Atrial Fibrillation in the 21st Century: The New Cardiac ‘Cinderella’ and New Horizons for Cardiovascular Nursing?

In recent years much has been written about the emergence of chronic heart failure as a major epidemic during the late 20th century [1] and the role of cardiovascular nurses in response to this epidemic [2]. Certainly, there is plenty of evidence to support the fact that chronic heart failure was a costly burden on the health-care system in the 1990s [3,4]. Moreover, despite some evidence that the ‘primary’ heart failure admissions are beginning to plateau [5], it also likely to exert a significant burden on both an individual and societal level in the first two decades of the 21st century [2,6,7]. Fortunately, there are growing signs to suggest that the public health response to chronic heart failure in many developed countries is reaching an appropriate level. As such, it might be reasonable to argue that chronic heart failure should lose its title as the ‘Cinderella’ of cardiac disease states [8]. It might also be argued that another cardiac illness deserving of special attention should assume the mantle of the neglected ‘step-daughter’ of fairy tale fame. It is within this context that this article reviews the case for adopting atrial fibrillation (AF) as the new ‘Cinderella’ of cardiovascular disease states [9,10]. It will also examine some of the key health care issues that will confront clinicians managing AF in the next few years and the type of opportunities that exist for cardiovascular nurses to take a greater role in managing this most common and insidious of cardiac arrhythmias. Based on contemporary epidemiological studies, it is estimated that approximately 1% of the population in developed countries currently have AF. More importantly, perhaps, its prevalence rises to more than 10% in those aged 75 years or more [11–14]. There is also strong evidence to suggest that the incidence and overall prevalence of AF is rising. For example, in a large epidemiologic study in the UK, Majeed et al. demonstrated that the prevalence of AF had increased markedly during the early to mid-1990s [13]. Consistent with these data, we have recently shown that: (a) the population rate of ‘incident’ AF admissions increased markedly during the period 1986–1995 in Scotland [15] and (b) that total AF-related hospitalizations during the same period had increased 2–3-fold [16]. Unlike heart failure [5,17], therefore, the observed trends suggested three important factors likely to shape the future burden of AF: AF-related hospitalization rates did not appear to be abating [16]. The contribution of ‘incident’ AF hospitalizations is steadily increasing. There are only modest declines in adjusted case-fatality rates [15]. Another important finding from these studies is that patients admitted to hospital with AF are becoming increasingly older (Fig. 1) and with a greater level comorbidity likely to complicate treatment [15,16,18,19]. Age and sex specific rates of admission for AF (principal diagnosis) in Scotland (1986–1996) in Scottish women aged 65 years and over. (1b) Age and sex specific rates of admission for AF (principal diagnosis) in Scotland (1986–1996) in Scottish men aged 65 years and over. Adapted from previously published data [16]. Absolute numbers of admissions are provided on the chart according to age group Such trends are not surprising considering the rapid ageing of the population of many ‘developed’ countries [20] and increasing survival rates in coronary heart disease [21–23] and heart failure [17]. As such, the prevalence of AF is likely to continue to rise in the next 20 years or more [9–11]; especially as the proportion of older individuals with a mixture of chronic hypertension, chronic ischaemic heart disease, diabetes, chronic heart failure, valvular disease and other factors that are closely linked with AF (e.g. a history of obesity and smoking) increases [24]. A key issue is whether we should accept the ‘rising tide’ of AF as an inevitable sign of our ability to prolong our lives through: (a) general improvements in health standards and, more specifically; (b) more effective treatment of previously fatal cardiac events. This clearly depends, of course, on whether AF simply represents a ‘benign’ marker of an ageing population. The overwhelming evidence to date would suggest otherwise. Initiated in 1948, The Framingham Heart Study identified AF as a major public health problem [25]. That study showed it to be an important cause of cardiovascular morbidity, especially stroke, within that population [26]. Subsequent clinical trials confirmed this risk in selected patient cohorts and quantified the benefit of anticoagulant therapy (see below) [27]. As well as being a strong independent risk factor for stroke, AF (both in its chronic and paroxysmal form) has been shown to be an independent predictor of mortality rather than just a marker for ‘high risk’ patients [26]. In a recent study of the Renfrew/Paisley cohort [14], we not only confirmed the long-term link between AF and the risk of subsequent stroke and all-cause mortality, but also showed it to be a strong independent risk factor for future heart failure-related events. In both the male (n=7052) and female (n=8354) cohort, AF was a strong independent predictor (P<0.01 for all risk ratios) of the following over 20 years follow-up [28]: All-cause death (RR 2.2 and 1.5). A major cardiovascular event (RR 3.0 and 1.8). A fatal or non-fatal stroke (RR 3.4 and 2.5) A major heart failure event (RR 3.4 and 2.2) over 20 years follow-up. As discussed, one of the more significant aspects of the AF-related admissions is the strong trend towards older patients with concurrent cardiac and non-cardiac disease states. Two of the most debilitating and costly of these disease states deserve special mention. Data from the Framingham cohort [25,26] and the SPAF study [29] suggest that the annualized risk of stroke in patients with sustained or paroxysmal non-rheumatic AF is approximately 3%: this risk is markedly increased in those with a history of prior stroke or left atrial dilatation and/or ventricular dysfunction. Despite the widespread availability of more effective treatment, in the unique Scottish dataset, we showed that whilst the proportion of strokes per AF admission fell between 1986 and 1996, the actual number of AF-related strokes (both non-fatal and fatal) more than doubled [16]. We also found that the number of patients with concurrent AF and heart failure is increasing with approximately 15% of total AF admissions being associated with a diagnosis of heart failure [16]. The concept of AF as an actual cause of heart failure (e.g. via a tachycardia-mediated cardiomyopathy) [10], rather than being a trigger is a relatively new one worthy of further investigation. Irrespective of the truth, however, the nexus between AF and heart failure, like that of AF and stroke, is one that is characterized by the requirement for more complex management and markedly increased morbidity and mortality rates [10]. As with any chronic disease state, the greatest burden in relation to AF is likely to fall on the hospital sector. For example, in another study of the Renfrew/Paisley cohort (one of the largest epidemiologic studies ever undertaken) we found that nearly 4% of the 15406 middle-aged men and women that comprised this cohort in Western Scotland were hospitalized with a diagnosis of AF over a period of 20 years ending in 1996 [14]. Largely based upon a continuing rate of increase in hospitalization rates relating to AF (Fig. 1), we have recently estimated that the direct cost AF to the National Health Service in the UK increased by over 50% in the period 1995–2000. It currently consumes around 1% of health care expenditure and indirectly contributes to an additional 2% of such costs [30]. As expected, hospital admissions account for approximately 60% of AF-related expenditure. It should be noted, however, that the majority of health care activity relating to AF occurs in the community. Major health care costs include visits to General Practitioners and drug therapy—particularly anti-coagulation therapy requiring active monitoring of coagulation status [31]. A major determinant of the cost of any disease state, of course, is the nature and effectiveness of treatment. As such, relatively inexpensive treatment options that provide a cure, or remain effective for a prolonged period, without the necessity for intensive follow-up and the risk of adverse effects are rare. There is certainly no such treatment currently available for AF! Indeed, the management of AF remains contentious with the mode of treatment dependent on a number of factors including the following: Its underlying cause of AF (e.g. valvular versus non-valvular). The level of chronicity (e.g. paroxysmal vs. chronic AF). The individual characteristics of the patient (e.g. concurrent disease states). Whether there is an intention to convert AF to sinus rhythm through electrical and pharmacologic means or achieve ventricular rate control [10]. It could be argued that there are some major advances in store for AF. For example, the AFFIRM study, which is currently examining the relative effectiveness of ventricular rate control plus anti-coagulation versus restoring patients to sinus rhythm via anti-arrhythmic therapy in chronic AF. This study will be reported in the near future [32]. Similarly, there has been some success in applying the Maze procedure [33] and implantable atrial defibrillators [34] to treat AF. Transoesophageal echocardiography, to determine thrombo-embolic risk, has also become an integral part of AF management in many academic centers [35]. However, as with any disease state that creates a large volume of older patients with complex management issues, the relevance of clinical trials and costly and complicated invasive procedures is inherently problematic. The emergence of a new ‘panacea’ in the prevention and treatment of AF in the near future is, therefore, unlikely. As a result, the immediate prospect for treating AF is ‘more of the same’. It is within this context that there is probably a large body of older patients with chronic AF who have been previously challenged with electrical or pharmacological cardioversion who have either: (a) immediately failed immediately to revert to sinus rhythm or (b) reverted to AF within a few months of cardioversion [36]. Such patients are particularly at risk of impaired cardiac output and a future thrombo-embolic event. Indeed, the reported success rates following electrical cardioversion for AF in ‘real life’ fall far short of those reported in clinical trials [36]. This type of patient often requires a complex pharmacologic regimen that requires close monitoring to: (a) ensure that a therapeutic benefit is being achieved and (b) reduce the risk of adverse effects. It should come as no surprise, therefore, to learn that because of the major effort and difficulty in accurately determining the benefit to risk ratio of treating older patients with AF [37], many patients receive sub-optimal care [38,39]. In the case of pharmacotherapy designed to reduce the ventricular rate in AF, there is a wide selection of drugs available. Whilst digoxin is a common choice in this regard, beta-blockers and calcium antagonists are also used and all have the potential to provoke adverse effects in older individuals [10]. Moreover, although warfarin therapy is of proven benefit in reducing the risk of stroke in AF [27,29] and remains under-prescribed [22], the risk of intracranial haemorrhage (particularly the older individual with an inadvertently high INR) is of major concern in clinical practice [39,40]. If it is accepted that AF is likely to remain a problem in the short to medium-term and we are unlikely to see enormous changes in treatment options, is there any room for improvement in how we currently manage patients with AF? For example, can we reduce AF-related morbidity and mortality rates whilst improving quality of life at the individual level? There are probably two key areas where much more could be done and both (to a varying degree) represent ‘new horizons’ for the scope of clinical practice in cardiovascular nursing. As discussed, individuals with AF are at high risk for developing stroke [25,26,40]. Whilst the benefits of antithrombotic therapy in preventing stroke in AF are well-recognised [27], in clinical practice, such therapy does not fully ‘immunise’ patients against the risk of thrombotic events. There is, therefore, further scope to delineate high-risk patients—both in terms of applying the benefits of anti-coagulation therapy and avoiding their potential adverse effects. To date, the increased risk of thrombotic events in patients with AF has been predicated on the fact that AF is associated with ‘abnormalities of blood flow’ within and immediately adjacent to the atrial chambers. This is particularly relevant in the setting of heart failure. It also predicated on concurrent ‘abnormalities of the vessel wall’ as suggested by the close association of AF with hypertension and atherosclerotic disease. These two phenomena comprise two of the three components of Virchow's triad for thrombogenesis [41]. Recently, there has been increasing interest in the concept that AF is associated with all three components of Virchow's triad for thrombogenesis. The last component in this triad being an AF-induced hypercoagulable state that can be altered by introducing antithrombotic therapy and cardioversion from AF to sinus rhythm [42]. If such a phenomenon does exist it is possible that a sub-set of patients with AF is at substantially greater risk for experiencing a thrombotic event. It may be argued that the usefulness of transoesophageal echocardiography to identify patients with pre-existing intra-cardiac thrombi and, therefore, at high risk of thrombotic events, is now well-established [35] and already provides a clinical basis for judicious use of thromboprophylaxis. However, like any other invasive procedure requiring specialist support, the inability to screen large number of patients in a cost-effective manner limits its cost-effectiveness. In addition to the likely deterioration in platelet function in the setting of AF, it must also be considered that genetic polymorphisms (common genetic variations that exist within a population) may contribute to the observed hypercoagulable state found in some patients with AF. For example, it is well established that polymorphisms within the prothrombin, fibrinogen, glycoprotein IIIa, glycoprotein Ib, platelet activation inhibitor are all associated with arterial thrombosis [43,44]. As arterial thrombosis is an integral component in the pathogenesis of arterial stroke, these genetic polymorphisms may be of clinical importance and, if found, could also provide further delineation of ‘high risk’ patients in the total AF population. It is clear that further developments in refining individual risk of thrombo-embolic events in the setting of AF via relatively simple and inexpensive screening tools are likely. In the future, therefore, clinicians may able to better delineate which patients have a greater risk of thrombotic events and those who will respond better to anti-platelet therapy. This, of course, will require both wider screening of patients and more individualised care thereafter. In the future, therefore, there may be an increasing demand for cardiovascular nurses who can undertake large-scale screening programs of older individuals to detect AF. If AF is detected, it is likely that the affected individual will require a combination of the following: Supportive counselling and education. Further screening to delineate their risk of future stroke and heart failure events. Referral to specialised, multidisciplinary management (see below). Remembering that over 10% of older individuals screened