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Key Points Question What are the overall burden and temporal trends in the rate of hospitalizations for worsening heart failure (WHF)? Findings This cohort study of 118 002 patients found that applying rigorous and prespecified diagnostic criteria to electronic health record data was associated with a more than 2-fold increase in the number of hospitalizations for WHF identified compared with estimates using a principal discharge diagnosis alone. There has been a gradual increase in the rate of hospitalizations for WHF over time, with a more noticeable increase observed among patients with heart failure with a preserved ejection fraction. Meaning These findings suggest that population temporal trends based on a principal hospital discharge diagnosis of heart failure may underreport the increasing burden of hospitalizations for WHF, particularly among those with heart failure with a preserved ejection fraction, compared with a comprehensive approach using structured and unstructured electronic health record data., Importance The current understanding of epidemiological mechanisms and temporal trends in hospitalizations for worsening heart failure (WHF) is based on claims and national reporting databases. However, these data sources are inherently limited by the accuracy and completeness of diagnostic coding and/or voluntary reporting. Objective To assess the overall burden of and temporal trends in the rate of hospitalizations for WHF. Design, Setting, and Participants This cohort study, performed from January 1, 2010, to December 31, 2019, used electronic health record (EHR) data from a large integrated health care delivery system. Exposures Calendar year trends. Main Outcomes and Measures Hospitalizations for WHF (ie, excluding observation stays) were defined as 1 symptom or more, 2 objective findings or more including 1 sign or more, and 2 doses or more of intravenous loop diuretics and/or new hemodialysis or continuous kidney replacement therapy. Symptoms and signs were identified using natural language processing (NLP) algorithms applied to EHR data. Results The study population was composed of 118 002 eligible patients experiencing 287 992 unique hospitalizations (mean [SD] age, 75.6 [13.1] years; 147 203 [51.1%] male; 1655 [0.6%] American Indian or Alaska Native, 28 451 [9.9%] Asian or Pacific Islander, 34 903 [12.1%] Black, 23 452 [8.1%] multiracial, 175 840 [61.1%] White, and 23 691 [8.2%] unknown), including 65 357 with a principal discharge diagnosis and 222 635 with a secondary discharge diagnosis of HF. The study population included 59 868 patients (20.8%) with HF with a reduced ejection fraction (HFrEF) (, This cohort study uses rule-based natural language processing algorithms applied to electronic health record data to examine the overall burden of and temporal trends in the rate of hospitalizations for worsening heart failure overall and by the degree of systolic dysfunction.

Objective: Patients with risk factors for or established atherosclerotic cardiovascular disease (ASCVD) remain at high risk for subsequent ischemic events despite statin therapy. Triglyceride (TG) levels may contribute to residual ASCVD risk, and the performance of global risk assessment calculators across a broad range of TG levels is unknown. Methods: We performed a retrospective cohort study of Kaiser Permanente Northern California members aged ≥45 years with ≥1 ASCVD risk factor (primary prevention cohort) or established ASCVD (secondary prevention cohort) between 2010 and 2017 who were receiving statin therapy and had a low-density lipoprotein cholesterol between 41–100 mg/dL. Global ASCVD risk assessment was performed using both the Kaiser Permanente ASCVD Risk Estimator (KPARE) and the ACC/AHA ASCVD Pooled Cohort Equation (PCE). Outcomes included major adverse cardiovascular events (MACE) defined as myocardial infarction, stroke, or peripheral artery disease, and expanded MACE (MACE + coronary revascularization + hospitalization for unstable angina). Results: Among 373,389 patients in the primary prevention cohort, median TG was 122 mg/dL (IQR 88–172 mg/dL) and there were 0.2 MACE events and 0.3 expanded MACE events per 100-person years. Among 97,832 patients in the secondary prevention cohort, median TG level was 116 mg/dL (IQR 84–164 mg/dL) and there were 9.6 MACE events and 22.0 expanded MACE events per 100-person years. KPARE and the ACC/AHA PCE stratified patients for MACE and expanded MACE over the entire range of TGs. Conclusion: In a cohort receiving statin therapy for primary or secondary prevention, we found global assessment further improves risk stratification for initial and/or recurrent ASCVD events irrespective of baseline TG level.

