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More than 40 years after the 1978 Bethesda Conference on the Declining Mortality from Coronary Heart Disease provided the scientific community with a blueprint for systematic analysis to understand declining rates of coronary heart disease, there are indications the decline has ended or even reversed despite advances in our knowledge about the condition and treatment. Recent data show a more complex situation, with mortality rates for overall cardiovascular disease, including coronary heart disease and stroke, decelerating, whereas those for heart failure are increasing. To mark the 40th anniversary of the Bethesda Conference, the National Heart, Lung, and Blood Institute and the American Heart Association cosponsored the "Bending the Curve in Cardiovascular Disease Mortality: Bethesda + 40" symposium. The objective was to examine the immediate and long-term outcomes of the 1978 conference and understand the current environment. Symposium themes included trends and future projections in cardiovascular disease (in the United States and internationally), the evolving obesity and diabetes epidemics, and harnessing emerging and innovative opportunities to preserve and promote cardiovascular health and prevent cardiovascular disease. In addition, participant-led discussion explored the challenges and barriers in promoting cardiovascular health across the lifespan and established a potential framework for observational research and interventions that would begin in early childhood (or ideally in utero). This report summarizes the relevant research, policy, and practice opportunities discussed at the symposium. [ABSTRACT FROM AUTHOR]

Background: The diagnostic utility of cardiovascular magnetic resonance (CMR) is limited during the early stages of myocarditis. This study examined whether ferumoxytol-enhanced CMR (FE-CMR) could detect an earlier stage of acute myocarditis compared to gadolinium-enhanced CMR. Methods: Lewis rats were induced to develop autoimmune myocarditis. CMR (3 T, GE Signa) was performed at the early- (day 14, n = 7) and the peak-phase (day 21, n = 8) of myocardial inflammation. FE-CMR was evaluated as % myocardial dephasing signal loss on gradient echo images at 6 and 24 h (6 h- & 24 h-FE-CMR) following the administration of ferumoxytol (300μmolFe/kg). Pre- and post-contrast T2* mapping was also performed. Early (EGE) and late (LGE) gadolinium enhancement was obtained after the administration of gadolinium-DTPA (0.5 mmol/kg) on day 14 and 21. Healthy rats were used as control (n = 6). Results: Left ventricular ejection fraction (LVEF) was preserved at day 14 with inflammatory cells but no fibrosis seen on histology. EGE and LGE at day 14 both showed limited myocardial enhancement (EGE: 11.7 ± 15.5%; LGE: 8.7 ± 8.7%; both p = ns vs. controls). In contrast, 6 h-FE-CMR detected extensive myocardial signal loss (33.2 ± 15.0%, p = 0.02 vs. EGE and p < 0.01 vs. LGE). At day 21, LVEF became significantly decreased (47.4 ± 16.4% vs control: 66.2 ± 6.1%, p < 0.01) with now extensive myocardial involvement detected on EGE, LGE, and 6 h-FE-CMR (41.6 ± 18.2% of LV). T2* mapping also detected myocardial uptake of ferumoxytol both at day 14 (6 h R2* = 299 ± 112 s− 1vs control: 125 ± 26 s− 1, p < 0.01) and day 21 (564 ± 562 s− 1, p < 0.01 vs control). Notably, the myocardium at peak-phase myocarditis also showed significantly higher pre-contrast T2* (27 ± 5 ms vs control: 16 ± 1 ms, p < 0.001), and the extent of myocardial necrosis had a strong positive correlation with T2* (r = 0.86, p < 0.001). Conclusions: FE-CMR acquired at 6 h enhance detection of early stages of myocarditis before development of necrosis or fibrosis, which could potentially enable appropriate therapeutic intervention. [ABSTRACT FROM AUTHOR]

Getting enough sleep, exercising, and limiting sedentary activities can greatly contribute to disease prevention and overall health and longevity. Measuring the full 24-h activity cycle-sleep, sedentary behavior (SED), light-intensity physical activity (LPA), and moderate-to-vigorous physical activity (MVPA)-may now be feasible using small wearable devices. PURPOSE: This study compared nine devices for accuracy in a 24-h activity measurement. METHODS: Adults (n = 40, 47% male) wore nine devices for 24 h: ActiGraph GT3X+, activPAL, Fitbit One, GENEactiv, Jawbone Up, LUMOback, Nike Fuelband, Omron pedometer, and Z-Machine. Comparisons (with standards) were made for total sleep time (Z-machine), time spent in SED (activPAL), LPA (GT3X+), MVPA (GT3X+), and steps (Omron). Analysis included mean absolute percent error, equivalence testing, and Bland-Altman plots. RESULTS: Error rates ranged from 8.1% to 16.9% for sleep, 9.5% to 65.8% for SED, 19.7% to 28.0% for LPA, 51.8% to 92% for MVPA, and 14.1% to 29.9% for steps. Equivalence testing indicated that only two comparisons were significantly equivalent to standards: the LUMOback for SED and the GT3X+ for sleep. Bland-Altman plots indicated GT3X+ had the closest measurement for sleep, LUMOback for SED, GENEactiv for LPA, Fitbit for MVPA, and GT3X+ for steps. CONCLUSIONS: Currently, no device accurately captures activity data across the entire 24-h day, but the future of activity measurement should aim for accurate 24-h measurement as a goal. Researchers should continue to select measurement devices on the basis of their primary outcomes of interest. [ABSTRACT FROM AUTHOR]

Background: A novel MRI technique, employing dual contrast manganese-enhanced MRI (MEMRI) and delayed enhancement MRI (DEMRI), can evaluate the physiologically unstable peri-infarct region. Dual contrast MEMRI-DEMRI enables comprehensive evaluation of telmisartan to salvage the peri-infarct injury to elucidate the underlying mechanism of restoring the ischemic cardiomyopathy in the diabetic mouse model. Methods and results: Dual contrast MEMRI-DEMRI was performed on weeks 1, 2, and 4 following initiation of telmisartan treatment in 24 left anterior descendent artery ligated diabetic mice. The MRI images were analyzed for core infarct, peri-infarct, left ventricular end-diastolic, end-systolic volumes, and the left ventricular ejection fraction (LVEF). Transmission electron microscopy (TEM) and real-time PCR were used for ex vivo analysis of the myocardium. Telmisartan vs. control groups demonstrated significantly improved LVEF at weeks 1, 2, and 4, respectively (33 ± 7 %*** vs. 19 ± 5 %, 29 ± 3 %*** vs. 22 ± 4 %, and 31 ± 2 %*** vs 18 ± 6 %, ***p < 0.001). The control group demonstrated significant differences in the scar volume measured by MEMRI and DEMRI, demonstrating peri-infarct injury. Telmisartan group significantly salvaged the peri-infarct injury. The myocardial effects were validated by TEM, which confirmed the presence of the injured but viable cardiomyocyte morphology in the peri-infarct region and by low cytometry of venous blood, which demonstrated significantly increased circulating endothelial progenitor cells (EPCs). Conclusion: The improved cardiac function in ischemic cardiomyopathy of diabetic mice by telmisartan is attributed to the attenuation of the peri-infarct injury by the angiogenic efects of EPCs to salvage the injured cardiomyocytes. Dual-contrast MEMRI-DEMRI technique tracked the therapeutic effects of telmisartan on the injured myocardium longitudinally. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRs) regulate gene expression at the posttranscriptional level and play crucial roles in vascular integrity. As such, they may have a role in modifying abdominal aortic aneurysm (AAA) expansion, the pathophysiological mechanisms of which remain incompletely explored. Here, we investigate the role of miRs in 2 murine models of experimental AAA: the porcine pancreatic elastase (PPE) infusion model in C57BL/6 mice and the AngII infusion model in Apoe-/- mice. AAA development was accompanied by decreased aortic expression of miR-29b, along with increased expression of known miR-29b targets, Col1a1, Col3a1, Col5a1, and Eln, in both models. In vivo administration of locked nucleic acid anti-miR-29b greatly increased collagen expression, leading to an early fibrotic response in the abdominal aortic wall and resulting in a significant reduction in AAA progression over time in both models. In contrast, overexpression of miR-29b using a lentiviral vector led to augmented AAA expansion and significant increase of aortic rupture rate. Cell culture studies identified aortic fibroblasts as the likely vascular cell type mediating the profibrotic effects of miR-29b modulation. A similar pattern of reduced miR-29b expression and increased target gene expression was observed in human AAA tissue samples compared with that in organ donor controls. These data suggest that therapeutic manipulation of miR- 29b and its target genes holds promise for limiting AAA disease progression and protecting from rupture. [ABSTRACT FROM AUTHOR]

