Overview of the Effect of Aging on Cardiac Electrophysiology and Evaluation of Arrhythmias
In older patients without apparent cardiovascular disease, the number of cardiac myocytes declines, while residual myocytes enlarge. Concurrently, there is an increase in elastic and collagenous tissue in all parts of the interstitial matrix and conduction system with advancing age. Around the sinoatrial node, adipose tissue accumulates with age, producing a partial or complete separation of the sinoatrial node from the surrounding musculature. The number of pacemaker cells steadily decreases with age, such that by the age of 75 years, less than 10% of pacemaker cells remain functional. Calcification of the cardiac skeleton, which includes the aortic and mitral annuli, the central fibrous body, and the summit of the atrioventricular (AV) septum, also increases with age. Because of their proximity to these structures, the AV node (AVN), His-Purkinje bundle, and right and left bundle branches are frequently affected by aging. Prolongation of action potential duration and diminished autonomic response are also integral components of the aging process. Taken together, these changes provide the substrate for the age-related increase in propensity for chronotropic and dromotropic incompetence and for the development of atrial and ventricular arrhythmias.
The Baltimore Longitudinal Study on Aging demonstrated that basal heart rates in the supine position do not differ significantly among younger and older healthy subjects. Heart rate response to orthostatic challenge decreases slightly in older men and women. Heart rate variability during respiration diminishes with advancing age, reflecting changes in autonomic regulation. The PR interval increases slightly with aging, most likely owing to a delay in AVN conduction.
The prevalence of atrial premature beats on ambulatory monitoring increases with age, exceeding 80% in healthy volunteers and asymptomatic elderly subjects, particularly those older than 80 years. Brief salvos of supraventricular tachycardia occur in up to 50% of older subjects, and the prevalence doubles between the seventh and ninth decades of life. These arrhythmias have not been shown to have adverse prognostic significance. Atrial fibrillation (AF) and tachycardia–bradycardia syndrome are predominant conditions of the elderly.
Ventricular arrhythmias also increase with age. In longitudinal studies, the prevalence of ventricular arrhythmias on ambulatory monitoring is as high as 60% to 90% in asymptomatic elderly subjects. Complex forms such as pairs and triplets occur in up to 10% of such individuals. Exercise testing may induce ventricular arrhythmias in up to 60% of subjects in the ninth decade of life. The prognostic significance of these arrhythmias is dependent in large part on the presence of underlying cardiovascular disease. In patients with cardiovascular disease, frequent ventricular ectopy may adversely affect quality of life, may contribute to deterioration in myocardial function increasing susceptibility to heart failure, and may be a harbinger of symptomatic and sustained ventricular arrhythmias and cardiac arrest. Conversely, the prognostic impact of rest or exercise-induced ventricular arrhythmias is limited in the absence of cardiovascular disease. Reduced heart rate variability by fractal analysis has also been linked to the occurrence of sudden cardiac death (SCD) and non-sudden cardiac death in an unselected population of elderly subjects.
Several clinical tools are available for identification of patients at risk of cardiac arrhythmias or its consequences that may benefit from interventions to reduce morbidity and risk of sudden death. These include noninvasive tests, such as a standard 12 lead electrocardiogram (ECG), exercise test or imaging to determine the severity of left ventricular systolic dysfunction, presence of late potentials on signal-average electrocardiography, severity of ventricular arrhythmias by ambulatory cardiac monitoring (Holter monitor or external or implantable event monitor), detection of repolarization instability by measurement of QT interval, QT dispersion and microvolt T-wave alternans, autonomic balance by heart rate variability or baroreflex sensitivity, or invasive tests to determine inducibility of sustained ventricular arrhythmias by programmed electrical stimulation. The effect of advanced age on predictability of these tests for risk stratification, however, has not been fully assessed.
A standard 12-lead ECG allows identification of underlying structural disease, such as conduction system abnormalities with heart block, bundle-branch block, ventricular hypertrophy, or prior infarction, as well as primary electrical disorders, such as the long-QT syndrome, short-QT syndrome, Brugada syndrome, or arrhythmogenic right ventricular cardiomyopathy. A prolonged QRS duration >120 milliseconds in patients with a severely depressed ventricular function or a prolonged QTc interval in the elderly predict higher risk of SCD. Absence of a slowly conducting zone, the electrophysiologic substrate for reentrant ventricular arrhythmias that is otherwise detected as late potentials on signal-average electrocardiography may be useful with its high negative predictive value to exclude a wide-complex tachycardia as a cause of unexplained syncope in the elderly patient with coronary artery disease.
