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Clinical Phenotypes of Atrial Fibrillation and Mortality Risk-A Cluster Analysis from the Nationwide Italian START Registry.

ABSTRACT: Patients with atrial fibrillation (AF) still experience a high mortality rate despite optimal antithrombotic treatment. We aimed to identify clinical phenotypes of patients to stratify mortality risk in AF. Cluster analysis was performed on 5171 AF patients from the nationwide START registry. The risk of all-cause mortality in each cluster was analyzed. We identified four clusters. Cluster 1 was composed of the youngest patients, with low comorbidities; Cluster 2 of patients with low cardiovascular risk factors and high prevalence of cancer; Cluster 3 of men with diabetes and coronary disease and peripheral artery disease; Cluster 4 included the oldest patients, mainly women, with previous cerebrovascular events. During 9857 person-years of observation, 386 deaths (3.92%/year) occurred. Mortality rates increased across clusters: 0.42%/year (cluster 1, reference group), 2.12%/year (cluster 2, adjusted hazard ratio (aHR) 3.306, 95% confidence interval (CI) 1.204−9.077, p = 0.020), 4.41%/year (cluster 3, aHR 6.702, 95%CI 2.433−18.461, p < 0.001), and 8.71%/year (cluster 4, aHR 8.927, 95%CI 3.238−24.605, p < 0.001). We identified four clusters of AF patients with progressive mortality risk. The use of clinical phenotypes may help identify patients at a higher risk of mortality.

SUBMITTER: Pastori D

PROVIDER: S-EPMC9143727 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Clinical Phenotypes of Atrial Fibrillation and Mortality Risk-A Cluster Analysis from the Nationwide Italian START Registry.

Pastori Daniele D Antonucci Emilia E Milanese Alberto A Menichelli Danilo D Palareti Gualtiero G Farcomeni Alessio A Pignatelli Pasquale P The Start Register Investigators

Journal of personalized medicine 20220512 5

Patients with atrial fibrillation (AF) still experience a high mortality rate despite optimal antithrombotic treatment. We aimed to identify clinical phenotypes of patients to stratify mortality risk in AF. Cluster analysis was performed on 5171 AF patients from the nationwide START registry. The risk of all-cause mortality in each cluster was analyzed. We identified four clusters. Cluster 1 was composed of the youngest patients, with low comorbidities; Cluster 2 of patients with low cardiovascu ...[more]

PMID: 35629207

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Project description:Background Thrombocytopenia is associated with increased mortality in the general population, but few data exist in patients with atrial fibrillation (AF) taking oral anticoagulants. We investigated factor determinants of thrombocytopenia in a large cohort of patients affected by AF and its association with total mortality. Methods and Results Multicenter prospective cohort study, including 5215 patients with AF from the START (Survey on Anticoagulated Patients Register) registry, 3877 (74.3%) and 1338 (25.7%) on vitamin K or non-vitamin K antagonist oral anticoagulants, respectively. Thrombocytopenia was defined by a platelet count <150×109/L. Determinants of thrombocytopenia were investigated, and all-cause mortality was the primary survival end point of the study. Thrombocytopenia was present in 592 patients (11.4%). At multivariable logistic regression analysis, chronic kidney disease (odds ratio [OR], 1.257; P=0.030), active cancer (OR, 2.065; P=0.001), liver cirrhosis (OR, 7.635; P<0.001), and the use of diuretics (OR, 1.234; P=0.046) were positively associated with thrombocytopenia, whereas female sex (OR, 0.387; P<0.001) and the use of calcium channel blockers (OR, 0.787; P=0.032) were negatively associated. During a median follow-up of 19.2 months (9942 patient-years), 391 deaths occurred (rate, 3.93%/year). Mortality rate increased from 3.8%/year to 9.9%/year in patients with normal platelet count and in those with moderate-severe thrombocytopenia, respectively (log-rank test, P=0.009). The association between moderate-severe thrombocytopenia and mortality persisted after adjustment for CHA2DS2 VASc score (hazard ratio, 2.431; 95% CI, 1.254-4.713; P=0.009), but not in the fully adjusted multivariable Cox regression analysis model. Conclusions Thrombocytopenia is common in patients with AF. Despite an increased incidence of mortality, thrombocytopenia was not associated with mortality at multivariable analysis. Thrombocytopenia may reflect the presence of comorbidities associated with poor survival in AF.

Project description:BackgroundAlthough anticoagulants are indicated for many elderly patients with non-valvular atrial fibrillation (NVAF), some patients do not receive anticoagulant therapy, whose characteristics and outcomes are diverse.Methods and resultsIn this sub-analysis of the All Nippon AF In the Elderly (ANAFIE) Registry, the phenotypes of patients who were not receiving anticoagulants at baseline were evaluated by cluster analysis using Ward's linkage hierarchical algorithm. Of 32,275 enrolled patients, 2445 (7.6%) were not receiving anticoagulants. Two clusters were identified: (1) elderly paroxysmal AF (PAF) patients with a high proportion of catheter ablation history (57%) and (2) very elderly patients with a high prevalence of previous major bleeding (43%). Respective mean ages were 80.9 and 84.2 years, mean CHA2DS2-VASc scores were 3.8 and 4.9, PAF prevalences were 100.0% and 31.4%, proportions of patients with catheter ablation history were 21.0% and 7.9%, and proportions of patients with a history of major bleeding were 4.0% and 10.8%. Annual incidence rates were 2.72% and 8.81% for all-cause death, 1.66% and 5.85% for major adverse cardiovascular or neurological events, 1.08% and 3.30% for stroke or systemic embolism, and 0.69% and 1.19% for major bleeding, respectively.ConclusionsIn this cohort of elderly NVAF patients from the ANAFIE Registry who were not receiving anticoagulants, over half had PAF with a high proportion of catheter ablation history and a low incidence of adverse outcomes; for them, non-prescription of anticoagulants may be partially understandable, but they should be carefully monitored regarding AF burden or atrial cardiomyopathy and be adequately anticoagulated when adverse findings are detected. The remaining were very elderly patients with a high prevalence of previous major bleeding and a high incidence of adverse outcomes; for them, non-prescription of anticoagulants is inappropriate because of the high thromboembolic risk.Trial registrationRegistration: http://www.umin.ac.jp/; Unique identifier: UMIN000024006.

