Effects of a patient-centered digital health intervention in patients referred to cardiac rehabilitation: the Smart HEART clinical trial.

BACKGROUND: Cardiac rehabilitation (CR) improves outcomes in heart disease yet remains vastly underutilized. Remote CR enhanced with a digital health intervention (DHI) may offer higher access and improved patient-centered outcomes over non-technology approaches. We sought to pragmatically determine whether offering a DHI improves CR access, cardiac risk profile, and patient-reported outcome measures. METHODS: Adults referred to CR at a tertiary VA medical center between October 2017 and December 2021 were offered enrollment into a DHI alongside other CR modalities using shared decision-making. The DHI consisted of remote CR with a structured, 3-month home exercise program enhanced with multi-component coaching, a commercial smartphone app, and wearable activity tracker. We measured completion rates among DHI participants and evaluated changes in 6-min walk distance, cardiovascular risk factors, and patient-reported outcomes from pre- to post-intervention. RESULTS: Among 1,643 patients referred to CR, 258 (16%) consented to the DHI where the mean age was 60 ± 9 years, 93% were male, and 48% were black. A majority (90%) of the DHI group completed the program. Over 3-months, significant improvements were seen in 6MWT (mean difference [MD] -29 m; 95% CI, 10 to 49; P < 0.01) and low-density lipoprotein cholesterol (MD -11 mg/dL; 95% CI, -17 to -5; P < 0.01), and the absolute proportion of patients who reported smoking decreased (10% vs 15%; MD, -5%; 95% CI, -8% to -2%; P < 0.01) among DHI participants with available data. No adverse events were reported. CONCLUSIONS: The addition of a DHI-enhanced remote CR program was delivered in 16% of referred veterans and associated with improved CR access, markers of cardiovascular risk, and healthy behaviors in this real-world study. These findings support the continued implementation of DHIs for remote CR in real-world clinical settings. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov: NCT02791685 (07/06/2016).

Racial Differences in Mental Stress-Induced Transient Endothelial Dysfunction and Its Association With Cardiovascular Outcomes.

OBJECTIVE: This study aimed to investigate differences in transient endothelial dysfunction (TED) with mental stress in Black and non-Black individuals with coronary heart disease (CHD), and their potential impact on cardiovascular outcomes. METHODS: We examined 812 patients with stable CHD between June 2011 and March 2016 and followed through February 2020 at a university-affiliated hospital network. Flow-mediated vasodilation (FMD) was assessed before and 30 minutes after mental stress. TED was defined as a lower poststress FMD than prestress FMD. We compared prestress FMD, post-stress FMD, and TED between Black and non-Black participants. In both groups, we examined the association of TED with an adjudicated composite end point of cardiovascular death or nonfatal myocardial infarction (first and recurring events) after adjusting for demographic, clinical, and socioeconomic factors. RESULTS: Prestress FMD was lower in Black than non-Black participants (3.7 [2.8] versus 4.9 [3.8], p < .001) and significantly declined with mental stress in both groups. TED occurred more often in Black (76%) than non-Black patients (67%; multivariable-adjusted odds ratio = 1.6, 95% confidence interval = 1.5-1.7). Over a median (interquartile range) follow-up period of 75 (65-82) months, 142 (18%) patients experienced either cardiovascular death or nonfatal myocardial infarction. Black participants had a 41.9% higher risk of the study outcome than non-Black participants (95% confidence interval = 1.01-1.95). TED with mental stress explained 69% of this excess risk. CONCLUSIONS: Among CHD patients, Black individuals are more likely than non-Black individuals to develop endothelial dysfunction with mental stress, which in turn explains a substantial portion of their excess risk of adverse events.

Passively Captured Interpersonal Social Interactions and Motion From Smartphones for Predicting Decompensation in Heart Failure: Observational Cohort Study.

