Contribuição dos novos conceitos Fisiopatológicos no Tratamento

Contribuição dos novos conceitos
Fisiopatológicos no Tratamento da FA
Dra Martha Pinheiro (QuintaD`Or)
Fibrilação atrial
Arritmia sustentada mais comum na
prática clínica;
Acomete 1-2% da população mundial
Doença multi-fatorial relacionada a
patologias cardíacas e não cardíacas
World map showing the age-adjusted prevalence rates (per 100 000 population) of atrial
fibrillation in the 21 Global Burden of Disease regions, 2010.
Sumeet S. Chugh et al. Circulation. 2014;129:837-847
Copyright © American Heart Association, Inc. All rights reserved.
Projected number of persons with
AF (millions)
Curva de prevalência da fibrilação atrial
14.3
15.2
15.9
13.1
11.7
10.2
8.9
5.1
5.9
5.1 5.6
6.7
7.7
6.1 6.8
7.5
8.4
Year
Miyasaka et.al Circulation 2006
9.4
10.3
11.1
11.7 12.1
Efeitos sistêmicos da FA
© The Author 2015. Published by Oxford University Press on behalf of the European Society of
Cardiology.
Rohan S. Wijesurendra, and Barbara Casadei Cardiovasc Res 2015;cvr.cvv001
Fatores de risco:
Clássicos:
•Envelhecimento
Prevalência de fibrilação atrial de acordo com a faixa etária.
Jason Andrade et al. Circulation Research. 2014;114:1453-1468
Copyright © American Heart Association, Inc. All rights reserved.
Fatores de risco:
Clássicos:
•Envelhecimento
•Gênero masculino
•HAS
•DM
•Doença valvar
•Insuficiência cardíaca
Fatores de risco:
Emergentes:
•Obesidade
•Síndrome da Apnéia Obstrutiva do Sono
•Estados inflamatórios sistêmicos
•Tabagismo
•Disfunção diastólica
•Variações genéticas
Fatores de risco:
Emergentes:
•Obesidade
•Síndrome da Apnéia Obstrutiva do Sono
•Estados inflamatórios sistêmicos
•Tabagismo
•Disfunção diastólica
•Variações genéticas
Risco de FA na Síndrome Metabólica
0,25
0
1
2
3
4
5
0,2
0,15
HR (CI)
Metabolic Syndrome Component
HR 1.67 CI (1.49-1.87)
1.40
Elevated waist circumference
(1.23-1.59)
1.95
Elevated blood pressure
0,1
(1.72-2.21)
0.95
Elevated triglycerides
0,05
(0.84-1.09)
1.20
Low HDL cholesterol
(1.06-1.37)
1.16
Impaired fasting glucose
0
0 2 4 6 8 10 12 14 16 18 20
Chamberlain et al, ARIC Study, AHJ 2010
(1.03-1.31)
Curva de evolução da obesidade
Proportion overweight
70%
60%
50%
USA
England
40%
Australia
30%
20%
1982
France
Korea
1992
2002
Years
Sassi et.al, OCED Publishing, 2014
2012
2022
Evolução de indicadores na população de 20+ anos de idade, por
sexo – Brasil
Obesity and the Risk of New-Onset Atrial Fibrillation
JAMA. 2004;292(20):2471-2477. doi:10.1001/jama.292.20.2471
Obesity is a risk factor for atrial fibrillation among fertile
young women: a nationwide cohort study
Deniz Karasoy et al. Europace 2013;15:781-786
Age- and sex-adjusted hazards of progression to permanent atrial fibrillation
stratified by body mass index categories and LA volume quartiles.
Teresa S.M. Tsang et al. Eur Heart J 2008;29:2227-2233
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author
2008. For permissions please email: [email protected]
Survival without conversion to permanent atrial fibrillation.
Teresa S.M. Tsang et al. Eur Heart J 2008;29:2227-2233
Pericardial Fat Is Associated With Atrial Fibrillation Severity and
Ablation Outcome
J Am Coll Cardiol. 2011;57(17):1745-1751. doi:10.1016/j.jacc.2010.11.045
Volumetric MRI Assessment of Periatrial and Periventricular Fat
Example magnetic resonance imaging (MRI) slices depicting volumetric assessment of periatrial (A) and periventricular (B) fat
depots. Areas of pericardial fat are shaded in blue.