for AF will be found to experience this arrhythmia, it is unlikely that general practitioners/primary care physicians will assume such a role. This is particularly true when considering the cost and diverse nature of the role. As such, if appropriately knowledgeable and skilled, it is likely that a cardiovascular nurse would represent a cost-effective option in this regard. As discussed, patients admitted to hospital with a diagnosis of AF are getting older and with a greater level of comorbidity [15]. Apart from its epidemiological significance, such a trend raises important management issues. Firstly, it is clear, that AF, as a relatively ‘new’ cardiac epidemic [9], will generate an increasing number of older patients requiring complex treatment to both: (a) improve symptom control and quality of life and (b) minimise typically high morbidity and mortality rates (e.g. particularly in relation to stroke and heart failure). The apparent inability of many individuals with chronic cardiac disease states to gain the maximal, clinical benefit from otherwise proven therapeutics is a multi-factorial problem. This is not surprising considering the complex interaction between individuals, their treatment and the many components of the health-care system in which they are managed. Sub-optimal treatment commonly reflects the end result of a series of problems that hinder what should be a harmonious and productive interaction between the patient and the health-care system. As with heart failure, the complexity of treating AF and the relatively inflexibility of the health-care system often predicates that patients are either: (a) prescribed a sub-optimal treatment regimen [39] or (b) unable to manage an otherwise ‘optimal’ treatment regimen that is too complex for them to manage in an effective manner [45]. Either way, patients often fail to obtain the maximal benefits from proven treatments and remain symptomatic (in the case of AF, palpitations, dizziness and dyspnoea). For example, we have recently shown that in ‘real life’, patients undergoing electrical cardioversion for AF have much higher recurrence and morbidity rates than would be predicted from clinical trials and, therefore, require much more intensive monitoring and more individualized treatment [36]. The management issues mentioned above are similar to those identified in relation to heart failure in the mid to late-1990s. As a result there has been a growing literature to describe specialist management programs for patients discharge from hospital with chronic heart failure in order to optimize its treatment and to prevent costly unplanned readmissions, prolong survival and improve quality of life—particularly in high-risk individuals [46]. Of the range of programs tested in randomized studies to date, the most cost-effective have been those that involve a strong component of multidisciplinary team work with a central role for a specialist heart failure nurse [46–48]. However, in spite of the obvious need to ensure that patients with AF receive optimal treatment and the potential to reduce health care costs via lower admission rates, there is a paucity of literature to describe the effects of a similar management program designed to optimize the treatment and subsequent in AF on a randomized or the increasing that the between ‘optimal’ and ‘real life’ care in AF is [36]. trials to improve and of anti-coagulation therapy and anti-coagulation have been reported in the As the body of literature relating to managing heart failure is most probably it is likely that such will fall short in terms of potential considering the complexity of anti-coagulation and anti-arrhythmic therapy in AF The of activity in this when considering the of new management programs for heart provides further evidence that AF is the ‘Cinderella’ of cardiac disease states. A more appropriate response to the burden by AF, would be the of multidisciplinary management programs to optimize the treatment and care of for older patients from hospital with chronic AF. These programs would have to examine of anti-coagulation therapy and increasing the ability of patients to manage anti-arrhythmic therapy and detect AF-induced clinical heart failure, such programs would be to reduce morbidity rates and improve quality of life and involve a central role for specialist cardiovascular In practice, the of such programs may require a series of clinical trials than those used to examine the of heart failure the of lower morbidity and mortality rates to those in heart and Despite some the scope for management programs is and at years that of heart failure. We have recently argued that cardiovascular nurses are in a unique to ensure better health in a range of and chronic cardiovascular disease states the emergence of AF as a major epidemic in the 21st century and its importance in relation to morbidity and mortality and the relative of response to AF as a of high public health cardiovascular nurses are well to take a role in this as the new ‘Cinderella’ of cardiovascular disease states. therefore, is to respond to the of the problems by AF through the and of effective of and multidisciplinary It will be an to the role of the cardiovascular nurse in relation to the management of AF in years is currently by the National Health and of