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Heart Rhythm Disorders in Older Adults

Heart Rhythm Disorders in Older Adults. Michael W Rich, MD Professor of Medicine Washington University School of Medicine St. Louis, Missouri. Disclosures: None. Outline. Effects of aging on the cardiac conduction system Bradyarrhythmias and pacemakers

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Heart Rhythm Disorders in Older Adults

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  1. Heart Rhythm Disordersin Older Adults Michael W Rich, MD Professor of Medicine Washington University School of Medicine St. Louis, Missouri Disclosures: None

  2. Outline • Effects of aging on the cardiac conduction system • Bradyarrhythmias and pacemakers • Supraventricular arrhythmias: Focus on atrial fibrillation • Ventricular arrhythmias: Focus on ICDs • Research directions: Unmet needs

  3. Effects of Aging on the Cardiac Conduction System Sinus node • Progressive decline in number of pacemaker cells (<10% remain by age 75) • Increased fat and collagen deposition surrounding the node contributing to sinus node exit block • Decreased parasympathetic activity • Decreased HR variability • No change in resting heart rate (HR) but decreased maximum HR with exercise: peak HR = 220 – age

  4. Effects of Aging on the Cardiac Conduction System Atrioventricular (AV) conduction • Fibrosis and calcification of the cardiac skeleton • 10-20% increase in PR interval (proximal to His bundle) • Increased prevalence of 1st degree AV-block but not 2nd or 3rd degree block (in the absence of CV disease) • No change in QRS duration but axis shifts to the left • Increased incidence and prevalence of LAHB, RBBB, and LBBB (the latter due primarily to concomitant CVD)

  5. Effects of Aging on the Cardiac Conduction System • Increased prevalence and frequency of APDs • Increased prevalence and frequency of short runs of SVT • Markedly increased incidence and prevalence of atrial fibrillation and atrial flutter • Increased prevalence and frequency of VPDs • Non-sustained VT (≥ 5 beats) rare in absence of CVD • With the exception of AF/AFL, the age-related increase in ectopy is generally benign in older adults without structural heart disease

  6. Bradyarrhythmias and Pacemakers Sinoatrial dysfunction (“sick sinus syndrome”) • Clinical features • Symptoms: fatigue, exercise intolerance, light-headedness, falls, pre-syncope/syncope • Inappropriate sinus bradycardia • Chronotropic incompetence • Sinus pauses (≥ 3 sec, may be up to 20 sec or longer) • AV block • Brady-tachy syndrome (alt. brady and tachyarrhythmias) • Diagnosis: correlation of symptoms with arrhythmia • Treatment: permanent pacemaker (PPM) • Prognosis: favorable with PPM, but increased risk of stroke in patients with brady-tachy syndrome (due to AF)

  7. Bradyarrhythmias and Pacemakers Pacemaker Selection • Compared to single-chamber ventricular pacing (VVI), dual-chamber pacing reduces AF, PM syndrome, and HF admissions, but has no effect on stroke or mortality; procedural complications and costs are higher • Atrial pacing preferred in patients with preserved AV conduction (with back-up V-pacing if needed) • VVI in patients with persistent/permanent AF • Role of biventricular pacing in SND remains undefined

  8. Supraventricular arrhythmias: Focus on atrial fibrillation

  9. Prevalence of Atrial Fibrillation by Age and Gender in the U.S. Among octogenarians with HF, the prevalence of AF is ~ 30%. JAMA 2001;285:2370-2375

  10. Distribution of AF by Age Over 50% of AF occurs in the 6% of the population ≥ 75 years of age. Arch Intern Med 1995;155:469-73

  11. Projected Age and Sex Distribution of Adults with Atrial Fibrillation in the U.S. – 2000-2050 2000 2025 2050 Women 48.6% 46.3% 47.4% Age group < 65 18.0% 15.5% 11.5% 65-79 45.3% 48.7% 35.9% ≥ 80 36.7% 35.8% 52.6% JAMA 2001;285:2370-75

