Risk-Based Disease Surveillance

FOR RELATED ARTICLE, SEE PAGE 510

Atrial fibrillation (AF), the most common sustained clinical arrhythmia, represents a global epidemic, with an estimated 33.5 million affected individuals in 2010.¹ Although AF is associated with substantial cardiovascular morbidity, including stroke, myocardial infarction, congestive heart failure, and mortality, it is often asymptomatic and intermittent, and therefore underdiagnosed. Patients may present initially with a thromboembolic event. In patients with no history of atrial arrhythmias presenting with cryptogenic stroke, an implantable loop recorder detected AF in 12.4% of cases over 12 months.²

Currently, long-term monitoring with implantable loop recorders is applied to screen for previously undiagnosed paroxysmal AF in patients only after a stroke occurs. There are a number of reasons to consider screening high-risk populations for incident AF. For example, identifying such populations may allow highly targeted application of long-term monitoring prior to presentation with stroke and also optimize timing of anticoagulation and/or ablation. Widespread use of implantable loop recorders for AF surveillance may not be cost-effective, but reliable smartphone applications for AF screening are currently commercially available. Early AF identification and prompt initiation of anticoagulation might be expected to reduce strokes in high-risk patient subsets.

Another potential benefit of intensified AF surveillance in high-risk patients is that identifying patients earlier in the natural history of their disease could improve the response to interventions such as ablation targeted at sinus rhythm restoration and maintenance. Decreasing the time between the diagnosis of AF and ablation is associated with improved ablation success rates.³

Finally, identifying patients at highest risk for developing AF may aid in the selection of patients for intensive risk factor modification and identify patients for clinical trials of AF primary prevention.

In this issue of CHEST, Li et al⁴ examine risk factors for incident AF in a population-based cohort of 471,446 individuals from the Chinese Yunnan Insurance Database (derivation cohort) to derive a clinical risk score the authors termed C₂HEST (C₂ = coronary artery disease/COPD [1 point each]; H = Hypertension; E = Elderly; S = Systolic heart failure; and T = Thyroid disease). The investigators then apply the new score to a cohort of 451,199 subjects from the Korean National Health Insurance Service (validation cohort). Notably, in the initial analysis, the authors observed that the presence of structural heart disease, defined as rheumatic heart disease and dilated cardiomyopathy, already conferred a high risk for AF, and excluded patients with these conditions from the analysis. In addition, AF was defined based on an ECG or Holter recording, and inclusion was limited to inpatients with documentation of new-onset AF. The C₂HEST score demonstrated good to moderate discrimination applied to the internal and external cohorts, respectively. Importantly, the C₂HEST score had significantly better predictive value for incident AF compared with the CHADS₂ (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, and stroke/transient ischemic attack) and CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) scores in both cohorts.

Multiple risk scores for predicting incident AF have been validated in predominantly white, Western populations.⁵ The value of these AF risk scores in Asian populations is less certain. Suenari et al⁶ reported that the HATCH score, designed to estimate the risk of progression from paroxysmal AF to permanent or persistent AF, was useful in risk estimation of new-onset AF in a cohort derived from the Taiwan National Health Insurance Research Database. Hamada et al⁷ published a 7-year prediction model from an outpatient Japanese cohort, identifying individuals with a high risk for incident AF. The findings of the present study extend our understanding of new-onset AF risk in Asian populations, suggesting that the C₂HEST score is a robust predictor of AF development in Chinese and Korean populations.

Compared with the Chinese cohort in the study by Li et al,⁴ the Korean group was older, had a higher incidence of AF, and a higher prevalence of hypertension. The validity of the C₂HEST score in two significantly different cohorts strongly supports the clinical utility of this score in the prediction of AF development in diverse populations.

Although the implications of identifying a robust scoring system to predict AF are exciting, there are some limitations to this study.⁴ First, in deriving and validating the C₂HEST score, patients with structural heart disease were eliminated from the analysis. Despite this exclusion, based on the strong association of structural heart disease with AF, systolic heart failure is included in the C₂HEST score. This seeming contradiction is not explained in the text of the article. As a large database study relying on medical records and the ability of physicians to identify and document disease, the true incidence of AF is likely underreported in the article, particularly as the inclusion criteria for AF cases were limited to inpatients.

The authors⁴ included a comparison of the novel C₂HEST score with the CHADS₂ and CHA₂DS₂VASc scores in both their derivation and validation cohorts, evaluating relative predictive value for incident AF. Both CHADS₂ and CHA₂DS₂VASc have been shown to be predictive of incident AF,⁸ even though they were developed to stratify risk of thromboembolism in existing AF. Although the C₂HEST score performed favorably relative to the other scores, it is unknown whether the C₂HEST score is also predictive of thromboembolic risk.

The clinical importance of the present study⁴ relates to the potential of the C₂HEST score to reduce AF-related morbidity through earlier identification of disease. The relatively high predictive value of the C₂HEST score for future AF risk may be of benefit not only in the prevention of thromboembolism but also in the management of heart failure and coronary disease in which AF imparts greater morbidity. Ultimately, patients who may benefit most from early identification are those at high risk both for AF and thromboembolic complications. Future investigations evaluating the predictive value of the C₂HEST score to stratify AF thromboembolic risk may be valuable in this regard. The widespread clinical application of this simple and novel score may usher in a new era in which accurate prediction and earlier detection of AF could reduce morbidity of this increasingly prevalent arrhythmia.