Roger, Véronique L.

Background: The focus of most existing phenotyping algorithms based on electronic health record (EHR) data has been to accurately identify cases and non-cases of specific diseases. However, a more challenging task is to accurately identify disease incidence, as identifying the first occurrence of disease is more important for efficient and valid clinical and epidemiological research. Moreover, stroke is a challenging phenotype due to diagnosis difficulty and common miscoding. This task generally requires utilization of multiple types of EHR data (e.g., diagnoses and procedure codes, unstructured clinical notes) and a more robust algorithm integrating both natural language processing and machine learning. In this study, we developed and validated an EHR-based classifier to accurately identify stroke incidence among a cohort of atrial fibrillation (AF) patients Methods: We developed a stroke phenotyping algorithm using International Classification of Diseases, Ninth Revision (ICD-9) codes, Current Procedural Terminology (CPT) codes, and expert-provided keywords as model features. Structured data was extracted from Rochester Epidemiology Project (REP) database. Natural Language Processing (NLP) was used to extract and validate keyword occurrence in clinical notes. A window of ±30 days was considered when including/excluding keywords/codes into the input vector. Frequencies of keywords/codes were used as input feature sets for model training. Multiple competing models were trained using various combinations of feature sets and two machine learning algorithms: logistic regression and random forest. Training data were provided by two nurse abstractors and included validated stroke incidences from a previously established atrial fibrillation cohort. Precision, recall, and F-score of the algorithm were calculated to assess and compare model performances. Results: Among 4,914 patients with atrial fibrillation, 1,773 patients were screened. 3,141 patients had no stroke-related codes or keywords and were presumed to be free of stroke during follow-up. Among the screened patients, 740 had validated strokes and 1,033 did not have a stroke based on review of the EHR by trained nurse abstractors. The best performing stroke incidence phenotyping classifier utilized Keywords+ICD-9+CPT features using a random forest classifier, achieving a precision of 0.942, recall of 0.943, and F-score of 0.943. Conclusion: In conclusion, we developed and validated a stroke algorithm that performed well for identifying stroke incidence in an enriched population (AF cohort), which extends beyond the typical binary case/non-case stroke identification problem. Future work will involve testing the generalizability of this algorithm in a general population.

Background: Type 2 myocardial infarction (T2MI) occurs because of an acute imbalance in myocardial oxygen supply and demand in the absence of atherothrombosis. Despite being frequently encountered in clinical practice, the population-based incidence and trends remain unknown, and the long-term outcomes are incompletely characterized. Methods: We prospectively recruited residents of Olmsted County, Minnesota, who experienced an event associated with a cardiac troponin T >99th percentile of a normal reference population (≥0.01 ng/mL) between January 1, 2003, and December 31, 2012. Events were retrospectively classified into type 1 myocardial infarction (T1MI, atherothombotic event), T2MI, or myocardial injury (troponin rise not meeting criteria for myocardial infarction [MI]) using the universal definition. Outcomes were long-term all-cause and cardiovascular mortality and recurrent MI. T2MI was further subclassified by the inciting event for supply/demand mismatch. Results: A total of 5460 patients had at least one cardiac troponin T ≥0.01 ng/mL; 1365 of these patients were classified as index T1MI (age, 68.5±14.8 years; 63% male) and 1054 were classified as T2MI (age, 73.7±15.8 years; 46% male). The annual incidence of T1MI decreased markedly from 202 to 84 per 100 000 persons between 2003 and 2012 ( P <0.001), whereas the incidence of T2MI declined from 130 to 78 per 100 000 persons ( P =0.02). In comparison with patients with T1MI, patients with T2MI had higher long-term all-cause mortality after adjustment for age and sex, driven by early and noncardiovascular death. Rates of cardiovascular death were similar after either type of MI (hazard ratio, 0.8 [95% CI, 0.7–1.0], P =0.11). Subclassification of T2MI by cause demonstrated a more favorable prognosis when the principal provoking mechanism was arrhythmia, in comparison with postoperative status, hypotension, anemia, and hypoxia. After index T2MI, the most common MI during follow-up was a recurrent T2MI, whereas the occurrence of a new T1MI was relatively rare (estimated rates at 5 years, 9.7% and 1.7%). Conclusions: There has been an evolution in the type of MI occurring in the community over a decade, with the incidence of T2MI now being similar to T1MI. Mortality after T2MI is higher and driven by early and noncardiovascular death. The provoking mechanism of supply/demand mismatch affects long-term survival. These findings underscore the healthcare burden of T2MI and provide benchmarks for clinical trial design.