Abstract: Atherosclerosis is a leading cause of death worldwide. Macrophages are key components of vascular inflammation, which contributes to the development and complications of atherosclerosis. Ferritin, an iron storage and transport protein, has been found to accumulate in macrophages in human atherosclerotic plaques. We hypothesized that ferritin could serve as an intrinsic nano-platform to target delivery of imaging agents to vascular macrophages to detect high-risk atherosclerotic plaques. Here we show that engineered human ferritin protein cages, either conjugated to the fluorescent Cy5.5 molecule or encapsulating a magnetite nanoparticle, are taken up in vivo by macrophages in murine atherosclerotic carotid arteries and can be imaged by fluorescence and magnetic resonance imaging. These results indicate that human ferritin can serve as a nanoparticle platform to image vascular inflammation in vivo. [ABSTRACT FROM AUTHOR]

Background: High systolic blood pressure (SBP) is one of the leading modifiable risk factors for premature cardiovascular death. The retinal vasculature exhibits well-documented adaptations to high SBP and these vascular changes are known to correlate with atherosclerotic cardiovascular disease (ASCVD) events., Objectives: The purpose of this study was to determine whether using artificial intelligence (AI) to predict an individual's SBP from retinal images would more accurately correlate with future ASCVD events compared to measured SBP., Methods: 95,665 macula-centered retinal images drawn from the 51,778 individuals in the UK Biobank who had not experienced an ASCVD event prior to retinal imaging were used. A deep-learning model was trained to predict an individual's SBP. The correlation of subsequent ASCVD events with the AI-predicted SBP and the mean of the measured SBP acquired at the time of retinal imaging was determined and compared., Results: The overall ASCVD event rate observed was 3.4%. The correlation between SBP and future ASCVD events was significantly higher if the AI-predicted SBP was used compared to the measured SBP: 0.067 v 0.049, P  = 0.008. Variability in measured SBP in UK Biobank was present (mean absolute difference = 8.2 mm Hg), which impacted the 10-year ASCVD risk score in 6% of the participants., Conclusions: With the variability and challenges of real-world SBP measurement, AI analysis of retinal images may provide a more reliable and accurate biomarker for predicting future ASCVD events than traditionally measured SBP., Competing Interests: D. M. S., S. Y., L. X., S. A. B., M. M., E. V., and M. V. M. are all employees of Toku Eyes. M. V. M. is also an advisor to Porter Health. Toku eyes funded this research., (© 2024 The Authors.)

Coronary artery calcium (CAC) scans contain valuable information beyond the Agatston Score which is currently reported for predicting coronary heart disease (CHD) only. We examined whether new artificial intelligence (AI) applied to CAC scans can predict non-CHD events, including heart failure, atrial fibrillation, and stroke. We applied AI-enabled automated cardiac chambers volumetry and calcified plaque characterization to CAC scans (AI-CAC) of 5830 asymptomatic individuals (52.2% women, age 61.7 ± 10.2 years) in the multi-ethnic study of atherosclerosis during 15 years of follow-up, 1773 CVD events accrued. The AUC at 1-, 5-, 10-, and 15-year follow-up for AI-CAC vs. Agatston score was (0.784 vs. 0.701), (0.771 vs. 0.709), (0.789 vs. 0.712) and (0.816 vs. 0.729) (p < 0.0001 for all), respectively. AI-CAC plaque characteristics, including number, location, density, plus number of vessels, significantly improved CHD prediction in the CAC 1-100 cohort vs. Agatston Score. AI-CAC significantly improved the Agatston score for predicting all CVD events., (© 2024. The Author(s).)

Background: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death globally, and early detection of high-risk individuals is essential for initiating timely interventions. The authors aimed to develop and validate a deep learning (DL) model to predict an individual's elevated 10-year ASCVD risk score based on retinal images and limited demographic data., Methods: The study used 89,894 retinal fundus images from 44,176 UK Biobank participants (96% non-Hispanic White, 5% diabetic) to train and test the DL model. The DL model was developed using retinal images plus age, race/ethnicity, and sex at birth to predict an individual's 10-year ASCVD risk score using the pooled cohort equation (PCE) as the ground truth. This model was then tested on the US EyePACS 10K dataset (5.8% non-Hispanic White, 99.9% diabetic), composed of 18,900 images from 8969 diabetic individuals. Elevated ASCVD risk was defined as a PCE score of ≥7.5%., Results: In the UK Biobank internal validation dataset, the DL model achieved an area under the receiver operating characteristic curve of 0.89, sensitivity 84%, and specificity 90%, for detecting individuals with elevated ASCVD risk scores. In the EyePACS 10K and with the addition of a regression-derived diabetes modifier, it achieved sensitivity 94%, specificity 72%, mean error -0.2%, and mean absolute error 3.1%., Conclusion: This study demonstrates that DL models using retinal images can provide an additional approach to estimating ASCVD risk, as well as the value of applying DL models to different external datasets and opportunities about ASCVD risk assessment in patients living with diabetes., (© 2024 Heart Rhythm Society.)

