Rate vs. Rhythm Control in Atrial Fibrillation Recent Perspectives Saeed Oraii MD Electrophysiologist Interventional Electrophysiologist Tehran Arrhythmia Clinic
“ Delirium Cordis ” • First described by Sir William Harvey in 17th century: observed chaotic motion of atria in open chest animal • Heart rhythm irregularity first described in 1903 by Hering • ECG findings described in 1909 by Sir Thomas Lewis: “ irregular or fibrillatory waves and irregular ventricular response ” or “ absent atrial activity with grossly irregular ventricular response ”
Prevalence of Diagnosed AF 12.0 Women 11.1 10.3 Men 10.0 9.1 8.0 7.3 7.2 6.0 5.0 5.0 4.0 3.4 3.0 1.7 1.7 2.0 1.0 0.9 0.4 0.1 0.2 0.0 <55 55-59 60-64 65-69 70-74 75-79 80-84 > 85 # Women 530 310 566 896 1498 1572 1291 1132 # Men 1529 634 934 1426 1907 1886 1374 759 Go AS, JAMA. 2001 May 9;285(18):2370-5. Pub Med PMID: 11343485
Incidence of AF Lifetime Risk for AF at Selected Index Ages by Sex Index Age, yrs Men Women 26.0% (24.0 – 27.0) 23.0% (21.0 – 24.0) 40 25.9% (23.9 – 27.0) 23.2% (21.3 – 24.3) 50 25.8% (23.7 – 26.9) 23.4% (21.4 – 24.4) 60 24.3% (22.1 – 25.5) 23.0% (20.9 – 24.1) 70 22.7% (20.1 – 24.1) 21.6% (19.3 – 22.7) 80 1 in 4 Lifetime risk if Men & women currently free >40 Years of AF will develop AF Lloyd-Jones DM, et al. Circulation. 2004 Aug 31;110(9):1042-6. Pub Med PMID: 15313941.
Atrial Fibrillation Demographics by Age U.S. population Population with AF x 1000 x 1000 Population with 30,000 500 atrial fibrillation 400 U.S. population 20,000 300 200 10,000 100 0 0 <5 5- 10- 15- 20- 25- 30- 35- 40- 45- 50- 55- 60- 65- 70- 75- 80- 85- 90- >95 9 14 19 24 29 34 39 44 49 54 59 64 69 74 79 84 89 94 Age, yr Adapted from Feinberg WM. Arch Intern Med. 1995;155:469-473.
Atrial Fibrillation: Clinical Problems • Chronic symptoms and reduced sense of well-being • Embolism and stroke (presumably due to left atrial clot) • Acute hospitalizations with onset of symptoms • Congestive heart failure – Loss of AV synchrony – Loss of atrial “ kick ” – Rate-related cardiomyopathy due to rapid and irregular ventricular response • Rate-related atrial myopathy and dilatation
Therapeutic Approaches to Atrial Fibrillation • Anticoagulation • Rate Control – Pharmacologic – Catheter modification/ablation of AV node • Rhythm Control – Antiarrhythmic suppression – Catheter ablation
Rate Control • Rate control is an integral part of the management of AF patients, and is often sufficient to improve AF-related symptoms. • Still very little robust evidence exists about the best type and intensity of rate control treatment. • Beta- blocker therapy is often the first-line rate-controlling agent followed by calcium channel blockers.
Digoxin: some words of caution • Oldest and still the most commonly prescribed drug for control of ventricular rate • Predominant acute effect is mediated by the autonomic nervous system • An important slowing effect of the AV node is mediated by enhanced vagal tone • Not effective during periods of increased sympathetic tone • Not effective in paroxysmal atrial fibrillation
Digoxin & Mortality • Observational studies have associated digoxin use with excess mortality in AF patients. • This association could possibly be due to selection and prescription biases as digoxin is commonly prescribed to sicker patients. • Lower doses of digoxin ( ≤ 250 mg once daily), corresponding to serum digoxin levels of 0.5 – 0.9 ng/mL, may be associated with better prognosis. AF Management Guidelines ESC 2016
Optimal Heart Rate • The optimal heart rate target in AF patients is unclear. • Essential in all patients as persistent tachycardia rates can induce cardiomyopathy. • Occasional follow-up holter monitor helps to ascertain rate control. • Classically the target had been 60-80 bpm rest and 90-115 bpm with exercise.
Lenient Rate Control • The RACE II study randomized 614 patients with permanent AF to either a target heart rate of 80 bpm at rest and 110 bpm during moderate exercise, or to a lenient heart rate target of 110 bpm.
