Contribuição dos novos conceitos Fisiopatológicos no ... D'OR/SabaD'Or/02... · Contribuição dos novos conceitos Fisiopatológicos no Tratamento da FA Dra Martha Pinheiro (QuintaD`Or)

Contribuição dos novos conceitosFisiopatológicos 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.

Year

Pro

ject

ed n

um

ber

of

pe

rso

ns

wit

h

AF

(mill

ion

s)

5.15.9

6.77.7

8.9

10.2

11.7

13.114.3

15.215.9

10.311.1

11.7 12.1

5.1 5.66.1 6.8

7.58.4

9.4

Miyasaka et.al Circulation 2006

Curva de prevalência da fibrilação atrial

Rohan S. Wijesurendra, and Barbara Casadei Cardiovasc Res 2015;cvr.cvv001

© The Author 2015. Published by Oxford University Press on behalf of the European Society of

Cardiology.

Efeitos sistêmicos da FA

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


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

0,05

0,1

0,15

0,2

0,25

0 2 4 6 8 10 12 14 16 18 20

0 1 2 3 4 5

Chamberlain et al, ARIC Study, AHJ 2010

HR 1.67 CI (1.49-1.87)

HR (CI)

Metabolic Syndrome Component

Elevated waist circumference1.40

(1.23-1.59)

Elevated blood pressure1.95

(1.72-2.21)

Elevated triglycerides0.95

(0.84-1.09)

Low HDL cholesterol1.20

(1.06-1.37)

Impaired fasting glucose1.16

(1.03-1.31)

20%

30%

40%

50%

60%

70%

1982 1992 2002 2012 2022

USAEngland

France

Australia

KoreaPro

po

rtio

n o

verw

eigh

t

Years

Sassi et.al, OCED Publishing, 2014

Curva de evolução da obesidade

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

Deniz Karasoy et al. Europace 2013;15:781-786

Obesity is a risk factor for atrial fibrillation among fertile young women: a nationwide cohort study

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 OutcomeJ 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.

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.

Tecido adiposo pericárdico está associado a severidade da FA

Mina K. Chung et al. Circulation. 2001;104:2886-2891


Inflamação e Fibrilação atrial

39

71

86

Nicolas Venteclef et al. Eur Heart J 2013;eurheartj.eht099

Tecido adiposo epicárdico induz fibrilação atrial



Fibrose atrial e arritmogênese



FA perpetua FA:

Rohan S. Wijesurendra, and Barbara Casadei Cardiovasc

Res 2015;cvr.cvv001© The Author 2015. Published by Oxford University Press on behalf of the European Society of

Cardiology.

Sinusal (controle) FA

Átrio

Ventrículo

Atrial Fibrosis: Mechanisms and Clinical Relevance in Atrial Fibrillation


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.

Rajeev K. Pathak; Melissa E. Middeldorp; Megan Meredith;Abhinav B. Mehta; Rajiv Mahajan; Walter P. Abhayaratna;

Dennis H. Lau; Prashanthan Sanders

Long-Term Effect of Goal Directed Weight Management in an Atrial Fibrillation Cohort:

A 5 Follow-Up StudY (LEGACY STUDY)



Long-Term Effect of Goal-Directed Weight Management in an Atrial

Fibrillation Cohort: A Long-Term Follow-Up Study (LEGACY)

Patients with BMI ≥ 27 N=825 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)

<3%WL or WGN=117

3-9%WLN=103

Final Cohort N=355

Assessed for EligibilityN=1415

≥10%WLN=135

Weight Management

<3% Wt LossGroup 3N= 117

3-9% Wt LossGroup 2N = 103

>10% Wt LossGroup 1N = 135

P Value

Age (years) 6111 6311 6511 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

BMI 32.94.8 32.74.4 33.64.7 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

Características basais

Impacto em sintomas relacionados a FA

*Group-Time P<0.001 *Group-Time P<0.001

Recorrência de FA

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

P<0.001

13%

22%Without AAD or ablation

46%46%

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

P<0.001

86%

66%

40%

With AAD and/or ablation

Recorrência de FA

Impacto nos fatores de risco

(ml/m2) (mg/L)

*Group-Time P<0.001 *Group-Time P<0.001

Remodelamento

Yearly Weight Trend (N=355)

>5%WF N=57

2-5%WF N=68

<2%WF N=54

Linear Weight Loss

(N=141)

Weight Fluctuation

(N=179)

Linear Gain(N=24)

Efeito do grau de flutuação do peso sobre a recorrência

de FA

50

70

90

110

1 2 3 4 5Years

90

95

100

105

110

115

120

1 2 3 4 5

Years

80

85

90

95

100

105

110

1 2 3 4 5

Years

Perfil da perda de peso

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

76%

59%

38%With AAD

and/or ablation

Efeito da flutuação do peso

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

P<0.001

85%

59%

44%With AAD and/or ablation

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


Cardiorespiratory Fitness and AF Recurrence: CARDIO-FIT trial

AF = atrial fibrillation; BP = blood pressure; CARDIO-FIT = CARDIOrespiratory FITness; CRF = cardiorespiratory fitness; MET =

metabolic equivalent.


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∗

Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in Obese Individuals With Atrial Fibrillation










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.




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

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


Apnéia do sono e Fibrilação atrial

Atrial Fibrillation Promotion With Long-Term Repetitive Obstructive Sleep

Apnea in a Rat ModelJ 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.

J. F. Garvey et al. Eur Respir J 2009;33:1195-1205

©2009 by European Respiratory Society

Ativação e interação de vias inflamatórias em resposta a hipóxia intermitente na Síndrome da Apnéia Obstrutiva do Sono

(A) Kaplan–Meier curves showing survival free of atrial fibrillation recurrence according to

dichotomized aponea/hypopnoea index (<15/≥15 events/h).

Andrea Mazza et al. Europace 2009;11:902-909



SAOS e risco de recorrência de FA em indivíduos submetidos a cardioversão elétrica




Inflamação e recorrência de FA em pacientes tratados com cardioversão elétrica




(A) Kaplan–Meier curves showing survival free of atrial fibrillation recurrence according to

dichotomized aponea/hypopnoea index (<15/≥15 events/h).

Índice de apnéia/hipopnéia e níveis de PCR combinados e recorrência de FA em pacientes tratados com cardioversão

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 conceitosFisiopatológicos 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


Yohei Sotomi et al. Europace 2013;15:1581-1586

Incidence and risk factors for very late recurrence of atrial fibrillation after radiofrequency catheter ablation

Aggressive Risk Factor Reduction Study for Atrial Fibrillation and

Implications for the Outcome of Ablation: The ARREST-AF Cohort

Study


Fibrotic Atrial Cardiomyopathy, Atrial Fibrillation, and Thromboembolism:

Mechanistic Links and Clinical Inferences


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.




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)).







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Contribuição dos novos conceitos Fisiopatológicos no ... D'OR/SabaD'Or/02... · Contribuição dos novos conceitos Fisiopatológicos no Tratamento da FA Dra Martha Pinheiro (QuintaD`Or)