Background Patients with risk factors or established atherosclerotic cardiovascular disease remain at high‐risk for ischemic events. Triglyceride levels may play a causal role. Methods and Results We performed a retrospective study of adults aged ≥45 years receiving statin therapy, with a low‐density lipoprotein cholesterol of 41 to 100 mg/dL, and ≥1 risk factor or established atherosclerotic cardiovascular disease between 2010 and 2017. Outcomes included death, all‐cause hospitalization, and major adverse cardiovascular events (myocardial infarction, stroke, or peripheral artery disease). The study sample included 373 389 primary prevention patients and 97 832 secondary prevention patients. The primary prevention cohort had a mean age of 65±10 years, with 51% women and 44% people of color, whereas the secondary prevention cohort had a mean age of 71±11 years, with 37% women and 32% people of color. Median triglyceride levels for the primary and secondary prevention cohorts were 122 mg/dL (interquartile range, 88–172 mg/dL) and 116 mg/dL (interquartile range, 84–164 mg/dL), respectively. In multivariable analyses, primary prevention patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (hazard ratio [HR], 0.91; 95% CI, 0.89–0.94) and higher risk of major adverse cardiovascular events (HR, 1.14; 95% CI, 1.05–1.24). In the secondary prevention cohort, patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (HR, 0.95; 95% CI, 0.92–0.97) and higher risk of all‐cause hospitalization (HR, 1.03; 95% CI, 1.01–1.05) and major adverse cardiovascular events (HR, 1.04; 95% CI, 1.05–1.24). Conclusions In a contemporary cohort receiving statin therapy, elevated triglyceride levels were associated with a greater risk of atherosclerotic cardiovascular disease events and lower risk of death.

BACKGROUND: Adults with chronic kidney disease (CKD) are at increased risk of heart failure (HF) morbidity and mortality. Despite well-characterized abnormalities in cardiac structure in CKD, it remains unclear how to optimally leverage echocardiography to risk stratify CKD patients. METHODS: We evaluated associations between echocardiographic parameters and risk of HF hospitalization and death using Cox proportional hazard models and forward selection with integrated discrimination improvement (IDI). RESULTS: The study included 3,505 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC). Mean age was 59±11 years, HF prevalence was 10%, and mean left ventricular (LV) ejection fraction (LVEF) was 54±9%. During mean 11 (interquartile range: 8 to 12) years of follow-up, event rates per 100-person years for HF hospitalizations and death, respectively, were 9.4 (95% Confidence Interval [CI]: 7.9–11.3) and 8.9 (95% CI: 7.6–10.5) for participants with LVEF

Objective: The MITIGATE study aims to evaluate the real-world clinical effectiveness of pre-treatment with icosapent ethyl (IPE), compared with usual care, on laboratory-confirmed viral upper respiratory infection (URI)-related morbidity and mortality in adults with established atherosclerotic cardiovascular disease (ASCVD). Background: IPE is a highly purified and stable omega-3 fatty acid prescription medication that is approved for cardiovascular risk reduction in high-risk adults on statin therapy with elevated triglycerides. Preclinical data and clinical observations suggest that IPE may have pleiotropic effects including antiviral and anti-inflammatory properties that may prevent or reduce the downstream sequelae and cardiopulmonary consequences of viral URIs. Methods: MITIGATE is a virtual, electronic health record (EHR)-based, open-label, randomized, pragmatic clinical trial enrolling ∼16,500 participants within Kaiser Permanente Northern California (KPNC) – a fully integrated and learning health care delivery system with 21 hospitals and >255 ambulatory clinics serving ∼4.5 million members. Adults ≥50 years with established ASCVD and no prior history of coronavirus disease 2019 (COVID-19) will be prospectively identified and pre-randomized in a 1:10 allocation ratio (∼1,500 IPE: ∼15,000 usual care) stratified by age and previous respiratory health status to the intervention (IPE two grams by mouth twice daily with meals) vs. the control group (usual care) for a minimum follow-up duration of 6 months. The co-primary endpoints are moderate-to-severe laboratory-confirmed viral URI and worst clinical status due to a viral URI at any point in time. Conclusion: The MITIGATE study will inform clinical practice by providing evidence on the real-world clinical effectiveness of pre-treatment with IPE to prevent and/or reduce the sequelae of laboratory-confirmed viral URIs in a high-risk cohort of patients with established ASCVD.