Purpose of Review: To discuss physiologic and methodologic advances in the echocardiographic assessment of right heart (RH) function, including the emergence of artificial intelligence (AI) and point-of-care ultrasound., Recent Findings: Recent studies have highlighted the prognostic value of right ventricular (RV) longitudinal strain, RV end-systolic dimensions, and right atrial (RA) size and function in pulmonary hypertension and heart failure. While RA pressure is a central marker of right heart diastolic function, the recent emphasis on venous excess imaging (VExUS) has provided granularity to the systemic consequences of RH failure. Several methodological advances are also changing the landscape of RH imaging including post-processing 3D software to delineate the non-longitudinal (radial, anteroposterior, and circumferential) components of RV function, as well as AI segmentation- and non-segmentation-based quantification. Together with recent guidelines and advances in AI technology, the field is shifting from specific RV functional metrics to integrated RH disease-specific phenotypes. A modern echocardiographic evaluation of RH function should focus on the entire cardiopulmonary venous unit-from the venous to the pulmonary arterial system. Together, a multi-parametric approach, guided by physiology and AI algorithms, will help define novel integrated RH profiles for improved disease detection and monitoring., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Physical activity is associated with decreased incidence of the chronic diseases associated with aging. We previously demonstrated that digital interventions delivered through a smartphone app can increase short-term physical activity., Methods and Results: We offered enrolment to community-living iPhone-using adults aged ≥18 years in the USA, UK, and Hong Kong who downloaded the MyHeart Counts app. After completion of a 1-week baseline period, e-consented participants were randomized to four 7-day interventions. Interventions consisted of: (i) daily personalized e-coaching based on the individual's baseline activity patterns, (ii) daily prompts to complete 10 000 steps, (iii) hourly prompts to stand following inactivity, and (iv) daily instructions to read guidelines from the American Heart Association (AHA) website. After completion of one 7-day intervention, participants subsequently randomized to the next intervention of the crossover trial. The trial was completed in a free-living setting, where neither the participants nor investigators were blinded to the intervention. The primary outcome was change in mean daily step count from baseline for each of the four interventions, assessed in a modified intention-to-treat analysis (modified in that participants had to complete 7 days of baseline monitoring and at least 1 day of an intervention to be included in analyses). This trial is registered with ClinicalTrials.gov, NCT03090321., Conclusion: Between 1 January 2017 and 1 April 2022, 4500 participants consented to enrol in the trial (a subset of the approximately 50 000 participants in the larger MyHeart Counts study), of whom 2458 completed 7 days of baseline monitoring (mean daily steps 4232 ± 73) and at least 1 day of one of the four interventions. Personalized e-coaching prompts, tailored to an individual based on their baseline activity, increased step count significantly (+402 ± 71 steps from baseline, P = 7.1⨯10 -8 ). Hourly stand prompts (+292 steps from baseline, P = 0.00029) and a daily prompt to read AHA guidelines (+215 steps from baseline, P = 0.021) were significantly associated with increased mean daily step count, while a daily reminder to complete 10 000 steps was not (+170 steps from baseline, P = 0.11). Digital studies have a significant advantage over traditional clinical trials in that they can continuously recruit participants in a cost-effective manner, allowing for new insights provided by increased statistical power and refinement of prior signals. Here, we present a novel finding that digital interventions tailored to an individual are effective in increasing short-term physical activity in a free-living cohort. These data suggest that participants are more likely to react positively and increase their physical activity when prompts are personalized. Further studies are needed to determine the effects of digital interventions on long-term outcomes., Competing Interests: Conflict of interest: M.T.W. reports grants and personal fees from Verily, Myokardia, and ArrayBio, and consultancy fees from BioTelemetry, outside the submitted work. E.A.A. reports advisory board fees from Apple and Foresite Labs. E.A.A. has ownership interest in Nuevocor, DeepCell, and Personalis, outside the submitted work. E.A.A. is a board member of AstraZeneca. E.A.A. and C.M.M. have ownership interest in SVEXA, outside of the submitted work. M.V.M. is an employee at identifeye HEALTH, a previous employee at Google/Fitbit (until 2022), a member of the medical advisory board of 4Catalyzer Corp., and on the board of directors of the National Fitness Foundation. S.G.H. is an employee of Biofourmis. D.S.K. is supported by the Wu-Tsai Human Performance Alliance. The remainder of authors report no potential conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Digital technology is now an integral part of medicine. Tools for detecting, screening, diagnosis, and monitoring health-related parameters have improved patient care and enabled individuals to identify issues leading to better management of their own health. Wearable technologies have integrated sensors and can measure physical activity, heart rate and rhythm, and glucose and electrolytes. For individuals at risk, wearables or other devices may be useful for early detection of atrial fibrillation or sub-clinical states of cardiovascular disease, disease management of cardiovascular diseases such as hypertension and heart failure, and lifestyle modification. Health data are available from a multitude of sources, namely clinical, laboratory and imaging data, genetic profiles, wearables, implantable devices, patient-generated measurements, and social and environmental data. Artificial intelligence is needed to efficiently extract value from this constantly increasing volume and variety of data and to help in its interpretation. Indeed, it is not the acquisition of digital information, but rather the smart handling and analysis that is challenging. There are multiple stakeholder groups involved in the development and effective implementation of digital tools. While the needs of these groups may vary, they also have many commonalities, including the following: a desire for data privacy and security; the need for understandable, trustworthy, and transparent systems; standardized processes for regulatory and reimbursement assessments; and better ways of rapidly assessing value., Competing Interests: Conflict of interest: C.L. receives consulting fees from Medtronic, Boston Scientific, Abbott, and Biotronik; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Medtronic, Boston Scientific, Abbott, and Biotronik. H.W. has stock or stock options from Pfizer. R.P.K. has stock or stock options from Medtronic; and employment by Medtronic. D.A. has multiple patents including those for AliveCor, and GE assignments; stock or stock options from AliveCor, Inc.; and salary/officer position with AliveCor, Inc. M.R.C. receives consulting fees from AstraZeneca, Servier, Medtronic, and Abbott; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Servier, Medtronic, Abbott, and Bayer; served as Chair for ESC-Digital Health Committee (unpaid), Chair for Clinical Advisory Board of Pumping Marvellous Foundation (unpaid), Trustee of the Atrial Fibrillation Association (unpaid), and Non-executive Director of NICE from 2016-2020 (paid). T.D. receives consulting fees from Farapulse; payment or honoraria for lectures from Biotronik and Abbott; participation on a clinical events committee for Boston Scientific; served as a board member for the German Cardiology Society. P.F. participated on advisory board for Abbot, Medtronic, and Boston Scientific; IP, licensing fees, and equity stake via Mayo Clinic (employer) in AliveCor, EkoHealth, and Anuman. I.L. has stock or stock options from Amgen; and employment by Amgen. M.V.M. served as Co-Chair for the Consumer Technology Association (CTA)-American College of Cardiology (ACC) CV Technology Working Group; stock or stock options from Google; and employment by Google. L.R. supports for the present manuscript from Medtronic; employment by Medtronic. E.S. has stock or stock options from GE Healthcare; and employment by GE Vingmed Ultrasound AS. M.P.T. receives consulting fees from Medtronic, Abbott, Biotronik, Sanofi, Pfizer, Bayer, Myokardia, Johnson & Johnson, Milestone Pharmaceuticals, InCarda Pharmaceuticals, 100Plus, AliveCor, Actus Medical, and BrightInsight; grants from Bristol-Myers Squibb, American Heart Association, Apple, Bayer, and the US Food and Drug Administration; and editorship with JAMA Cardiology. J.P.S. receives consulting fees from Abbott, Biotronik, Boston Scientific, Cardiologs, CVRx, Cardiac Rhythm Group, EBR, Impulse Dynamics, Implicity, Medtronic, Medscape, Microport, New Century Health, Nopras, Orchestra BioMed, Octagos Health, and Sanofi. E.S. receives institutional research grants from the Stockholm County Council, the Åke Wiberg Foundation, and the Swedish Heart Foundation; consulting fees from Bayer, Bristol-Myers Squibb-Pfizer, Boehringer-Ingelheim, Johnson & Johnson, Merck Sharp & Dohme; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Bayer, Johnson & Johnson, Merck Sharp & Dohme, Bristol-Myers Squibb-Pfizer, Boehringer-Ingelheim; participation on a data safety monitoring board or advisory board for Bristol-Myers Squibb-Pfizer; board membership for the European Heart Rhythm Association (EHRA), served as Chair of the Digital Committee for EHRA, and membership on the Digital Committee of the Heart Rhythm Society. M.W. supports for the present manuscript from Biotelemetry; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Biotelemetry; support for meeting attendance and/or travel from Biotelemetry; patents for Biotelemetry; stock or stock options from Biotelemetry. Other authors have none to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Disruption of vulnerable atherosclerotic plaques often leads to myocardial infarction and stroke, the leading causes of morbidity and mortality in the United States. A diagnostic method that detects high-risk atherosclerotic plaques at early stages could prevent these sequelae. The abundance of immune cells in the arterial wall, especially inflammatory Ly-6C hi monocytes and foamy macrophages, is indicative of plaque‎ inflammation, and may be associated with plaque vulnerability. Hence, we sought to develop a new method that specifically targets these immune cells to offer clinically-relevant diagnostic information about cardiovascular disease. We combine ultra-selective nanoparticle targeting of Ly-6C hi monocytes and foamy macrophages with clinically-viable photoacoustic imaging (PAI) in order to precisely and specifically image inflamed plaques ex vivo in a mouse model that mimics human vulnerable plaques histopathologically. Within the plaques, high-dimensional single-cell flow cytometry (13-parameter) showed that our nanoparticles were almost-exclusively taken up by the Ly-6C hi monocytes and foamy macrophages that heavily infiltrate plaques. PAI identified inflamed atherosclerotic plaques that display ~6-fold greater signal compared to controls ( P <0.001) six hours after intravenous injection of ultra-selective carbon nanotubes, with in vivo corroboration via optical imaging. Our highly selective strategy may provide a targeted, non-invasive imaging strategy to accurately identify and diagnose inflamed atherosclerotic lesions.