The indications for ambulatory ECG recordings are similar between the younger and elderly populations. To detect a suspected arrhythmic event occurring frequently (e.g., greater than once every 48 hours or reproducible by outpatient activities), detect a precise count of ectopy, evaluate daily ventricular rate control in AF, or detect asymptomatic nonsustained ventricular tachycardia, a continuous ECG recorder such as a Holter is useful. Less frequent arrhythmias (e.g. ≥1 event per month but not occurring daily) can be investigated using an event recorder. A pre-event loop recorder is needed for patients with syncope or symptoms of brief duration. Even less frequent events or in patients who are unable to activate the event recorder, an implantable loop recorder such as the reveal device, which may record either automatically or by patient activation, can be very helpful in correlating symptoms to arrhythmias. Exercise ECG with or without cardiac imaging with echocardiogram or nuclear scan may also provide useful diagnostic and prognostic information in the evaluation of patients with known or suspected coronary artery disease or exercise-induced arrhythmias triggered by ischemia or catecholamine. Assessment of left ventricular systolic function and other structural and functional information about myocardial dimensions, wall thickness, and valvular and congenital heart disorders with imaging technique, such as echocardiogram, is an essential part of risk stratification of patients with ventricular arrhythmias at risk of SCD.
In most cases, the indications for invasive electrophysiologic study (EPS) in elderly patients are also the same as in younger patients (Table 79-1) and vary with the type and severity of heart disease. It is useful for arrhythmia assessment and risk stratification for SCD in elderly patients with ischemic heart disease and left ventricular dysfunction or syncope but plays only a minor role in the evaluation of patients with nonischemic cardiomyopathy or inherited arrhythmia syndromes, such as the long- or short-QT syndrome. It should be noted that Table 79-1 is based on the AHA/ACC guidelines from 1995, and there has been no recent update on indications for EPS. Some of the recommendations have changed as more data become available through multiple recent device trials, e.g., as discussed later in the chapter, EPS is no longer considered necessary for recommending device implantation in many patients with ischemic or nonischemic cardiomyopathy or in patients with documented out-of-hospital cardiac arrest. This section provides a brief overview of criteria for the selection of elderly patients for EPS, as well as a discussion of procedural risks.
CLINICAL CONDITION OR INDICATION | CLASS I (APPROPRIATE)* | CLASS II (EQUIVOCAL)† | CLASS III (INAPPROPRIATE)‡ |
|---|---|---|---|
Recurrent syncope | Patients with recurrent syncope that remains unexplained after appropriate evaluation | Patients with recurrent unexplained syncope without structural heart disease and negative tilt | Patients with a known cause of syncope in whom treatment will not be guided by invasive EPS |
Sinus node dysfunction | To establish association between symptoms and arrhythmia | Patients with documented sinus node dysfunction in whom other arrhythmias are suspected | Patients in whom an association has already been established or who are asymptomatic |
Atrioventricular block | Symptomatic patients in whom atrioventricular block is suspected | Patients in whom knowledge of the site of block would help guide therapy | Patients in whom an association has already been established or who are asymptomatic or have pauses only during sleep |
Intraventricular conduction delay | Symptomatic patients in whom the cause is unknown | Asymptomatic patients in whom pharmacologic therapy is planned | Symptomatic patients in whom an association has already been established or asymptomatic patients |
Narrow complex tachycardia (QRS <120 ms) | Frequent or poorly tolerated tachycardia; patient preference | Intolerance of antiarrhythmic or atrioventricular nodal blocking drugs | Patients with few episodes of tachycardia or in whom ablation is not appropriate |
Wide-complex tachycardia | Mechanism unclear or to help guide appropriate management | None | Patients in whom knowledge of the mechanism is clear from ECG or in whom knowledge is unnecessary |
Out-of-hospital cardiac arrest | Survivors of cardiac arrest without obvious reversible cause | Cardiac arrest caused by documented bradycardia; patients in whom the results of EPS may be nondiagnostic or equivocal | Cardiac arrest within 48 h of AMI Cardiac arrest owing to clearly definable cause |
Risk stratification for patients who may be candidates for implantable cardioverter defibrillator | Primary prevention in patients with MI, impaired LV function and nonsustained VT, or out-of-hospital cardiac arrest§ | Patients with syncope and structural heart disease | Patients who are not candidates for implantable cardioverter defibrillator |