Low transferrin saturation (TSAT) or reduced serum ferritin level are suggestive of iron deficiency but the relationship between iron parameters and outcomes has not been systematically evaluated in older adults with heart failure (HF) and anemia.We identified a multicenter cohort of adults age ≥ 65 years with HF and incident anemia (hemoglobin13 g/dL [men] or 12 g/dL [women]) between 2005 and 2012. Patients were included if ferritin (ng/mL) and TSAT (%) were evaluated within 90 days of incident anemia. HF hospitalizations and all-cause death were ascertained from electronic health records.Among 4103 older adults with HF and incident anemia, 47% had TSAT20% and the median (IQR) ferritin was 126 (53, 256) ng/mL. In multivariable analyses, compared with TSAT ≥20%, patients with TSAT20% were at increased risk of HF hospitalization for serum ferritin100 ng/mL (adjusted HR [aHR] 1.40, 95% CI:1.16-1.70) and 100-300 ng/mL (aHR 1.24, 95% CI:1.01-1.52) but not for a ferritin300 ng/mL (aHR 0.89, 95% CI 0.65-1.23). In addition, TSAT20% was independently associated with an increased risk of all-cause death regardless of serum ferritin level (100 ng/mL: aHR 1.42, 95% CI:1.20-1.68; 100-300 ng/mL: aHR 1.18, 95% CI:1.00-1.38;300 ng/mL: aHR 1.33, 95% CI:1.06-1.69).Among older adults with HF and incident anemia who had iron studies tested, nearly half had a TSAT20%, which was independently associated with higher rates of morbidity and death.

Narrow complex bigeminy is a common electrocardraphic finding that can be caused by second degree sinoatrial exit block or ectopic atrial bigeminy. These rhythms can be very challenging to distinguish on a 12-lead electrocardiogram. In this case of an elderly woman who presented with narrow complex bigeminy, we review the differentiating features of second degree sinoatrial exit block and ectopic atrial bigeminy.

Left ventricular (LV) hypertrophy is strongly associated with increased cardiovascular morbidity and mortality. The 2-dimensional LV mass algorithms suffer from measurement variability that can lead to misclassification of patients with LV hypertrophy as normal, or vice versa. Among the 4 echocardiographic measurements required by the 2-dimensional LV mass algorithms, epicardial and endocardial area have the lowest interobserver variation and could be used to corroborate LV mass calculations. We sought cut-off values that are able to discriminate between elevated and normal LV mass based on endocardial or epicardial area alone. Using data from 664 men enrolled in the Mind Your Heart Study, we calculated the correlation of LV mass index with epicardial area and endocardial area. We then used receiver operator characteristic curves to identify epicardial and endocardial area cut-points that could discriminate subjects with normal LV mass and LV hypertrophy. LV mass index was more strongly correlated with epicardial area compared with endocardial area, r = 0.70 versus r = 0.27, respectively. Epicardial area had a significantly higher area under the receiver operator characteristic curve (p 0.001) compared with endocardial area, 0.90 (95% confidence interval 0.86 to 0.93) versus 0.63 (95% confidence interval 0.57 to 0.71). An epicardial area cut-point of ≥38.0 cm

