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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.

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