Gender and Age Differences in the Evaluation and Clinical Outcomes of Patients with Palpitations.

BACKGROUND: Palpitations represent a common clinic complaint. OBJECTIVE: To explore gender and age differences in the evaluation and outcomes of patients with palpitations in outpatient settings. DESIGN/PARTICIPANTS: This is a retrospective observational study of 58,543 patients with no known structural cardiac disease or arrythmias presenting to primary care and cardiology clinics in an integrated health system in California with palpitations between January 2017 and December 2021. The primary and secondary endpoints were hospitalization for arrhythmia and all-cause mortality at 1 year. Multivariable logistic regression models evaluated the association between gender, age, and outcomes. RESULTS: Men and women were equally as likely to be started on beta-blockers (adjusted OR 0.96, 95% CI 0.90-1.02) and evaluated with electrocardiograms (adjusted OR 0.95, 95% CI 0.90-1.01) and cardiac monitors (adjusted OR 1.04, 95% CI 0.99-1.08). Patients who completed Holter or event monitors had a lower rate of hospitalization for cardiovascular disease at 1 year than those without (2.3% vs. 2.7%, p = 0.001). At 1 year, women had a lower risk of all-cause mortality (adjusted OR 0.47, 95% CI 0.35-0.64) and hospitalization for atrial fibrillation (adjusted OR 0.47, 95% CI 0.30-0.72) and arrhythmias (adjusted OR 0.73, 95% CI 0.58-0.91) compared to men. Among older women and men (≥ 80 years), there was no significant difference in 1-year all-cause mortality (adjusted OR 0.57, 95% CI 0.29-1.12), hospitalization for atrial fibrillation (adjusted OR 0.58, 95% CI 0.17-1.97), or arrhythmias (adjusted OR 1.15, 95% CI 0.12-11.07). CONCLUSIONS: There were no gender differences in referrals for cardiac monitoring or prescriptions for beta-blockers. Women had a better prognosis with a lower risk of hospitalization for arrhythmias and death at 1 year compared to men. However, 1-year risks for mortality and hospitalization for arrythmias among older women were comparable to those of older men, underscoring the importance of considering age and gender in managing patients with palpitations.

Association Between Coronary Artery Disease Testing in Patients with New-Onset Heart Failure and Heart Failure Readmission and Mortality.

BACKGROUND: In patients with new-onset heart failure (HF), coronary artery disease (CAD) testing remains underutilized. Whether widespread CAD testing in patients with new-onset HF leads to improved outcomes remains to be determined. OBJECTIVE: We sought to examine whether CAD testing, and its timing, among patients hospitalized with new-onset HF with reduced ejection fraction (HFrEF), is associated with improved outcomes. DESIGN: Retrospective cohort study. PARTICIPANTS: Adult (≥ 18 years) non-pregnant patients with new-onset HFrEF hospitalized within one of 15 Kaiser Permanente Southern California medical centers between 2016 and 2021. Key exclusion criteria included history of heart transplant, hospice, and a do-not-resuscitate order. MAIN MEASURES: Primary outcome was a composite of HF readmission or all-cause mortality through end of follow-up on 12/31/2022. KEY RESULTS: Among 2729 patients hospitalized with new-onset HFrEF, 1487 (54.5%) received CAD testing. The median age was 66 (56-76) years old, 1722 (63.1%) were male, and 1074 (39.4%) were White. After a median of 1.8 (0.6-3.4) years, the testing group had a reduced risk of HF readmission or all-cause mortality (aHR [95%CI], 0.71 [0.63-0.79]). These results were consistent across subgroups by history of atrial fibrillation, diabetes, renal disease, myocardial infarction, and elevated troponin during hospitalization. In a secondary analysis where CAD testing was further divided to early (received testing before discharge) and late testing (up to 90 days after discharge), there was no difference in late vs early testing (0.97 [0.81-1.16]). CONCLUSIONS: In a contemporary and diverse cohort of patients hospitalized with new-onset HFrEF, CAD testing within 90 days of hospitalization was associated with a lower risk of HF readmission or all-cause mortality. Testing within 90 days after discharge was not associated with worse outcomes.

Management of Adults with Newly Diagnosed Atrial Fibrillation with and without CKD.