Background: Maximal oxygen consumption (VO 2 max) is one of the most predictive biometrics for cardiovascular health and overall mortality. However, VO 2 max is rarely measured in large-scale research studies or routine clinical care because of the high cost, participant burden, and requirement for specialized equipment and staff., Objective: To overcome the limitations of clinical VO 2 max measurement, we aim to develop a digital VO 2 max estimation protocol that can be self-administered remotely using only the sensors within a smartphone. We also aim to validate this measure within a broadly representative population across a spectrum of smartphone devices., Methods: Two smartphone-based VO 2 max estimation protocols were developed: a 12-minute run test (12-MRT) based on distance measured by GPS and a 3-minute step test (3-MST) based on heart rate recovery measured by a camera. In a 101-person cohort, balanced across age deciles and sex, participants completed a gold standard treadmill-based VO 2 max measurement, two silver standard clinical protocols, and the smartphone-based 12-MRT and 3-MST protocols in the clinic and at home. In a separate 120-participant cohort, the video-based heart rate measurement underlying the 3-MST was measured for accuracy in individuals across the spectrum skin tones while using 8 different smartphones ranging in cost from US $99 to US $999., Results: When compared with gold standard VO 2 max testing, Lin concordance was p c =0.66 for 12-MRT and p c =0.61 for 3-MST. However, in remote settings, the 12-MRT was significantly less concordant with the gold standard (p c =0.25) compared with the 3-MST (p c =0.61), although both had high test-retest reliability (12-MRT intraclass correlation coefficient=0.88; 3-MST intraclass correlation coefficient=0.86). On the basis of the finding that 3-MST concordance was generalizable to remote settings whereas 12-MRT was not, the video-based heart rate measure within the 3-MST was selected for further investigation. Heart rate measurements in any of the combinations of the six Fitzpatrick skin tones and 8 smartphones resulted in a concordance of p c ≥0.81. Performance did not correlate with device cost, with all phones selling under US $200 performing better than p c >0.92., Conclusions: These findings demonstrate the importance of validating mobile health measures in the real world across a diverse cohort and spectrum of hardware. The 3-MST protocol, termed as heart snapshot, measured VO 2 max with similar accuracy to supervised in-clinic tests such as the Tecumseh (p c =0.94) protocol, while also generalizing to remote and unsupervised measurements. Heart snapshot measurements demonstrated fidelity across demographic variation in age and sex, across diverse skin pigmentation, and between various iOS and Android phone configurations. This software is freely available for all validation data and analysis code., (©Dan E Webster, Meghasyam Tummalacherla, Michael Higgins, David Wing, Euan Ashley, Valerie E Kelly, Michael V McConnell, Evan D Muse, Jeffrey E Olgin, Lara M Mangravite, Job Godino, Michael R Kellen, Larsson Omberg. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 04.06.2021.)

Contact tracing is increasingly used to combat COVID-19, and digital implementations are now being deployed, many based on Apple and Google's Exposure Notification System. These systems utilize non-traditional smartphone-based technology, presenting challenges in understanding possible outcomes. In this work, we create individual-based models of three Washington state counties to explore how digital exposure notifications combined with other non-pharmaceutical interventions influence COVID-19 disease spread under various adoption, compliance, and mobility scenarios. In a model with 15% participation, we found that exposure notification could reduce infections and deaths by approximately 8% and 6% and could effectively complement traditional contact tracing. We believe this can provide health authorities in Washington state and beyond with guidance on how exposure notification can complement traditional interventions to suppress the spread of COVID-19.

Each decade, the American Heart Association (AHA) develops an Impact Goal to guide its overall strategic direction and investments in its research, quality improvement, advocacy, and public health programs. Guided by the AHA's new Mission Statement, to be a relentless force for a world of longer, healthier lives, the 2030 Impact Goal is anchored in an understanding that to achieve cardiovascular health for all, the AHA must include a broader vision of health and well-being and emphasize health equity. In the next decade, by 2030, the AHA will strive to equitably increase healthy life expectancy beyond current projections, with global and local collaborators, from 66 years of age to at least 68 years of age across the United States and from 64 years of age to at least 67 years of age worldwide. The AHA commits to developing additional targets for equity and well-being to accompany this overarching Impact Goal. To attain the 2030 Impact Goal, we recommend a thoughtful evaluation of interventions available to the public, patients, providers, healthcare delivery systems, communities, policy makers, and legislators. This presidential advisory summarizes the task force's main considerations in determining the 2030 Impact Goal and the metrics to monitor progress. It describes the aspiration that these goals will be achieved by working with a diverse community of volunteers, patients, scientists, healthcare professionals, and partner organizations needed to ensure success.

Background: Smartphone apps might enable interventions to increase physical activity, but few randomised trials testing this hypothesis have been done. The MyHeart Counts Cardiovascular Health Study is a longitudinal smartphone-based study with the aim of elucidating the determinants of cardiovascular health. We aimed to investigate the effect of four different physical activity coaching interventions on daily step count in a substudy of the MyHeart Counts Study., Methods: In this randomised, controlled crossover trial, we recruited adults (aged ≥18 years) in the USA with access to an iPhone smartphone (Apple, Cupertino, CA, USA; version 5S or newer) who had downloaded the MyHeart Counts app (version 2.0). After completion of a 1 week baseline period of interaction with the MyHeart Counts app, participants were randomly assigned to receive one of 24 permutations (four combinations of four 7 day interventions) in a crossover design using a random number generator built into the app. Interventions consisted of either daily prompts to complete 10 000 steps, hourly prompts to stand following 1 h of sitting, instructions to read the guidelines from the American Heart Association website, or e-coaching based upon the individual's personal activity patterns from the baseline week of data collection. Participants completed the trial in a free-living setting. Due to the nature of the interventions, participants could not be masked from the intervention. Investigators were not masked to intervention allocation. The primary outcome was change in mean daily step count from baseline for each of the four interventions, assessed in the modified intention-to-treat analysis set, which included all participants who had completed 7 days of baseline monitoring and at least 1 day of one of the four interventions. This trial is registered with ClinicalTrials.gov, NCT03090321., Findings: Between Dec 12, 2016, and June 6, 2018, 2783 participants consented to enrol in the coaching study, of whom 1075 completed 7 days of baseline monitoring and at least 1 day of one of the four interventions and thus were included in the modified intention-to-treat analysis set. 493 individuals completed the full set of assigned interventions. All four interventions significantly increased mean daily step count from baseline (mean daily step count 2914 [SE 74]): mean step count increased by 319 steps (75) for participants in the American Heart Association website prompt group (p<0·0001), 267 steps (74) for participants in the hourly stand prompt group (p=0·0003), 254 steps (74) for participants in the cluster-specific prompts group (p=0·0006), and by 226 steps (75) for participants in the 10 000 daily step prompt group (p=0·0026 vs baseline)., Interpretation: Four smartphone-based physical activity coaching interventions significantly increased daily physical activity. These findings suggests that digital interventions delivered via a mobile app have the ability to increase short-term physical activity levels in a free-living cohort., Funding: Stanford Data Science Initiative., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Thin-cap fibroatheroma (TCFA) are the unstable lesions in coronary artery disease that are prone to rupture, resulting in substantial morbidity and mortality worldwide. However, their small size and complex morphologic and biologic features make early detection and risk assessment difficult. We tested our newly developed catheter-based C ircumferential- I ntravascular- R adioluminescence- P hotoacoustic- I maging (CIRPI) system in vivo to enable detection and characterization of vulnerable plaque structure and biology in rabbit abdominal aorta. Methods: The CIRPI system includes a novel optical probe combining circumferential radioluminescence imaging and photoacoustic tomography (PAT). The probe's CaF 2 :Eu-based scintillating imaging window captures radioluminescence images (360° view) of plaques by detecting β-particles during 18 F-FDG decay. A tunable laser-based PAT characterizes tissue constituents of plaque at 7 different wavelengths-540 and 560 nm (calcification), 920 nm (cholesteryl ester), 1040 nm (phospholipids), 1180 nm (elastin/collagen), 1210 nm (cholesterol), and 1235 nm (triglyceride). A single B-scan is concatenated from 330 A-lines captured during a 360° rotation. The abdominal aorta was imaged in vivo in both atherosclerotic rabbits (Watanabe Heritable Hyper Lipidemic [WHHL], 13-mo-old male, n = 5) and controls (New Zealand White, n = 2). Rabbits were fasted for 6 h before 5.55 × 10 7 Bq (1.5 mCi) of 18 F-FDG were injected 1 h before the imaging procedure. Rabbits were anesthetized, and the right or left common carotid artery was surgically exposed. An 8 French catheter sheath was inserted into the common carotid artery, and a 0.035-cm (0.014-in) guidewire was advanced to the iliac artery, guided by x-ray fluoroscopy. A bare metal stent was implanted in the dorsal abdominal aorta as a landmark, followed by the 7 French imaging catheters that were advanced up to the proximal stent edge. Our CIRPI and clinical optical coherence tomography (OCT) were performed using pullback and nonocclusive flushing techniques. After imaging with the CIRPI system, the descending aorta was flushed with contrast agent, and OCT images were obtained with a pullback speed of 20 mm/s, providing images at 100 frames/s. Results were verified with histochemical analysis. Results: Our CIRPI system successfully detected the locations and characterized both stable and vulnerable aortic plaques in vivo among all WHHL rabbits. Calcification was detected from the stable plaque (540 and 560 nm), whereas TCFA exhibited phospholipids/cholesterol (1040 nm, 1210 nm). These findings were further verified with the clinical OCT system showing an area of low attenuation filled with lipids within TCFA. PAT images illustrated broken elastic fiber/collagen that could be verified with the histochemical analysis. All WHHL rabbits exhibited sparse to severe macrophages. Only 4 rabbits showed both moderate-to-severe level of calcifications and cholesterol clefts. However, all rabbits exhibited broken elastic fibers and collagen deposition. Control rabbits showed normal wall thickness with no presence of plaque tissue compositions. These findings were verified with OCT and histochemical analysis. Conclusion: Our novel multimodality hybrid system has been successfully translated to in vivo evaluation of atherosclerotic plaque structure and biology in a preclinical rabbit model. This system proposed a paradigm shift that unites molecular and pathologic imaging technologies. Therefore, the system may enhance the clinical evaluation of TCFA, as well as expand our understanding of coronary artery disease., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To demonstrate the association between coronary vessel wall thickness (VWT) measured at MRI and coronary artery disease (CAD) risk in asymptomatic groups at low and intermediate risk on the basis of Framingham score., Materials and Methods: A total of 131 asymptomatic adults were prospectively enrolled. All participants underwent CT angiography for scoring CAD, and coronary VWT was measured at 3.0-T MRI. Nonlinear single and multivariable regression analyses with consideration for interaction with sex were performed to investigate the association of traditional atherosclerotic risk factors and VWT with CT angiography-based CAD scores., Results: The analysis included 62 women and 62 men with low or intermediate Framingham score of less than 20%. Age (mean age, 45.0 years ± 14.5 [standard deviation]) and body mass index were not different between the groups. Age, sex, and VWT were individually significantly associated with all CT angiography-based CAD scores ( P < .05). Additionally, sex was a significant effect modifier of the associations with all CAD scores. In men, age was the only statistically significant independent risk factor of CAD; in women, VWT was the only statistically significant independent surrogate associated with increased CAD scores ( P < .05)., Conclusion: In asymptomatic women, VWT MRI was the primary independent surrogate of CAD, whereas age was the strongest risk factor in men. This study suggests that VWT may be used as a CAD surrogate in women at low or intermediate risk of CAD. Further longitudinal studies are required to determine the potential implication and use of this MRI technique for the preventative management of CAD in women.© RSNA, 2019., (2019 by the Radiological Society of North America, Inc.)

