Atrial Fibrillation and Heart Failure: A Cause or a Consequence Rajat Deo, MD, MTR Assistant Professor of Medicine Division of Cardiology, Electrophysiology Section University of Pennsylvania November 20, 2015 No relevant disclosures Disclosures 1
Objectives 1. Burden of atrial fibrillation (AF) and Heart Failure (HF) 2. Pathophysiology linking AF and HF 3. Risk of adverse outcomes when AF and HF coexist 4. Management Strategies Prevalence of AF in the United States Prevalence (%) 12 11 10 9 8 7 6 5 4 3 2 1 0 Women Men 1.7 1.7 0.9 1.0 0.1 0.2 0.4 3.0 <55 55 59 60 64 65 69 70 74 75 79 80 84 85 3.4 5.0 5.0 Age (years) 7.3 7.2 10.3 Go AS et al. JAMA 2001;285:2370 2375. 9.1 11.1 2
Future Prevalence of AF Mozaffarian D, et al. Heart Disease and Stroke Statistics. Circulation. 2015; 131:434-41. Background on Heart Failure 2012 Prevalence, Age 20 yrs. Incidence (New Cases), Age 55 yrs. 2011 Mortality / Any Mortality Hospital Discharges, 2010, All ages Cost, 2012 5,700,000 (2.2%%) 870,000 58,309/ 284,000 1,023,000 $30.7 billion HF is a major public health problem resulting in substantial morbidity and mortality Despite recent advances a substantial number of patients are not receiving optimal care Mozaffarian D, et al. Heart Disease and Stroke Statistics. Circulation. 2015; 131:434-41. 3
Atrial Fibrillation Heart Failure AF AF - HF Luong C, et al. Curr Heart Fail Rep. 2014;11:463-470. Aging Hypertension Metabolic Syndrome Diabetes Obesity Valve Dis. Cardiomyopathy Coronary Dis. Thyroid Dis. Sleep Apnea Alcohol Genetics Pulmonary Dis. Inflammation Smoking HF AF - HF Atrial Fibrillation Leads to HF Tachycardia induced cardiomyopathy Hemodynamic changes Atrial enlargement / stretch L type Ca++ channel down-regulation Electrical-contractile remodeling Neuroendocrine stimulation Atrial-ventricular fibrosis Atrial-ventricular remodeling Pro-inflammatory state LV remodeling leads to more LV remodeling HF begets HF Luong C, et al. Curr Heart Fail Rep. 2014;11:463-470. 4
Heart Failure leads to AF LV systolic and diastolic dysfunction Increased LV filling pressures Atrial enlargement/stretch Ventricular remodeling Atrial-ventricular fibrosis Neuroendocrine activation Sympathetic activation Apoptosis, altered gene expression Oxidative stress Calcium cycling Electrical remodeling AF begets AF Luong C, et al. Curr Heart Fail Rep. 2014;11:463-470. AF and HF: Coexisting Conditions Comorbidity Patient Comorbidities; n (%) HF-pEF N = 119 HF-rEF N = 430 P value Hypertension 97 (81.5) 329 (76.5) 0.27 Hyperlipidemia 87 (73.1) 334 (77.7) 0.38 Coronary artery disease 79 (66.4) 305 (70.8) 0.37 Hx myocardial infarction 45 (37.8) 226 (52.6) 0.005 Diabetes mellitus 59 (58.0) 200 (46.5) 0.030 Atrial tachycardia/flutter/fib 61 (51.3) 193 (44.9) 0.25 COPD 38 (31.9) 121 (28.1) 0.43 Chronic renal failure 22 (18.5) 86 (20.0) 0.79 Pulmonary edema 20 (16.6) 68 (15.8) 0.78 CVA 23 (19.3) 48 (11.2) 0.030 Adamson PB, et al. Circ Heart Fail. 2014;7:935-944. 5
