In:
PLOS Medicine, Public Library of Science (PLoS), Vol. 18, No. 8 ( 2021-8-2), p. e1003736-
Abstract:
Cardiovascular disease is a leading cause of death in general population and the second leading cause of mortality and morbidity in cancer survivors after recurrent malignancy in the United States. The growing awareness of cancer therapy–related cardiac dysfunction (CTRCD) has led to an emerging field of cardio-oncology; yet, there is limited knowledge on how to predict which patients will experience adverse cardiac outcomes. We aimed to perform unbiased cardiac risk stratification for cancer patients using our large-scale, institutional electronic medical records. Methods and findings We built a large longitudinal (up to 22 years’ follow-up from March 1997 to January 2019) cardio-oncology cohort having 4,632 cancer patients in Cleveland Clinic with 5 diagnosed cardiac outcomes: atrial fibrillation, coronary artery disease, heart failure, myocardial infarction, and stroke. The entire population includes 84% white Americans and 11% black Americans, and 59% females versus 41% males, with median age of 63 (interquartile range [IQR]: 54 to 71) years old. We utilized a topology-based K-means clustering approach for unbiased patient–patient network analyses of data from general demographics, echocardiogram (over 25,000), lab testing, and cardiac factors (cardiac). We performed hazard ratio (HR) and Kaplan–Meier analyses to identify clinically actionable variables. All confounding factors were adjusted by Cox regression models. We performed random-split and time-split training-test validation for our model. We identified 4 clinically relevant subgroups that are significantly correlated with incidence of cardiac outcomes and mortality. Among the 4 subgroups, subgroup I ( n = 625) has the highest risk of de novo CTRCD (28%) with an HR of 3.05 (95% confidence interval (CI) 2.51 to 3.72). Patients in subgroup IV ( n = 1,250) had the worst survival probability (HR 4.32, 95% CI 3.82 to 4.88). From longitudinal patient–patient network analyses, the patients in subgroup I had a higher percentage of de novo CTRCD and a worse mortality within 5 years after the initiation of cancer therapies compared to long-time exposure (6 to 20 years). Using clinical variable network analyses, we identified that serum levels of NT-proB-type Natriuretic Peptide (NT-proBNP) and Troponin T are significantly correlated with patient’s mortality (NT-proBNP 〉 900 pg/mL versus NT-proBNP = 0 to 125 pg/mL, HR = 2.95, 95% CI 2.28 to 3.82, p 〈 0.001; Troponin T 〉 0.05 μg/L versus Troponin T ≤ 0.01 μg/L, HR = 2.08, 95% CI 1.83 to 2.34, p 〈 0.001). Study limitations include lack of independent cardio-oncology cohorts from different healthcare systems to evaluate the generalizability of the models. Meanwhile, the confounding factors, such as multiple medication usages, may influence the findings. Conclusions In this study, we demonstrated that the patient–patient network clustering methodology is clinically intuitive, and it allows more rapid identification of cancer survivors that are at greater risk of cardiac dysfunction. We believed that this study holds great promise for identifying novel cardiac risk subgroups and clinically actionable variables for the development of precision cardio-oncology.
Type of Medium:
Online Resource
ISSN:
1549-1676
DOI:
10.1371/journal.pmed.1003736
DOI:
10.1371/journal.pmed.1003736.g001
DOI:
10.1371/journal.pmed.1003736.g002
DOI:
10.1371/journal.pmed.1003736.g003
DOI:
10.1371/journal.pmed.1003736.g004
DOI:
10.1371/journal.pmed.1003736.g005
DOI:
10.1371/journal.pmed.1003736.g006
DOI:
10.1371/journal.pmed.1003736.t001
DOI:
10.1371/journal.pmed.1003736.s001
DOI:
10.1371/journal.pmed.1003736.s002
DOI:
10.1371/journal.pmed.1003736.s003
DOI:
10.1371/journal.pmed.1003736.s004
DOI:
10.1371/journal.pmed.1003736.s005
DOI:
10.1371/journal.pmed.1003736.s006
DOI:
10.1371/journal.pmed.1003736.s007
DOI:
10.1371/journal.pmed.1003736.s008
DOI:
10.1371/journal.pmed.1003736.s009
DOI:
10.1371/journal.pmed.1003736.s010
DOI:
10.1371/journal.pmed.1003736.s011
DOI:
10.1371/journal.pmed.1003736.s012
DOI:
10.1371/journal.pmed.1003736.s013
DOI:
10.1371/journal.pmed.1003736.s014
DOI:
10.1371/journal.pmed.1003736.s015
DOI:
10.1371/journal.pmed.1003736.s016
DOI:
10.1371/journal.pmed.1003736.s017
DOI:
10.1371/journal.pmed.1003736.s018
DOI:
10.1371/journal.pmed.1003736.s019
DOI:
10.1371/journal.pmed.1003736.s020
DOI:
10.1371/journal.pmed.1003736.s021
DOI:
10.1371/journal.pmed.1003736.s022
DOI:
10.1371/journal.pmed.1003736.s023
DOI:
10.1371/journal.pmed.1003736.s024
DOI:
10.1371/journal.pmed.1003736.s025
DOI:
10.1371/journal.pmed.1003736.s026
DOI:
10.1371/journal.pmed.1003736.s027
DOI:
10.1371/journal.pmed.1003736.s028
DOI:
10.1371/journal.pmed.1003736.s029
DOI:
10.1371/journal.pmed.1003736.s030
DOI:
10.1371/journal.pmed.1003736.s031
DOI:
10.1371/journal.pmed.1003736.s032
DOI:
10.1371/journal.pmed.1003736.r001
DOI:
10.1371/journal.pmed.1003736.r002
DOI:
10.1371/journal.pmed.1003736.r003
DOI:
10.1371/journal.pmed.1003736.r004
DOI:
10.1371/journal.pmed.1003736.r005
DOI:
10.1371/journal.pmed.1003736.r006
DOI:
10.1371/journal.pmed.1003736.r007
DOI:
10.1371/journal.pmed.1003736.r008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2164823-2
Permalink