Abstract Aims While data from randomized trials suggest a declining incidence of sudden cardiac death (SCD) among heart failure patients, the extent to which such a trend is present among patients with cardiac resynchronization therapy (CRT) has not been evaluated. We therefore assessed changes in SCD incidence, and associated factors, in CRT recipients over the last 20 years. Methods and results Literature search from inception to 30 April 2018 for observational and randomized studies involving CRT patients, with or without defibrillator, providing specific cause-of-death data. Sudden cardiac death was the primary endpoint. For each study, rate of SCD per 1000 patient-years of follow-up was calculated. Trend line graphs were subsequently constructed to assess change in SCD rates over time, which were further analysed by device type, patient characteristics, and medical therapy. Fifty-three studies, comprising 22 351 patients with 60 879 patient-years of follow-up and a total of 585 SCD, were included. There was a gradual decrease in SCD rates since the early 2000s in both randomized and observational studies, with rates falling more than four-fold. The rate of decline in SCD was steeper than that of all-cause mortality, and accordingly, the proportion of deaths which were due to SCD declined over the years. The magnitude of absolute decline in SCD was more prominent among CRT-pacemaker (CRT-P) patients compared to those receiving CRT-defibrillator (CRT-D), with the difference in SCD rates between CRT-P and CRT-D decreasing considerably over time. There was a progressive increase in age, use of beta-blockers, and left ventricular ejection fraction, and conversely, a decrease in QRS duration and antiarrhythmic drug use. Conclusion Sudden cardiac death rates have progressively declined in the CRT heart failure population over time, with the difference between CRT-D vs. CRT-P recipients narrowing considerably.

Abstract Abstract 2656 Background Treatment of non-Hodgkin lymphoma (NHL) can lead to development of cardiovascular disease (CVD). We sought to describe the cumulative incidence of CVD in adult NHL survivors diagnosed in the recent treatment era (since 2002) and identify clinical and treatment predictors for its development. Methods All patients were from the Mayo component of the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE). The MER offers enrollment to all consecutive patients with newly diagnosed NHL who are US residents and age >18 years. Clinical data from the time of diagnosis and treatment data are abstracted from medical records using a standard protocol. Patients are prospectively contacted via telephone or in person per protocol every 6 months for the first 3 years from diagnosis and yearly afterwards to assess disease status and development of comorbid conditions. CVD events, including heart failure (HF), myocardial infarction (MI), arrhythmia, pericarditis, and valvular heart disease, occurring after diagnosis were identified during follow-up and validated against medical records. HF was validated with the Cardiovascular Health Study Criteria and/or the Framingham Criteria. MI was validated using case definition standards of coronary heart disease, while arrhythmia, pericarditis, and valvular heart disease were validated using clinical definitions. The prevalence of CVD and associations between CVD and clinical characteristics (sex, age) and treatment (radiation, anthracyclines) were performed using Cox models with a competing risk approach. Results 1164 patients with NHL were enrolled into the MER at Mayo Clinic between 9/1/2002–2/28/2008. 646 were male (56%) and median age at diagnosis was 62 years (range 20–93). Median follow-up of all cases was 59 months (range 1–105). 131 patients reported CVD prior to the diagnosis of NHL and were excluded from analyses. An additional 76 patients did not have follow-up and were excluded. Of the 957 remaining patients, 75 (7.8%) self-reported a new diagnosis of CVD. Of these, 71 cases had available medical records. 57 of the 71 reviewed cases (80%) were validated (18 HF, 9 MI, 21 arrhythmia, 2 pericarditis, and 10 valvular heart disease). Cumulative incidence of CVD at 1, 3, 5, and 7 years was 1.3%, 3.7%, 5.2%, and 7.4%, respectively. Median time from NHL diagnosis to CVD was 26.5 months (range 1–84). Older age was associated with increased risk of overall CVD (p-value<0.001). Gender (p=0.59), radiation therapy (p=0.61), and anthracycline treatment (p=0.25) were not associated with the incidence of overall CVD. Among types of CVD, anthracycline use was associated with development of HF (HR=5.30; p-value=0.008) and arrhythmia (HR=2.68; p-value=0.04). Radiation was associated with development of arrhythmia (HR=2.73; p-value=0.03), while older age was associated with development of HF (HR=1.36 per 5 year increment; p-value=0.003) and arrhythmia (HR=1.25 per 5 year increment; p-value=0.02). Conclusions The risk of CVD in patients with NHL is approximately 1% per year after the initial diagnosis of lymphoma. The most commonly occurring CVDs in this cohort of NHL survivors were arrhythmia and HF. Treatment with anthracyclines and radiation are associated with increased risk of developing some types of CVD. 80% of self-reported CVD events in NHL survivors were validated using epidemiologic criteria. Future studies will include building models incorporating comorbid health conditions and lifestyle factors to determine risk of CVD as well as the impact of CVD on quality of life. Disclosures: No relevant conflicts of interest to declare.