BACKGROUND: Atrial fibrillation (AF) is highly prevalent in CKD and is associated with worse cardiovascular and kidney outcomes. Limited data exist on use of AF pharmacotherapies and AF-related procedures by CKD status. We examined a large "real-world" contemporary population with incident AF to study the association of CKD with management of AF. METHODS: We identified patients with newly diagnosed AF between 2010 and 2017 from two large, integrated health care delivery systems. eGFR (≥60, 45-59, 30-44, 15-29, <15 ml/min per 1.73 m2) was calculated from a minimum of two ambulatory serum creatinine measures separated by ≥90 days. AF medications and procedures were identified from electronic health records. We performed multivariable Fine-Gray subdistribution hazards regression to test the association of CKD severity with receipt of targeted AF therapies. RESULTS: Among 115,564 patients with incident AF, 34% had baseline CKD. In multivariable models, compared with those with eGFR >60 ml/min per 1.73 m2, patients with eGFR 30-44 (adjusted hazard ratio [aHR] 0.91; 95% CI, 0.99 to 0.93), 15-29 (aHR, 0.78; 95% CI, 0.75 to 0.82), and <15 ml/min per 1.73 m2 (aHR, 0.64; 95% CI, 0.58-0.70) had lower use of any AF therapy. Patients with eGFR 15-29 ml/min per 1.73 m2 had lower adjusted use of rate control agents (aHR, 0.61; 95% CI, 0.56 to 0.67), warfarin (aHR, 0.89; 95% CI, 0.84 to 0.94), and DOACs (aHR, 0.23; 95% CI, 0.19 to 0.27) compared with patients with eGFR >60 ml/min per 1.73 m2. These associations were even stronger for eGFR <15 ml/min per 1.73 m2. There was also a graded association between CKD severity and receipt of AF-related procedures (vs eGFR >60 ml/min per 1.73 m2): eGFR 30-44 ml/min per 1.73 (aHR, 0.78; 95% CI, 0.70 to 0.87), eGFR 15-29 ml/min per 1.73 m2 (aHR, 0.73; 95% CI, 0.61 to 0.88), and eGFR <15 ml/min per 1.73 m2 (aHR, 0.48; 95% CI, 0.31 to 0.74). CONCLUSIONS: In adults with newly diagnosed AF, CKD severity was associated with lower receipt of rate control agents, anticoagulation, and AF procedures. Additional data on efficacy and safety of AF therapies in CKD populations are needed to inform management strategies.

Effectiveness and Safety of Dabigatran in Atrial Fibrillation Patients with Severe Obesity: a Real-World Retrospective Cohort Study.

BACKGROUND: Direct oral anticoagulants such as dabigatran are the preferred anticoagulant in treating atrial fibrillation (AF) patients due to their effectiveness and safety. Whether this applies to severely obese patients needs to be determined. OBJECTIVE: To compare the effectiveness and safety of dabigatran with warfarin among AF patients with severe obesity. DESIGN: Retrospective cohort study. PARTICIPANTS: AF patients with a BMI >40kg/m2 or a weight >120kg receiving dabigatran or warfarin between 10/01/2010 and 12/31/2019 in a large integrated health system and followed through 08/01/2020. INTERVENTIONS: Not applicable. MAIN MEASURES: Primary effectiveness outcome was composite thromboembolism including transient ischemic attack, ischemic stroke, or systemic embolism. Primary safety outcome was composite bleeding including gastrointestinal bleeding, intracranial bleeding, or other bleeding. Secondary outcomes included the individual outcomes and all-cause mortality. Propensity score matching (PSM) was performed to create a 1:1 matched cohort and Cox proportional hazards model was used to estimate the hazard ratio (HR) of each outcome for dabigatran users compared to warfarin users. KEY RESULTS: A total of 6848 patients receiving either dabigatran or warfarin were identified. In a 1:1 matched cohort, dabigatran users had a HR of 0.71 (95% confidence interval (CI): 0.56-0.91) for composite thromboembolism, a HR of 1.24 (95%CI: 1.07-1.42) for composite bleeding, and a HR of 0.57 (95% CI: 0.45-0.71) for all-cause mortality when compared to warfarin users. CONCLUSIONS: Among AF patients with a BMI >40kg/m2 or a weight >120kg in a real-world clinical setting, dabigatran was effective in reducing the risk of thromboembolism and mortality but was associated with an increased risk of bleeding when compared to warfarin. Dabigatran may be a reasonable option for AF patients with severe obesity.

Does Hospital Admission/Observation for Chest Pain Improve Patient Outcomes after Emergency Department Evaluation for Suspected Acute Coronary Syndrome?