New Onset AF in HF: Predictors of In-Hospital Mortality Age Male gender New-onset AF Previous AF Rapid AF Left atrial dilation Ejection fraction Ischemic heart disease Valvular heart disease Hypertension Diabetes mellitus Prior renal failure Prior stroke 1.03 (1.02-1.04) 0.88 (0.75-1.03) 1.53 (1.14-2.06) 0.84 (0.69-1.00) 1.28 (1.00-1.63) 1.31 (1.16-1.48) 1.27 (1.12-1.45) 1.04 (0.89-1.22) 0.89 (0.68-1.15) 0.76 (0.65-0.88) 1.08 (0.92-1.28) 1.74 (1.42-2.13) 1.14 (0.94-1.39) 0.5 5 *No AF used as reference group. Rivero-Ayerza M, et al. Euro Heart J 2008;29:1618-24. Prognostic Significance of Atrial Fibrillation in HF-rEF& HF-pEF Meta-analysis: 20 Reports of AF in Chronic HF Pooled HR of AF for all-cause mortality was: 1.17 (95% CI, 1.11 1.23) Moderate heterogeneity between studies; (I 2 = 44.5%, P= 0.017) Pooled HR of AF for cardiovascular mortality was: 1.15 (95% CI, 0.98 1.34, P = 0.08) without significant heterogeneity between studies Cheng M, et al. Euro J Heart Fail. 2014;16:1317-1322. 6
AF prognosis in HFpEF and HFrEF 6 HF-pEF Reports 8 HF-rEF Reports HF-pEF vs. HF-rEF; P < 0.05 Cheng M, et al. Euro J Heart Fail. 2014;16:1317-1322. New Onset AF Predicts HF Progression BAF, Baseline AF NAF, New-onset AF NAF patients: ~4.5-fold increase in all-cause or HF hospitalization days / patient (hospitalization burden), both P <.0001 Aleong RG, et al. Am J Med. 2014;127:963-971. 7
AF, HF and the risk of Stroke Sub-study of Irbesartan in HF w Preserved EF Trial: During 53 month (median) follow-up Fatal or nonfatal stroke occurred in: 6.5% (79/1209) pts with Hx AF 3.9% (114/2901) with no AF Hazard ratio of stroke if HxAF vs no Hxof AF HR: 2.2; 95% CI, 1.6-3.2; P<0.0001 Oluleye OW, et al. Circ Heart Fail. 2014;7:960-969. CHADS 2 scores establish risk of stroke CHADS 2, developed and validated by Gage et al, is a system for establishing the risk of stroke in patients with non-rheumatic atrial fibrillation 1 Patients are awarded points based on comorbidities Condition Points C Congestive heart failure 1 H Hypertension 1 A Age 75 years 1 D Diabetes mellitus 1 S 2 Previous stroke or TIA 2 European Society of Cardiology Guidelines 2 CHADS 2 Score Treatment 0 Aspirin 1 Aspirin or warfarin* 2 Warfarin Risk of Stroke 20% 18% 15% 13% 10% 8% 5% 3% 0% Annual Risk of Stroke 18.2% 12.5% 8.5% 5.9% 4.0% 2.8% 1.9% 0 1 2 3 4 5 6 CHADS 2 Score * Use of aspirin or warfarin is based on additional patient characteristics such as age, number of risk factors, etc. 1 Gage BF et al, JAMA 2001;285:2864 2870 2 Camm AJ et al, Eur Heart J 2010;31:2369 2429 8
CHA 2 DS 2 VASc is preferred scoring system CHA 2 DS 2 VASc, developed by Lip et al, is a refinement of the older CHADS 2 Score which includes additional stroke risk factors and puts greater emphasis on age as a risk factor 1 Condition/Risk Factor Points C Congestive heart failure 1 H Hypertension 1 A Age 75 years 2 D Diabetes mellitus 1 S 2 Previous stroke or TIA 2 V Vascular disease 1 A Age 65-74 years 1 Sc Sex (female gender) 1 2014 AHA/ACC/HRS Guidelines Risk of Stroke 18% 15% 12% 9% 6% 3% 0% CHA 2 DS 2 -VAScScore Treatment 0 No treatment 1 Aspirin or warfarin or NOAC 2 Warfarin or NOAC Annual Risk of Stroke 15.2% 9.8% 9.6% 6.7% 6.7% 3.2% 4.0% 2.2% 1.3% 0.0% 0 1 2 3 4 5 6 7 8 9 CHA 2 DS 2 VASc Score 1 Lip GY et al, Chest. 2010;137(2):263-72 2 Camm AJ et al, Eur Heart J. 2010;31:2369 2429 3. January C et al. Circulation. 2014 Management of Atrial Fibrillation in the setting of Heart Failure 9