AbstractIntroductionMyocardial infarction (MI) is associated with an increase in subsequent heart failure (HF), recurrent ischemic events, sudden cardiac arrest, and ventricular arrhythmias (SCA‐VA). The primary objective of the study to determine the role of intercurrent HF and ischemic events on the development of SCA‐VA following first type I MI.Methods and resultsA retrospective cohort study of patients experiencing first type 1 MI in Olmsted County, Minnesota (2002‐2012) was conducted by identifying patients using the medical records linkage system (Rochester epidemiology project). Patients aged ≥18 years were followed from the time of MI till death or 31 July, 2017. Intercurrent HF and ischemic events were the primary exposures following MI and their association with outcome SCA‐VA was assessed. Eight hundred and sixty‐seven patients (mean age was 63 ± 14.5 years; 69% male; 49.8% ST‐elevation myocardial infarction) who had their first type I MI during the study period were included. Majority of acute MI patients were revascularized using percutaneous coronary intervention and bypass surgery (628 [72.43%] and 87 [10.03%] respectively). During a mean follow‐up of 7.69 ± 4.17 years, HF, recurrent ischemic events and SCA‐VA occurred in 155 (17.9%), 245 (28.3%), and 40 (4.61%) patients respectively. Low ejection fraction (adjusted hazard ratio [HR] 0.95; 95% confidence interval [CI], 0.93‐0.98; P < .001), intercurrent HF (adjusted HR 3.11; 95% CI, 1.39‐6.95; P = .006) and recurrent ischemic events (adjusted HR 3.47; 95% CI, 1.68‐7.18; P < .001) were associated with subsequent SCA‐VA.ConclusionSCA‐VA occurred in a small proportion of patients after MI and is associated with intercurrent HF and recurrent ischemic events.

Background Current treatment guidelines strongly recommend statin therapy for secondary prevention. However, it remains unclear whether patients’ perceptions of cardiovascular risk, beliefs on cholesterol, or the intensity of prescribed statin therapy differs for patients with coronary artery disease ( CAD ) versus cerebrovascular disease (Ce VD ) versus both CAD and Ce VD ( CAD &Ce VD ). Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry collected data on statin use, intensity, and core laboratory low‐density lipoprotein cholesterol levels for 3232 secondary prevention patients treated at 133 US clinics. Among individuals with Ce VD only (n=403), CAD only (n=2202), and Ce VD & CAD (n=627), no significant differences were observed in patient‐perceived cardiovascular disease risk, beliefs on cholesterol lowering, or perceived effectiveness and safety of statin therapy. However, patients with Ce VD only were less likely to receive any statin therapy (76.2% versus 86.2%; adjusted odds ratio 0.64, 95% CI 0.45–0.91), or guideline‐recommended statin intensity (34.6% versus 50.4%; adjusted odds ratio 0.60, 95% CI 0.45–0.81) than those with CAD only. Individuals with Ce VD only were also less likely to achieve low‐density lipoprotein cholesterol <100 mg/ dL (59.2% versus 69.7%; adjusted odds ratio 0.79, 95% CI 0.64–0.99) than individuals with CAD alone. There were no significant differences in the use of any statin therapy or guideline‐recommended statin intensity between individuals with CAD &Ce VD and those with CAD only. Conclusions Despite lack of significant differences in patient‐perceived cardiovascular risk or statin beliefs, patients with Ce VD were significantly less likely to receive higher intensity statin or achieve low‐density lipoprotein cholesterol <100 mg/ dL than those with CAD only.