BACKGROUND: Chest pain is the top reason for hospitalization/observation in the USA, but it is unclear if this strategy improves patient outcomes. OBJECTIVE: The objective of this study was to compare 30-day outcomes for patients admitted versus discharged after a negative emergency department (ED) evaluation for suspected acute coronary syndrome. DESIGN: A retrospective, multi-site, cohort study of adult encounters with chest pain presenting to one of 13 Kaiser Permanente Southern California EDs between January 1, 2015, and December 1, 2017. Instrumental variable analysis was used to mitigate potential confounding by unobserved factors. PATIENTS: All adult patients presenting to an ED with chest pain, in whom an acute myocardial infarction was not diagnosed in the ED, were included. MAIN MEASURES: The primary outcome was 30-day acute myocardial infarction or all-cause mortality, and secondary outcomes included 30-day revascularization and major adverse cardiac events. KEY RESULTS: In total, 77,652 patient encounters were included in the study (n=11,026 admitted, 14.2%). Three hundred twenty-two (0.4%) had an acute myocardial infarction (n=193, 0.2%) or death (n=137, 0.2%) within 30 days of ED visit (1.5% hospitalized versus 0.2% discharged). Very few (0.3%) patients underwent coronary revascularization within 30 days (0.7% hospitalized versus 0.2% discharged). Instrumental variable analysis found no adjusted differences in 30-day patient outcomes between the hospitalized cohort and those discharged (risk reduction 0.002, 95% CI -0.002 to 0.007). Similarly, there were no differences in coronary revascularization (risk reduction 0.003, 95% CI -0.002 to 0.007). CONCLUSION: Among ED patients with chest pain not diagnosed with an acute myocardial infarction, risk of major adverse cardiac events is quite low, and there does not appear to be any benefit in 30-day outcomes for those admitted or observed in the hospital compared to those discharged with outpatient follow-up.

Automated abstraction of myocardial perfusion imaging reports using natural language processing.

BACKGROUND: Findings and interpretations of myocardial perfusion imaging (MPI) studies are documented in free-text MPI reports. MPI results are essential for research, but manual review is prohibitively time consuming. This study aimed to develop and validate an automated method to abstract MPI reports. METHODS: We developed a natural language processing (NLP) algorithm to abstract MPI reports. Randomly selected reports were double-blindly reviewed by two cardiologists to validate the NLP algorithm. Secondary analyses were performed to describe patient outcomes based on abstracted-MPI results on 16,957 MPI tests from adult patients evaluated for suspected ACS. RESULTS: The NLP algorithm achieved high sensitivity (96.7%) and specificity (98.9%) on the MPI categorical results and had a similar degree of agreement compared to the physician reviewers. Patients with abnormal MPI results had higher rates of 30-day acute myocardial infarction or death compared to patients with normal results. We identified issues related to the quality of the reports that not only affect communication with referring physicians but also challenges for automated abstraction. CONCLUSION: NLP is an accurate and efficient strategy to abstract results from the free-text MPI reports. Our findings will facilitate future research to understand the benefits of MPI studies but requires validation in other settings.

ß-Blocker Use and Risk of Mortality in Heart Failure Patients Initiating Maintenance Dialysis.

RATIONAL & OBJECTIVE: Beta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including with respect to their removal by hemodialysis. We sought to evaluate whether ß-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned to dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults patients with chronic kidney disease (aged≥18 years) and HF who initiated either hemodialysis or peritoneal dialysis during January 1, 2007, to June 30, 2016, within an integrated health system were included. EXPOSURES: Patients were considered treated with ß-blockers if they had a quantity of drug dispensed covering the dialysis transition date. OUTCOMES: All-cause mortality within 6 months and 1 year or hospitalization within 6 months after transition to maintenance dialysis. ANALYTICAL APPROACH: Inverse probability of treatment weights using propensity scores was used to balance covariates between treatment groups. Cox proportional hazard analysis and logistic regression were used to investigate the association between ß-blocker use and study outcomes. RESULTS: 3,503 patients were included in the study. There were 2,115 (60.4%) patients using ß-blockers at transition. Compared with nonusers, the HR for all-cause mortality within 6 months was 0.79 (95% CI, 0.65-0.94) among users of any ß-blocker and 0.68 (95% CI, 0.53-0.88) among users of metoprolol at transition. There were no observed differences in all-cause or cardiovascular-related hospitalization. LIMITATIONS: The observational nature of our study could not fully account for residual confounding. CONCLUSIONS: Beta-blockers were associated with a lower rate of mortality among incident hemodialysis patients with HF. Similar associations were not observed for hospitalizations within the first 6 months following transition to dialysis.

