Come implementare le linee guida per l’ablazione della fibrillazione atriale nella pratica clinica: Precocità del trattamento per aumentare l’efficacia Recnti trials hanno dimostrato che il trattamento precoce della fibrillazione atriale migliora gli outcomes, riduce la mortalità cardiovascolare e riduce il rischio di ictus

1. Pasquale Vergara
Ospedale San Raffaele - Milano
Come implementare le linee guida
per l’ablazione della fibrillazione
atriale nella pratica clinica:
Precocità del trattamento
per aumentare l’efficacia

2. Guidelines for AF management EHJ 2020

3. EAST-AFNET 4 Trial Kirchhof NEJM 2020;383:1305-1316
Anticoagulation, rate control in all patients and treatment of cardiovascular conditions
Early rhythm control
Antiarrhythmic drugs or atrial fibrillation ablation,
cardioversion of persistent AF early after
randomization
Usual care
Monitoring: single-lead ECG 2 per week & when symptomatic
Rhythm-control therapy was used only to mitigate
uncontrolled AF–related symptoms during
adequate rate-control therapy
Primary outcomes:
• composite of death from cardiovascular causes, stroke (either ischemic and hemorrhagic), or
hospitalization with worsening of HF or acute coronary syndrome, analyzed in a time-to-
event analysis.
• number of nights spent in the hospital per year.
Secondary outcomes
• each component of the first primary outcome, rhythm, left ventricular function, quality of life, atrial
fibrillation–related symptoms, cognitive function
R
Early atrial fibrillation: AF diagnosed ≤12 months before enrollment
• older than 75 years of age
• had a previous transient ischemic attack or stroke
• 2 of the following criteria:
 age ≥ 65 years
 female sex
 heart failure
 Hypertension
 diabetes mellitus
 severe coronary artery disease
 chronic kidney disease
 left ventricular hypertrophy
2789 patients

4. EAST-AFNET 4 Trial
⇝ A strategy of initiating rhythm-control therapy in all patients with early AF and
concomitant cardiovascular conditions was associated with a lower risk of death from
cardiovascular causes, stroke, or hospitalization for heart failure or acute coronary
syndrome than usual care over a follow-up time of more than 5 years
Kirchhof NEJM 2020;383:1305-1316
HR:0.79;
96% CI: 0.66 to 0.94;
P = 0.005
Cumulative
incidence
Primary composite outcome
21%
reduction

5. EAST-AFNET 4 Trial Kirchhof NEJM 2020;383:1305-1316

6. What are the drivers of
the reduction in outcomes within this
treatment strategy?

7. EAST-AFNET4 Trial # causal mediation analysis
Eckard EHJ 2022; 43; 4127–4144
Treatment
Outcome ⇣ Primary outcome
Blood
pressure
Mediator
Early rhythm control
Mediator
Sinus
Rhythm
AF
recurrence

8. ⇝Early rhythm control reduced the first primary outcome
from 12 months on up to the study end.
⇝Sinus rhythm at 12 months visit explained 81%
of the treatment effect of ERC therapy compared with usual care
during the remainder of FU
⇝In patients not in sinus rhythm at 12 months, ERC did
not reduce further cardiovascular outcomes
Early rhythm control effect on primary endpoint
Eckard EHJ 2022

9. ⇝Atrial fibrillation recurrence in the first 12 months of
follow-up only explained 31% of the treatment effect
⇝Systolic blood pressure at the 12-month visits explained
only 10% of the treatment effect
Early rhythm control effect on primary endpoint
Eckard EHJ 2022

10. EAST-AFNET4 #Effect of AF ablation
2810 patients assessed for elegibility
2789 patients randomized
21 patients did not meet
inclusion criteria
1395 Early Rhythm
Control
390
received
ablation
1394 Usual Care
1055
no
ablation
168
received
ablation
1226
no
ablation
98
early
ablated
242
late
ablated
<8 weeks after
randomization
>8 weeks after
randomization
⇝ Use of AF ablation did not affect the
primary outcome
⇝Early ablated within ERC patients had
reduced cardiovascular outcomes
compared with non-ablated (HR 0.66,
95%CI 0.35–1.25)
⇝Late AF ablation was associated with
increased cardiovascular
outcomes compared with non-ablated
(HR 1.27, 95%CI 0.87–1.84 ).
Eckard EHJ 2022

