The document discusses recent developments in left atrial appendage closure. Key points include: - Long term results and meta-analyses from randomized trials of warfarin vs. Watchman leading to FDA approval. - Differences between trial populations and real-world patients. - Results from studies of patients who cannot take oral anticoagulants. - Technical advances in devices. - Role of CT imaging.

1. Novedades en el Cierre
de Orejuela Izquierda
José Ramón López Mínguez
Hospital Infanta Cristina
Badajoz

2. NOVEDADES en el Cierre de la
Orejuela Izquierda
• Resultados a largo plazo y metanálisis en
estudios randomizados de warfarina vs
Watchman => Aprobación FDA
• Realidad de las poblaciones diana vs trials
• Resultados en estudios de pacientes que no
pueden tomar ACOs
• Avances técnicos dispositivos
• Papel del TAC

3. Trials Patient Risk Factors Across
Characteristic
PROTECT AF
N=707
PREVAIL
N=407
CAP
N=566
CAP2
N=579 p-value
CHADS2 Score 2.2 ± 1.2 2.6 ± 1.0 2.4 ± 1.2 2.7 ± 1.1 <.0001
CHADS2 Risk Factors (% of Patients)
CHF 26.9 19.1 23.3 27.1 0.004
Hypertension 89.8 88.8 91.4 92.5 0.15
Age ≥ 75 43.1 51.8 53.6 59.7 <0.001
Diabetes 26.2 24.9 32.4 33.7 0.001
Stroke/TIA 18.5 30.4 27.8 29.0 <0.0001
CHA2DS2-VASc 3.5 ± 1.6 4.0 ± 1.2 3.9 ± 1.5 4.5 ± 1.3 <0.0001
Holmes, DR et al. JACC 2015.
Total patients >2,000 ~6,000 Patient-Years of Follow-up

7. (Composite: Stroke / SE / CV Death)
(Ischemic Stroke and SE)

15. Resultados a 4 años del
PROTECT AF
• In patients at elevated risk of stroke
and bleeding with suitable anatomy,
occlusion of the left atrial appendage
with the catheter-deployed Watchman
device is associated with:
– lower risks of major bleeding post
procedure,
– hemorrhagic stroke,
– and mortality than long-term
warfarin therapy.
CONCLUSIONES DEL
METANALISIS

16. Finalmente tras esos resultados
Esto llevara a un posible cambio de la indicación IIb en las guías

17. NOVEDADES en el Cierre de la
Orejuela Izquierda
• Resultados a largo plazo y metanálisis en
estudios randomizados de warfarina vs
Watchman => Aprobación FDA
• Realidad de las poblaciones diana vs trials
• Resultados en estudios de pacientes que no
pueden tomar ACOs
• Avances técnicos dispositivos
• Papel del TAC

18. Mensajes de los estudios NACOs que se
pueden interpretar de forma equívoca
• Matizaciones sobre la cifra mágica de Sangrados Graves < 3%
• Los ancianos (> 75 a) sangran más (> graves 4,5%) y es acumulable por año
• El porcentaje de casos con historia de sangrados previos no figura en estos
trials o es mínimo (16%) vs > 70% en pacientes a los que se realiza cierre de
Orejuela
• Los sangrados relevantes son de 2 a 7 veces más (6-21 %)
• Por ello los abandonos a dos años > 25%
• Las conclusiones de los trials se aplican sólo al 60% de la población que
podría entrar en esos estudios.
• Así, aún hoy > 30-40% de pacientes que deberían recibir ACO no los reciben

20. En los ancianos el riesgo
de Sangrados es mayor

22. Bleeding Rates After Percutaneous Coronary Intervention
Cumulative rates of first post-discharge bleeding event increased over time in all patients;
a similar pattern was seen when patients were stratified according to requirement for blood transfusion.
Incidence, Predictors, and Impact of Post-Discharge Bleeding After
Percutaneous Coronary Intervention
J Am Coll Cardiol. 2015;66(9):1036-1045. Genereux P et al.
8582 all-comers
Tº medio al primer PDB 300 d

23. All-Cause and Cardiac Mortality According to PDB
Kaplan-Meier estimates demonstrate higher rates of all-cause mortality (solid line) and cardiac mortality (dotted line)
according to the occurrence of post-discharge bleeding (PDB) (salmon) compared to no PDB (blue) over 2 years of
follow-up (A) as well as the landmark analysis at 30-day and 1-year follow-up (B).
Incidence, Predictors, and Impact of Post-Discharge Bleeding After
Percutaneous Coronary Intervention
J Am Coll Cardiol. 2015;66(9):1036-1045. Genereux P et al.

