Ictus criptogenetico: possiamo ridurre questa diagnosi?

Transcription

1 FIBRILLAZIONE ATRIALE Ictus criptogenetico: possiamo ridurre questa diagnosi? Maurizio Landolina MD, FESC Direttore U.O.C. Cardiologia, Ospedale Maggiore di Crema

2 Disclosures Speakers bureau appointment with: Boston Scientific LivaNova Medtronic St. Jude Medical Advisory board relationship with Medtronic.

3 ICTUS L ictus cerebrale è la seconda causa di morte WW (dopo le malattie cardiovascolari e prima delle neoplasie) e la principale causa di disabilità. La mortalità a un anno dopo il primo ictus è del 22%. Il rischio assoluto di recidiva di ictus cerebrale è del 10-15% nei dodici mesi seguenti l evento e, successivamente del 4-9% per ogni anno nei primi cinque anni. Lozano R et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study Lancet. 2012;380: ; dati SPREAD 2012; Donnan et al. "Stroke". Lancet 371 (9624):

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6 Identification and Diagnostic Evaluation of Patients with Cryptogenic Ischemic Stroke or TIA N Engl J Med 2016; 374:

7 ICTUS CRIPTOGENICO & FIBRILLAZIONE ATRIALE La fibrillazione atriale si traduce in un rischio totale 5 volte maggiore di sviluppare ictus L ictus ischemico associato alla FA, ha una prognosi peggiore, in termini di mortalità e disabilità residua rispetto agli ictus senza FA Determinare la presenza di FA permette di instaurare una terapia anticoagulante, che ha una efficacia preventiva di ictus maggiore rispetto alla terapia antiaggregante (raccomandata se l FA non è documentata)

8 ATRIAL FIBRILLATION Silent but deadly! Furberg CD, Am J Cardiol 1994; 74:

9 The Clinical Presentation of AF Asymptomatic Atrial Fibrillation Symptomatic Atrial Fibrillation Crypto Stroke Ischemic Stroke Sudden Death Heart Failure Palpitations Hemodymanic Dizzyness Heart Failure Syncope Tachy Arrhythmias Cognitive Decline Medical Attention Dementia

10 Improvement of device technology allows greater quantification of AF burden Botto GL. JCE. 2009;20:

11 STUDI CON MONITORAGGIO ESTERNO IN PAZIENTI POST-ICTUS CRIPTOGENICO Study (Year) N AF Definition Monitoring Duration AF Yield Tayal (2006) 56 Any duration MCOT 21 Days Gaillard (2010) seconds TTM 30 days 9% Bhatt (2011) seconds MCOT 28 days Flint (2012) seconds MCOT 30 days Kamel (2013) seconds MCOT 21 days 0% Miller (2013) seconds MCOT 30 days Gladstone (2014) seconds Event Monitor 30 days vs 24 Holter Overall 23% AF < 30 sec 18% AF > 30 sec 5% 24% AF > 5 min 9% Overall 11% AF < 30 sec 4% AF > 30 sec 7% Overall 17% AF < 30 sec 12% AF > 30 sec 4% 16.1% in event monitor vs. 3.2% Holter Glotzer TV, Ziegler PD. Heart Rhythm. 2015;12:

12 STUDI CON LOOP RECORDER IMPIANTABILE IN PAZIENTI CON ICTUS CRIPTOGENICO Study Study size Mean Age (years) Duration of monitoring (months) Definition of AF Time to Diagnosis (days) AF detection rate (%) Ritter 1 60 NA 10 >30 seconds Etgen >6 minutes Cotter minutes SURPRISE >2 minutes Rojo-Martinez minutes Ziegler minutes Poli > 2 minutes Jorfida > 5 minutes CRYSTAL AF 9 (ICM arm) >30 seconds Ritter et al, Stroke. 2013, 44: ; 2Etgen et al, Stroke. 44: ; 3Cotter et al, Neurology. 2013, 80: ; 4Christensen et al, Eur J Neurol. 2014, 21:884-89; 5Rojo-Martinez Rev Neurol 2013; 57 (6): ; 6Ziegler et al, Cerebrovasc Dis. 2015, 40: Poli Eur J Neurol Oct 16 Epub ahead of print ;8 Jorfida J 17Cardiovasc Med (Hagerstown) Nov 15. [Epub ahead of print] 9Sanna T et al, NEJM. 2014;370: ;

