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  • Figure 1. Cumulative Incidence of Trial Outcomes, According to Treatment Group. Panel A shows the cumulative incidence of the primary end point (stroke, myocardial infarction, non-central nervous system systemic embolism, or death from vascular causes). The relative risk for aspirin plus clopidogrel, as compared with aspirin alone, was 0.89 (95% confidence interval [CI], 0.81 to 0.98; P=0.01). Panel B shows the cumulative incidence of stroke. The relative risk for aspirin plus clopidogrel, as compared with aspirin alone, was 0.72 (95% CI, 0.62 to 0.83; P<0.001). The insets show the data on a compressed scale.
  • Figure 1. Cumulative Hazard Rates for the Primary Outcome of Stroke or Systemic Embolism, According to Treatment Group.
  • Background: The impact of atrial fibrillation (AF) on mortality, stroke, and medical costs is unknown. Methods: We conducted a prospective cohort study of hospitalized Medicare patients with AF and 1 other cardiovascular diagnosis (CVD) compared with a matched group without AF (n=26 753), randomly selected in 6 age-sex strata from 1989 MedPAR files of more than 1 million patients diagnosed as having AF. Stroke rates were also determined in another cohort free of CVD (n=14 267). Total medical costs after hospitalization were available from a 1991 cohort. Cumulative mortality, stroke rates, and costs following index admission were adjusted by multivariate and proportional hazard regression analyses. Results: Mortality rates were high in individuals with CVD, ranging from 19.0% to 52.1% in 1 year. Adjusted relative mortality risk was approximately 20% higher in patients with AF in all age-sex strata during each of the 3 years studied ( P ,.05). Incidence of stroke was high in individuals with CVD, 6.2% to 15.4% in 1 year, with and without AF, and was at least 5-fold higher than in individuals without CVD. In those with CVD, stroke rates were approximately 25% higher in women with AF ( P ,.05) but only 10% higher in men. Adjusted total Medicare spending in 1 year was 8.6- to 22.6-fold greater in men, and 9.8- to 11.2-fold greater in women with AF ( P ,.05). Secondand third-year costs were increased as well. Conclusion: Prevention of AF and treatment of patients with AF and associated CVD may yield benefits in reduced mortality and stroke as well as reducing health care costs. Arch Intern Med. 1998;158:229-234
  • Echocardiographic and clinical predictors for outcome of elective cardioversion of atrial fibrillation. Dittrich HC , Erickson JS , Schneiderman T , Blacky AR , Savides T , Nicod PH . Division of Cardiology, University of California San Diego Medical Center 92103. Previous studies have suggested that success of elective direct-current cardioversion for atrial fibrillation (AF) can be predicted from clinical features and M-mode echocardiographic left atrial diameter. We evaluated clinical variables as well as M-mode and 2-dimensional echocardiographic measurements of atrial size in 85 patients undergoing electrical cardioversion for AF. Of 65 patients who were initially converted to sinus rhythm, 45 (69%) and 38 (58%) remained in sinus rhythm at 1 and 6 months, respectively. No historical feature predicted initial success, although patients with cardiomyopathy or pulmonary disease underlying their AF had significantly lower success rates compared with those having other etiologies. Furthermore, no M-mode or 2-dimensional echocardiographic measurements of atrial size predicted initial success of cardioversion. Maintenance of sinus rhythm at 1 month was related to short duration of AF before cardioversion (less than 3 months vs greater than 12 months, p less than 0.05). Left atrial area and long axis dimension by 2-dimensional echocardiography were significantly larger in patients remaining in sinus rhythm than in those who had reverted to AF at 1 month (28 +/- 7 vs 24 +/- 5 cm2 and 65 +/- 9 vs 59 +/- 8 mm, respectively, both p less than 0.05), but overlap was great. No significant difference in atrial dimensions was noted at 6-month follow-up. It appears that, although no clinical or echocardiographic variable predicts initial success for cardioversion of AF, duration of AF does predict maintenance of sinus rhythm 1 month after initial success
  • So our unifying theory of atrial fibrillation is that it is multifactorial.
  • Figure 1. Cumulative Mortality from Any Cause in the Rhythm-Control Group and the Rate-Control Group. Time zero is the day of randomization. Data have been truncated at five years.