Tecido adiposo pericárdico está associado a severidade da FA
J Am Coll Cardiol. 2011;57(17):1745-1751. doi:10.1016/j.jacc.2010.11.045
Pericardial Fat According to the Presence and Severity of AF
Box plots are shown depicting specific pericardial fat depot volumes according to the presence and chronicity of atrial fibrillation
(AF). There is a clear dose-response relationship between pericardial fat volumes and both the presence of and chronicity of AF.
Inflamação e Fibrilação atrial
39
86
71
Mina K. Chung et al. Circulation. 2001;104:2886-2891
Copyright © American Heart Association, Inc. All rights reserved.
Tecido adiposo epicárdico induz fibrilação atrial
Nicolas Venteclef et al. Eur Heart J 2013;eurheartj.eht099
Jason Andrade et al. Circulation Research. 2014;114:1453-1468
Copyright © American Heart Association, Inc. All rights reserved.
Fibrose atrial e arritmogênese
Jason Andrade et al. Circulation Research. 2014;114:1453-1468
Copyright © American Heart Association, Inc. All rights reserved.
FA perpetua FA:
Sinusal (controle)
FA
Átrio
Ventrículo
Rohan S. Wijesurendra, and Barbara Casadei Cardiovasc
© The Author 2015. Published by Oxford University
Press
on behalf of the European Society of
Res
2015;cvr.cvv001
Cardiology.
Atrial Fibrosis: Mechanisms and Clinical Relevance in Atrial Fibrillation
J Am Coll Cardiol. 2008;51(8):802-809. doi:10.1016/j.jacc.2007.09.064
Mechanisms by Which CHF Leads to AF
In turn, AF causes changes that can impair cardiac function, leading to potentially deleterious positive-feedback systems. Figure
illustration by Rob Flewell. AF = atrial fibrillation; CHF = congestive heart failure.
Long-Term Effect of Goal Directed Weight
Management in an Atrial Fibrillation Cohort:
A 5 Follow-Up StudY (LEGACY STUDY)
Rajeev K. Pathak; Melissa E. Middeldorp; Megan Meredith;
Abhinav B. Mehta; Rajiv Mahajan; Walter P. Abhayaratna;
Dennis H. Lau; Prashanthan Sanders
J Am Coll Cardiol. 2015;65(20):2159-2169. doi:10.1016/j.jacc.2015.03.002
Long-Term Effect of Goal-Directed Weight Management in an Atrial
Fibrillation Cohort: A Long-Term Follow-Up Study (LEGACY)
J Am Coll Cardiol. 2015;65(20):2159-2169. doi:10.1016/j.jacc.2015.03.002
Assessed for Eligibility
N=1415
Patients with BMI ≥ 27
N=825
Weight Management
Met Exclusion Criteria (N=293)
Terminal Cancer (N=10)
Inflammatory Dx (N=20)
Permanent AF (N=84)
AV Node ablation (N=12)
AF ablation (N=90)
Severe Medical Illness (N=77)
Final Cohort
N=355
≥10%WL
N=135
3-9%WL
N=103
<3%WL or WG
N=117
Características basais
<3% Wt Loss
Group 3
N= 117
3-9% Wt Loss
Group 2
N = 103
Age (years)
6111
6311
6511
0.06
Male gender, n (%)
83 (71)
65 (63)
86 (64)
0.4
Non-Paroxysmal AF, n (%)
45 (56)
46 (45)
64 (47)
0.9
32.94.8
32.74.4
33.64.7
0.2
Hypertension
90 (78)
75 (73)
109 (81)
0.3
DM/IGT, n (%)
34 (29)
28 (27)
41 (30)
0.5
Hyperlipidemia, n (%)
56 (48)
45 (44)
66 (49)
0.7
CAD, n (%)
14 (12)
12 (12)
21 (16)
0.3
AHI>30, n (%)
61 (52)
52 (50)
69 (51)
0.1
Smoker, n (%)
47 (40)
41 (40)
50 (37)
0.9
ETOH (>30g/week), n (%)
34 (29)
35 (34)
42 (31)
0.7
BMI
>10% Wt Loss P Value
Group 1
N = 135
Impacto em sintomas relacionados a FA
*Group-Time P<0.001
*Group-Time P<0.001
Recorrência de FA
P<0.001
46%