Convenient and painless blood pressure measurement can enable increased user adoption of regular monitoring and early intervention for hypertension, which is a significant cause of mortality worldwide. This paper introduces a fingerwearable blood pressure measurement device to enable frequent daytime and nocturnal monitoring. The blood pressure measurement is achieved using a two-dimensional capacitive tactile sensor array that is located next to a digital artery. A pumpdriven pneumatic bladder presses the tactile array and the finger towards each other to obtain a pressure sweep versus time. The digital artery pressure waveform data collected during this sweep are used to estimate arterial blood pressure. A clinical study (N =97) was conducted to obtain training (N =49) and validation (N =19) data for blood pressure algorithm development and test (N =29) data to determine the estimation accuracy compared to brachial dual-observer auscultation. On the test set, the mean and standard deviation of the error in the systolic blood pressure estimate are 0.9 mmHg and 6.9 mmHg, respectively, while the corresponding quantities for diastolic blood pressure are -3.2 mmHg and 7.0 mmHg, respectively. These results compare favorably to blood pressure accuracy requirements specified by international standards.

Atherosclerosis is a progressive inflammatory condition caused by an unstable lesion, called thin-cap fibro atheromata (TCFA) that underlies coronary artery disease (CAD)-one of the leading causes of death worldwide. Therefore, early clinical diagnosis and effective risk stratification is important for CAD management as well as preventing progression to catastrophic events. However, early detection could be difficult due to their small size, motion, obscuring 18 F-FDG uptake by adjacent myocardium, and complex morphological/biological features. To overcome these limitations, we developed a catheter-based Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system that can detect vulnerable plaques in coronary arteries and characterizes them with respect to pathology and biology. Our CIRPI system combined two imaging modalities: Circumferential Radioluminescence Imaging (CRI) and PhotoAcoustic Tomography (PAT) within a novel optical probe. The probe's CaF 2 :Eu based scintillating imaging window provides a 360° view of human (n = 7) and murine carotid (n = 10) arterial plaques by converting β-particles into visible photons during 18 F-FDG decay. A 60× and 63× higher radioluminescent signals were detected from the human and murine plaque inflammations, respectively, compared to the control. The system's photoacoustic imaging provided a comprehensive analysis of the plaque compositions and its morphologic information. These results were further verified with IVIS-200, immunohistochemical analysis, and autoradiography.

The growing recognition that "health" takes place outside of the hospital and clinic, plus recent advances in mobile and wearable devices, have propelled the field of mobile health (mHealth). Cardiovascular disease and prevention are major opportunities for mHealth, as mobile devices can monitor key physiological signals (e.g., physical activity, heart rate and rhythm) for promoting healthy behaviors, detecting disease, and aid in ongoing care. In this review, the authors provide an update on cardiovascular mHealth by highlighting recent progress and challenges with mobile and wearable devices for assessing and promoting physical activity and fitness, and for monitoring heart rate and rhythm for the detection and management of atrial fibrillation., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Traditionally, medical discoveries are made by observing associations, making hypotheses from them and then designing and running experiments to test the hypotheses. However, with medical images, observing and quantifying associations can often be difficult because of the wide variety of features, patterns, colours, values and shapes that are present in real data. Here, we show that deep learning can extract new knowledge from retinal fundus images. Using deep-learning models trained on data from 284,335 patients and validated on two independent datasets of 12,026 and 999 patients, we predicted cardiovascular risk factors not previously thought to be present or quantifiable in retinal images, such as age (mean absolute error within 3.26 years), gender (area under the receiver operating characteristic curve (AUC) = 0.97), smoking status (AUC = 0.71), systolic blood pressure (mean absolute error within 11.23 mmHg) and major adverse cardiac events (AUC = 0.70). We also show that the trained deep-learning models used anatomical features, such as the optic disc or blood vessels, to generate each prediction.

Objectives: Myocardial infarction (MI) causes significant loss of cardiomyocytes, myocardial tissue damage, and impairment of myocardial function. The inability of cardiomyocytes to proliferate prevents the heart from self-regeneration. The treatment for advanced heart failure following an MI is heart transplantation despite the limited availability of the organs. Thus, stem-cell-based cardiac therapies could ultimately prevent heart failure by repairing injured myocardium that reverses cardiomyocyte loss. However, stem-cell-based therapies lack understanding of the mechanisms behind a successful therapy, including difficulty tracking stem cells to provide information on cell migration, proliferation and differentiation. In this study, we have investigated the interaction between different types of stem and inflammatory cells and cell-targeted imaging molecules, 18F-FDG and 6-NBDG, to identify uptake patterns and pharmacokinetics in vitro., Methods: Macrophages (both M1 and M2), human induced pluripotent stem cells (hiPSCs), and human amniotic mesenchymal stem cells (hAMSCs) were incubated with either 18F-FDG or 6-NBDG. Excess radiotracer and fluorescence were removed and a 100 μm-thin CdWO4 scintillator plate was placed on top of the cells for radioluminescence microscopy imaging of 18F-FDG uptake, while no scintillator was needed for fluorescence imaging of 6-NBDG uptake. Light produced following beta decay was imaged with a highly sensitive inverted microscope (LV200, Olympus) and an Electron Multiplying Charge-Couple Device (EM-CCD) camera. Custom-written software was developed in MATLAB for image processing., Results: The average cellular activity of 18F-FDG in a single cell of hAMSCs (0.670±0.028 fCi/μm2, P = 0.001) was 20% and 36% higher compared to uptake in hiPSCs (0.540±0.026 fCi/μm2, P = 0.003) and macrophages (0.430±0.023 fCi/μm2, P = 0.002), respectively. hAMSCs exhibited the slowest influx (0.210 min-1) but the fastest efflux (0.327 min-1) rate compared to the other tested cell lines for 18F-FDG. This cell line also has the highest phosphorylation but exhibited the lowest rate of de-phosphorylation. The uptake pattern for 6-NBDG was very different in these three cell lines. The average cellular activity of 6-NBDG in a single cell of macrophages (0.570±0.230 fM/μm2, P = 0.004) was 38% and 14% higher compared to hiPSCs (0.350±0.160 fM/μm2, P = 0.001) and hAMSCs (0.490±0.028 fM/μm2, P = 0.006), respectively. The influx (0.276 min-1), efflux (0.612 min-1), phosphorylation (0.269 min-1), and de-phosphorylation (0.049 min-1) rates were also highest for macrophages compared to the other two tested cell lines., Conclusion: hAMSCs were found to be 2-3× more sensitive to 18F-FDG molecule compared to hiPSCs/macrophages. However, macrophages exhibited the most sensitivity towards 6-NBDG. Based on this result, hAMSCs targeted with 18F-FDG could be more suitable for understanding the mechanisms behind successful therapy for treating MI patients by gathering information on cell migration, proliferation and differentiation.

