The current standard of care for coronary artery disease (CAD) requires an intake of radioactive or contrast enhancement dyes, radiation exposure, and stress and may take days to weeks for referral to gold-standard cardiac catheterization. The CAD diagnostic pathway would greatly benefit from a test to assess for CAD that enables the physician to rule it out at the point of care, thereby enabling the exploration of other diagnoses more rapidly. We sought to develop a test using machine learning to assess for CAD with a rule-out profile, using an easy-to-acquire signal (without stress/radiation) at the point of care. Given the historic disparate outcomes between sexes and urban/rural geographies in cardiology, we targeted equal performance across sexes in a geographically accessible test. Noninvasive photoplethysmogram and orthogonal voltage gradient signals were simultaneously acquired in a representative clinical population of subjects before invasive catheterization for those with CAD (gold-standard for the confirmation of CAD) and coronary computed tomographic angiography for those without CAD (excellent negative predictive value). Features were measured from the signal and used in machine learning to predict CAD status. The machine-learned algorithm achieved a sensitivity of 90% and specificity of 59%. The rule-out profile was maintained across both sexes, as well as all other relevant subgroups. A test to assess for CAD using machine learning on a noninvasive signal has been successfully developed, showing high performance and rule-out ability. Confirmation of the performance on a large clinical, blinded, enrollment-gated dataset is required before implementation of the test in clinical practice.

Phase space is a mechanical systems approach and large-scale data representation of an object in 3-dimensional space. Whether such techniques can be applied to predict left ventricular pressures non-invasively and at the point-of-care is unknown. This study prospectively validated a phase space machine-learned approach based on a novel electro-mechanical pulse wave method of data collection through orthogonal voltage gradient (OVG) and photoplethysmography (PPG) for the prediction of elevated left ventricular end diastolic pressure (LVEDP). Consecutive outpatients across 15 US-based healthcare centers with symptoms suggestive of coronary artery disease were enrolled at the time of elective cardiac catheterization and underwent OVG and PPG data acquisition immediately prior to angiography with signals paired with LVEDP (IDENTIFY; NCT #03864081). The primary objective was to validate a ML algorithm for prediction of elevated LVEDP using a definition of ≥25 mmHg (study cohort) and normal LVEDP ≤ 12 mmHg (control cohort), using AUC as the measure of diagnostic accuracy. Secondary objectives included performance of the ML predictor in a propensity matched cohort (age and gender) and performance for an elevated LVEDP across a spectrum of comparative LVEDP (<12 through 24 at 1 mmHg increments). Features were extracted from the OVG and PPG datasets and were analyzed using machine-learning approaches. The study cohort consisted of 684 subjects stratified into three LVEDP categories, ≤12 mmHg (N = 258), LVEDP 13–24 mmHg (N = 347), and LVEDP ≥25 mmHg (N = 79). Testing of the ML predictor demonstrated an AUC of 0.81 (95% CI 0.76–0.86) for the prediction of an elevated LVEDP with a sensitivity of 82% and specificity of 68%, respectively. Among a propensity matched cohort (N = 79) the ML predictor demonstrated a similar result AUC 0.79 (95% CI: 0.72–0.8). Using a constant definition of elevated LVEDP and varying the lower threshold across LVEDP the ML predictor demonstrated and AUC ranging from 0.79–0.82. The phase space ML analysis provides a robust prediction for an elevated LVEDP at the point-of-care. These data suggest a potential role for an OVG and PPG derived electro-mechanical pulse wave strategy to determine if LVEDP is elevated in patients with symptoms suggestive of cardiac disease.