24. Clinical outcomes of atrial fibrillation patients receiving NSAIDs in the
RELY trial.
European Society of Cardiology Congress; 2015. Ezekowtiz M.
NSAID use (12,6%) was accompanied by increases in the rates of hospitalization, major
bleeding, GI major bleeding, life-threatening bleeding, and any bleeding

25. Poblaciones actuales a los que se
realiza cierre de Orejuela
• Habitualmente ancianos > 75 años, con alto riesgo de sangrado a los
que su médico no se atreve a anticoagular
• Pacientes que han sangrado previamente ya con, o sin ACO, la mayoría
de ellos no entrarían en los estudios NACO. Pacientes con anomalías
vasculares digestivas o cerebrales (cavernomas), que tb son excluidos
de los estudios.
• Pacientes que han abandonado por sangrado previo o por no
compliance con ACO
• Pacientes que han hecho ictus a pesar de ACO
• Pacientes que precisan de forma crónica DAAP

26. NOVEDADES en el Cierre de la
Orejuela Izquierda
• Seguimiento a4 años del PROTECT AF y
Resultados metanálisis en estudios
randomizados de warfarina vs Watchman =>
Aprobación FDA
• Realidad de las poblaciones diana vs trials
• Resultados en estudios de pacientes que no
pueden tomar ACOs
• Avances técnicos dispositivos
• Papel del TAC
• Estudios de cierre de orejuela en estos pacientes
con > 150 casos:
- ASAP
- ACP European Registry
- ACP Multicenter Experience
- Iberian Registry

27. Clopidogrel for 6 months & ASA for life - 4 European Centers (Czech Re 1, Germany 3) 150 pts:
CHADS2 = 2.8 ± 1.2 (Prior CVA/TIA in 40.7%),
Mean Follow-up: 16.5 months
(ASA Plavix Feasibility Study With
Watchman Left Atrial Appendage
Closure Technology)

29. ACP Post Market European Registry

32. Baseline and procedure-associated characteristics (n = 167)
Age (in years)
≥ 75 years: 84 (53.2%); ≥ 78 years: 63 (39.9%)
74.68 ± 8.58
Men 102 (61.1%)
CHADS2 3 (2-4)
CHA2DS2-VASC 4 (3-6)
HAS.BLED 3 (3-4)
Procedure indication
Gastrointestinal haemorrhage 51 (30.5%)
Cranial haemorrhage 38 (22.8%)
Other haemorrhages 28 (16.8%)
CVA/Embolism with OAC 12 (7.2%)
High risk of bleeding 7 (4.2%)
Others 32 (19.2%)
Device size 24 (22-25)
Need to change device 6 (3.5%)
Successful implantation 158 (94.6%)
Procedural complications 9 (5.38%)
TIA 2 (1.2%)
Vascular complication 4 (2.39%)
Cardiac tamponade 2 (1.2%)
Device migration (percutaneously snared) 1 (0.6%)
Values expressed as: Number (percentage), Mean ± Standard deviation or median (25th -75th percentiles). OAC: Oral anticoagulants;
TIA: transient ischaemic attack.
Results
70,1 BE
REGISTRO
IBÉRICO
Heart 2015

33. Events
12-month (158 patients year) Global follow-up (annual event
rates, 290 patients year)
Observed Expected* p-value Observed Expected* p-value
Death 9 (5.8%) 17 (5.8%)
Major
Bleeding
8 (5.2%)
6.6%
HASBLED
0.400 9 (3.1%)
6.6%
HASBLED
0.047
Total bleeding
(Major + Relevant)
15 (9.5%) > 17.55 % * 16 (5.5%)
Stroke/TIA 6 (3.9%) 9.6%
CHADS2
0,007
7 (2.4%) 9.6%
CHADS2
<0.001
8.3%
CHA2DS2-VASC
0,025
8.3%
CHA2DS2-VASC
0.003
Results: Comparison of observed and expected events at 12- and 24-month follow-up
(patient-year)
* Mean of any bleeding rate in the 3 new OAC trials
Alta 1 mes 6 meses 12 meses
Only AAS or Clopi 14 (8.9%) 26 (16.6%) 111 (73.5%) 130 (87.8%)
DPAT 138 (87.3%) 128 (81.5%) 33 (21.9%) 7 (4.7%)
ACO 5 (3.2%) 2 (1.3%) 6 (3.9%) 6 (4.1%)

34. Results : Comparison of observed and expected events at 24-month follow-up
expressed as global follow-up (annual event rates, 290 patients year)
6.6%
3.1%
9,6%
2.4%
Expected rates based on Swedish Registry (Friberg et al, Eur Heart J. 2012;33:1500-10) using event rates not adjusted for reduction by aspirin.
55%
75%

35. Expected and observed stroke rates in patients
implanted with the ACP device

36. NOVEDADES en el Cierre de la
Orejuela Izquierda
• Resultados a largo plazo y metanálisis en
estudios randomizados de warfarina vs
Watchman => Aprobación FDA
• Realidad de las poblaciones diana vs trials
• Resultados en estudios de pacientes que no
pueden tomar ACOs
• Avances técnicos dispositivos
• Papel del TAC

42. WATCHMAN

43. • Safety of left atrial appendage exclusion with the Lariat device: a systematic
review of published reports and analytic review of the FDA MAUDE database.
• Chatterjee S, Herrmann HC, Wilensky RL, et al. JAMA Intern Med. 2015;Epub ahead of print.
• In 5 studies involving 309 patients, procedural success was 90.3%. Cardiac
surgery was urgently needed in 2.3% of patients and 0.3% died in the hospital.
• Pericardial Effusion Cited as a Problem
Implications
Until Lariat receives FDA approval specifically for LAA occlusion, its current off-label use in
clinical practice “should be questioned,” says Dr. Paul Varosy.