Background The ventricular-vascular coupling ratio (Ea/Ees) is defined as the ratio of arterial elastance (Ea) to left ventricular elastance (Ees) and is a key determinant of cardiac performance. Ventricular-vascular coupling has not been examined in populations with coronary artery disease (CAD) and its association with heart failure (HF) in this population is unknown. Methods We measured baseline ventricular-vascular coupling at rest and after exercise using echocardiography and cuff blood pressure in 815 patients with stable CAD enrolled in the Heart and Soul Study. Patients were prospectively followed for the endpoint of HF hospitalization. We used Cox proportional hazard models, adjusted for baseline demographics and medical comorbidities, to evaluate the association between ventricular-vascular coupling and HF hospitalizations. Results Ea and Ees increased with exercise, while the Ea/Ees ratio decreased modestly. After a median of 8.9 years, 144 (18%) patients were hospitalized for HF. After multivariable adjustment, patients in the highest tertile of resting Ees (HR 0.24, CI 0.13 to 0.43, P Conclusions The Ea/Ees ratio, at rest and after exercise, is strongly associated with future HF hospitalizations in patients with stable CAD and low rates of baseline HF. The association is driven primarily by Ees, while Ea has little prognostic significance.

Background Left ventricular hypertrophy (LVH) is strongly associated with the development of heart failure. The two-dimensional left ventricular mass (LVM) algorithms suffer from measurement variability that can lead to misclassification of patients with LVH as normal, or vice versa. Among the four echocardiographic measurements required by the two-dimensional LVM algorithms, epicardial and endocardial area have the lowest inter-observer variation and could be used to corroborate LVM calculations. We sought cut-off values able to discriminate between elevated and normal LVM based on endocardial or epicardial area alone. Methods Using data from 664 men enrolled in the Mind Your Heart Study, we calculated the correlation of left ventricular mass index (LVMI) with epicardial area and endocardial area. We then used receiver operator characteristic curves to identify epicardial and endocardial area cut-points that could discriminate among individuals with normal LVM and LVH. Results LVMI was more strongly correlated with epicardial area compared to endocardial area, r = 0.70 versus r = 0.27, respectively. As a screening test for LVH, epicardial area significantly outperformed endocardial area as reflected by a considerably higher area under the ROC curve, 0.90 (95% CI = 0.86 to 0.93) versus 0.63 (95% CI = 0.57 to 0.71). An epicardial area cut-point of ≥ 38.0 cm2 corresponded to a sensitivity of 95.0% and specificity of 54.4% for detecting LVH. The seven participants who had epicardial areas below our cut-point but still met criteria for LVH by LVMI (false negatives), had lower body surface areas and lower left ventricular cavity volumes than the cohort average. Conclusions Epicardial area showed promise as a method of rapid screening for LVH and could be used to validate formal LVM calculations. Figure 1

Polybrominated diphenyl ethers (PBDEs), flame retardant chemicals added to polymer products, have become ubiquitous in the environment, and they are bioaccumulating in humans and wildlife. Therefore, understanding their biological effects is important for public health. We have previously observed learning deficits in rats exposed to DE-71, a commercial PBDE mixture consisting primarily of pentabrominated diphenyl ethers, at a dose of 30 mg/kg/day from postnatal day (PND) 6 to 12. The purpose of the current study was to determine if this effect could be seen with lower doses of DE-71. Long–Evans rats were administered daily oral doses of corn oil alone or DE-71, 5 or 15 mg/kg/day, dissolved in corn oil, from PND 6 to 12. As young adults, the rats were administered a series of five-choice visual learning and attention tasks. No effects of DE-71 were found on learning, attention, or inhibitory control. Given that developmental DE-71 exposure at similar doses and for shorter time periods has been shown in other laboratories to affect locomotion and hyperactivity, the current results suggest that cognitive functions may not be as sensitive as neuromotor functions to the effects of acute DE-71 exposure.