11. EARLY-AF Cryoablation vs Drugs for initial AF Andrade, NEJM 2021;384:305-15
AF detected ≤24 before randomization
 adults (>18 years of age)
 symptomatic AF
 within 24 months before randomization
303 patients
Cryobalooon ablation AAD
Primary outcomes:
• first recurrence of any atrial tachyarrhythmia (AF, AT)
Secondary outcomes
• first recurrence of symptomatic atrial tachyarrhythmia (AF, AT)
Continuous monitoring by Reveal LINQ, Medtronic
R

12. EARLY-AF Cryoablation vs Drugs for initial AF Andrade, NEJM 2021;384:305-15
Primary outcome: 1st recurrence of any atrial tachycardia (AF/AT>30”)

13. EARLY-AF Cryoablation vs Drugs for initial AF Andrade, NEJM 2021;384:305-15
Secondary outcome:
1st recurr of symptomatic atrial tachy
Primary outcome:
1st recurr of any atrial tachy

14. Atrial fibrillation Better Care
Anticoagulation / Avoid
stroke
Better symptom
management
Cardiovascular and
comorbidity optimization
A
B
C
Rate control
Rhythm control

15. shift
EAST-AFNET4
of rhythm control therapy
from a symptom-driven therapy to a
risk-reducing strategy

16. shift
EAST-AFNET4
restoring and maintaining sinus rhythm
as the default therapy in patients with
recently diagnosed AF and stroke risk
factors

17. Generalizability of EAST-AFNET 4 Trial Dickow JAHA 2022
720’516 Atrial Fibrillation patients with diagnosis 07/2011 – 12/2016
Exclusions
- Prior AF/ A Flutter diagnosis, CA, Cardioversion, AAD fill in prior 12 months
- Age < 18 yeas, missing demographics
- ≤12mo medical coverage before/after AF diag.
- No AAD, CA or rate control in 12mo after AF diagnosis; n=47’468
Overall cohort with new AF 109’739 patients
Elegible for EAST-AFNET 4 - 79’948 pts
Early Rhythm Control
18307 patients
Usual Care
61641 patients
• AAD 17’996 pts (98.3%)
• Catheter ablation 1543 (8.4%)
Inelegible for EAST-AFNET4
29’791 pts
• Β-block 54’475 pts (88.4%)
• Ca++ ch block 12’998 (21.1%)
• Digitalis 5’943 (9.6%)
⇝ no inclusion criterion:
age <75 years without 2 stroke risk
factors
⇝ at least 1 exclusion criteria

18. Generalizability of EAST-AFNET 4 Trial Dickow JAHA 2022
⇝ The majority of patients (72.9%) treated in routine US practice meet
enrollment criteria for EAST-AFNET 4.
⇝ Observed results associated with ERC in routine practice are largely
consistent with the Trial results
34% stroke
risk reduction

19. The trial vs real world data
EAST-AFNET US data elegible
Control Early rhythm HR Control Early rhythm HR
Composite 5 11
Stroke 0.9 1.9
HF 2.6 3.6
MI 1 1.6
Mortality
* all-cause 6.2
* cardiovasc causes 1.3
EAST-AFNET US data elegible
Control Early rhythm HR Control Early rhythm HR
Composite 5 3.9 0.79 11 9.8 0.89
Stroke 0.9 0.6 0.65 1.9 1.3 0.67
HF 2.6 2.1 0.81 3.6 3.7 1.03
MI 1 0.8 0.83 1.6 1.2 0.78
Mortality
* all-cause 6.2 5.4 0.87
* cardiovasc causes 1.3 1 0.72
Age 70.2 68.9
Cardiovasc comorb
CHA2DS2-VASc 3.4 4.7
Anticoagulation 91.2% 32.70%

20. CONCLUSIONI
⇝ L’ablazione transcatetere è indicata nelle attuali Linee Guida
come first-line strategy di controllo del ritmo per migliorare
i sintomi
⇝ Nel EAST-AFNET 4 il trattamento precoce (entro 12 mesi dalla
diagnosi di FA) reduce outcomes hard
⇝ L’ablazione precoce di FA riduce significativamente sia le recidive
sintomatiche che asintomatiche di tachiaritmie atriali
⇝ L’ablazione di FA si candida a diventare il trattamento standard per i pazienti
con Fibrillazione atriale di recente diagnosi e fattori di rischio per stroke