44. NOVEDADES en el Cierre de la
Orejuela Izquierda
• Seguimiento a4 años del PROTECT AF y
Resultados metanálisis en estudios
randomizados de warfarina vs Watchman =>
Aprobación FDA
• Realidad de las poblaciones diana vs trials
• Resultados en estudios de pacientes que no
pueden tomar ACOs
• Avances técnicos dispositivos
• Papel del TAC

45. Journal of Invasive Cardiology. 2014.

46. Aspecto Endocárdico de los Tipos AAI
ANATOMICAL CLASSIFICATION OF LEFT ATRIAL APPENDAGES IN SPECIMENS APPLICABLE TO CT IMAGING TECHNIQUES
FOR IMPLANTATION OF AMPLATZER CARDIAC PLUG. López-Mínguez, JR et alJournal of Cardiovascular Electrophysiology.
2014. Vol 25: 976-984

47. Aspecto Epicárdico de los Tipos AAI

48. Ver situación del disco
externo en relación a la CLI
en dos casos diferentes

49. 30%
19%
3%
48%

50. Does the Left Atrial Appendage Morphology Correlate With the
Risk of Stroke in Patients With Atrial Fibrillation?
Results From a Multicenter Study. DiBiasse. J Am Coll Cardiol 2012;60:531–8
• Of the 932 patients, (8%) had a history of
ischemic stroke or TIA. The prevalence of pre-
procedure stroke/TIA in Cactus, Chicken
Wing, Windsock, and Cauliflower
morphologies was 12%, 4%, 10%, and 18%,
respectively (p 0.003).
• After controlling for CHADS2 score, gender,
and AF types in a multivariable logistic model,
Chicken Wing morphology was found to be
79% less likely to have a stroke/TIA history
• Compared with Chicken Wing, Cactus was
4.08 times (p 0.046), Windsock was 4.5 times
(p 0.038), and Cauliflower was 8.0 times (p
0.056) more likely to have had a stroke/TIA.
• (J Am Coll Cardiol 2012;60:531–8)

51. Predictores de
trombo
• Qualitative identification of thrombus
in LAA by CCTA compared with TEE
detection of thrombus had a
sensitivity of 100%, a specificity of
77.9%, a positive predictive value
(PPV) of 51.6%, an NPV of 100%, and
a total accuracy of 82.1%.
• The optimal LAA HU density cutoff for
thrombus detection was 119 with a
sensitivity of 88%, a specificity of 86%,
PPV 56%, and an area under the curve
of 0.923 (p [ 0.0004).
• Comparison of Transesophageal Echocardiography Versus
Computed Tomography for Detection of Left Atrial Appendage
Filling Defect (Thrombus). Budoff et al. Am J Cardiol
2014;113:173e177

52. Otros Articulos de TAC y predicción de trombos en AAI
LAA orifice enlargement was related to stroke risk in patients with NVAF even
after adjustment for other risk factors, and it could be the cause of decreased
flow velocity in LAA. Impact of Increased Orifice Size and Decreased Flow Velocity of Left Atrial Appendage on Stroke in
Nonvalvular Atrial FibrillationLee Jm et al. Am J Cardiol 2014;113:963e969
It is proposed a new scoring system to predict LAAT (LAV ≥50 ml: score 2; EF <56
%: score 1; BNP >75 pg/ml: score 1). Patients with a score ≥2 have a higher risk of
LAAT, whereas all patients with score ≤1 have no LAATs. Our scoring system is
useful for evaluation the risk of LAAT in AF patients even with low CHADS2 score
Prevalence and Clinical Determinants of Left Atrial Appendage Thrombus in Patients with Atrial Fibrillation Prior to Pulmonary Vein
Isolation. Nishikii-Tachibana M et al. The American Journal of Cardiology (2015),
A superior LAA takeoff (OR: 9.1) was the only independent predictor of TE while LAA
morphologies, inferior takeoff, and other LAA characteristics were similar between groups
CONCLUSION: A higher LAA takeoff is associated with a tachycardia-mediated
thrombogenic flow and an increased thromboembolic risk. These findings may have
implications for anticoagulation management of AF patients with low CHA2 DS2 -VASc
scores and higher LAA takeoff.
Cardiogenic Stroke Despite Low CHA2 DS2 -VASc Score: Assessing Stroke risk by Left Atrial Appendage Anatomy (ASK LAA). Nedios S et al. J
Cardiovasc Electrophysiol. 2015

53. ©2015EuroIntervention.Allrightsreserved.
EuroIntervention 2015;10:1109-1125
EHRA/EAPCI expert consensus statement on catheter-based left atrial appendage occlusion