  • Figure 2. Hazard Ratios for Death in Prespecified Subgroups. The numbers in the groups do not total 4060 for all variables because of incomplete reporting. The ratios shown are for the rhythm-control group as compared with the rate-control group.
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atrial fibrillation talk 2009 Presentation Transcript

  • 1. Atrial Fibrillation: EmergingAtrial Fibrillation: Emerging ConceptsConcepts New Treatment Paradigms John Hakim, MD, FACC
  • 2. The hallmark of AF is chaotic atrial impulsesThe hallmark of AF is chaotic atrial impulses leading to irregularly irregular ventricularleading to irregularly irregular ventricular contraction, usually with incessant tachycardiacontraction, usually with incessant tachycardia
  • 3. OVERVIEWOVERVIEW Atrial fibrillation is a progressive diseaseAtrial fibrillation is a progressive disease Atrial fibrillation has hemodynamic and myocardialAtrial fibrillation has hemodynamic and myocardial consequences (i.e., reduced cardiac output and heart failure)consequences (i.e., reduced cardiac output and heart failure) There is significant morbidity and mortality consequencesThere is significant morbidity and mortality consequences --increased hospitalizationsincreased hospitalizations --reduced quality of lifereduced quality of life -increased risk of thromboembolism and stroke-increased risk of thromboembolism and stroke (accounts for 75,000(accounts for 75,000 strokes per year in the United States alone)strokes per year in the United States alone) --decreased survivaldecreased survival (AF is associated with increased mortality, but(AF is associated with increased mortality, but whether it is the cause or an innocent bystanderwhether it is the cause or an innocent bystander is not well established)is not well established)1-81-8 Atrial fibrillation can be a treatable disorder, especially with earlyAtrial fibrillation can be a treatable disorder, especially with early interventionintervention What’s new in atrial fibrillation treatmen.tWhat’s new in atrial fibrillation treatmen.t 1 Benjamim EJ, et al. Impact of AF on the risk of death: The Framinham Heart Study. Circulation. 1998; 98: 946-52. 2 Gajewski J, et al. Mortality in an insured population with AF. JAMA. 1981; 245: 1540-44. 3 Krahn AD, et al. The natural history of AF. Am J Med. 1995; 98: 476-84. 4 Flegel KM, et al. Risk of stroke in non-rheumatic AF. Lancet. 1987; 1: 526-9. 5 Kulbertus HE, et al. AF in elderly, ambulatory patients. AF; 1982: 148-57. 6 Lake FR, et al. AF and mortality in an elderly population. Aus N Z J Med. 1989; 19: 321-6. 7 Kannel WB, et al. Epidemiologic features of chronic AF: the Framingham Study. NEJM 1982; 306: 1018-22. 8 Kitchin AH, et al. Longitudinal survey of ischemic heart disease in randomly selected older population. Br Heart J 1977; 39: 889-93.
  • 4. Classification and Patterns of AFClassification and Patterns of AF ParoxysmalParoxysmal: terminates spontaneously, typically: terminates spontaneously, typically duration is <7 days (most<24 hours). May beduration is <7 days (most<24 hours). May be recurrent.recurrent. PersistentPersistent: medication or electrical intervention is: medication or electrical intervention is required to restore sinus rhythm; does not self-required to restore sinus rhythm; does not self- terminate. Typically lasts > 7 days. May beterminate. Typically lasts > 7 days. May be recurrent.recurrent. PermanentPermanent: sinus rhythm cannot be restored or: sinus rhythm cannot be restored or maintained despite interventionmaintained despite intervention *** Evaluate for thrombotic risk each of these*** Evaluate for thrombotic risk each of these situations.*****situations.*****