Association between mid-term worsening renal function and mortality after transcatheter aortic valve replacement in patients with chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD), acute kidney injury (AKI) and worsening renal function at 30 days after transcatheter aortic valve replacement (TAVR) portend poor outcomes. We sought to evaluate the association between worsening renal function at 3-6 months and mortality among patients with baseline renal dysfunction undergoing TAVR. METHODS: This is a retrospective study of patients with glomerular filtration rate (GFR) < 60 ml/min undergoing TAVR between June 2011 and March 2019 at the Regional Cardiac Catheterization Lab at Kaiser Permanente Los Angeles. Worsening renal function at 3-6 months post-TAVR was defined as: increase in serum creatinine >1.5 times compared to baseline, absolute increase of ≥0.3 mg/dl, or initiation of dialysis. RESULTS: Of 683 patients reviewed, 176 were included in the analysis (median age 84 [IQR 79-88] years, 56% female). Of these, 27 (15.3%) had worsening renal function. AKI post-TAVR (OR 2.9, 95% CI 1.1-7.4, p = .03) and transfusion of ≥4 units red blood cells (OR 8.4, 95% CI 1.2-59, p = .03) were independent predictors of worsening renal function. Worsening renal function increased risk for mortality (HR 2.2, 95% CI 1.17-4.27, p = .015) at a median follow-up of 691 days. Those with improved/stable function with baseline GFR < 60 ml/min had comparable mortality risk to those with baseline GFR ≥ 60 ml/min (18% vs. 16.5%; HR 1.1, 95% CI 0.72-1.75, p = .62). CONCLUSION: Among patients with baseline renal dysfunction, only 15% developed worsening renal function at 3-6 months after TAVR, which was associated with increased mortality. Predictors for worsening renal function include AKI and blood transfusions. Preventative measures peri-procedurally and continued monitoring post-discharge are warranted to improve outcomes.

The role of neighborhood disadvantage in predicting mortality in patients after transcatheter aortic valve replacement.

BACKGROUND: Neighborhoods have a powerful impact on health. Prior investigations into disparities associated with transcatheter aortic valve replacement (TAVR) have focused on race and access to the procedure. We sought to investigate the role of neighborhood disadvantage on mortality post-TAVR. METHODS: Patients who underwent TAVR at Kaiser Permanente Los Angeles Medical Center between June, 2011 and March, 2019 were evaluated. Neighborhood disadvantage was defined using the area deprivation index, an established and validated index that considers multiple socioeconomic metrics. Cutoffs used for disadvantage were national percentile ≥25% and state decile ≥6. Cox proportional hazards regression analysis was used to assess outcomes. RESULTS: A total of 668 patients (age 82.1 ± 7.5 years, 49% female) were included, of which 215 (32.2%) were from disadvantaged neighborhoods by state decile, and 167 (25%) by national percentile. At a median follow-up of 18.8 months (interquartile range 8.7-36.5 months), neighborhood disadvantage was independently associated with increased all-cause mortality (National percentile: hazard ratio [HR] 1.91, 95% confidence interval [CI] 1.35-2.69; state decile: HR 1.68, 95% CI 1.21-2.34). On propensity scored analysis, neighborhood disadvantaged remained independently associated with increased all-cause mortality (National percentile: IPTW HR 1.86, 95% CI 1.52-2.28, PSM HR 1.67, 95% CI 1.11-2.51; state decile: IPTW HR 1.55, 95% CI 1.26-1.91, PSM HR 2.0, 95% CI 1.33-2.99). CONCLUSION: Living in a disadvantaged neighborhood was independently associated with increased mortality post-TAVR on multivariate and propensity score matched analysis. Further investigations into the role of neighborhood disadvantage are needed to address disparities and improve outcomes post-TAVR.

Evaluating Sex Disparities in the Emergency Department Management of Patients With Suspected Acute Coronary Syndrome.