Objectives: The study investigated whether a dose response exists between myocardial salvage and the depth of therapeutic hypothermia., Background: Cardiac protection from mild hypothermia during acute myocardial infarction (AMI) has yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve myocardial salvage., Methods: Swine (n = 24) undergoing AMI were assigned to 3 reperfusion groups: normothermia (38°C) and mild (35°C) and moderate (32°C) hypothermia. One-hour anterior myocardial ischemia was followed by rapid endovascular cooling to target reperfusion temperature. Cooling began 30 min before reperfusion. Target temperature was reached before reperfusion and was maintained for 60 min. Infarct size (IS) was assessed on day 6 using cardiac magnetic resonance, triphenyl tetrazolium chloride, and histopathology., Results: Triphenyl tetrazolium chloride area at risk (AAR) was equivalent in all groups (p = 0.2), but 32°C exhibited 77% and 91% reductions in IS size per AAR compared with 35°C and 38°C, respectively (AAR: 38°C, 45 ± 12%; 35°C, 17 ± 10%; 32°C, 4 ± 4%; p < 0.001) and comparable reductions per LV mass (LV mass: 38°C, 14 ± 5%; 35°C, 5 ± 3%; 32°C 1 ± 1%; p < 0.001). Importantly, 32°C showed a lower IS AAR (p = 0.013) and increased immunohistochemical granulation tissue versus 35°C, indicating higher tissue salvage. Delayed-enhancement cardiac magnetic resonance IS LV also showed marked reduction at 32°C (38°C: 10 ± 4%, p < 0.001; 35°C: 8 ± 3%; 32°C: 3 ± 2%, p < 0.001). Cardiac output on day 6 was only preserved at 32°C (reduction in cardiac output: 38°C, -29 ± 19%, p = 0.041; 35°C: -17 ± 33%; 32°C: -1 ± 28%, p = 0.041). Using linear regression, the predicted IS reduction was 6.7% (AAR) and 2.1% (LV) per every 1°C reperfusion temperature decrease., Conclusions: Moderate (32°C) therapeutic hypothermia demonstrated superior and near-complete cardioprotection compared with 35°C and control, warranting further investigation into clinical applications., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Right ventricular (RV) adaptation to pressure overload is a major prognostic factor in patients with pulmonary arterial hypertension (PAH). The objectives were first to define the relation between RV adaptation and load using allometric modeling, then to compare the prognostic value of different indices of load adaptability in PAH. Both a derivation (n = 85) and a validation cohort (n = 200) were included. Load adaptability was assessed using 3 approaches: (1) surrogates of ventriculo-arterial coupling (e.g., RV area change/end-systolic area), (2) simple ratio of function and load (e.g., tricuspid annular plane systolic excursion/right ventricular systolic pressure), and (3) indices assessing the proportionality of adaptation using allometric pressure-function or size modeling. Proportional hazard modeling was used to compare the hazard ratio for the outcome of death or lung transplantation. The mean age of the derivation cohort was 44 ± 11 years, with 80% female and 74% in New York Heart Association class III or IV. Mean pulmonary vascular resistance index (PVRI) was 24 ± 11 with a wide distribution (1.6 to 57.5 WU/m 2 ). Allometric relations were observed between PVRI and RV fractional area change (R 2  = 0.53, p < 0.001) and RV end-systolic area indexed to body surface area right ventricular end-systolic area index (RVESAI) (R 2  = 0.29, p < 0.001), allowing the derivation of simple ratiometric load-specific indices of RV adaptation. In right heart parameters, RVESAI was the strongest predictor of outcomes (hazard ratio per SD = 1.93, 95% confidence interval 1.37 to 2.75, p < 0.001). Although RVESAI/PVRI 0.35 provided small incremental discrimination on multivariate modeling, none of the load-adaptability indices provided stronger discrimination of outcome than simple RV adaptation metrics in either the derivation or the validation cohort. In conclusion, allometric modeling enables quantification of the proportionality of RV load adaptation but offers small incremental prognostic value to RV end-systolic dimension in PAH., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: We tested whether providing a genetic risk score (GRS) for coronary artery disease (CAD) would serve as a motivator to improve adherence to risk-reducing strategies., Methods: We randomized 94 participants with at least moderate risk of CAD to receive standard-of-care with ( N  = 49) or without ( N  = 45) their GRS at a subsequent 3-month follow-up visit. Our primary outcome was change in low density lipoprotein cholesterol (LDL-C) between the 3- and 6-month follow-up visits (ΔLDL-C). Secondary outcomes included other CAD risk factors, weight loss, diet, physical activity, risk perceptions, and psychological outcomes. In pre-specified analyses, we examined whether there was a greater motivational effect in participants with a higher GRS., Results: Sixty-five participants completed the protocol including 30 participants in the GRS arm. We found no change in the primary outcome between participants receiving their GRS and standard-of-care participants (ΔLDL-C: -13 vs. -9 mg/dl). Among participants with a higher GRS, we observed modest effects on weight loss and physical activity. All other secondary outcomes were not significantly different, including anxiety and worry., Conclusion: Adding GRS to standard-of-care did not change lipids, adherence, or psychological outcomes. Potential modest benefits in weight loss and physical activity for participants with high GRS need to be validated in larger trials.

This study determined whether novel right heart echocardiography metrics help to detect pulmonary hypertension (PH) in patients with advanced lung disease (ALD). We reviewed echocardiography and catheterization data of 192 patients from the Stanford ALD registry and echocardiograms of 50 healthy controls. Accuracy of echocardiographic right heart metrics to detect PH was assessed using logistic regression and area under the ROC curves (AUC) analysis. Patients were divided into a derivation (n = 92) and validation cohort (n = 100). Experimental validation was assessed in a piglet model of mild PH followed longitudinally. Tricuspid regurgitation (TR) was not interpretable in 52% of patients. In the derivation cohort, right atrial maximal volume index (RAVI), ventricular end-systolic area index (RVESAI), free-wall longitudinal strain and tricuspid annular plane systolic excursion (TAPSE) differentiated patients with and without PH; 20% of patients without PH had moderate to severe RV enlargement by RVESAI. On multivariate analysis, RAVI and TAPSE were independently associated with PH (AUC = 0.77, p < 0.001), which was confirmed in the validation cohort (0.78, p < 0.001). Presence of right heart metrics abnormalities did not improve detection of PH in patients with interpretable TR (p > 0.05) and provided moderate detection value in patients without TR. Only two patients with more severe PH (mean pulmonary pressure 35 and 36 mmHg) were missed. The animal model confirmed that right heart enlargement discriminated best pigs with PH from shams. This study highlights the frequency of right heart enlargement and dysfunction in ALD irrespectively from presence of PH, therefore limiting their use for detection of PH.

