca overload Oxid stress AF begets AF Upstream therapy

19 AF ablation. ESC guidelines 2010 Camm et al, ESC Guidelines on Atrial Fibrillation, EHJ 2010.

20 Randomized Trials of AF Ablation vs AA Drugs - PAF/Persist AF ABL AAD Forleo G Jais 112 Pappone 198 Oral 146 Stabile 137 Wazni 70 One year AF-Free Study Forleo, % Persist. Jais et al, PAF. (A 4 study) Pappone et al, (APAF) Oral et al, Persist AF only. Pts Ablation 1 year AF free AAD % % 23% (63% cross over) % 29% (51% cross) % 4% without amiodarone; (77% cross over) Stabile et al, % PAF (CACAF) % 9% Wazni et al, PAF (RAAFT) 37 % 66 % 58 % (57% cross over) 70 % 70 87% 37% (54% after 2 nd AAD) 47 % % 50 %

21 RF ablation reduced the risk of AF recurrence at 1 year by 65% compared with antiarrhythmic medications. J Cardiovasc Electrophysiol 2009

22 Freedom from arrhythmia at 12 mo: all AF randomised controlled trials. All included controlled studies favour ablation over AAD-based management, but extremely high degree of statistical heterogeneity between studies

23 Freedom from arrhythmia at 12 mo: PAF randomised controlled trials. Meta-analysis of 3 RCTs: 97% paroxysmal AF Majority of pats (75%, 87%, 93%) free of structural heart disease Only 6% repeat ablation procedures

24 1. Ablation strategies which target the PVs and/or PV antrum are the cornerstone for most AF ablation procedures. 2. If the PVs are targeted, complete electrical isolation should be the goal. Careful identification of the PV ostia is mandatory to avoid ablation within the PVs. Heart Rhythm, Vol 4, No 6, June 2007

25 Techniques for AF ablation PV isolation: Isolating PV triggers Haissaguerre Complex Fractionated Atrial Electrograms: Dominant Rotors Nademanee WACA / Antrum Isolation: Linear lesion sets Substrate Modification Pappone Ganglionated Plexi Ablation: Autonomic triggers Scherlag, Nakagawa, Jackman, Platt, Lemery

26 Left Atrial Circumferential vs Segmental Ostial PV Ablation in recurrent PAF Randomized 80 pats: LACA+mitral isthmus+post. LA: SOCA: PVI. Randomized 100 pats: Ostial PVI: Circumferential PVs + mitral isthmus. left atrial catheter ablation segmental ostial ablation Oral, Circ 2003 Karch, Circul 2005

27 Complications - RF AF ablation The risk is higher than for ablation of most other arrhythmias (~ 5 10 x) Esophagus

28 Retrospective AF ablation series: / 546 identified centers worldwide: 32 deaths/32,569 pats (~ 1 / 1,000 pats); 45,115 procedures. Causes of deaths (no pats): 8 tamponades (1 later than 30 days), 5 strokes (2 later than 30 days), 5 atrioesophageal fistulas, 2 massive pneumonias. 1 of each: MI, intractable TdP, septicemia, sudden respiratory arrest, PV perforation, lateral PV occlusion, hemothorax, and anaphylaxis. 1 of each: subclavian hematoma, intracranial bleed, ARDS, and esophageal perforation (perop echo probe)- late death. Cappato, JACC 2009

29 Am J Cardiol 2009;104: ) N = 71 pats PVI for PAF Followed > 5 yrs after index ablation procedure. 5-year outcomes at last clinic visit telephone encounters cardiac monitoring if available.

30 Hypertension independent predictor of AF recurrence

31 Current therapies do not address the multiple impacts of AF AF causes morbidity and mortality through a variety of mechanisms 1 Current therapies do not address the multiple impacts of AF Rate control leaves patients in AF 2 Rhythm control may achieve sinus rhythm, but is limited by adverse events and recurrences 2 Anticoagulation therapy reduces stroke-related mortality but not other CV risk factors 3 1. Kirchhof P et al. Europace 2007; 9: Nattel S, Opie LH. Lancet 2006;367: Hylek EM, et al. N Engl J Med. 2003;349:

32 Comprehensive Management of AF Should Address its Multiple Impacts Management of AF should aim at reducing both CV morbidity and mortality Prevent thromboembolism Reduce AF burden* QoL Symptoms Reduce risk of CV events and hospitalizations Reduce mortality *Total percentage of time a patient has AF as determined by the number and duration of AF episodes 1. Wolf et al. Stroke 1991;22: Singh SN, et al. J Am Coll Cardiol. 2006;48: Prystowsky EN. J Cardiovasc Electrophysiol 2006;17(suppl 2):S7-S Hohnloser S, et al. J Cardiovasc Electrophysiol. 2008;19: Camm AJ, Reiffel JA. European Heart Journal Supplements 2008;10(SH): H55-H78

33 AF treatment 1980 Cox left atrial isolation procedure Sinus rhythm Atrial fibrillation Williams JM,Cox JL: J Thorac Cardiovasc Surg 1980

34 Carina Blomström Lundqvist, Dept.of Cardiology, University Hospital, Uppsala