  • 5. Causes of Atrial FibrillationCauses of Atrial Fibrillation HypertensionHypertension Heart attacks/ CADHeart attacks/ CAD Valvular Heart DiseaseValvular Heart Disease Congenital heart defectsCongenital heart defects Hyperthyroid or other metabolicHyperthyroid or other metabolic imbalanceimbalance Exposure to stimulants such asExposure to stimulants such as medications, caffeine or tobacco, or tomedications, caffeine or tobacco, or to alcohol (holliday heart)alcohol (holliday heart) Sick sinus syndrome — improperSick sinus syndrome — improper functioning of the heart's naturalfunctioning of the heart's natural pacemakerpacemaker Emphysema or other lung diseasesEmphysema or other lung diseases CABG/ Previous heart surgeryCABG/ Previous heart surgery Viral infections /PericarditisViral infections /Pericarditis Stress due to pneumonia, surgery orStress due to pneumonia, surgery or other illnesses (Cathecholamines)other illnesses (Cathecholamines) Pulmonary EmbolusPulmonary Embolus PneumoniaPneumonia Sleep ApneaSleep Apnea PericarditisPericarditis Lone A fib (younger people)Lone A fib (younger people) Left ventricular HypertrophyLeft ventricular Hypertrophy CardiomyopathyCardiomyopathy CHF –Systolic or DiastolicCHF –Systolic or Diastolic Idiopathic – mostly in younger people –Idiopathic – mostly in younger people – Lone Atrial FibLone Atrial Fib Familial Predisposition.Familial Predisposition. glucocorticoidsglucocorticoids
  • 6. Risk Factors for AF: DiabetesRisk Factors for AF: Diabetes AF was 44% more prevalent and 38% more likely to develop whenAF was 44% more prevalent and 38% more likely to develop when diabetes was present in an adult populationdiabetes was present in an adult population Prevalence and incidence of AF in 17,372 patients with diabetes and inPrevalence and incidence of AF in 17,372 patients with diabetes and in the same amount of age- and sex-matched controls without type 2the same amount of age- and sex-matched controls without type 2 diabetes included in a Kaiser Permanente diabetes registry. Thediabetes included in a Kaiser Permanente diabetes registry. The researchers followed patients without AF for the comparison of AFresearchers followed patients without AF for the comparison of AF incidence while controlling for known risk factors.incidence while controlling for known risk factors. Prevalence for AF was significantly higher among patients withPrevalence for AF was significantly higher among patients with diabetes compared with those without (3.6% vs. 2.5%;diabetes compared with those without (3.6% vs. 2.5%; PP<.0001).<.0001). Over 7.2 years, patients with diabetes without AF at baselineOver 7.2 years, patients with diabetes without AF at baseline developed AF at an age- and sex-adjusted rate of 9.1 per 1,000 person-developed AF at an age- and sex-adjusted rate of 9.1 per 1,000 person- years vs. 6.6 per 1,000 person-years for patients without diabetes.years vs. 6.6 per 1,000 person-years for patients without diabetes. Diabetes was associated with a 26% increased risk for AF amongDiabetes was associated with a 26% increased risk for AF among women after adjusting for other risk factors (HR=1.26; 95% CI, 1.08-women after adjusting for other risk factors (HR=1.26; 95% CI, 1.08- 1.46). Diabetes was not a statistically significant risk factor among men.1.46). Diabetes was not a statistically significant risk factor among men. Men had a higher prevalence of AF in all age groups regardless ofMen had a higher prevalence of AF in all age groups regardless of diabetesdiabetes
  • 7. Original Article Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation --- ACTIVE TRIAL N Engl J Med Volume 360(20):2066-2078 May 14, 2009 • A randomized trial enrolled 7554 patients with AF who were at increased risk of stroke but not candidates for vitamin K antagonists • Participants were assigned to aspirin or aspirin plus clopidogrel • At a median of 3.6 years, the risk of major vascular events decreased significantly with clopidogrel, primarily because of reduced risk of stroke • The risk of major bleeding increased significantly with clopidogrel
  • 8. Cumulative Incidence of Trial Outcomes, According to Treatment Group The ACTIVE Investigators. N Engl J Med 2009;360:2066-2078
  • 9. The ACTIVE InvestigatorsThe ACTIVE Investigators In patients with atrial fibrillation forIn patients with atrial fibrillation for whom vitaminwhom vitaminK–antagonist therapyK–antagonist therapy was unsuitable, the addition ofwas unsuitable, the addition of clopidogrelclopidogrelto aspirin reduced the riskto aspirin reduced the risk of major vascular events, especiallyof major vascular events, especially stroke, and increased the risk of majorstroke, and increased the risk of major hemorrhage.hemorrhage.