Because of their growing popularity and functionality, smartphones are increasingly valuable potential tools for health and medical research. Using ResearchKit, Apple's open-source platform to build applications ("apps") for smartphone research, collaborators have developed apps for researching asthma, breast cancer, cardiovascular disease, type 2 diabetes, and Parkinson disease. These research apps enhance widespread participation by removing geographical barriers to participation, provide novel ways to motivate healthy behaviors, facilitate high-frequency assessments, and enable more objective data collection. Although the studies have great potential, they also have notable limitations. These include selection bias, identity uncertainty, design limitations, retention, and privacy. As smartphone technology becomes increasingly available, researchers must recognize these factors to ensure that medical research is conducted appropriately. Despite these limitations, the future of smartphones in health research is bright. Their convenience grants unprecedented geographic freedom to researchers and participants alike and transforms the way clinical research can be conducted.

Importance: Studies have established the importance of physical activity and fitness, yet limited data exist on the associations between objective, real-world physical activity patterns, fitness, sleep, and cardiovascular health., Objectives: To assess the feasibility of obtaining measures of physical activity, fitness, and sleep from smartphones and to gain insights into activity patterns associated with life satisfaction and self-reported disease., Design, Setting, and Participants: The MyHeart Counts smartphone app was made available in March 2015, and prospective participants downloaded the free app between March and October 2015. In this smartphone-based study of cardiovascular health, participants recorded physical activity, filled out health questionnaires, and completed a 6-minute walk test. The app was available to download within the United States., Main Outcomes and Measures: The feasibility of consent and data collection entirely on a smartphone, the use of machine learning to cluster participants, and the associations between activity patterns, life satisfaction, and self-reported disease., Results: From the launch to the time of the data freeze for this study (March to October 2015), the number of individuals (self-selected) who consented to participate was 48 968, representing all 50 states and the District of Columbia. Their median age was 36 years (interquartile range, 27-50 years), and 82.2% (30 338 male, 6556 female, 10 other, and 3115 unknown) were male. In total, 40 017 (81.7% of those who consented) uploaded data. Among those who consented, 20 345 individuals (41.5%) completed 4 of the 7 days of motion data collection, and 4552 individuals (9.3%) completed all 7 days. Among those who consented, 40 017 (81.7%) filled out some portion of the questionnaires, and 4990 (10.2%) completed the 6-minute walk test, made available only at the end of 7 days. The Heart Age Questionnaire, also available after 7 days, required entering lipid values and age 40 to 79 years (among 17 245 individuals, 43.1% of participants). Consequently, 1334 (2.7%) of those who consented completed all fields needed to compute heart age and a 10-year risk score. Physical activity was detected for a mean (SD) of 14.5% (8.0%) of individuals' total recorded time. Physical activity patterns were identified by cluster analysis. A pattern of lower overall activity but more frequent transitions between active and inactive states was associated with equivalent self-reported cardiovascular disease as a pattern of higher overall activity with fewer transitions. Individuals' perception of their activity and risk bore little relation to sensor-estimated activity or calculated cardiovascular risk., Conclusions and Relevance: A smartphone-based study of cardiovascular health is feasible, and improvements in participant diversity and engagement will maximize yield from consented participants. Large-scale, real-world assessment of physical activity, fitness, and sleep using mobile devices may be a useful addition to future population health studies.

Background: Despite evidence for higher risk of coronary artery disease among HIV+ individuals, the underlying mechanisms are not well understood. We investigated associations of inflammatory markers with subclinical coronary artery disease in 923 participants of the Multicenter AIDS Cohort Study (575 HIV+ and 348 HIV- men) who underwent noncontrast computed tomography scans for coronary artery calcification, the majority (n=692) also undergoing coronary computed tomography angiography., Methods and Results: Outcomes included presence and extent of coronary artery calcification, plus computed tomography angiography analysis of presence, composition, and extent of coronary plaques and severity of coronary stenosis. HIV+ men had significantly higher levels of interleukin-6 (IL-6), intercellular adhesion molecule-1, C-reactive protein, and soluble-tumor necrosis factor-α receptor (sTNFαR) I and II (all P<0.01) and a higher prevalence of noncalcified plaque (63% versus 54%, P=0.02) on computed tomography angiography. Among HIV+ men, for every SD increase in log-interleukin-6 and log intercellular adhesion molecule-1, there was a 30% and 60% increase, respectively, in the prevalence of coronary stenosis ≥50% (all P<0.05). Similarly, sTNFαR I and II in HIV+ participants were associated with an increase in prevalence of coronary stenosis ≥70% (P<0.05). Higher levels of interleukin-6, sTNFαR I, and sTNFαR II were also associated with greater coronary artery calcification score in HIV+ men (P<0.01)., Conclusions: Higher inflammatory marker levels are associated with greater prevalence of coronary stenosis in HIV+ men. Our findings underscore the need for further study to elucidate the relationships of inflammatory pathways with coronary artery disease in HIV+ individuals., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Physical activity (PA) interventions constitute a critical component of cardiovascular disease (CVD) risk reduction programs. Objective mobile health (mHealth) software applications (apps) and wearable activity monitors (WAMs) can advance both assessment and integration of PA counseling in clinical settings and support community-based PA interventions. The use of mHealth technology for CVD risk reduction is promising, but integration into routine clinical care and population health management has proven challenging. The increasing diversity of available technologies and the lack of a comprehensive guiding framework are key barriers for standardizing data collection and integration. This paper reviews the validity, utility and feasibility of implementing mHealth technology in clinical settings and proposes an organizational framework to support PA assessment, counseling and referrals to community resources for CVD risk reduction interventions. This integration framework can be adapted to different clinical population needs. It should also be refined as technologies and regulations advance under an evolving health care system landscape in the United States and globally., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Purpose: Atherosclerosis is a leading cause of mortality worldwide, contributing to both strokes and heart attacks. Macrophages are key players in atherogenesis, promoting vascular inflammation and arterial remodeling through cysteine cathepsin proteases. We used a cathepsin-targeted activity-based probe in human carotid plaque to assess its diagnostic potential and evaluate macrophage subtypes ex vivo., Methods: Carotid plaque specimens surgically removed during endarterectomy from 62 patients (age range, 38% female, 28% symptomatic) were graded pathologically as either stable (Grade 1) or unstable (Grade 2 or 3). A cathepsin activity-based probe was used to quantify individual cathepsins in plaque tissue and macrophage subtypes., Results: Cathepsin B and S activities were increased in unstable carotid plaques. They were quantified using the probe to biochemically investigate individual cathepsins (Cathepsin B and S: 0.97 and 0.90 for grade 3 versus 0.51 and 0.59 for grade 1; P=0.006 and P=0.03 arbitrary units (AU), respectively). Higher cathepsin activity was observed in carotid plaques from symptomatic patients (Cathepsin B and S: 0.65 and 0.77 for asymptomatic, 0.99 and 1.17 for symptomatic; P=0.008 and P=0.005 AU, respectively). Additionally, it was demonstrated that M2 macrophages from unstable plaques express cathepsin activity 5-fold higher than M2 macrophages from stable plaques (25.52 versus 5.22; P=0.008 AU)., Conclusions: Targeting cathepsin activity in human carotid plaques may present a novel diagnostic tool for characterizing high-risk plaques. Novel cathepsin activity patterns within plaques and macrophage subpopulations suggest their involvement in the transition to active disease., (© 2016 American Heart Association, Inc.)

Regional right ventricular (RV) dysfunction (RRVD) is an echocardiographic feature in acute pulmonary embolism (PE), primarily reported in patients with moderate-to-severe RV dysfunction. This study investigated the clinical importance of RRVD by assessing its relationship with clot burden and biomarkers. We identified consecutive patients admitted to the emergency department between 1999 and 2014 who underwent computed tomographic angiography, echocardiography, and biomarker testing (troponin and NT-proBNP) for suspected acute PE. RRVD was defined as normal excursion of the apex contrasting with hypokinesis of the mid-free wall segment. RV assessment included measurements of ventricular dimensions, fractional area change, free-wall longitudinal strain and tricuspid annular plane systolic excursion. Clot burden was assessed using the modified Miller score. Of 82 patients identified, 51 had acute PE (mean age 66 ± 17 years, 43% male). No patient had RV myocardial infarction. RRVD was present in 41% of PEs and absent in all patients without PE. Among patients with PE, 86% of patients with RRVD had central or multi-lobar PE. Patients with RRVD had higher prevalence of moderate-to-severe RV dilation (81 vs. 30%, p < 0.01) and dysfunction (86 vs. 23%, p < 0.01). There was a strong trend for higher troponin level in PE patients with RRVD (38 vs. 13% in PE patients without RRVD, p = 0.08), while there was no significant difference for NT-proBNP (67 vs. 73%, p = 0.88). RRVD showed good concordance between readers (87%). RRVD is associated with an increased clot burden in acute PE and is more prevalent among patients with moderate-to-severe RV enlargement and dysfunction.