Indications for catheter ablation procedures | Patients with symptomatic supraventricular arrhythmias owing to AVNRT or AVRT in whom ablation is preferred | Patients found to have a tachycardia substrate that is different from that suspected clinically | Patients with well-tolerated PSVT and who prefer conservative treatment to ablation |
Patients with symptomatic atrial tachyarrhythmias, such as typical atrial flutter, that may be amenable to catheter ablation therapy | Patients with atrial tachyarrhythmias in which catheter ablation may be successful in some cases | Patients with atrial tachyarrhythmias that are well tolerated or in whom catheter ablation is not preferred | |
Patients with some forms of ventricular tachycardia that are amenable to catheter ablation therapy | Selected patients with VT because of reentry around a scar after (remote) myocardial infarction | Patients with well-tolerated ventricular arrhythmias or patients with multiple VT morphologic findings |
Indications for EPS can be divided broadly into diagnostic and therapeutic purposes. In any patient, but especially in the elderly, the use of an intervention such as EPS, whether for diagnosis or therapy, should be determined from the clinical presentation and the specific goals of the study. Therefore, two key questions should be addressed before proceeding with EPS. First, is information obtained from the history and noninvasive evaluation sufficient to explain the clinical presentation, or is invasive EPS necessary to ensure an accurate diagnosis? Second, will the results of invasive EPS help guide therapy, or is catheter ablation being considered as a therapeutic option? Importantly, the decision to proceed with EPS remains a clinical judgment based on the history and physical findings, the probability of a cardiac cause of symptoms, and the likelihood that the results of EPS will substantially improve patient care and outcomes.
In general, procedural complications in the elderly are similar to those in younger patients. These include complications related to the procedure itself, such as (1) vascular damage, pneumothorax, or myocardial perforation leading to pericardial effusion and tamponade, and (2) exacerbation of preexisting medical conditions (e.g., chronic obstructive pulmonary disease and chronic heart failure). Exacerbation of preexisting conditions is most common with prolonged procedures, such as complicated ablation, and is rarely a problem during diagnostic EPS or straightforward catheter ablation. A widely held belief is that morbidity and mortality associated with invasive EPS are higher in elderly patients. Although this is not borne out by available data, which suggest similar rates of complications even in very elderly patients, one must be cognizant that patient selection bias is inevitably present in these observational studies. Thus, the potential risks and benefits of invasive EPS should be weighed on an individual basis and not merely by age.
Bradyarrhythmia and Cardiac Pacemaker Therapy in the Elderly
Aging is associated with progressive fibrosis of the sinoatrial node and AV conduction system, resulting in bradycardia, which may be further exacerbated by disease and medications, resulting in symptoms requiring permanent pacemaker implantation. More than 80% of pacemaker recipients in the United States are older than 65 years, and the median age is 75 years. As the population ages, it is anticipated that the number of older persons requiring permanent pacemakers, as well as the associated costs, will continue to rise.
Current guidelines for pacemaker implantation are updated regularly by the American College of Cardiology, American Heart Association, and North American Society of Pacing and Electrophysiology (now the Heart Rhythm Society). This section provides a synopsis of current indications for pacemaker implantation and outcomes from recent clinical trials relevant to pacemaker selection in older adults.
Class I indications for permanent pacemaker implantation include third-degree AV block and advanced second-degree AV block in symptomatic patients. Pacing therapy is also recommended in patients with neuromuscular diseases and third-degree AV block whether or not they are symptomatic, because progression of AV conduction slowing is not predictable in such patients.
Symptomatic patients (syncope and presyncope) with conduction system disease manifesting as bifascicular or trifascicular block on ECG in the absence of an alternative explanation for their symptoms are candidates for an EPS and/or permanent pacing. Prolongation of the HV interval beyond 80 milliseconds may be an index of potential high-degree AV block, and some clinicians recommend prophylactic permanent pacing in this setting. Other experts consider HV prolongation a marker of underlying heart disease and increased risk for sudden death but do not recommend pacemaker therapy unless the patient is symptomatic. According to the current guidelines, in the absence of syncope or presyncope, an HV interval of 100 milliseconds or more and/or nonphysiological infra-His block demonstrated during EPS are class IIa indications for pacemaker insertion.