  • 10. Cumulative Hazard Rates for the Primary Outcome of Stroke or Systemic Embolism, According to Treatment Group Connolly SJ et al. N Engl J Med 2009;361:1139-1151
  • 11. Dabigatran versus Warfarin in Patients withDabigatran versus Warfarin in Patients with Atrial Fibrillation (NEJM 9/7/2009)Atrial Fibrillation (NEJM 9/7/2009) In patients with AF, dabigatranIn patients with AF, dabigatrangiven at a dose of 110given at a dose of 110 mg was associated with rates of strokemg was associated with rates of stroke and systemicand systemic embolism that were similar to those associatedembolism that were similar to those associated withwith warfarin, as well as lower rates of major hemorrhage.warfarin, as well as lower rates of major hemorrhage. DabigatranDabigatranadministered at a dose of 150 mg, asadministered at a dose of 150 mg, as compared with warfarin,compared with warfarin,was associated with lowerwas associated with lower rates of stroke and systemic embolismrates of stroke and systemic embolism but similarbut similar rates of major hemorrhagerates of major hemorrhage
  • 12. If clinicians do not try to maintain normal sinus rhythm in the present, it becomes more difficult over time. Patients converted to normal sinus rhythm within 3 months have a 69% chance of remaining in sinus rhythm at 6 months compared to only 27% if they are allowed to remain in AF for > 12 months.2 2 Dittrich HC, et al. Am J Cardiol 1989; 63: 193-7.
  • 13. Therapeutic Goals in the Treatment of AF •Prevent Stroke/TE •Prevention of CHF •Relief of symptoms •Improved quality of life •Reduction in cost of care to medical system
  • 14. Atrial Fibrillation: A UnifyingAtrial Fibrillation: A Unifying TheoryTheory Focal triggering initiationFocal triggering initiation Multiple wavelets for AF maintenanceMultiple wavelets for AF maintenance Parasympathetic effects on atrial substrateParasympathetic effects on atrial substrate Varying importance among population of lone,Varying importance among population of lone, vagally-mediated, PAF, persistent , andvagally-mediated, PAF, persistent , and permanent atrial fibrillation.permanent atrial fibrillation.
  • 15. Electrophysiologic mechanisms of AFElectrophysiologic mechanisms of AF AUTONOMIC INFLUENCE WAVELETS AND ROTORS PV AND LA TRIGGERS FOCAL TRIGGERS LEADING TO INITIATION OF REENTRY AND WAVELETS
  • 16. Substrate Evolution Hints at a Patient-Substrate Evolution Hints at a Patient- Tailored approachTailored approach -The role of pulmonary veins in the perpetuation and initiation of paroxysmal AF have been demonstrated; hence the effectiveness of pulmonary vein isolation techniques in this cohort of patients. -As atrial fibrillation progresses to persistent and permanent, the role of “muscle, scar, and fibrosis”, that is structural disease, becomes more prominent, hence a hybrid approach is more effective both targeting the substrate and the triggers Fisher JD, et al. PACE 2006; 29: 523. Wyse DG, Gersh BJ. Circ 2004; 109: 3089.
