RHYTHM-AF was a large prospective multinational registry and provides a unique prospective snapshot of cardioversion practices and short term clinical outcomes across Europe, Australia and Brazil. Rhythm control by cardioversion is an important treatment modality especially for symptomatic patients with recent onset AF. There are several management options for acute or recent onset AF, but the broad picture of how patients are managed with acute rate control in clinical practice has not been extensively studied . On the basis of our inventory through a questionnaire it appears that the cardioversion strategies vary considerably in the 10 countries studied. Most significant variations relate to type of conversion (PCV versus ECV versus mixed cardioversion countries) and the implementation of cardioversion (with differences in the relative frequency and of cardioversion and preferred conversion drugs). The inclusion rate was fairly consistent between countries (Figure 2), though constant rates within countries were not expected or demonstrated.
The questionnaire allowed sites to opt for more than one preferred antiarrhythmic drug therapy (since treatment preference may vary depending on patients' profiles). Amiodarone was well represented, though this agent usually does not provide rapid cardioversion. Nevertheless, it may relieve symptoms early on after start of infusion through rate control. The latter also holds for sotalol and the typical rate control drugs. In addition, amiodarone and sotalol, when used orally, may cause conversion to sinus rhythm at similar rates, i.e. between 18 and 27% of patients after 1 month of oral treatment and may therefore be seen as “wait-and-see” drugs [18, 19]. Class 1C drugs are also well represented as preferred drug. The mutual exclusivity demonstrated in preferences for flecainide and propafenone among some countries may be indicative of differences in marketing activities and/or past/current availability of the drugs in these respective countries. Only a minority of hospitals across all participating countries reported use of beta-blockade for conversion, not surprising as these agents mainly control heart rate rather than prompt conversion through direct antiarrhythmic action (Figure 3). Overall, adoption of the “wait-and-see approach” did not differ substantially between countries; only a few considered this appropriate for subsets of their patients. Results suggest current practice of cardioversion uses true antiarrhythmic drugs rather than rate control drugs, reflecting a goal of early cardioversion. On the other hand, amiodarone is very frequently preferred, which may relate to the fact that patients in whom cardioversion is considered frequently harbor significant underlying heart disease, including coronary disease and heart failure. Amiodarone would indeed be reserved for the sicker patients in need of cardioversion but in whom an early and acute conversion is not required. The eventual data from RHYTHM-AF will shed more light on these questions.
Interestingly, 70% of sites overall used a stringent rate control target, as opposed to what the current ESC guidelines advise. This also varied significantly per country, i.e. between 40 and 100%, the ‘stringent countries’ being Australia, Germany, Italy, and Poland (all >80% of practices chose stringent control). It is anticipated that rate control targets will become more lenient as was shown to be acceptable in the RACE-II study .
Almost all centers had TEE available and implanted pacemakers. Between 50 and 100% of hospitals (within each country) in this survey performed cardioverter-defibrillator implantations. Availability of electrophysiology and ablation varied between 21% and 100% of practices in the countries, averaging 66.5%. As such, there seems to be an overrepresentation of specialized AF or arrhythmia centers. On the other hand, there was a large variation in the availability of specialized clinics among countries. To what extent these differences affect patient outcomes remains to be seen in the eventual dataset of RHYTHM-AF. Recently it has been shown that use of specialized AF clinic may significantly reduce AF-related events compared to usual care .
As with any observational study, this study has several limitations. It was conducted in 175 different sites, across 10 different countries, with eCRFs in 3 different languages. Protocols, eCRFs and clinical language were standardized with guidance from scientific leaders with clinical expertise in their respective countries. Nonetheless, some vulnerability to variability due to differences in practice patterns, clinical training, cultural differences, environmental variability and language subtleties must be acknowledged. In addition, although sites were selected with the aim to achieve adequate heterogeneity to be representative of each country, we cannot assess to what extent country representativeness was achieved by participating sites. In addition, while the study was designed to collect prospective data of short term outcomes, relative to the course of a chronic disease such as AF, the data collected here still reflects only a small glimpse of the course of disease and health sequelae of each patient.
Notably, in some countries, the proportion of emergency departments included in the study was greater than cardiology departments, which may be indicative of local nuance rather usual practice across the globe. It is possible that inclusion of a greater number of emergency departments (as opposed to cardiology departments) in the study may also yield differential perceptions of physician preference for PCV over ECV procedures. This can also be considered a strength in this study as it provides data of previously underrepresented clinical settings that accounts for a large and increasing number of AF patients.
In a diverse environment, where there is much heterogeneity of practice, we designed and carried out a single consistent protocol. The participants were largely defined by the “intention to cardiovert” and not necessarily by individual patient characteristics. While this renders some of the patient inclusion criterion subjective and prone to the interpretations of the treating physician, this also captures a true picture of treatment practice in that patients are treated by subjective physicians who base their decisions not only on existing published guidelines, objective patient characteristics, and hospital protocols, but also on personal experience, local practice and personal preference. Differences observed, while reflecting true differences between various settings among patients who are “considered for cardioversion” may not reflect the true differences (in treatment, outcomes, etc.) among objectively clinically homogenous patients. Results from a study designed such as this needs to be interpreted with caution and in context: observations and data collected in a homogenous manner among very heterogeneous settings.