Functional arrays of human pluripotent stem cell-derived cardiac microtissues.

To accelerate the cardiac drug discovery pipeline, we set out to develop a platform that would be capable of quantifying tissue-level functions such as contractile force and be amenable to standard multiwell-plate manipulations. We report a 96-well-based array of 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues - termed Cardiac MicroRings (CaMiRi) - in custom 3D-print-molded multiwell plates capable of contractile force measurement. Within each well, two elastomeric microcantilevers are situated above a circumferential ramp. The wells are seeded with cell-laden collagen, which, in response to the gradual slope of the circumferential ramp, self-organizes around tip-gated microcantilevers to form contracting CaMiRi. The contractile force exerted by the CaMiRi is measured and calculated using the deflection of the cantilevers. Platform responses were robust and comparable across wells, and we used it to determine an optimal tissue formulation. We validated the contractile force response of CaMiRi using selected cardiotropic compounds with known effects. Additionally, we developed automated protocols for CaMiRi seeding, image acquisition, and analysis to enable the measurement of contractile force with increased throughput. The unique tissue fabrication properties of the platform, and the consequent effects on tissue function, were demonstrated upon adding hPSC-derived epicardial cells to the system. This platform represents an open-source contractile force screening system useful for drug screening and tissue engineering applications.

Underuse of Effective Cardiac Medications Among Women, Middle-Aged Adults, and Racial/Ethnic Minorities With Coronary Artery Disease (from the National Health and Nutrition Examination Survey 2005 to 2014).

Given the proven effectiveness of several cardiac medications for patients with coronary artery disease (CAD), we examined the national use of 4 classes of effective medications, overall and by age, sex, and race/ethnicity in 2005 to 2014. We used data from the National Health and Nutrition Examination Survey, including a self-reported diagnosis of CAD and independently verified medication use. Weighting procedures extrapolated our data to the adult US population with CAD. Analyses included 1,789 US adults aged ≥45 years with a history of CAD. The average age of this population was 68 years; 40% were women and 79% were non-Hispanic whites. In 2005 to 2014, 53.2% (standard error [SE] = 1.5) reported use of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, 58.5% (SE = 1.5) ß blockers, and 67.2% (SE = 1.4) statins. Two of these medications were used by 64.1% (SE = 1.5) of the study population and all 3 by 29.1% (SE = 1.3). In 2011 to 2014, 68.5% (SE = 2.4) of American adults with a history of CAD reported use of aspirin. The use of statins increased from 63.1% in 2005/2006 to 76.8% in 2013/2014. Adults aged 45 to 64 years old, women, and racial/ethnic minorities had lower use of effective cardiac medications compared with older adults, men, and non-Hispanic whites. In conclusion, the use of statins, but not other medications, has increased over the past 10 years among American adults with previously diagnosed CAD. Continued targeted efforts are needed to increase the receipt of effective cardiac medications among all US adults with CAD, especially those aged 45 to 64 years, women, and racial/ethnic minorities.