  • 17. Benefits of rhythm control include: decreasedBenefits of rhythm control include: decreased hospitalizations, improved cardiac function, improvedhospitalizations, improved cardiac function, improved exercise tolerance, and improvement in quality of lifeexercise tolerance, and improvement in quality of life Consequences of failure to maintain sinus rhythm: atrialConsequences of failure to maintain sinus rhythm: atrial remodeling and permanent atrial fibrillationremodeling and permanent atrial fibrillation The goals of antiarrhythmic therapy to maintain normal sinusThe goals of antiarrhythmic therapy to maintain normal sinus rhythm should be:rhythm should be: 1. To reduce the frequency, severity, and duration of AF1. To reduce the frequency, severity, and duration of AF to a degree acceptable to the patientto a degree acceptable to the patient 2. To do so with the lowest likelihood of adverse effects2. To do so with the lowest likelihood of adverse effects Rate versus Rhythm controlRate versus Rhythm control
  • 18. So the Question in atrialSo the Question in atrial fibrillation, which is better:fibrillation, which is better: rate control or rhythmrate control or rhythm control?control? First answered in 2002First answered in 2002
  • 19. A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators NEJM 347:1825-1833347:1825-1833 December 5, 2002December 5, 2002
  • 20. There are two approaches to the treatment of AF: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate- controlling drugs, allowing AF to persist. In both approaches, the use of anticoagulant drugs is recommended. AFFIRM was a randomized, multicenter comparison of these two treatment strategies in patients with AF and a high risk of stroke or death. The primary end point was overall mortality. Results A total of 4060 patients (mean [±SD] age, 69.7±9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percentgroup of high-risk patients. AFFIRM Trial
  • 21. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. N Engl J Med 2002;347:1825-1833 Cumulative Mortality from Any Cause in the Rhythm-Control Group and the Rate-Control Group
  • 22. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators. N Engl J Med 2002;347:1825-1833 Hazard Ratios for Death in Prespecified Subgroups
  • 23. Result of AFFIRM TrialResult of AFFIRM Trial . There were 356 deaths among the patients assignedto rhythm- control therapy and 310 deaths among those assignedto rate- control therapy (mortality at five years, 23.8 percentand 21.3 percent, respectively; hazard ratio, 1.15 [95 percentconfidence interval, 0.99 to 1.34]; P=0.08). More patients inthe rhythm-control group than in the rate-control group werehospitalized, and there were more adverse drug effects in therhythm-control group as well. In both groups, the majority ofstrokes occurred after warfarin had been stopped or when theinternational normalized ratio was subtherapeutic. Conclusions Management of AF with the rhythm- controlstrategy offers no survival advantage over the rate-controlstrategy, and there are potential advantages, such as a lowerrisk of adverse drug effects, with the rate-control strategy.Anticoagulation should be continued in this (NEJM 2002)
  • 24. Which Strategy is Better inWhich Strategy is Better in Heart Failure Patients?Heart Failure Patients? Rhythm Control versus Rate Control for AtrialRhythm Control versus Rate Control for Atrial Fibrillation and Heart Failure TrialFibrillation and Heart Failure Trial NEJM 358:2667-2677NEJM 358:2667-2677 June 19, 2008June 19, 2008
  • 25. Rhythm Control versus Rate Control for Atrial Fibrillation and Heart FailureRhythm Control versus Rate Control for Atrial Fibrillation and Heart Failure (AF- CHF TRIAL)(AF- CHF TRIAL) NEJM 2008; 358: 2667-2677NEJM 2008; 358: 2667-2677 Common practice is to restore and maintain sinus rhythm in patients with AF and heart failure. This approach is based in part on data indicating that AF is a predictor of death in patients with heart failure and suggesting that the suppression of AF may favorably affect the outcome. Methods A multicenter, randomized trial comparing the maintenance of sinus rhythm (rhythm control) with control of the ventricular rate (rate control) in patients with EF 35% or less, symptoms of congestive heart failure, and a history of AF. The primary outcome was the time to death from cardiovascular causes. as compared with a rate-control strategy
  • 26. RESULTS of AF CHFRESULTS of AF CHF ResultsResults A total of 1376 patients were enrolled (682 in the rhythm-A total of 1376 patients were enrolled (682 in the rhythm- controlcontrolgroup and 694 in the rate-control group) and weregroup and 694 in the rate-control group) and were followed forfollowed fora mean of 37 months. Of these patients, 182 (27%)a mean of 37 months. Of these patients, 182 (27%) in the rhythm-controlin the rhythm-controlgroup died from cardiovascular causes, asgroup died from cardiovascular causes, as compared with 175compared with 175(25%) in the rate-control group (hazard ratio(25%) in the rate-control group (hazard ratio in the rhythm-controlin the rhythm-controlgroup, 1.06; 95% confidence interval, 0.86group, 1.06; 95% confidence interval, 0.86 to 1.30; P=0.59 byto 1.30; P=0.59 bythe log-rank test).the log-rank test). Secondary outcomes also did not differ significantly between the two treatmentSecondary outcomes also did not differ significantly between the two treatment strategies:strategies: – All-cause death: 32% and 33%, P = 0.73All-cause death: 32% and 33%, P = 0.73 – Stroke: 3% and 4%, P = 0.32Stroke: 3% and 4%, P = 0.32 – Worsening heart failure: 28% and 31%, P = 0.17Worsening heart failure: 28% and 31%, P = 0.17 – Composite of CV death, stroke, worsening heart failure: 43% and 46%, P =Composite of CV death, stroke, worsening heart failure: 43% and 46%, P = 0.200.20 There were also no significantThere were also no significant differences favoring either strategydifferences favoring either strategy in any predefined subgroup.in any predefined subgroup.