Photoplethysmography (PPG) is a noninvasive optical technology with applications including vital sign extraction and patient monitoring. However, its current use is primarily limited to heart rate and oxygenation monitoring. This study aims to demonstrate the utility of PPG for physiological investigations. In particular, we sought to demonstrate the utility of simultaneous data acquisition from several regions of tissue using remote/contactless PPG (rPPG). Specifically, using a high-speed scientific-grade camera, we collected rPPG from the hands (palmar/dorsal) of 22 healthy volunteers. Data collected through the red and green channels of the RGB CMOS sensor were analyzed. We found a statistically significant difference in the amplitude of the glabrous skin signal over the non-glabrous skin signal (1.41 ± 0.85 in the red channel and 2.27 ± 0.88 in the green channel). In addition, we found a statistically significant lead of the red channel over the green channel, which is consistent between glabrous (17.13 ± 10.69 ms) and non-glabrous (19.31 ± 12.66 ms) skin. We also found a statistically significant lead time (32.69 ± 55.26 ms in the red channel and 40.56 ± 26.97 ms in the green channel) of the glabrous PPG signal over the non-glabrous, which cannot be explained by bilateral variability. These results demonstrate the utility of rPPG imaging as a tool for fundamental physiological studies and can be used to inform the development of PPG-based devices.

Many clinical studies have shown wide performance variation in tests to identify coronary artery disease (CAD). Coronary computed tomography angiography (CCTA) has been identified as an effective rule-out test but is not widely available in the USA, particularly so in rural areas. Patients in rural areas are underserved in the healthcare system as compared to urban areas, rendering it a priority population to target with highly accessible diagnostics. We previously developed a machine-learned algorithm to identify the presence of CAD (defined by functional significance) in patients with symptoms without the use of radiation or stress. The algorithm requires 215 s temporally synchronized photoplethysmographic and orthogonal voltage gradient signals acquired at rest. The purpose of the present work is to validate the performance of the algorithm in a frozen state (i.e., no retraining) in a large, blinded dataset from the IDENTIFY trial. IDENTIFY is a multicenter, selectively blinded, non-randomized, prospective, repository study to acquire signals with paired metadata from subjects with symptoms indicative of CAD within seven days prior to either left heart catheterization or CCTA. The algorithm’s sensitivity and specificity were validated using a set of unseen patient signals (n = 1816). Pre-specified endpoints were chosen to demonstrate a rule-out performance comparable to CCTA. The ROC-AUC in the validation set was 0.80 (95% CI: 0.78–0.82). This performance was maintained in both male and female subgroups. At the pre-specified cut point, the sensitivity was 0.85 (95% CI: 0.82–0.88), and the specificity was 0.58 (95% CI: 0.54–0.62), passing the pre-specified endpoints. Assuming a 4% disease prevalence, the NPV was 0.99. Algorithm performance is comparable to tertiary center testing using CCTA. Selection of a suitable cut-point results in the same sensitivity and specificity performance in females as in males. Therefore, a medical device embedding this algorithm may address an unmet need for a non-invasive, front-line point-of-care test for CAD (without any radiation or stress), thus offering significant benefits to the patient, physician, and healthcare system.

Central venous pressure is an estimate of right atrial pressure and is often used to assess hemodynamic status. However, since it is measured invasively, non-invasive alternatives would be of great utility. The aim of this preliminary study was a) to investigate whether photoplethysmography (PPG) can be used to characterize venous system fluid motion and b) to find the model for venous blood volume modulations. For this purpose, we monitored the internal jugular veins using contact (cPPG) and video PPG during clinically validated physiological tests: abdominojugular test (AJT) and breath holding (BH). Video PPG and cPPG signals were captured simultaneously on the left and right sides of the neck, respectively. ECG was also captured using the same clinical monitor as cPPG. Two volunteers underwent AJT and BH with head up/down, each with: baseline (15s), experiment (15s), and recovery (15s). Video PPG was split into remote PPG (rPPG) and micromotion detection. All signal modalities were significantly affected by physiological testing. Moreover, cPPG and micromotion waveforms exhibited primary features of jugular vein waveforms and, therefore, have great potential for venous blood flow monitoring. Specifically, remote patient monitoring applications may be enabled by this methodology, facilitating physical collection without a specially trained care provider.