13 CRYPTOGENIC STROKE AND UNDERLYING ATRIAL FIBRILLATION (CRYSTAL AF) 441 Pazienti con Stroke criptogenico/tia Randomizzati a SoC monitoring o Reveal XT AF definita se 30 sec Identificata dall investigatore Aggiudicata da un comitato indipendente Endpoint primario AF detection a 6 mesi Endpoint secondari AF detection a 12 mesi AF duration Correlazione con i sintomi Azioni mediche intraprese Sanna T et al. N Engl J Med. 2014; 370:

14 CRYSTAL AF: ENDPOINT PRIMARIO E SECONDARI Detection of AF at 6 months ICM finds 6x more patients with AF 8.4% Detection of AF at 12 months ICM finds 7x more patients with AF 12.4% 1.4% 2.0% ICM Control Median time to AF Detection 41 days 32 days ICM Control Median time to AF Detection 84 days 52.5 days Patients found to have AF 19 3 % Asymptomatic Episodes 74% 33% Tests required to detect AF Auto. AF detection 88 ECGs hr Holters 1 Event Recorder Patients found to have AF 29 4 % Asymptomatic Episodes 79% 50% Tests required to detect AF Auto. AF detection 121 ECGs hr Holters 1 Event Recorder Sanna T et al. N Engl J Med. 2014; 370:

15 CRYSTAL AF: A 36 MESI 8.8x more than standard follow-up arm 30.0% ICM Control Median time to AF Detection 252 days 72 days 3.0% Patients found to have AF 42 5 % Asymptomatic Episodes 81% 40% Tests required to detect AF Auto. AF detection 202 ECGs, hr Holters 1 Event Recorder Sanna T et al. N Engl J Med. 2014; 370:

16 PREDICTORS OF AF OFFER ONLY MODERATE PREDICTIVE ABILITY CRYSTAL AF sub-analysis: Thijs, Neurology (2016) Parameters tested: Age, sex, race Body Mass Index, Type and severity of index event CHADS 2 score PR-interval Diabetes, hypertension Congestive heart failure Patent foramen ovale Premature atrial contractions Increasing age and a prolonged PR-interval were independently associated with AF, but the predictive ability of these parameters was only moderate Thijs 21 et al. Predictors for Atrial Fibrillation Detection after Cryptogenic Stroke: Results from CRYSTAL AF. Neurology 86.3 (2016):

17 STROKE & AF: SYSTEMATIC REVIEW AND META-ANALYSIS Sposato Lancet Neurol, April studi; pazienti post stroke Emergency room In Hospital 1 ambulatory period 2 ambulatory period 7.7% 5.1% 10.7% 16.9% Sposato et al. Lancet Neurol 2015; 14:

18 Embolic Stroke of Undetermined Source and Detection of Atrial Fibrillation on Follow-Up: How Much Causality Is There? Among 275 ESUS pts, AF was detected during follow-up in 80 (29.1%), either during repeated ECG monitoring (18.2%) or during hospitalization for stroke recurrence (10.9%). More recurrent strokes or peripheral embolisms occurred in the AF group compared with the non-af group (42.5% versus 13.3%, P =.001). All patients Patients on antiplatelets 26 Ntaios G et al., J Stroke Cerebrovasc Dis 2016 (in press)

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20 AF Burden (0 to 100%, log scale) Temporal Relationship of Atrial Fibrillation & Thromboembolism Months from TE

21 Temporal Proximity of Silent AF Episodes to Thromboembolic Event Trial AF prior to stroke (at any time) AF prior to stroke (<30 days) New AF after stroke TRENDS (Daoud EG, et al Heart Rhythm 2011;8: ) ASSERT (Brambatti M et al Circulation 2014 Mar 14) IMPACT (all) Martin DT, ACC Session, 2014, March 29 20/40 (50%) 9/40 (22%) 6/40 (15%) 18/51 (35%) 4/51 (8%) 8/51 (16%) 20/69 (29%) n.a. 9/69 (13%)