  • 27. AF CHF resultsAF CHF results ConclusionsConclusions In patients with AF andIn patients with AF and congestivecongestiveheart failure, a routineheart failure, a routine strategy of rhythm control does notstrategy of rhythm control does not reduce the rate of cardiovascular death.reduce the rate of cardiovascular death. Comment:Comment: The investigators caution that, "OurThe investigators caution that, "Our results cannot be generalized to patients with heartresults cannot be generalized to patients with heart failure and preserved left ventricular function.“failure and preserved left ventricular function.“ NEJM 358:2667-2677NEJM 358:2667-2677 June 19, 2008June 19, 2008
  • 28. Why hasn’t rhythm controlWhy hasn’t rhythm control worked in trials?worked in trials? Drugs used in trials don’t guarantee rhythm controlDrugs used in trials don’t guarantee rhythm control Toxicity of Anti arrythmic drugs contribute to lack ofToxicity of Anti arrythmic drugs contribute to lack of benefit of rhythm control groups.benefit of rhythm control groups. AF may be a marker of poor prognosis, in whichAF may be a marker of poor prognosis, in whichthethe primary problem is poor ventricular function,primary problem is poor ventricular function, neurohormonalneurohormonalactivation, or inflammation, with noactivation, or inflammation, with no independent effect of atrialindependent effect of atrialfibrillation on outcome.fibrillation on outcome.
  • 29. IF Drugs Don’t work, WillIF Drugs Don’t work, Will Ablation?Ablation? AF AblationAF Ablation – eliminates confoundingeliminates confoundingcontributions of lowcontributions of low efficacy and high toxicity associated withefficacy and high toxicity associated with antiarrhythmic drug therapyantiarrhythmic drug therapy – may better determine the desirabilitymay better determine the desirabilityofof maintaining sinus rhythm in patients with atrialmaintaining sinus rhythm in patients with atrial fibrillation.fibrillation. – Clinical Trials are in progress comparing catheterClinical Trials are in progress comparing catheter ablation of atrialablation of atrialfibrillation to conventionalfibrillation to conventional antiarrhythmic drugantiarrhythmic drugtherapy.therapy. – AF Ablation has yet to be proven to be better thanAF Ablation has yet to be proven to be better than rate control.rate control.
  • 30. Rate versus Rhythm ControlRate versus Rhythm Control
  • 31. DigoxinDigoxin Described by WilliamDescribed by WilliamWithering, 1785 to treat rapid heart rateWithering, 1785 to treat rapid heart rate and CHFand CHF decreases conduction ofdecreases conduction of electrical impulseselectrical impulses through thethrough the AV nodeAV node, making it a commonly used, making it a commonly used antiarrhythmic agentantiarrhythmic agent inin controlling thecontrolling the heart rateheart rate duringduring atrial fibrillationatrial fibrillation oror atrial flutteratrial flutter.. An increase ofAn increase of forceforce ofof contractioncontraction via inhibition of the Navia inhibition of the Na++ /K/K++ ATPase pumpATPase pump
  • 32. Quinidine- OLD schoolQuinidine- OLD school seen as too dangerous nowseen as too dangerous now A stereoisomer of quinine initially derived from the bark of theA stereoisomer of quinine initially derived from the bark of the cinchona tree has been used for decades for AF.  Chinchona iscinchona tree has been used for decades for AF.  Chinchona is an evergreen native to the mountainous areas of Central andan evergreen native to the mountainous areas of Central and South America. Quinine is the base flavor in most bitters andSouth America. Quinine is the base flavor in most bitters and contributes the bitter essence to tonic water.contributes the bitter essence to tonic water. Discovered by a Danish Merchant seaman with AF who tookDiscovered by a Danish Merchant seaman with AF who took quinine for malaria prophylaxis during trips to India.  He notedquinine for malaria prophylaxis during trips to India.  He noted his pulse was regular while in India but irregular at home.his pulse was regular while in India but irregular at home. Chichonism describes tinnitus and hearing loss with quinidineChichonism describes tinnitus and hearing loss with quinidine excess. excess.  Quinidine can cause thrombocytopenia, granulomatousQuinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis, and torsades de pointes and forhepatitis, myasthenia gravis, and torsades de pointes and for that reason is not used much today. Torsades can occur afterthat reason is not used much today. Torsades can occur after the first dose.the first dose.