  12. Attributable Risk of AF for Stroke:The Framingham Heart Study 23.5% 9.9% 2.8% 1.5% Stroke 1991;22:983-8

  13. Stroke Rates in Patients with Atrial Fibrillation without Anti-thrombotic Therapy Arch Intern Med 1994;154:1449–57

  14. Aging and the Hemostatic System • Increase in coagulation factors V, VIII, IX, XIIIa, vWF, and fibrinogen • Increase in platelet activity • Rise in IL-6: increases fibrinogen, PAI-1, CRP, and platelet aggregability • Increase no. of adipocytes: increases PAI-1, IL-6, TNF-α, angiotensinogen, complement • Increase in endogenous inhibitors of angiogenesis: PAI-1, PF 4, α2-antiplasmin Net effect:shift in balance between thrombosis and fibrinolysis in favor of thrombosis

  15. Stroke Risk in Patients with Non-valvularAtrial Fibrillation: the CHADS2 Index Risk factor Score Congestive heart failure 1 Hypertension 1 Age ≥ 75 years 1 Diabetes 1 Stroke or TIA 2 JAMA 2001;285:2864-2870

  16. Annual Stroke Rate By CHADS2 Score in Patients Not Receiving Anti-thrombotic Therapy N=1733, mean age 81 yrs, 58% women CHADS2 Score JAMA 2001;285:2864-2870

  17. Effect of Gender on Risk of Ischemic Stroke and Peripheral Embolism in Atrial Fibrillation N=13,559, 57.3% men Circulation 2005;112:1687-1691

  18. CHA2DS2-VASc Risk factor Score Congestive heart failure 1 Hypertension 1 Age ≥ 75 years 2 Diabetes 1 Stroke or TIA 2 Vascular disease (CAD, PAD) 1 Age ≥ 65 years 1 Sex category = female 1

  19. Meta-Analysis of Anti-thrombotic Therapy for Stroke Prevention in Atrial Fibrillation Warfarin 68% Aspirin 21% W vs. A 52% Prog Cardiovasc Dis 2005;48(2):108-124

  20. Birmingham Atrial Fibrillation Treatment of the Aged Study: BAFTA • 973 pts ≥ 75 yrs (mean 81.5 yrs, 55% male) • Randomized to warfarin (INR 2.0-3.0) or aspirin 75 mg/day • Mean follow-up: 2.7 yrs • Primary endpoint: fatal or disabling stroke, ICH, or arterial embolism Lancet 2007;370:493-503

  21. BAFTA: Primary Endpoint RR 0.48, (0.28-0.80) P=0.003 Similar effects in men and women, and in pts 75-79, 80-84, and ≥ 85 years of age Lancet 2007;370:493-503

  22. Atrial Fibrillation Follow-up Investigationof Rhythm Management: AFFIRM • 4080 pts, mean age 69.7 yrs, 39.3% female, with paroxysmal or persistent atrial fibrillation • All pts treated with warfarin • Randomized to “rate control” or “rhythm control” strategy • Primary outcome: all-cause mortality • Mean follow-up: 3.5 years N Engl J Med 2002;347:1825-33

  23. AFFIRM Results: All-cause Mortality HR for rhythm vs. rate control: 1.15 (0.99-1.34) P=0.08 N Engl J Med 2002;347:1825-33

  24. AFFIRM Results: Secondary Endpoints • No difference between groups in strokes, other neurological events, or systemic emboli • Rhythm control was associated with significantly greater number of hospital admissions and medication side effects • In both groups, most strokes occurred after warfarin was discontinued

  25. AFFIRM: Subgroup Analysis by Age N Engl J Med 2002;347:1825-33

  26. RACE-2 Study Design • 614 pts with permanent AF • Mean age 68 yrs, 34% female, mean CHADS2 1.4 • Randomized to lenient rate control (resting HR < 110/min) or strict rate control (resting HR < 80/min, exercise HR < 110/min) • Primary outcome: death from CV causes, HF admission, stroke or systemic embolism, bleeding, or life-threatening arrhythmic event • Follow-up: 2-3 years NEJM 2010;362:1363-73

  27. RACE-2 Primary Results NEJM 2010;362:1363-73

  28. HAS-BLED Bleeding Risk Score Hypertension 1 Age ≥ 65 or abnormal renal or hepatic function 1 each Stroke history 1 Bleeding history or tendency 1 Labile INRs 1 Ethanol use 1 Drugs (ASA, NSAIDs) 1 Score: 0-9; a score of 3 or more indicates increased 1-year risk for serious bleeding (incl. ICH)