STUDY OBJECTIVE: We compare clinical management and outcomes of emergency department (ED) encounters by sex after implementation of a clinical care pathway in 15 community EDs that standardized recommendations based on patient risk, using the History, ECG, Age, Risk Factors, and Troponin (HEART) score. METHODS: This was a retrospective analysis of adult ED encounters evaluated for suspected acute coronary syndrome with a documented HEART score from May 20, 2016, to December 1, 2017. The primary outcomes were hospitalization or 30-day stress testing. Secondary outcomes included 30-day acute myocardial infarction or all-cause death (major adverse cardiac event). A generalized estimating equation regression model was used to compare the odds of hospitalization or stress testing by sex; we report HEART scores (0 to 10) stratified by sex and describing major adverse cardiac events. RESULTS: A total of 34,715 adult ED encounters met the inclusion criteria (56.0% women). A higher proportion of women were classified as low risk (60.5% versus 52.4%; odds ratio [OR] 1.39; 95% confidence interval [CI] 1.33 to 1.45). Women were hospitalized or received stress testing less frequently than men for low HEART scores (18.8% versus 22.8%; OR 0.79; 95% CI 0.73 to 0.84) and intermediate ones (46.7% versus 49.7%; OR 0.88; 95% CI 0.83 to 0.95), but similarly for high-risk ones (74.1% versus 74.4%; OR 0.99; 95% CI 0.77 to 1.28). Women had 18% lower odds of hospitalization or noninvasive cardiac testing (OR 0.82; 95% CI 0.78 to 0.86), even after adjusting for HEART score and comorbidities. Men had higher risks of major adverse cardiac events than women for all HEART score categories but the risk for men was significantly higher among low-risk HEART scores (0.4% versus 0.1%). CONCLUSION: Women with low-risk HEART scores are hospitalized or stress tested less than men, which is likely appropriate, and women have better outcomes than men. Use of the HEART score has the potential to reduce sex disparities in acute coronary syndrome care.

Temporal trends in heart failure mortality in an integrated healthcare delivery system, California, and the US, 2001-2017.

BACKGROUND: In recent years, decreases in mortality rates attributable to cardiovascular diseases have slowed but mortality attributable to heart failure (HF) has increased. METHODS: Between 2001-2017, trends in age-adjusted mortality with HF as an underlying cause for Kaiser Permanente Southern California (KPSC) members were derived through linkage with state death files and compared with trends among California residents and the US. Average annual percent change (AAPC) and 95% confidence intervals (CI) were calculated using Joinpoint regression. Analyses were repeated examining HF as a contributing cause of death. RESULTS: In KPSC, the age-adjusted HF mortality rates were comparable to California but lower than the US, increasing from 23.9 per 100,000 person-years (PY) in 2001 to 44.7 per 100,000 PY in 2017, representing an AAPC of 1.3% (95% CI 0.0%, 2.6%). HF mortality also increased in California from 33.9 to 46.5 per 100,000 PY (AAPC 1.5%, 95% CI 0.3%, 2.7%), while remaining unchanged in the US at 57.9 per 100,000 PY in 2001 and 2017 (AAPC 0.0%, 95% CI - 0.5%, 0.5%). Trends among KPSC members ≥ 65 years old were similar to the overall population, while trends among members 45-64 years old were flat between 2001-2017. Small changes in mortality with HF as a contributing cause were observed in KPSC members between 2001 and 2017, which differed from California and the US. CONCLUSION: Lower rates of HF mortality were observed in KPSC compared to the US. Given the aging of the US population and increasing prevalence of HF, it will be important to examine individual and care-related factors driving susceptibility to HF mortality.

Physician adjudication of angioedema diagnosis codes in a population of patients with heart failure prescribed angiotensin-converting enzyme inhibitor therapy.

PURPOSE: Our objective was to calculate the positive predictive value (PPV) of the ICD-9 diagnosis code for angioedema when physicians adjudicate the events by electronic health record review. Our secondary objective was to evaluate the inter-rater reliability of physician adjudication. METHODS: Patients from the Cardiovascular Research Network previously diagnosed with heart failure who were started on angiotensin-converting enzyme inhibitors (ACEI) during the study period (July 1, 2006 through September 30, 2015) were included. A team of two physicians per participating site adjudicated possible events using electronic health records for all patients coded for angioedema for a total of five sites. The PPV was calculated as the number of physician-adjudicated cases divided by all cases with the diagnosis code of angioedema (ICD-9-CM code 995.1) meeting the inclusion criteria. The inter-rater reliability of physician teams, or kappa statistic, was also calculated. RESULTS: There were 38 061 adults with heart failure initiating ACEI in the study (21 489 patient-years). Of 114 coded events that were adjudicated by physicians, 98 angioedema events were confirmed for a PPV of 86% (95% CI: 80%, 92%). The kappa statistic based on physician inter-rater reliability was 0.65 (95% CI: 0.47, 0.82). CONCLUSIONS: ICD-9 diagnosis code of 995.1 (angioneurotic edema, not elsewhere classified) is highly predictive of angioedema in adults with heart failure exposed to ACEI.

