Contribuição dos novos conceitos Fisiopatológicos no Tratamento
Transcription
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: journals.permissions@oxfordjournals.org 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) 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 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 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: journals.permissions@oxfordjournals.org 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: journals.permissions@oxfordjournals.org 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: journals.permissions@oxfordjournals.org 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: journals.permissions@oxfordjournals.org 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