Pacemaker therapy is indicated in patients with symptomatic bradycardia (syncope, presyncope, dyspnea, and exercise intolerance) correlated to sinus node dysfunction (pauses, persistent bradycardia, or chronotropic incompetence). In elderly patients, sinus node dysfunction is often associated with atrial tachyarrhythmias, including AF. Because of the frequent association of sinus node dysfunction with AF, VVI and VVIR pacing were once considered the preferred pacing modes. Recent studies suggest that atrial-based pacing in patients with sinus node dysfunction is beneficial for preventing progression of AF. Current pacemaker technology allows mode switching from DDD to VVI or DDI in case of paroxysmal AF, thus avoiding ventricular tracking of fast atrial rates. These considerations have led to a progressive increase in the use of dual-chamber pacemakers in elderly patients. Some clinicians advocate AAI or AAIR pacing as the best pacing mode because these modes provide more physiological ventricular activation and are technically less complex. This approach has not been widely adopted in clinical practice because progression to AV block during long-term follow-up has been reported in up to 10% of elderly patients with sinus node dysfunction. Although maintaining AV synchrony during AV block and the availability of mode switch to reduce or eliminate inappropriate tracking during atrial tachyarrhythmia support the rationale for dual-chamber pacing in patients with sinus node dysfunction, recent data raised concerns whether excessive ventricular pacing from the right ventricular apex may cause increased incidence of heart failure and heart failure-mediated hospital admission. The clinical advantages of programmable features such as “AV delay hysteresis” or “managing ventricular pacing” to minimize ventricular pacing in the presence of AV conduction are currently under investigation.
In 1998, the results of the Pacemaker Selection in the Elderly trial were published. This randomized comparison of ventricular and dual-chamber pacing included 407 patients 65 years or older followed for 30 months. Patients with sinus node dysfunction, but not those with AV block, had a moderately better quality of life and cardiovascular functional status with dual-chamber pacing. One-fourth of all patients assigned to the VVI mode crossed over to dual-chamber operation because of symptoms suggesting “pacemaker syndrome.” In the same year, Mattioli et al. reported a randomized trial involving 210 patients, which showed a higher incidence of AF and stroke in patients randomized to ventricular pacing.
Although the above trials were too small to assess the effect of pacemaker mode on mortality, three large mortality trials have now been completed (Table 79-2). The Canadian Trial of Physiologic Pacing enrolled 2568 patients who were scheduled for an initial implantation of a pacemaker to correct symptomatic bradycardia, did not have chronic AF, and were at least 18 years old. These patients were then randomized to ventricular pacing (VVIR) or a physiologic mode (AAIR or DDDR). At 4 years follow-up, there were no differences between the two groups in the primary study end point, the combination of cardiovascular death or stroke. In addition, all-cause mortality, stroke or arterial thromboembolism, hospitalization for heart failure, and performance on a 6-minute walk test did not differ between groups. Physiological pacing had a modest benefit in association with less new onset of AF, but there were also more perioperative complications, such as lead dislodgment or inadequate atrial pacing or sensing, in patients receiving physiological pacemakers.
RELATIVE RISK WITH VENTRICULAR VERSUS ATRIAL OR DUAL-CHAMBER PACING | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
TRIAL,* YEAR REPORTED | NO. ENROLLED | MEAN (Age yr) | GROUP | FOLLOW-UP (yr) | MODE OF PACING | Mortality | CHF | HF Hospitalization | AF | TE | QOL |
PASE, 1998 | 407 | 76 | SND or AVB | 2.5 | VVIR versus DDDR | NS | NS | NS | ↑ | NS | NS,† ↓ in SND |
CTOPP, 2000 | 2568 | 73 | SND or AVB | 3 | VVIR versus DDDR or AAIR | NS† | NS | NS | ↑ | NS† | Not stated |
MOST, 2002 | 2010 | 74 | SND | 2.7 | VVIR versus DDDR | NS† | ↑ | NS | ↑ | NS† | ↓ |
UK-PACE, 2003 | 2021 | 80 | AVB | 4.6 | VVI/VVIR versus DDD/DDDR | NS† | NS | NS | ↑‡ | Not stated | |
The Mode Selection Trial randomized 2010 patients with sinus node dysfunction to single- or dual-chamber pacing. After a mean follow-up of 2.7 years, there was no difference between groups in the primary end point, death, or stroke. However, progression to chronic AF and heart failure symptoms were less frequent, and quality of life was better in the dual-chamber pacing arm.
In the prospective U.K. Pacing and Cardiovascular Events trial that enrolled 2021 patients older than 70 years with AV block, morbidity and mortality were similar with VVI and DDD pacing, and there was also no difference in the incidence of AF between groups.