Risk of Acute Myocardial Infarction, Heart Failure, and Death in Migraine Patients Treated with Triptans.

OBJECTIVE: The goal of this study is to determine the strength of association between treatment with triptans and acute myocardial infarction, heart failure, and death. BACKGROUND: Case reports in the literature have raised concerns over an association between treatment of migraine headaches with triptans and cardiovascular events. This study aims to systematically evaluate this association in a contemporary population-based cohort. We hypothesized that triptan exposure is not associated with increased cardiovascular events. METHODS: A retrospective cohort study was conducted within an integrated healthcare delivery system in Southern California. From January 2009 to December 2018, 189,684 patients age ≥18 years had a diagnosis of migraine. In this group, 130,656 were exposed to triptans. Patients treated with triptans were matched 1:1 to those not exposed to triptans by using a propensity score. The primary outcome was acute myocardial infarction; secondary outcomes were heart failure, all-cause death, and combined acute myocardial infarction, heart failure, and death. RESULTS: The incidence rate of acute myocardial infarction was 0.67 per 1000 person-year in triptan-exposed vs 1.44 per 1000 person-year in not exposed patients. In propensity-matched analyses, the adjusted hazard ratio for triptan exposure was 0.95 (95% confidence interval [CI] 0.84-1.08) for acute myocardial infarction; 1.00 (95% CI 0.93-1.08) for all-cause death; 0.93 (95% CI 0.81-1.08) for heart failure; and 0.99 (95% CI 0.93-1.06) for a composite of acute myocardial infarction, heart failure, or death. Sensitivity analyses focusing on stratified subgroups based on age, gender, ethnicity, and several cardiac risk factors also revealed no significant association between triptan exposure and cardiovascular events. CONCLUSIONS: No association was found between exposure to triptans and an increased risk of cardiovascular events. These data provide reassurance regarding the cardiovascular safety of utilizing triptans for the medical management of migraine headaches.

Evaluation of Outpatient Cardiac Stress Testing After Emergency Department Encounters for Suspected Acute Coronary Syndrome.

STUDY OBJECTIVE: Professional guidelines recommend 72-hour cardiac stress testing after an emergency department (ED) evaluation for possible acute coronary syndrome. There are limited data on actual compliance rates and effect on patient outcomes. Our aim is to describe rates of completion of noninvasive cardiac stress testing and associated 30-day major adverse cardiac events. METHODS: We conducted a retrospective analysis of ED encounters from June 2015 to June 2017 across 13 community EDs within an integrated health system in Southern California. The study population included all adults with a chest pain diagnosis, troponin value, and discharge with an order for an outpatient cardiac stress test. The primary outcome was the proportion of patients who completed an outpatient stress test within the recommended 3 days, 4 to 30 days, or not at all. Secondary analysis described the 30-day incidence of major adverse cardiac events. RESULTS: During the study period, 24,459 patients presented with a chest pain evaluation requiring troponin analysis and stress test ordering from the ED. Of these, we studied the 7,988 patients who were discharged home to complete diagnostic testing, having been deemed appropriate by the treating clinicians for an outpatient stress test. The stress test completion rate was 31.3% within 3 days and 58.7% between 4 and 30 days, and 10.0% of patients did not complete the ordered test. The 30-day rates of major adverse cardiac events were low (death 0.0%, acute myocardial infarction 0.7%, and revascularization 0.3%). Rapid receipt of stress testing was not associated with improved 30-day major adverse cardiac events (odds ratio 0.92; 95% confidence interval 0.55 to 1.54). CONCLUSION: Less than one third of patients completed outpatient stress testing within the guideline-recommended 3 days after initial evaluation. More important, the low adverse event rates suggest that selective outpatient stress testing is safe. In this cohort of patients selected for outpatient cardiac stress testing in a well-integrated health system, there does not appear to be any associated benefit of stress testing within 3 days, nor within 30 days, compared with those who never received testing at all. The lack of benefit of obtaining timely testing, in combination with low rates of objective adverse events, may warrant reassessment of the current guidelines.