BACKGROUND: Heart failure (HF) is a major cause of frequent hospitalization and death. Early detection of HF symptoms using smartphone-based monitoring may reduce adverse events in a low-cost, scalable way. OBJECTIVE: We examined the relationship of HF decompensation events with smartphone-based features derived from passively and actively acquired data. METHODS: This was a prospective cohort study in which we monitored HF participants' social and movement activities using a smartphone app and followed them for clinical events via phone and chart review and classified the encounters as compensated or decompensated by reviewing the provider notes in detail. We extracted motion, location, and social interaction passive features and self-reported quality of life weekly (active) with the short Kansas City Cardiomyopathy Questionnaire (KCCQ-12) survey. We developed and validated an algorithm for classifying decompensated versus compensated clinical encounters (hospitalizations or clinic visits). We evaluated models based on single modality as well as early and late fusion approaches combining patient-reported outcomes and passive smartphone data. We used Shapley additive explanation values to quantify the contribution and impact of each feature to the model. RESULTS: We evaluated 28 participants with a mean age of 67 years (SD 8), among whom 11% (3/28) were female and 46% (13/28) were Black. We identified 62 compensated and 48 decompensated clinical events from 24 and 22 participants, respectively. The highest area under the precision-recall curve (AUCPr) for classifying decompensation was with a late fusion approach combining KCCQ-12, motion, and social contact features using leave-one-subject-out cross-validation for a 2-day prediction window. It had an AUCPr of 0.80, with an area under the receiver operator curve (AUC) of 0.83, a positive predictive value (PPV) of 0.73, a sensitivity of 0.77, and a specificity of 0.88 for a 2-day prediction window. Similarly, the 4-day window model had an AUC of 0.82, an AUCPr of 0.69, a PPV of 0.62, a sensitivity of 0.68, and a specificity of 0.87. Passive social data provided some of the most informative features, with fewer calls of longer duration associating with a higher probability of future HF decompensation. CONCLUSIONS: Smartphone-based data that includes both passive monitoring and actively collected surveys may provide important behavioral and functional health information on HF status in advance of clinical visits. This proof-of-concept study, although small, offers important insight into the social and behavioral determinants of health and the feasibility of using smartphone-based monitoring in this population. Our strong results are comparable to those of more active and expensive monitoring approaches, and underscore the need for larger studies to understand the clinical significance of this monitoring method.

Quantification of MicroRNAs by Coupling Cyclic Enzymatic Amplification with Microfluidic Voltage-Assisted Liquid Desorption Electrospray Ionization Mass Spectrometry.

Quantitative assay of microRNAs (miRNAs) with mass spectrometric detection currently suffers from two major disadvantages, i.e., being insufficient in sensitivity and requiring an extraction or chromatographic separation prior to MS detection. In this work, we developed a facile and sensitive assay of targeted miRNAs based on the combination of cyclic enzymatic amplification (CEA) with microfluidic voltage-assisted liquid desorption electrospray ionization tandem mass spectrometry (VAL-DESI-MS/MS). The single-stranded DNA (ssDNA) probe was designed to have a sequence complementary to the miRNA target with an extension of a two-base nucleotide fragment (i.e., CpC) at the 3'-position as MS signal reporter, thus being easy to prepare and high in stability. In the proposed CEA-VAL-DESI-MS/MS assay, an ssDNA probe was added to a sample solution, forming a DNA-miRNA hybrid. Duplex-specific nuclease (DSN) was then added to cleave specifically the DNA probe in the heteroduplex strands. As the hybridization-cleavage cycle repeated itself for many rounds, a large quantity of CpC molecules was produced that was quantified by VAL-DESI-MS/MS with accuracy and specificity. miRNA-21 was tested as the model target. The assay had a linear calibration equation in the range from 2.5 pM to 1.0 nM with a limit of detection of 0.25 pM. Determination of miRNA-21 in cellular samples was demonstrated. miRNA-21 was found to be 95.3 ± 13.95 amol ( n = 3) in 100 mouse peritoneal macrophages with a recovery of 94.2 ± 2.6% ( n = 3). Interestingly, analysis of exosomes secreted from these cells revealed that exposure of the cells to chemical stimuli caused a 3-fold increase in exosomal level of miRNA-21. The results suggest that the proposed assay may provide an accurate and cost-effective means for quantification of targeted miRNAs in biomedical samples.