A novel breakthrough in wrist-worn transdermal troponin-I-sensor assessment for acute myocardial infarction.

Aims: Clinical differentiation of acute myocardial infarction (MI) from unstable angina and other presentations mimicking acute coronary syndromes (ACS) is critical for implementing time-sensitive interventions and optimizing outcomes. However, the diagnostic steps are dependent on blood draws and laboratory turnaround times. We tested the clinical feasibility of a wrist-worn transdermal infrared spectrophotometric sensor (transdermal-ISS) in clinical practice and assessed the performance of a machine learning algorithm for identifying elevated high-sensitivity cardiac troponin-I (hs-cTnI) levels in patients hospitalized with ACS. Methods and results: We enrolled 238 patients hospitalized with ACS at five sites. The final diagnosis of MI (with or without ST elevation) and unstable angina was adjudicated using electrocardiography (ECG), cardiac troponin (cTn) test, echocardiography (regional wall motion abnormality), or coronary angiography. A transdermal-ISS-derived deep learning model was trained (three sites) and externally validated with hs-cTnI (one site) and echocardiography and angiography (two sites), respectively. The transdermal-ISS model predicted elevated hs-cTnI levels with areas under the receiver operator characteristics of 0.90 [95% confidence interval (CI), 0.84-0.94; sensitivity, 0.86; and specificity, 0.82] and 0.92 (95% CI, 0.80-0.98; sensitivity, 0.94; and specificity, 0.64), for internal and external validation cohorts, respectively. In addition, the model predictions were associated with regional wall motion abnormalities [odds ratio (OR), 3.37; CI, 1.02-11.15; P = 0.046] and significant coronary stenosis (OR, 4.69; CI, 1.27-17.26; P = 0.019). Conclusion: A wrist-worn transdermal-ISS is clinically feasible for rapid, bloodless prediction of elevated hs-cTnI levels in real-world settings. It may have a role in establishing a point-of-care biomarker diagnosis of MI and impact triaging patients with suspected ACS.

Early Changes in Acute Myocardial Infarction in Pigs: Achieving Early Detection with Wearable Devices.

We examined the changes in variables that could be recorded on wearable devices during the early stages of acute myocardial infarction (AMI) in an animal model. Early diagnosis of AMI is important for prognosis; however, delayed diagnosis is common because of patient hesitation and lack of timely evaluations. Wearable devices are becoming increasingly sophisticated in the ability to track indicators. In this study, we retrospectively reviewed the changes in four variables during AMI in a pig model to assess their ability to help predict AMI onset. AMI was created in 33 pigs by 90-min balloon occlusion of the left anterior descending artery. Blood pressure, EKG, and lactate and cardiac troponin I levels were recorded during the occlusion period. Blood pressure declined significantly within 15 min after balloon inflation (mean arterial pressure, from 61 ± 8 to 50 ± 8 mmHg) and remained at this low level. Within 5 min of balloon inflation, the EKG showed ST-elevation in precordial leads V1-V3. Blood lactate levels increased gradually after occlusion and peaked at 60 min (from 1.48 to 2.53 mmol/L). The continuous transdermal troponin sensor demonstrated a gradual increase in troponin levels over time. Our data suggest that significant changes in key indicators (blood pressure, EKG leads V1-V3, and lactate and troponin levels) occurred at the onset of AMI. Monitoring of these variables could be used to develop an algorithm and alert patients early at the onset of AMI with the help of a wearable device.

Development and preliminary validation of infrared spectroscopic device for transdermal assessment of elevated cardiac troponin.

Background: The levels of circulating troponin are principally required in addition to electrocardiograms for the effective diagnosis of acute coronary syndrome. Current standard-of-care troponin assays provide a snapshot or momentary view of the levels due to the requirement of a blood draw. This modality further restricts the number of measurements given the clinical context of the patient. In this communication, we present the development and early validation of non-invasive transdermal monitoring of cardiac troponin-I to detect its elevated state. Methods: Our device relies on infrared spectroscopic detection of troponin-I through the dermis and is tested in stepwise laboratory, benchtop, and clinical studies. Patients were recruited with suspected acute coronary syndrome. Results: We demonstrate a significant correlation (r = 0.7774, P < 0.001, n = 52 biologically independent samples) between optically-derived data and blood-based immunoassay measurements with and an area under receiver operator characteristics of 0.895, sensitivity of 96.3%, and specificity of 60% for predicting a clinically meaningful threshold for defining elevated Troponin I. Conclusion: This preliminary work introduces the potential of a bloodless transdermal measurement of troponin-I based on molecular spectroscopy. Further, potential pitfalls associated with infrared spectroscopic mode of inquiry are outlined including requisite steps needed for improving the precision and overall diagnostic value of the device in future studies.

Protein secondary structure analysis of dried blood serum using infrared spectroscopy to identify markers for colitis screening.

There remains a great need for diagnosis of inflammatory bowel disease, for which the current technique, colonoscopy, is costly and also has risks for complications. Attenuated total reflectance Fourier transform infrared spectroscopy is a new screening technique to evaluate colitis. Using second derivative spectral deconvolution of the absorbance spectra, a full set of spectral markers were identified based on statistical analysis. Using this method, Amide I group frequencies, (specifically, α-helix to ß-sheet ratio of the protein secondary structure) were identified in addition to the previously reported glucose and mannose signatures in sera of chronic and acute mice models of colitis. We also used the same technique to demonstrate that these spectral markers (α-helix/ß-sheet ratio, glucose and mannose) are recovering to basal levels upon anti-TNFα therapy. Hence, this technique will be able to identify changes in the sera due to diseases.

Minimally invasive screening for colitis using attenuated total internal reflectance fourier transform infrared spectroscopy.

This article describes a rapid, simple and cost-effective technique that could lead to a screening method for colitis without the need for biopsies or in vivo measurements. This screening technique includes the testing of serum using Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy for the colitis-induced increased presence of mannose. Chronic (Interleukin 10 knockout) and acute (Dextran Sodium Sulphate-induced) models for colitis are tested using the ATR-FTIR technique. Arthritis (Collagen Antibody Induced Arthritis) and metabolic syndrome (Toll like receptor 5 knockout) models are also tested as controls. The marker identified as mannose uniquely screens and distinguishes the colitic from the non-colitic samples and the controls. The reference or the baseline spectrum could be the pooled and averaged spectra of non-colitic samples or the subject's previous sample spectrum. This shows the potential of having individualized route maps of disease status, leading to personalized diagnosis and drug management.