  29. Fall Risk and Intracranial Hemorrhage in Elderly Patients with Atrial Fibrillation • 1245 pts at high-fall risk (mean 83 yrs, 60% female) compared to 18,261 other pts with atrial fibrillation (mean 79 yrs, 56% female) • High-fall risk associated with 6-fold increase in the risk of traumatic intracranial hemorrhage (ICH) but no increased risk of non-traumatic ICH • Warfarin associated with increased mortality in pts with ICH, but was not a risk factor for ICH • In pts with CHADS 2 2-6, warfarin associated with a 25% reduction in death, stroke, MI, or major hemorrhage Am J Med 2005;118:612-617

  30. New Drug Therapies for Atrial Fibrillation • Dronedarone (ATHENA, ANDROMEDA, others) • Aspirin + clopidogrel (ACTIVE-A) • Dabigatran (RE-LY) • Rivaroxaban (ROCKET-AF) • Apixaban (ARISTOTLE)

  31. RE-LY Study Design • 18,113 pts with AF at risk for stroke • Mean age 71.5 yrs, 63.5% women, CHADS2 2.1 • Randomized to blinded dabigatran 110 mg or 150 mg BID or to unblinded adjusted dose warfarin (INR 2-3) • Primary outcome: stroke or systemic embolization • Median follow-up 2.0 years NEJM 2009;361:1139-51

  32. RE-LY: Primary Outcome No interactions across subgroups for either dose but age subgroups were not reported. NEJM 2009;361:1139-51

  33. Bleeding Risk with Dabigatranin the Frail Elderly • 44 episodes of bleeding on dabigatran over a 2 mo period • 12 episodes considered “major”, incl. 2 SDH • 66% ≥ 80yrs, 50% < 60kg, 58% CrCl < 50 ml/min • RE-LY: mean age 71.2 yrs, mean weight 83 kg, mean CrCl 68 ml/min NEJM 2012;366:864-6

  34. ROCKET-AF Study Design • 14,264 pts with AF at risk for stroke • Median age 73 yrs, 39.7% women, CHADS2 3.5 • Randomized double-blind to rivaroxaban 20 mg daily (15 mg if eGFR 30-49 ml/min) or to adjusted dose warfarin (INR 2-3) • Primary outcome: stroke or systemic embolization • Median follow-up 1.9 years NEJM 2011;365:883-91

  35. ROCKET-AF Primary Outcome AHR 0.88 (0.74-1.03) P<0.001 for non-inferiority P=0.12 for superiority No interactions across subgroups NEJM 2011;365:883-91

  36. ARISTOTLE Study Design • 18,201 pts with AF at risk for stroke • Median age 70 yrs, 35% women, CHADS2 2.1 • Randomized double-blind to apixaban 5 mg BID (2.5 mg BID if ≥ 2 of: age ≥ 80, weight ≤ 60 kg, creatinine ≥ 1.5 mg/dl) or to adjusted dose warfarin (INR 2-3) • Primary outcome: stroke or systemic embolization • Median follow-up 1.8 years NEJM 2011;365:981-92

  37. ARISTOTLE Primary Outcome and Major Bleeding AHR 0.79 (0.66-0.95) P=0.01 for superiority AHR 0.69 (0.60-0.80) P<0.001 NEJM 2011;365:981-92

  38. ARISTOTLE Subgroup Analysis NEJM 2011;365:981-92

  39. Mechanical Interventions • AV-node ablation with VVI pacing (ablate and pace) • AF ablation (pulmonary vein isolation) • Cox maze procedure

  40. Ventricular Arrhythmias: Focus on ICDs

  41. Criteria for ICD Implantation Class I indications: • NYHA class II-III symptoms • LVEF ≤ 30-35% • Life expectancy > 1 year • “Good functional status” ACC/AHA/HRS Guidelines for Device-Based Therapy J Am Coll Cardiol2008;51:e1-e62