Objective: To understand the interaction of multimorbidity and functional limitations in determining health-care utilization and survival in older adults. Methods: Olmsted County, Minnesota, residents aged 60–89 years in 2005 were categorized into four cohorts based on the presence or absence of multimorbidity (≥3 chronic conditions from a list of 18) and functional limitations (≥1 limitation in an activity of daily living from a list of 9), and were followed through December 31, 2016. Andersen–Gill and Cox regression estimated hazard ratios (HRs) for emergency department (ED) visits, hospitalizations, and death using persons with neither multimorbidity nor functional limitations as the reference (interaction analyses). Results: Among 13,145 persons, 34% had neither multimorbidity nor functional limitations, 44% had multimorbidity only, 4% had functional limitations only, and 18% had both. Over a median follow-up of 11 years, 5906 ED visits, 2654 hospitalizations, and 4559 deaths occurred. Synergistic interactions on an additive scale of multimorbidity and functional limitations were observed for all outcomes; however, the magnitude of the interactions decreased with advancing age. The HR (95% confidence interval) for death among persons with both multimorbidity and functional limitations was 5.34 (4.40–6.47) at age 60–69, 4.16 (3.59–4.83) at age 70–79, and 2.86 (2.45–3.35) at age 80–89 years. Conclusion: The risk of ED visits, hospitalizations, and death among persons with both multimorbidity and functional limitations is greater than additive. The magnitude of the interaction was strongest for the youngest age group, highlighting the importance of interventions to prevent and effectively manage multimorbidity and functional limitations early in life.

Background: Female patients have historically received less aggressive lipid management than male patients. Contemporary care patterns and the potential causes for these differences are unknown. Methods and Results: Examining the Patient and Provider Assessment of Lipid Management Registry—a nationwide registry of outpatients with or at risk for atherosclerotic cardiovascular disease—we compared the use of statin therapy, guideline-recommended statin dosing, and reasons for undertreatment. We specifically analyzed sex differences in statin treatment and guideline-recommended statin dosing using multivariable logistic regression. Among 5693 participants (43% women) eligible for 2013 American College of Cardiology/American Heart Association Cholesterol Guideline–recommended statin treatment, women were less likely than men to be prescribed any statin therapy (67.0% versus 78.4%; P <0.001) or to receive a statin at the guideline-recommended intensity (36.7% versus 45.2%; P <0.001). Women were more likely to report having previously never been offered statin therapy (18.6% versus 13.5%; P <0.001), declined statin therapy (3.6% versus 2.0%; P <0.001), or discontinued their statin (10.9% versus 6.1%; P <0.001). Women were also less likely than men to believe statins were safe (47.9% versus 55.2%; P <0.001) or effective (68.0% versus 73.2%; P <0.001) and more likely to report discontinuing their statin because of a side effect (7.9% versus 3.6%; P <0.001). Sex differences in both overall and guideline-recommended intensity statin use persisted after adjustment for demographics, socioeconomic factors, clinical characteristics, patient beliefs, and provider characteristics (adjusted odds ratio, 0.70; 95% CI, 0.61–0.81; P <0.001; and odds ratio, 0.82; 95% CI, 0.73–0.92; P <0.01, respectively). Sex differences were consistent across primary and secondary prevention indications for statin treatment. Conclusions: Women eligible for statin therapy were less likely than men to be treated with any statin or guideline-recommended statin intensity. A combination of women being offered statin therapy less frequently, while declining and discontinuing treatment more frequently, accounted for these sex differences in statin use.