Project description:ImportanceAtrial fibrillation (AF) is usually classified on the basis of the disease subtype. However, this characterization does not capture the full heterogeneity of AF, and a data-driven cluster analysis reveals different possible classifications of patients.ObjectiveTo characterize patients with AF based on a cluster analysis and to evaluate the association between these phenotypes, treatment, and clinical outcomes.Design, setting, and participantsThis cluster analysis used data from an observational cohort that included 9749 patients with AF who had been admitted to 174 US sites participating in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry. Data analysis was completed from January 2017 to October 2017.ExposurePatients with diagnosed AF who were included in the registry.Main outcomes and measuresComposite of major adverse cardiovascular or neurological events and major bleeding, as defined by the International Society of Thrombosis and Hemostasis criteria.ResultsOf 9749 total patients, 4150 (42.6%) were female; 8719 (89.4%) were white and 477 (4.9%) were African American. A cluster analysis was performed using 60 baseline clinical characteristics, and it classified patients with AF into 4 statistically driven clusters: (1) those with considerably lower rates of risk factors and comorbidities than all other clusters (n = 4673); (2) those with AF at younger ages and/or with comorbid behavioral disorders (n = 963); (3) those with AF who had similarities to patients with tachycardia-brachycardia and had device implantation owing to sinus node dysfunction (n = 1651); and (4) those with AF and prior coronary artery disease, myocardial infarction, and/or atherosclerotic comorbidities (n = 2462). Conventional classifications, such as AF subtype and left atrial size, did not drive cluster formation. Compared with the low comorbidity AF cluster, adjusted risks of major adverse cardiovascular or neurological events were significantly higher in the other 3 clusters (behavioral comorbidity cluster: hazard ratio [HR], 1.49; 95% CI, 1.10-2.00; device implantation cluster: HR, 1.39; 95% CI, 1.15-1.68; and atherosclerotic comorbidity cluster: HR, 1.59; 95% CI, 1.31-1.92). For major bleeding, adjusted risks were higher in the behavioral disorder comorbidity cluster (HR, 1.35; 95% CI, 1.05-1.73), those with device implantation (HR, 1.24; 95% CI, 1.05-1.47), and those with atherosclerotic comorbidities (HR, 1.13; 95% CI, 0.96-1.33) compared with the low comorbidity cluster. The same clusters were identified in an external validation in the ORBIT AF II registry.Conclusions and relevanceCluster analysis identified 4 clinically relevant phenotypes of AF that each have distinct associations with clinical outcomes, underscoring the heterogeneity of AF and importance of comorbidities and substrates.

Project description:Whereas insurance status has been previously associated with care patterns, little is currently known about the association between Medicaid insurance and the clinical characteristics, treatment, or outcomes of patients with atrial fibrillation (AF).We used data from adults with AF enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF), a national outpatient registry conducted at 176 community, multispecialty sites. The primary outcome of interest was the proportion of patients prescribed any oral anticoagulation (OAC; warfarin or novel oral anticoagulants [NOAC]). Secondary outcomes of interest included the proportion of patients prescribed NOACs (dabigatran or rivaroxaban); time in therapeutic range (TTR) for warfarin users, all-cause mortality, stroke/systemic embolism, and major bleed. Of 10 133 patients, N=470 (4.6%) had Medicaid insurance. Medicaid patients were similarly likely to receive OAC at baseline (72.8% vs 76.3%; unadjusted P=0.079), but less likely to receive NOAC at baseline or follow-up (12.1% vs 16.3%; unadjusted P=0.019). After risk adjustment, Medicaid status was associated with lower use of OAC at baseline among patients with high stroke risk (odds ratio [OR]=0.68; 95% CI=0.49, 0.94), but was not associated with OAC use overall (OR=0.82; 95% CI=0.61, 1.09). Among warfarin users, median TTR was lower among Medicaid patients (60% vs 68%; P<0.0001; adjusted TTR difference, -2.9; 95% CI=-5.7, -0.2; P=0.04). Use of an NOAC over 2 years of follow-up was not statistically different by insurance. Compared with non-Medicaid patients, Medicaid patients had higher unadjusted rates of mortality, stroke/systemic embolism, and major bleeding; however, these differences were attenuated following adjustment for clinical characteristics.In a contemporary AF cohort, use of OAC overall and use of NOACs were not significantly lower among Medicaid patients relative to others. However, among warfarin users, Medicaid patients spent less time in therapeutic range compared with those with other forms of insurance.

Dataset Information

Clinical Phenotypes of Atrial Fibrillation and Mortality Risk-A Cluster Analysis from the Nationwide Italian START Registry.

Publications

Clinical Phenotypes of Atrial Fibrillation and Mortality Risk-A Cluster Analysis from the Nationwide Italian START Registry.

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