Without AAD
or ablation
22%
13%
Days
0
365
730
1095
1460
1825
>10%WL
135
101
72
42
31
18
3-9% WL
103
62
36
22
13
7
<3% WL
117
66
44
22
11
9
Recorrência de FA
86%
66%
40%
With AAD
and/or ablation
P<0.001
Days
0
365
730
1095
1460
1825
>10%WL
135
130
114
86
67
36
3-9% WL
103
93
83
57
35
22
<3% WL
117
105
85
53
32
22
Impacto nos fatores de risco
Remodelamento
*Group-Time P<0.001
(ml/m2)
*Group-Time P<0.001
(mg/L)
Yearly Weight Trend
(N=355)
Efeito do grau de flutuação
do peso sobre a recorrência
de FA
110
120
110
105
115
100
110
90
Linear
Weight Loss
(N=141)
Weight
Fluctuation
(N=179)
95
105
Linear Gain
(N=24)
90
100
70
85
95
50
80
90
1
<2%WF
N=54
2-5%WF
N=68
>5%WF
N=57
2
3 44
Years
Years
55
Perfil da perda de peso
76%
59%
38%
With AAD
and/or ablation
P<0.001
Days
0
365
730
1095
1460
1825
Linear Loss
141
130
122
80
52
29
Linear Gain
24
20
18
12
8
5
Wt.
Fluctuation
179
165
140
99
71
44
Efeito da flutuação do peso
85%
59%
44%
With AAD
and/or ablation
P<0.001
Days
0
365
730
1095
1460
1825
<2% WF
54
52
49
39
33
19
2-5% WF
68
62
54
39
27
15
>5% WF
57
53
45
31
19
14
Conclusões do Estudo Legacy
Perda sustentada de peso está associada com
redução na taxa de eventos de FA e manutenção
do ritmo sinusal;
Redução dos eventos é proporcional ao
grau de perda de peso.
Flutuações de peso acima de 5% amortece o
benefício conferido pela perda ponderal
Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in
Obese Individuals With Atrial Fibrillation: The CARDIO-FIT Study
J Am Coll Cardiol. 2015;66(9):985-996. doi:10.1016/j.jacc.2015.06.488
Cardiorespiratory Fitness and AF Recurrence: CARDIO-FIT trial
AF = atrial fibrillation; BP = blood pressure; CARDIO-FIT = CARDIOrespiratory FITness; CRF = cardiorespiratory fitness; MET =
metabolic equivalent.
Impact of CARDIOrespiratory FITness on
Arrhythmia Recurrence in Obese Individuals
With Atrial Fibrillation
Rajeev K. Pathak, MBBS∗; Adrian Elliott, PhD∗; Melissa E. Middeldorp∗;
Megan Meredith∗; Abhinav B. Mehta, M Act St†; Rajiv Mahajan, MD, PhD∗;
Jeroen M.L. Hendriks, PhD∗; Darragh Twomey, MBBS∗; Jonathan M.
Kalman, MBBS, PhD‡; Walter P. Abhayaratna, MBBS, PhD§; Dennis H. Lau,
MBBS, PhD∗; Prashanthan Sanders, MBBS, PhD∗
J Am Coll Cardiol. 2015;66(9):985-996. doi:10.1016/j.jacc.2015.06.488
Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in
Obese Individuals With Atrial Fibrillation: The CARDIO-FIT Study
J Am Coll Cardiol. 2015;66(9):985-996. doi:10.1016/j.jacc.2015.06.488
Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in
Obese Individuals With Atrial Fibrillation: The CARDIO-FIT Study
J Am Coll Cardiol. 2015;66(9):985-996. doi:10.1016/j.jacc.2015.06.488
Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in
Obese Individuals With Atrial Fibrillation: The CARDIO-FIT Study
J Am Coll Cardiol. 2015;66(9):985-996. doi:10.1016/j.jacc.2015.06.488
Outcomes of AF Freedom According to Cardiorespiratory Fitness Gain (<2 METs Gain vs. ≥2 METs Gain)
(A) Kaplan-Meier curve for total AF-free survival (multiple ablation procedures ± drugs) according to weight trend. (B) Kaplan-Meier
curve for total AF-free survival (multiple ablation procedures ± drugs) according to weight fluctuation. Abbreviations as in Figure 1.
Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in
Obese Individuals With Atrial Fibrillation: The CARDIO-FIT Study
J Am Coll Cardiol. 2015;66(9):985-996. doi:10.1016/j.jacc.2015.06.488
Outcomes of AF Freedom According to Cardiorespiratory Fitness Gain (<2 METs Gain vs. ≥2 METs Gain) and Weight Loss (<10%
vs. ≥10% Weight Loss)
(A) Kaplan-Meier curve for total AF-free survival (multiple ablation procedures ± drugs) according to weight trend. (B) Kaplan-Meier
curve for total AF-free survival (multiple ablation procedures ± drugs) according to weight fluctuation. WL = weight loss; other
abbreviations as in Figure 1.
Conclusões do Estudo Cardio-Fit
Ganho no condicionamento cardiorrespiratório
aumenta em cerca de 12% o benefício da perda
de peso na manutenção do ritmo sinusal;
Apnéia do sono e Fibrilação atrial
Sleep-disordered breathing: a novel predictor of atrial
fibrillation after coronary artery bypass surgery.
Mooe T1, Gullsby S, Rabben T, Eriksson P
Coron Artery Dis. 1996 Jun;7(6):475-8
Sobrecarga hemodinâmica , ativação simpática e estresse hemodinâmico podem
desencadear arritmias.
Risco de fibrilação atrial em pós-operatório de cirurgia cardíaca:
121 pacientes consecutivos submetidos a cirurgia de revascularização miocárdica;
Apnéia do sono aumenta 2 x o risco de FA no pós-operatório
Apnéia do sono e Fibrilação atrial
Proportion and 95% CI of patients with OSA. Prevalence of OSA is significantly higher in patients
with AF than in patients without past or current AF in general cardiology practice (49% [95% CI 41%
to 57%] vs 32% [95% CI 27% to 37%], P=0.0004).
Apoor S. Gami et al. Circulation. 2004;110:364-367
Copyright © American Heart Association, Inc. All rights reserved.
Atrial Fibrillation Promotion With Long-Term Repetitive Obstructive Sleep
Apnea in a Rat Model
J Am Coll Cardiol. 2014;64(19):2013-2023. doi:10.1016/j.jacc.2014.05.077
AF Susceptibility Changes at Study End
Examples of atrial fibrillation (AF) induction attempts in (A) an open airway rat and (B) an OSA rat, respectively. (C) AF duration.
(D) AF inducibility. (E) AF inducibility during acute OSA. *p < 0.05 vs. sham. AF duration compared by using 1-way analysis of
variance; AF inducibility compared by using the Fisher exact test. EGM = electrogram; OSA = obstructive sleep apnea; SR = sinus
rhythm.
Ativação e interação de vias inflamatórias em resposta a hipóxia
intermitente na Síndrome da Apnéia Obstrutiva do Sono
J. F. Garvey et al. Eur Respir J 2009;33:1195-1205
©2009 by European Respiratory Society
SAOS e risco de recorrência de FA em indivíduos submetidos a
cardioversão elétrica
Andrea Mazza et al. Europace 2009;11:902-909
(A) Kaplan–Meier curves showing survival free of atrial fibrillation recurrence according to
dichotomized aponea/hypopnoea index (<15/≥15 events/h).
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author
2009. For permissions please email: [email protected]
Inflamação e recorrência de FA em pacientes tratados com cardioversão
elétrica
Andrea Mazza et al. Europace 2009;11:902-909
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author
2009. For permissions please email: [email protected]
Índice de apnéia/hipopnéia e níveis de PCR combinados e recorrência
de FA em pacientes tratados com cardioversão
Andrea Mazza et al. Europace 2009;11:902-909
(A) Kaplan–Meier curves showing survival free of atrial fibrillation recurrence according to
dichotomized aponea/hypopnoea index (<15/≥15 events/h).
