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. 2021 Oct 20;19(1):256.
doi: 10.1186/s12916-021-02120-3.

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Marco Proietti #  1   2   3 , Marco Vitolo #  4   5   6 , Stephanie L Harrison  4 , Deirdre A Lane  4   7 , Laurent Fauchier  8 , Francisco Marin  9 , Michael Nabauer  10 , Tatjana S Potpara  11   12 , Gheorghe-Andrei Dan  13 , Giuseppe Boriani #  5 , Gregory Y H Lip #  14   15 ; ESC-EHRA EORP-AF Long-Term General Registry Investigators
Collaborators, Affiliations

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Marco Proietti et al. BMC Med. .

Abstract

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients' clinical phenotypes and analyse the differential clinical course.

Methods: We performed a hierarchical cluster analysis based on Ward's Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry.

Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients' prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P < .001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27-3.62; HR 3.42, 95%CI 2.72-4.31; HR 2.79, 95%CI 2.32-3.35), and Cluster 1 (HR 1.88, 95%CI 1.48-2.38; HR 2.50, 95%CI 1.98-3.15; HR 2.09, 95%CI 1.74-2.51) reported a higher risk for the three outcomes respectively.

Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes.

Keywords: Atrial fibrillation; Clinical management; Clinical phenotypes; Cluster analysis; Major adverse outcomes.

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Conflict of interest statement

DL has received investigator-initiated educational grants from Bristol-Myers Squibb (BMS), has been a speaker for Boehringer Ingelheim and BMS/Pfizer and has consulted for BMS, Boehringer Ingelheim and Daiichi Sankyo. LF has been a consultant or speaker for Bayer, BMS/Pfizer, Boehringer Ingelheim, Medtronic, Novartis; GB received small speaker’s fees from Medtronic, Boston, Boehringer Ingelheim and Bayer; GYHL has been a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi Sankyo. No fees are directly received personally. All the disclosures happened outside the submitted work. All other authors have nothing to declare.

Figures

Fig. 1
Fig. 1
Patients’ cluster membership. Legend: CV = cardiovascular; RFs = risk factors
Fig. 2
Fig. 2
Multivariable logistic regression analysis for secondary clinical outcomes. Legend: adjusted for type of AF, EHRA score, use of OAC; AF = atrial fibrillation; CV = cardiovascular; OAC = oral anticoagulant
Fig. 3
Fig. 3
Kaplan-Meier curves for primary clinical study outcomes. Legend: A Cardiovascular events = log-rank 85.975, P < .001. B All-cause death = log-rank 132.790, P < .001. C Composite outcome = log-rank 132.997, P < .001. All pairwise comparisons were significant for P < .001. Green line = Cluster 2; orange line = Cluster 1; yellow line = Cluster 3
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