The main findings of these prospective randomized trials assessing the effect of pacing mode on long-term clinical outcomes are summarized in Table 79-2. The three largest trials conducted in three countries (United Kingdom, United States, and Canada), enrolling more than 6500 patients, did not find a beneficial effect of dual-chamber pacing for the prevention of stroke or improvement in survival when compared with ventricular pacing. However, the incidence and progression to chronic AF were reduced moderately in two of these studies. In addition, heart failure symptoms were reduced slightly and quality of life was better in patients receiving dual-chamber pacemakers for sinus node dysfunction, most likely because of the prevention of pacemaker syndrome.
Syncope in the Elderly
Carotid sinus hypersensitivity (≥3-second pause or a decrease in systolic blood pressure ≥50 mm Hg during carotid sinus massage) predominantly affects elderly patients, although the prevalence in the general population has not been precisely defined. In elderly patients with recurrent syncope, carotid sinus hypersensitivity has been reported in up to 35% of cases. Permanent pacing in patients with carotid sinus syndrome (carotid sinus hypersensitivity associated with syncope) is indicated. Observational and randomized studies have shown that recurrent symptoms are significantly reduced after permanent pacemaker implantation in patients with carotid sinus syndrome. Dual-chamber pacing is considered the best choice for these patients, although data are lacking from randomized trials. Newer algorithms, such as the “rate-drop response” or “sudden-brady response,” which accelerates the pacing rate when bradycardia is detected, are now available. However, the clinical utility of pacemakers with these newer algorithms compared with conventional pacemakers has not been determined in patients with carotid sinus syndrome.
Vasovagal syncope is more common in younger patients but also should be considered in elderly patients with unexplained syncope. Although the triggering mechanisms are complex and may differ among young and elderly patients, the efferent responses generally can be categorized as cardioinhibitory (pauses of ≥3 seconds or heart rate <40 beats per minute for more than 10 seconds), vasodepressor (systolic blood pressure falls by 50 mm Hg or more without symptoms or 30 to 50 mm Hg with symptoms of syncope or presyncope, and the heart rate does not decrease by more than 10%), or mixed (heart rate decreases but the ventricular rate does not fall below 40 beats per minute for more than 10 seconds, and there are no pauses >3 seconds; blood pressure usually decreases before the heart rate drop). Of note, the vasodepressor component is frequently present in patients with vasovagal syncope, and pacing therapy does not necessarily eliminate or significantly reduce vasodepressor-mediated symptoms.
In three recent unblinded randomized trials (Vasovagal Pacemaker Study, Vasovagal International Study, and Syncope Diagnosis and Treatment) comparing pacing with conventional therapy (conservative or drug), recurrent symptoms were significantly reduced with pacemaker therapy. As a result, pacing for “significantly symptomatic and recurrent neurocardiogenic syncope associated with bradycardia documented spontaneously or at the time of tilt-table testing” is considered a class IIa indication for pacemaker implantation. However, following publication of these guidelines in 2002, the Vasovagal Pacemaker Study II trial, in which patients and investigators were blinded to pacing mode, failed to confirm a beneficial effect from pacing therapy in patients with vasovagal syncope.
In general, outcomes from pacing and drugs for treating vasovagal syncope reflect the heterogeneous patient population, complex underlying mechanisms, and sporadic nature of the neurocardiogenic reflex. On the basis of available evidence, it is reasonable to consider pacing as a class II indication in elderly patients who have recurrent syncope with documented bradycardia during a vasovagal response. Current data are insufficient to determine whether pacemakers with rate-drop or sudden-brady response features provide additional benefit.
Syncope is a common cause of falls, injuries, and hospitalizations in older adults. Normal age-related physiological changes often combine with pathological mechanisms to impair cerebral perfusion and induce syncope. Elderly community-dwelling patients have an average of 3.5 chronic illnesses, many of which predispose to syncope. In addition, elderly patients receive three times as many medications as the general population, further increasing their vulnerability to syncope. Numerous age-related autonomic and humoral changes also predispose older patients to syncope. Decreased heart rate responsiveness to postural changes and diminished baroreceptor sensitivity impair the ability to adapt to orthostatic stress. Reduced concentrations of plasma aldosterone, coupled with impaired thirst, place elderly patients at risk of volume depletion. These age-dependent changes, in combination with comorbid medical illnesses, increase the propensity for multiple potential etiologies of syncope in elderly patients. In turn, multiple-cause syncope is an independent predictor of poor clinical outcome.