Effect of a HEART Care Pathway on Chest Pain Management Within an Integrated Health System.

STUDY OBJECTIVE: We describe the association of implementing a History, ECG, Age, Risk Factors, and Troponin (HEART) care pathway on use of hospital care and noninvasive stress testing, as well as 30-day patient outcomes in community emergency departments (EDs). METHODS: We performed a prospective interrupted-time-series study of adult encounters for patients evaluated for suspected acute coronary syndrome. The primary outcome was hospitalization or observation, noninvasive stress testing, or both within 30 days. The secondary outcome was 30-day all-cause mortality or acute myocardial infarction. A generalized estimating equation segmented logistic regression model was used to compare the odds of the primary outcome before and after HEART implementation. All models were adjusted for patient and facility characteristics and fit with physicians as a clustering variable. RESULTS: A total of 65,393 ED encounters (before, 30,522; after, 34,871) were included in the study. Overall, 33.5% (before, 35.5%; after, 31.8%) of ED chest pain encounters resulted in hospitalization or observation, noninvasive stress testing, or both. Primary adjusted results found a significant decrease in the primary outcome postimplementation (odds ratio 0.984; 95% confidence interval [CI] 0.974 to 0.995). This resulted in an absolute adjusted month-to-month decrease of 4.39% (95% CI 3.72% to 5.07%) after 12 months' follow-up, with a continued trend downward. There was no difference in 30-day mortality or myocardial infarction (0.6% [before] versus 0.6% [after]; odds ratio 1.02; 95% CI 0.97 to 1.08). CONCLUSION: Implementation of a HEART pathway in the ED evaluation of patients with chest pain resulted in less inpatient care and noninvasive cardiac testing and was safe. Using HEART to risk stratify chest pain patients can improve the efficiency and quality of care.

THSD1 (Thrombospondin Type 1 Domain Containing Protein 1) Mutation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: A ruptured intracranial aneurysm (IA) is the leading cause of a subarachnoid hemorrhage. This study seeks to define a specific gene whose mutation leads to disease. METHODS: More than 500 IA probands and 100 affected families were enrolled and clinically characterized. Whole exome sequencing was performed on a large family, revealing a segregating THSD1 (thrombospondin type 1 domain containing protein 1) mutation. THSD1 was sequenced in other probands and controls. Thsd1 loss-of-function studies in zebrafish and mice were used for in vivo analyses and functional studies performed using an in vitro endothelial cell model. RESULTS: A nonsense mutation in THSD1 was identified that segregated with the 9 affected (3 suffered subarachnoid hemorrhage and 6 had unruptured IA) and was absent in 13 unaffected family members (LOD score 4.69). Targeted THSD1 sequencing identified mutations in 8 of 507 unrelated IA probands, including 3 who had suffered subarachnoid hemorrhage (1.6% [95% confidence interval, 0.8%-3.1%]). These THSD1 mutations/rare variants were highly enriched in our IA patient cohort relative to 89 040 chromosomes in Exome Aggregation Consortium (ExAC) database (P<0.0001). In zebrafish and mice, Thsd1 loss-of-function caused cerebral bleeding (which localized to the subarachnoid space in mice) and increased mortality. Mechanistically, THSD1 loss impaired endothelial cell focal adhesion to the basement membrane. These adhesion defects could be rescued by expression of wild-type THSD1 but not THSD1 mutants identified in IA patients. CONCLUSIONS: This report identifies THSD1 mutations in familial and sporadic IA patients and shows that THSD1 loss results in cerebral bleeding in 2 animal models. This finding provides new insight into IA and subarachnoid hemorrhage pathogenesis and provides new understanding of THSD1 function, which includes endothelial cell to extracellular matrix adhesion.

Posterior thoracic echocardiography for assessment of native and prosthetic aortic valves in the presence of pleural effusion.

Many patients with aortic stenosis have difficult imaging windows due to advanced age, kyphosis, prior chest surgeries, radiation-induced skin changes, or hyperinflated lungs from pulmonary disease. Here we describe 4 cases to illustrate that in a subset of patients with pleural effusion, a posterior imaging approach can be used to obtain diagnostic images for native and prosthetic aortic valves. In these cases, nondiagnostic transthoracic echocardiographic images were obtained from conventional imaging windows, leading to inaccurate or incomplete assessment of the aortic valve. In all cases, images obtained from a posterior thoracic approach provided important additional diagnostic information.