22 Visione distorta: ictus da cause differenti?

23 Is AF a Cause or a Marker of STROKE?

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25 Association of Left Atrial Fibrosis Detected by Delayed-Enhancement MRI and the Risk of Stroke in AF Patients 387 pts,mean age yrs, 36.8% female, 9.3% with a history of previous stroke Stage I Stage III Stage II Stage IV Daccarett M, JACC 2011; 57: 831-8

26 Hypercoagulability and atrial fibrillation: a two-way road? Schematic diagram showing the potential association between hypercoagulability and atrial fibrillation (AF). On the one hand, AF promotes a hypercoagulable state which is directly associated with the presence of thrombo-embolic complications. On the other, hypercoagulability induces atrial fibrosis further enhancing AF, mainly through the activation of the protease-activated receptor (PAR) signalling pathway. IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; α SMA, α smooth muscle actin; TGFβ1, transforming growth factor β1. Eur Heart J. 2016;38(1):51-52

27 How Much AF Warrants Anticoagulation? Will Long-Term Monitoring for AF in Cryptogenic Stroke Patients Impact Hard Outcomes? 36 Reveal LINQ Insertable Cardiac Monitoring System Confidential, for Internal Use Only

28 AF monitoring by pacemakers. The issue of anticoagulant therapy 725 pts with brady-tachy syndrome, implanted with a MDT AT- 500 followed for 2 years Capucci A et al., JACC 2005; 46:

29 AF monitoring by pacemakers. The issue of anticoagulant therapy a. Lamas GA, NEJM 2002; 346: b. Glotzer TV, Circ Arrhyth Electrophysiol 2009; 2:

30 AF monitoring by pacemakers. The issue of anticoagulant therapy Subclinical atrial tachyarrhythmia: >6 minutes duration, >6 hours duration or >24 hours duration ASSERT Trial, NEJM 2012; 366: 120-9

31 CHADS 2 Score, AF Duration and Stroke Risk 568 Pts with MDT AT500 IPG Continuously Monitored for 1 Year CHADS 2 score No AF at FU (AT/AF < 5 min in 1 day) 1.7% 0% 0% 25% 5 min < AT/AF Episodes < 24 h 1.8% 1.3% 2.4% 0% AT/AF Episodes > 24 h 0% 4.4% 4.4% 33% (3 out of 351 Pts) 0.8 % vs 5 % (11 out of 217 Pts) P = Botto GL. J Cardiovasc Electrophys 2009; 20:

32 Sensitivity, Specificity and Predictive Ability for the CHA 2 DS 2 -VASc stroke risk score. Relation to AF Burden Boriani G, Stroke 2011; 42:

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35 Ongoing Studies on Pts with Potentially Asymptomatic AF Study Inclusion criteria Randomization/ Design Size (N) Endpoint Estimated completion date ARTESiA Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub- Clinical Atrial Fibrillation Clinicaltrials.gov NCT Permanent PM, ICD or CRT CHA 2 DS 2 -VASc score of 4. Age 65 At least one episode of symptomatic AF 6-min (Atrial rate >175/min if an atrial lead is present) but no single episode >24 h in duration. NO pts with clinical AF Apixaban 5 (or 2,5) mg x 2 vs Aspirin 81 mg x1 daily 4,000 1.Composite of - ischemic stroke - systemic embolism 2.Major Bleeding 2019 NOAH AFNET 6 Non-vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes Clinicaltrials.gov NCT Permanent PM or ICD. Age 65 + additional CHA 2 DS 2 -VASc score point of 2, i.e. CHA 2 DS 2 -VASc 3 At least one episode of AHRE 6 min (Atrial rate >180/min if an atrial lead is present), but no single episode > 24 h in duration. NO pts with overt AF Edoxaban 60 (30 if renal ins) mg x1 vs Aspirin 100 mg x1 daily. Double-blinded double-dummy 3,400 Composite of time to - first stroke - systemic embolism - CV death 2019 The (Danish) LOOP study Clinicaltrials.gov NCT Age > 70 years and at least one of the following diseases: - Diabetes - Hypertension - Heart failure - Previous stroke ILR or Standard treatment of care (ratio 1:3) 6,000 Composite of - ischemic stroke - systemic embolism????

36 Quando la posta in gioco è alta e la causa dello stroke non è così «CRISTALLINA» 46 Reveal LINQ Insertable Cardiac Monitoring System Confidential, for Internal Use Only