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author
2009. For permissions please email: [email protected]
Freedom from arrhythmia recurrences after a single ablation procedure.
Maria Matiello et al. Europace 2010;12:1084-1089
Effect of Obstructive Sleep Apnea Treatment on Atrial Fibrillation Recurrence:
A Meta-Analysis
JACCCEP. 2015;1(1):41-51. doi:10.1016/j.jacep.2015.02.014
AF Recurrence in Users Versus Nonusers of CPAP in 2 Groups of Patients With OSA: PVI and Non-PVI Groups
PVI = pulmonary vein isolation;
Contribuição dos novos conceitos
Fisiopatológicos no Tratamento da FA
Conclusão:
•Influência da obesidade e Síndrome da Apnéia do Sono
sobre o risco de desencadeamento e perpetuação de
Fibrilação atrial;
•Necessidade de controle destes fatores de risco
modificáveis para reduzir o risco de desencadeamento
da FA e otimizar o efeito das estratégias de controle do
ritmo cardíaco.
Aggressive Risk Factor Reduction Study for Atrial Fibrillation and Implications for
the Outcome of Ablation: The ARREST-AF Cohort Study
J Am Coll Cardiol. 2014;64(21):2222-2231. doi:10.1016/j.jacc.2014.09.028
Incidence and risk factors for very late recurrence of atrial
fibrillation after radiofrequency catheter ablation
Yohei Sotomi et al. Europace 2013;15:1581-1586
Aggressive Risk Factor Reduction Study for Atrial Fibrillation and
Implications for the Outcome of Ablation: The ARREST-AF Cohort
Study
J Am Coll Cardiol. 2014;64(21):2222-2231. doi:10.1016/j.jacc.2014.09.028
Fibrotic Atrial Cardiomyopathy, Atrial Fibrillation, and Thromboembolism:
Mechanistic Links and Clinical Inferences
J Am Coll Cardiol. 2015;65(20):2239-2251. doi:10.1016/j.jacc.2015.03.557
3D Cardiac Magnetic Resonance Reconstructions of LA Fibrosis in the RAO and PA Projections
Reconstructions are according to the percent of fibrosis, as graded by the UTAH staging system. UTAH I: <5% fibrosis; II: 5% to
19% fibrosis; III: 20% to 35% fibrosis; and IV: >35% fibrosis. Green indicates LA fibrosis. Reprinted with permission from Akoum
et al. (96). 3D = 3-dimensional; LA = left atrium; PA = postero-anterior; RAO = right anterior oblique.
Fibrotic Atrial Cardiomyopathy, Atrial Fibrillation, and Thromboembolism:
Mechanistic Links and Clinical Inferences
J Am Coll Cardiol. 2015;65(20):2239-2251. doi:10.1016/j.jacc.2015.03.557
Cardiac Magnetic Resonance Imaging: Segmentation of the LA
Acquisition of high-resolution 3D delayed-enhancement cardiac magnetic resonance (CMR) imaging of the LA (step 1). The LA wall
is defined by identification of epicardial and endocardial borders in each cardiac magnetic resonance (CMR) section (step 2). Wall
segmentations include both the LA wall and the antral regions of the pulmonary veins, but exclude the mitral valve. Fibrosis is
quantified on the basis of the relative intensity of contrast enhancement (step 3). The 3D model of the LA is rendered from the
endocardial (LA cavity) and LA wall segmentations, and the maximum enhancement intensities are projected on the surface of the
model (step 4). Images provided courtesy of Dr. Nassir Marrouche and Dr. Alan Morris, University of Utah. Abbreviations as in
Figure 1.
Time to atrial fibrillation recurrence based on apnoea/hypopnoea index and
high sensitivity C-reactive protein (patients (n)).
Andrea Mazza et al. Europace 2009;11:902-909
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author
2009. For permissions please email: [email protected]
Fibrotic Atrial Cardiomyopathy, Atrial Fibrillation, and Thromboembolism:
Mechanistic Links and Clinical Inferences
J Am Coll Cardiol. 2015;65(20):2239-2251. doi:10.1016/j.jacc.2015.03.557