  • 33. Drugs used for atrial fibDrugs used for atrial fib FlecanideFlecanide DofetilideDofetilide PropafenonePropafenone SotololSotolol AmiodaroneAmiodarone
  • 34. What is the Future of A FibWhat is the Future of A Fib Advances in AnticoagulationAdvances in Anticoagulation New Drugs: Substantial resources areNew Drugs: Substantial resources are being invested in the developmentbeing invested in the development ofof new drugs that promise to be morenew drugs that promise to be more efficacious and safer forefficacious and safer foruse in patientsuse in patients with atrial fibrillationwith atrial fibrillation Advances in AblationAdvances in Ablation
  • 35. Things that Havent workedThings that Havent worked in Atrial Fibin Atrial Fib DronedaroneDronedarone: a novel antiarrhythmic drug with: a novel antiarrhythmic drug with electrophysiologicalelectrophysiologicalproperties that are similar to those ofproperties that are similar to those of amiodarone, but it doesamiodarone, but it doesnot contain iodine and thus does notnot contain iodine and thus does not cause iodine-related adversecause iodine-related adverse reactions. In patients with severereactions. In patients with severe heart failure and left ventricularheart failure and left ventricular systolic dysfunction, treatmentsystolic dysfunction, treatment with dronedarone was associatedwith dronedarone was associated with increased early mortalitywith increased early mortality related to the worsening of heartrelated to the worsening of heartfailure NEJM358: 2725-2727failure NEJM358: 2725-2727 June 19, 2008June 19, 2008 Atrial Defibrillators – Convert the Atrial Fib, but not toleratedAtrial Defibrillators – Convert the Atrial Fib, but not tolerated by patients.by patients.
  • 36. Indications for Catheter ablation ofIndications for Catheter ablation of Atrial fibrillationAtrial fibrillation
  • 37. Left Atrial Circumferential Ablation (1) PV isolation for trigger initiation of AF (2) Ablation of areas of potential reentry rotors/wavelets (4) Vagal denervation altering electrophysiologic substrate (3) Transect the vein of Marshall VOM
  • 38. HIFUHIFU (High-(High- frequencyfrequency Ultrasound) :Ultrasound) : noncontact techniquenoncontact technique with tissue heatingwith tissue heating CryoablationCryoablation: tissue: tissue contact and freezingcontact and freezing LaserLaser (infrared):(infrared): tissue contact and heatingtissue contact and heating Balloon Catheter Technology in AFBalloon Catheter Technology in AF AblationAblation
  • 39. Catheter ablationCatheter ablation *Ablation strategies target the PVs and or PV antrum. *Complete electrical isolation should be the goal.
  • 40. Image Integration and Image-GuidedImage Integration and Image-Guided Mapping and AblationMapping and Ablation 3-Dimensional Electroanatomical Mapping (EAM)3-Dimensional Electroanatomical Mapping (EAM) systems are used to construct image of the left atriumsystems are used to construct image of the left atrium This image is merged into a LA CT or MRI scanThis image is merged into a LA CT or MRI scan Using intracardiac ultrasound, the antrum of theUsing intracardiac ultrasound, the antrum of the pulmonary veins can be reliably determinedpulmonary veins can be reliably determined The location and delivery of radiofrequency energyThe location and delivery of radiofrequency energy can be monitored and tracked with the 3-D EAMcan be monitored and tracked with the 3-D EAM systemsystem
  • 41. Common Lesion Sets used in AFCommon Lesion Sets used in AF AblationAblation
  • 42. ICE IMAGES
  • 43. NON-PULMONARY VEIN TRIGGERS OF AFIB