Key Treatment Principles 1. Evaluate anticoagulation therapies to protect against the risk of stroke 2. Manage ventricular rate response 3. Rhythm control with antiarrhythmic agents 4. Rhythm control with radiofrequency ablation Anticoagulation in non-valvular AF Warfarin Better Control Better AFASAK SPAF BAATAF Reduction of all-cause mortality RRR 26% CAFA SPINAF EAFT All trials Reduction of stroke RRR 62% 100% 50% 0-50% -100% Hart et al. Ann Intern Med. 1999;131:492-501 10
Anticoagulation for nonvalvular AF Pooled data from AFASAK, SPAF, and BAATAF For every 1000 patients with nonvalvular AF in clinical trials treated with warfarin for 1 year: Benefit Risk 31 fewer thromboembolic events* 1 more intracranial or major bleed* Stroke risk reduced from 4.5% to 1.4% / yr *Compared with control 35 more minor bleeds occurred with warfarin Intention-to-treat analysis Albers GW et al. Ann Neurol. 1991;30:511-8. Warfarin effective but limitations exist When taken appropriately, warfarin is effective Monitoring required to ensure therapeutic range (INR) Narrow therapeutic window Time in therapeutic range 55-66% Many foods and medicines interact with warfarin Despite efficacy, warfarin exposes patients to risks (e.g. intracranial hemorrhage and hemorrhagic stroke) Warfarin use represents a challenge to surgeries High rates of discontinuation and non-adherence to therapy Warfarin tops the list for emergency hospitalizations for adverse drug events in older Americans 1 Budnitz DS, et al. NEJM 2011, 365: 2002-2012 11
The Coagulation Cascade Antiplatelet agents: Aspirin, clopidogrel, NSAIDS, dipyridamole Rivaroxaban, Apixaban, Edoxaban Dabigatran The Ideal Anticoagulant Oral administration Rapid onset/offset of action Wide therapeutic window Predictable therapeutic effect with fixed dosing Minimal food or drug-drug interactions No monitoring required (but able to if desired) Defined PK in the presence of renal or hepatic disease Easily reversible Cost effective 12
Ventricular Rate Response 1. Tachycardia induced cardiomyopathies can evolve in asymptomatic patients 2. Treat with AV nodal blocking agents including nondihydropyridine calcium blockers, beta blockers 3. Rhythm control with cardioversion, antiarrhythmic agents +/- ablation therapy AHA Guidelines for AF management in the setting of Heart Failure 13
AHA Guidelines for AF management in the setting of Heart Failure Beta Blockers in AF/HF: Mortality 10 randomized studies (18,254 pts) 13,946 NSR, 3,066 AF Normal Sinus Rhythm Atrial Fibrillation Kotecha D, et al. Lancet. 2014;384: 2235 43. 14
Beta Blockers in AF/HF: CV Hospitalization Normal Sinus Rhythm Atrial Fibrillation Kotecha D, et al. Lancet. 2014;384: 2235 43. Meta-Analysis of Beta Blocker Use All Cause Mortality in Patients with Atrial Fib. Kotecha D, et al. Lancet. 2014;384:2235 43. 15
Indications for Catheter Ablation (2014 Guidelines) Indications -- Symptomatic AF refractory or intolerant to 1 Class 1 or 3 antiarrhythmic drug -- Reasonable initial rhythm control strategy Should not be performed with the sole intent of obviating the need for anticoagulation Catheter Placement during Atrial Fibrillation Ablation and Conduction Block of Pulmonary- Vein Triggers by Means of Ablation. Wazni O et al. N Engl J Med 2011;365:2296-2304 16
Conclusions Burden of AF and HF is increasing Coexisting conditions that increase CV risk Many AF patients, who should be anticoagulated, are not being treated PROTECT THE BRAIN! Rate and rhythm control are important control sxs and reduce AF complications 17