The diagnostic approach to syncope is similar in older and younger patients and begins with a careful history and physical examination, recognizing that cardiogenic causes of syncope are more common in the elderly. Factors associated with an increased risk of cardiogenic syncope include a history of coronary artery disease, prior myocardial infarction, chronic heart failure, abrupt onset of symptoms (no prodrome), event occurring in the supine position, older age, abnormal cardiovascular examination (aortic stenosis murmur and S3 gallop), abnormal ECG (Q waves, bundle branch block, or sinus bradycardia), and an abnormal echocardiogram (structural abnormality or reduced ejection fraction). Carotid sinus massage should be a routine part of examination in elderly patients presenting with syncope, unless there is a carotid bruit or prior history of stroke. In elderly patients with unexplained syncope and an increased risk of a cardiogenic cause, EPS should be considered. In patients at low risk of cardiogenic syncope, noninvasive cardiac monitoring or tilt-table testing may be appropriate. An implantable loop recorder should be considered in elderly patients with recurrent syncope of unknown cause, especially if structural heart disease is present. Once a cause of syncope has been established, treatment is similar in older and younger patients.
Despite advances in diagnostic technology for syncope evaluation, the cause of syncope remains undetermined in approximately 20% of patients after medical evaluation; many are elderly with an increased tendency for multiple etiologies. Current guidelines do not recommend “empirical” pacemaker therapy in elderly patients with recurrent syncope if carotid sinus massage, tilt-table testing, and EPS are all nondiagnostic. In such cases, an implantable loop recorder may be helpful in establishing a diagnosis. Data from implantable loop recorders for unexplained syncope have shown a predominance of bradycardic events among patients with recurrent symptoms during follow-up.
Tachyarrhythmias and Cardiac Implantable Defibrillator Therapy in the Elderly
Atrial Fibrillation affects approximately 2.3 million people in the United States and is the most common rhythm disorder among U.S. patients hospitalized with a primary diagnosis of an arrhythmia. The median age of AF patients is 75 years; 84% are older than 65 years. Pooled data from studies of chronic AF in North America, Britain, and Iceland suggest a prevalence of 0.5% to 1% in the general population. In two separate studies restricted to patients older than 60 years, the incidence was 5% to 9% after 5 to 15 years of follow-up. In the United States, hospitalization for AF has increased two- to threefold in the past 15 years and the size of the AF population is projected to triple by 2050. The genesis of this AF “epidemic” is strongly linked to the expanding elderly population.
AF has a substantial impact on both morbidity and mortality. It is a strong independent risk factor for stroke, responsible for an estimated 75 000 cerebrovascular accidents annually. AF is also associated with a more than twofold increase in all-cause mortality. Although AF frequently coexists with other medical conditions, especially cardiovascular and pulmonary disorders, mortality remains higher after adjusting for these and other conditions. (For a comprehensive review of AF, see: ACC/AHA/ESC Guidelines for the Management of Patients with Atrial Fibrillation; http://www.cardiosource.com/guidelines/guidelines/atrial_fib/pdfs/AF_final.pdf.)
Data supporting the use of anticoagulation for primary and secondary stroke prevention are more compelling than those for any other pharmacologic intervention in AF. The annual incidence of stroke in elderly patients with nonvalvular, chronic, or paroxysmal AF is approximately 5% in the absence of anticoagulation, compared with approximately 1% for comparable populations in sinus rhythm. Clinical risk factors for stroke in patients with AF include prior cerebrovascular accident, history of hypertension, diabetes mellitus, heart failure, and advanced age. Echocardiographic risk factors include increased left atrial size and decreased left ventricular systolic function.
Data from a pooled analysis of primary prevention studies indicate that the annual risk of stroke in patients with one or more clinical risk factors varies from 4% to 12% and that warfarin therapy reduces the risk by 60% to 70% (i.e., down to 1.2–4%). In patients older than 75 years, the beneficial effect of warfarin in embolic stroke prevention is offset by increased serious bleeding complications, especially in women. In the Stroke Prevention in Atrial Fibrillation (SPAF) II trial, combined embolic and hemorrhagic stroke rates were approximately 2% in patients less than 75 years of age and 5% in patients older than 75 years. From these data, current guidelines recommend maintaining the international normalized ratio (INR) near 2.0 in patients older than 75 years, particularly women.
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