Devils in the Details • The average heart rates over the 3-year duration of the RACE II study were approximately 85 (lenient) bpm and 75 (strict) bpm. • There were at least 8 components in the composite end points. – In some cases, it is difficult to imagine how heart rate would have an important impact (e.g., the risk of bleeding)! D. George Wyse . Lenient Versus Strict Rate Control in Atrial Fibrillation: Some Devils in the Details . J. Am. Coll. Cardiol. 2011;58;950-952
Devils in the Details • The main “ devil ” is that there is little or no background information about the time course. – The median duration of any AF and permanent AF was around 18 and 3 months, respectively. – Tachycardia-induced cardiomyopathy takes some time to develop. • In a larger AFFIRM/RACE substudy, heart rates above 100 beats/min in permanent AF patients significantly the increased risk. Van Gelder IC, et al. Does intensity of rate control influence outcome in atrial fibrillation? Europace 2006;8:935 – 42.
Guideline Recommendations • 2014 AHA/ACC/HRS – A lenient rate-control strategy (resting heart rate <110 bpm) may be reasonable when patients remain asymptomatic and LV systolic function is preserved. COR IIB, LOE B • 2016 ESC/EHRA – A resting heart rate of <110 bpm (i.e. lenient rate control) should be considered as the initial heart rate target for rate control therapy. COR IIA, LOE B
Rate vs. Rhythm Management • At least 9 randomized, controlled trials have compared the 2 strategies between the years 2000 and 2009. • Over 6000 patients are enrolled in these trials. • The first patients entering these trials were enrolled in 1995, a little more than 20 years ago.
AFFIRM - RESULTS - All-cause mortality Cumulative 30 mortality (%) 25 20 15 P=0.08 10 5 Rhythm control Rate control 0 0 1 2 3 4 5 Years after randomization AFFIRM Investigators. N Engl J Med 2002; 347 :1825 – 33.
RACE Hagens VE, et al. Rate control versus rhythm control for patients with persistent atrial fibrillation with mild to moderate heart failure: results from the RAte Control versus Electrical cardioversion (RACE) study. Am Heart J 2005;149:1106 – 11.
RACE
Limitations • Approximately one-third of AFFIRM trial patients were enrolled after their first episode. • Most of the patients enrolled were elderly (mean ages in AFFIRM and RACE were 70 and 68 years, respectively) and either asymptomatic or only minimally symptomatic. • Only 63% of those assigned randomly to a rhythm control strategy maintained sinus rhythm, whereas one third of patients in the rate control arm were in sinus rhythm.
Post-hoc Analyses • Maintaining sinus rhythm was an independent predictor of survival. • The survival benefit of maintaining sinus rhythm seemed to be offset by an increased mortality risk of antiarrhythmic drug therapy. • The presence of sinus rhythm throughout the study carried a small-but statistically significant improvement in NYHA functional class. Edward P. Gerstenfeld. Rhythm Control Improve Functional Status in Patients With Atrial Fibrillation? J. Am. Coll. Cardiol. 2005;46;1900-1901
Sinus Rhythm & Survival • A subsequent report provided evidence that the trend toward increased mortality with rhythm control was due to the deleterious effects of antiarrhythmic drugs. • The use of antiarrhythmic drugs was associated with a significant increase in mortality (HR 1.49), while the presence of SR was associated with a significant reduction in mortality (hazard ratio 0.53). Corley SD, et al. Relationships between sinus rhythm, treatment, and survival in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Study. Circulation 2004; 109:1509.
Discontinuation of Anticoagulation and Mortality • Both trials allowed for cessation of anticoagulant therapy four weeks after documentation of SR, leading to a higher rate of stroke. It has been postulated that continued anticoagulation might have led to a lower mortality in the rhythm control group.
Canadian Health Care Database Study • “ Real world ” populations • 26,130 patients 66 years or older who were hospitalized with AF • Mean follow-up of 3.1 years • During the first six months, there was a small increase in the risk of death for patients treated with rhythm control (HR 1.07, 95% CI 1.01- 1.14). Ionescu-Ittu R, Abrahamowicz M, Jackevicius CA, et al. Comparative effectiveness of rhythm control vs rate control drug treatment effect on mortality in patients with atrial fibrillation. Arch Intern Med 2012; 172:997.
Canadian Health Care Database Study • Mortality was similar between the two groups until year four. • However, the relative risk of death, comparing rhythm to rate control, fell thereafter and the risk was lower at five and eight years (HR 0.89, 95% CI 0.81-0.96 and 0.77, 95% CI 0.62-0.95, respectively).
How to choose a strategy? • In older, asymptomatic patients with AF, a rate control strategy often is preferable to the side effects and toxicity of antiarrhythmic drug therapy and multiple cardioversions. • For patients with severe symptoms while in AF, a rhythm control strategy is mandatory.
Recommend
More recommend