  42. ICDs in Patients ≥ 75 Years:Pooled Results from AVID, CASH, and CIDS N=252 Eur Heart J 2007;28:1746-9

  43. Age and Effectiveness of ICDs for Primary Prevention of SCD: Meta-analysis of RCTs • 5783 pts from 5 RCTs (MADIT-II, DINAMIT, DEFINITE, SCD-HeFT, IRIS) • 44% “elderly” (defined as age ≥ 60-65 yrs) • Mean follow-up: 32 months • Impact of ICD therapy on all-cause mortality: • Younger pts: HR 0.65 (95% CI 0.50-0.83, p < 0.001) • Older pts: HR 0.81 (95% CI 0.62-1.05, p = 0.11) • Exclusion of DINAMIT and IRIS did not change results Ann Intern Med 2010; 153:592-9

  44. ICD Considerations in Older Adults • With increasing age, the relative likelihood of dying from VT/VF decreases, while the likelihood of dying from worsening HF, MI, or other non-cardiac causes increases • The risk for “inappropriate” shocks may be higher in older adults due to increasing incidence of AF/RVR • Procedural complications increase with age, esp. after 80 yrs • Therefore, the benefit/risk ratio of ICD implantation decreases with age • “Routine” generator replacement at end of battery life is not warranted and must be considered on an individual basis

  45. 43.4% ICDs Implanted in US: 1995-2008 Age at Implant Number % of total Under 20 1,290 0.6 20-29 2,250 1.0 30-39 5,450 2.4 40-49 16,500 7.2 50-59 39,100 17.0 60-69 63,150 27.6 70-79 74,350 32.4 80-89 24,600 10.7 90-99 665 0.3 100 and over 10 0.0 Unknown 1,850 0.8 Total 229,215 100.0

  46. ICDs and End-of-Life Care • Terminally ill patients with previously implanted ICDs often receive 1 or more shocks in the last 30 days of life • Given the choice, many patients and families prefer disabling the ICD to allow a natural death rather than suffering unwanted shocks (but this almost never happens!) • Device disablement is consistent with patient autonomy (the right to refuse treatment) and is considered legal and ethical in all states • All patients with ICDs should be asked about preferences for device disablement in the event of terminal illness Heart Rhythm 2010;7:1008-26

  47. Research Directions: Unmet Needs • Effects of aging on the conduction system • Elucidate mechanisms • Develop interventions for attenuating age-related effects • Bradyarrhythmias and pacemakers • Prevention of age-associated bradyarrhythmias • Pacemaker selection and mode optimization • Novel therapies (e.g. stem cells, other devices) • Atrial fibrillation • Primary prevention • Develop safer and more effective anti-thrombotic and anti-arrhythmic agents • Define role of AF ablation and other interventions (e.g. LAA occluders) • Ventricular arrhythmias and ICDs • Patient selection (i.e. improved risk stratification) • Refine criteria for generator replacement • Enhance communication about risks/benefits • Incorporate patient preferences and goals of care into decision-making

  48. Question 1 • All of the following changes in the cardiac conduction system • occur with normal aging EXCEPT: • Marked decrease in the number of functioning sinus node • pacemaker cells • Impaired conduction from the sinus node to the atrial • conduction system • C. Gradual decline in resting heart rate • D. Slowing of conduction through the AV node • Increased prevalence of both left bundle branch block and • right bundle branch block

  49. Question 2 • All of the following statements about atrial fibrillation in older • adults are true EXCEPT: • More than 50% of all patients in the U.S. with atrial • fibrillation are ≥ 75 years of age • The incidence of atrial fibrillation is higher in older women • than in older men • The proportion of ischemic strokes attributable to atrial • fibrillation increases exponentially with age • In older patients with atrial fibrillation, the risk of stroke • is higher in women than in men • In most cases, high fall risk is not a contraindication to • warfarin in older adults with atrial fibrillation

  50. Question 3 • All of the following statements about implantable cardioverter- • defibrillators (ICDs) in patients 80 years of age or older are • true EXCEPT: • The efficacy of ICDs in terminating life-threatening • ventricular tachyarrhythmias declines with increasing age • (esp. after age 80) • Compared to younger patients, older patients with ICDs are • at increased risk for ‘inappropriate’ shocks (i.e. in the • absence of a life-threatening ventricular tachyarrhythmia) • ICDs have been shown to reduce mortality in appropriately • selected octogenarians • It is legal and ethical for a physician to disable an ICD in an • older patient approaching the end-of-life • In the absence of shocks (appropriate or inappropriate), ICDs • have minimal impact on quality of life in older adults

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