Rates of diabetic ketoacidosis with empagliflozin use during hospitalization for acute heart failure.

There is concern that sodium-glucose cotransporter-2 inhibitors during hospitalization for acute heart failure (aHF) may precipitate diabetic ketoacidosis (DKA). A retrospective study of all hospitalization encounters for aHF defined by a primary HF International Classification of Diseases (ICD)-10 code in 15 Kaiser Permanente Southern California medical centers hospitalized between January 1, 2021 and August 31, 2023 was performed to describe rates of DKA with empagliflozin use. DKA was defined by the presence of either a DKA ICD-10 code or ketoacidosis lab criteria (bicarbonate <18 mmol/L and urine ketone 1+ or more or elevated serum beta-hydroxybutyrate within 12 h) during hospitalization. Among 21,630 hospital encounters (15,518 patients) for aHF, 1678 (8%) had empagliflozin use. There were 2 (0.1%) probable DKA cases in empagliflozin encounters and 15 (0.1%) in nonexposed encounters. These rates were similar when stratified by diabetes status and ejection fraction. Empagliflozin may be safe during aHF hospitalization.

Prognostic Value of Stress Myocardial Perfusion Imaging Across the Spectrum of Cardiovascular Risk.

BACKGROUND: Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is widely used to identify ischemia. There is limited research to evaluate if there is a risk threshold below which SPECT-MPI may not add significant prognostic value. METHODS: Between January 1, 2012, and December 31, 2018, individuals who underwent SPECT-MPI were stratified into 4 risk groups. The primary outcome was acute myocardial infarction (MI) or death. Multivariable Cox proportional hazards regression analysis was used to calculated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Among 48,845 patients (52.3% male, median age 67 years), 8.5% were low risk, 4.8% borderline risk, 18.1% intermediate risk, and 68.6% high risk based on the American College of Cardiology pooled cohort equation. Ischemia was more commonly detected in the high-risk cohort (19.4% in high-risk vs 6.5% in low-risk). SPECT-MPI testing was associated with a significantly increased use of preventive medications such as statin therapy, regardless of stress test results. At a median follow-up of 4.2 years, there was no significant association between ischemia and death or MI in the low-risk cohort (adjusted HR, 1.91; 95% CI, 0.94-3.92) or the borderline-risk cohort (adjusted HR, 1.58; 95% CI, 0.79-3.15). Ischemia was associated with a higher risk of death or MI in the intermediate-risk (adjusted HR, 1.57; 95% CI, 1.24-1.99) and high-risk groups (adjusted HR, 1.54; 95% CI, 1.44-1.64). CONCLUSIONS: SPECT-MPI was less useful for risk stratification among low-risk patients because of their low event rates regardless of test results.

Identification of recurrent atrial fibrillation using natural language processing applied to electronic health records.

AIMS: This study aimed to develop and apply natural language processing (NLP) algorithms to identify recurrent atrial fibrillation (AF) episodes following rhythm control therapy initiation using electronic health records (EHRs). METHODS AND RESULTS: We included adults with new-onset AF who initiated rhythm control therapies (ablation, cardioversion, or antiarrhythmic medication) within two US integrated healthcare delivery systems. A code-based algorithm identified potential AF recurrence using diagnosis and procedure codes. An automated NLP algorithm was developed and validated to capture AF recurrence from electrocardiograms, cardiac monitor reports, and clinical notes. Compared with the reference standard cases confirmed by physicians' adjudication, the F-scores, sensitivity, and specificity were all above 0.90 for the NLP algorithms at both sites. We applied the NLP and code-based algorithms to patients with incident AF (n = 22 970) during the 12 months after initiating rhythm control therapy. Applying the NLP algorithms, the percentages of patients with AF recurrence for sites 1 and 2 were 60.7% and 69.9% (ablation), 64.5% and 73.7% (cardioversion), and 49.6% and 55.5% (antiarrhythmic medication), respectively. In comparison, the percentages of patients with code-identified AF recurrence for sites 1 and 2 were 20.2% and 23.7% for ablation, 25.6% and 28.4% for cardioversion, and 20.0% and 27.5% for antiarrhythmic medication, respectively. CONCLUSION: When compared with a code-based approach alone, this study's high-performing automated NLP method identified significantly more patients with recurrent AF. The NLP algorithms could enable efficient evaluation of treatment effectiveness of AF therapies in large populations and help develop tailored interventions.