Among individuals with CAC = 0, conversion to CAC >0 is nonlinear and occurs at low frequency before 4 years. No clinical factor seems to mandate earlier repeat CAC scanning.

Biosensors play a critical role in the real-time determination of relevant functional physiological needs. However, typical in vivo biosensors only approximate endogenous function via the measurement of surrogate signals and, therefore, may often lack a high degree of dynamic fidelity with physiological requirements. To overcome this limitation, we have developed an excitable tissue-based implantable biosensor approach, which exploits the inherent electropotential input-output relationship of cardiac myocytes to measure the physiological regulatory inputs of chronotropic demand via the detection of blood-borne signals. In this study, we report the improvement of this application through the modulation of host-biosensor communication via the enhancement of vascularization of chronotropic complexes in mice. Moreover, in an effort to further improve translational applicability as well as molecular plasticity, we have advanced this approach by employing stem cell-derived cardiac myocyte aggregates in place of whole cardiac tissue. Overall, these studies demonstrate the potential of biologically based biosensors to predict endogenous physiological dynamics and may facilitate the translation of this approach for in vivo monitoring.

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Presence and severity of coronary artery calcium (CAC) by Agatston scoring is a well established index for stratification of cardiovascular prognosis. Absence of CAC is associated with excellent clinical prognosis. To date, for patients with baseline absence of CAC, rates of conversion to positive CAC (i.e., CAC>0) and severity of CAC at the time of conversion is unknown. 9,838 asymptomatic individuals underwent CAC screening with multidetector row or electron-beam computed tomography. Within this cohort, 422 asymptomatic subjects (mean age 48.8±8.9 yrs; 52.1% male, 9% diabetes; 46.0% hypertension, 66% dyslipidemia, 32% smoker) with an initial baseline CAC Agatston score of zero agreed to undergo annual CAC screening for five consecutive years or until conversion to a positive CAC. 106 patients (25.1%) converted from no CAC to a positive CAC within the 5-year follow-up period (mean conversion time 4.08±1.10 yrs). No subject exhibited CAC conversion within the first year. Rates of CAC conversion were low in year 2 (2/422, 0.5%) and year 3 (5/420, 1.1%). No differences were noted for time to CAC conversion in patients with or without diabetes, hypertension, dyslipidemia, or tobacco use (p=NS for all). Similarly, time to CAC conversion was similar among male and female subjects (p=NS). However, subjects with diabetes (p=0.001), hypertension (p=0.02) and tobacco use (p<0.0001) were more likely to transition from absence to presence of CAC during the entire study period, compared to non-diabetic, normotensive and non-smoking subjects. Furthermore, for subjects who exhibited conversion from absence to presence of CAC, Agatston CAC scores at the time of conversion were higher for diabetic (33.0 vs. 16.0, p=0.005) and hypertensive (24.3 vs. 12.4, p=0.001) subjects, compared to their non-diabetic and normotensive counterparts. In subjects with baseline absence of CAC, rates of conversion to positive CAC scores is low during five-year follow-up with rare conversion in the first three years. Conversion rates and severity of CAC at time of conversion is highest amongst individuals with diabetes, hypertension and tobacco use.