Background: There is currently controversy over whether echocardiography provides reliable estimations of pulmonary pressures. The objective of this study was to determine the factors influencing the accuracy and reliability of estimating right ventricular systolic pressure (RVSP) using echocardiography in patients with advanced lung disease or pulmonary arterial hypertension., Methods: Between January 2001 and December 2012, 667 patients with advanced lung disease or pulmonary arterial hypertension underwent right heart catheterization and transthoracic echocardiography. Of those, 307 had both studies within 5 days of each other. The correlation and bias in estimating RVSP according to tricuspid regurgitation (TR) signal quality and reader expertise were retrospectively determined. Reasons for under- and overestimation were analyzed. The diagnostic performance of estimated RVSP, relative right ventricular size, eccentricity index, and tricuspid annular plane systolic excursion was compared for classifying patients with pulmonary hypertension (mean pulmonary artery pressure ≥ 25 mm Hg)., Results: Invasive mean and systolic pulmonary artery pressures were strongly correlated (R(2) = 0.95, P < .001), with mean pulmonary artery pressure = 0.60 × systolic pulmonary artery pressure + 2.1 mm Hg. Among patients undergoing right heart catheterization and transthoracic echocardiography within 5 days, level 3 readers considered only 61% of TR signals interpretable, compared with 72% in clinical reports. Overestimation in the clinical report was related mainly to not assigning peak TR velocity at the modal frequency and underestimation to overreading of uninterpretable signals. When the TR signal was interpretable, the areas under the curve for classifying pulmonary hypertension were 0.97 for RVSP and 0.98 for RVSP and eccentricity index (P > .05). When TR signals were uninterpretable, eccentricity index and right ventricular size were independently associated with pulmonary hypertension (area under the curve, 0.77)., Conclusions: Echocardiography reliably estimates RVSP when attention is given to simple quality metrics., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop a self-gated alternating repetition time balanced steady-state free precession (ATR-SSFP) pulse sequence for fat-suppressed cardiac cine imaging., Methods: Cardiac gating is computed retrospectively using acquired magnetic resonance self-gating data, enabling cine imaging without the need for electrocardiogram (ECG) gating. Modification of the slice-select rephasing gradients of an ATR-SSFP sequence enables the acquisition of a one-dimensional self-gating readout during the unused short repetition time (TR). Self-gating readouts are acquired during every TR of segmented, breath-held cardiac scans. A template-matching algorithm is designed to compute cardiac trigger points from the self-gating signals, and these trigger points are used for retrospective cine reconstruction. The proposed approach is compared with ECG-gated ATR-SSFP and balanced steady-state free precession in 10 volunteers and five patients., Results: The difference of ECG and self-gating trigger times has a variability of 13 ± 11 ms (mean ± SD). Qualitative reviewer scoring and ranking indicate no statistically significant differences (P > 0.05) between self-gated and ECG-gated ATR-SSFP images. Quantitative blood-myocardial border sharpness is not significantly different among self-gated ATR-SSFP ( 0.61±0.15 mm -1), ECG-gated ATR-SSFP ( 0.61±0.15 mm -1), or conventional ECG-gated balanced steady-state free precession cine MRI ( 0.59±0.15 mm -1)., Conclusion: The proposed self-gated ATR-SSFP sequence enables fat-suppressed cardiac cine imaging at 1.5 T without the need for ECG gating and without decreasing the imaging efficiency of ATR-SSFP., (© 2014 Wiley Periodicals, Inc.)

Identification and treatment of abdominal aortic aneurysm (AAA) remain among the most prominent challenges in vascular medicine. MicroRNAs (miRNAs) are crucial regulators of cardiovascular pathology and represent intriguing targets to limit AAA expansion. Here we show, by using two established murine models of AAA disease along with human aortic tissue and plasma analysis, that miR-24 is a key regulator of vascular inflammation and AAA pathology. In vivo and in vitro studies reveal chitinase 3-like 1 (Chi3l1) to be a major target and effector under the control of miR-24, regulating cytokine synthesis in macrophages as well as their survival, promoting aortic smooth muscle cell migration and cytokine production, and stimulating adhesion molecule expression in vascular endothelial cells. We further show that modulation of miR-24 alters AAA progression in animal models, and that miR-24 and CHI3L1 represent novel plasma biomarkers of AAA disease progression in humans.

Purpose: Inflammation and angiogenesis are important contributors to vascular disease. We evaluated imaging both of these biological processes, using Arg-Gly-Asp (RGD)-conjugated human ferritin nanoparticles (HFn), in experimental carotid and abdominal aortic aneurysm (AAA) disease., Procedures: Macrophage-rich carotid lesions were induced by ligation in hyperlipidemic and diabetic FVB mice (n = 16). AAAs were induced by angiotensin II infusion in apoE(-/-) mice (n=10). HFn, with or without RGD peptide, was labeled with Cy5.5 and injected intravenously for near-infrared fluorescence imaging., Results: RGD-HFn showed significantly higher signal than HFn in diseased carotids and AAAs relative to non-diseased regions, both in situ (carotid: 1.88 ± 0.30 vs. 1.17 ± 0.10, p = 0.04; AAA: 2.59 ± 0.24 vs. 1.82 ± 0.16, p = 0.03) and ex vivo. Histology showed RGD-HFn colocalized with macrophages in carotids and both macrophages and neoangiogenesis in AAA lesions., Conclusions: RGD-HFn enhances vascular molecular imaging by targeting both vascular inflammation and angiogenesis, and allows more comprehensive detection of high-risk atherosclerotic and aneurysmal vascular diseases.

The purpose of this article is to validate numerical simulations of flow and pressure incorporating deformable walls using in vitro flow phantoms under physiological flow and pressure conditions. We constructed two deformable flow phantoms mimicking a normal and a restricted thoracic aorta, and used a Windkessel model at the outlet boundary. We acquired flow and pressure data in the phantom while it operated under physiological conditions. Next, in silico numerical simulations were performed, and velocities, flows, and pressures in the in silico simulations were compared to those measured in the in vitro phantoms. The experimental measurements and simulated results of pressure and flow waveform shapes and magnitudes compared favorably at all of the different measurement locations in the two deformable phantoms. The average difference between measured and simulated flow and pressure was approximately 3.5 cc/s (13% of mean) and 1.5 mmHg (1.8% of mean), respectively. Velocity patterns also showed good qualitative agreement between experiment and simulation especially in regions with less complex flow patterns. We demonstrated the capabilities of numerical simulations incorporating deformable walls to capture both the vessel wall motion and wave propagation by accurately predicting the changes in the flow and pressure waveforms at various locations down the length of the deformable flow phantoms.

Background: Obstructive sleep apnea (OSA) has been associated with cardiovascular disease (CVD), but whether OSA is an independent risk factor for CVD is controversial. The purpose of this study is to determine if patients with OSA have subclinical cardiovascular disease that is detectable by multi-modality cardiovascular imaging and whether these abnormalities improve after nasal continuous positive airway pressure (nCPAP)., Results: Of the 35 consecutive subjects with newly diagnosed moderate to severe OSA recruited from the Stanford Sleep Disorders Clinic, 20 patients were randomized to active vs. sham nCPAP. Active nCPAP was titrated to pressures that would prevent sleep disordered breathing based on inpatient polysomnography. OSA patients had baseline vascular function abnormalities including decreased myocardial perfusion reserve (MPR), brachial flow mediated dilation (FMD) and nitroglycerin-induced coronary vasodilation. Patients randomized to active nCPAP had improvement of MPR (1.5 ± 0.5 vs. 3.0 ± 1.3, p = 0.02) and brachial FMD (2.5% ± 5.7% vs. 9.0% ± 6.5%, p = 0.03) after treatment, but those randomized to sham nCPAP showed no significant improvement. There were no significant changes seen in chamber sizes, systolic and diastolic function, valvular function and coronary vasodilation to nitroglycerin., Conclusions: Patients with moderate to severe OSA had decreased MPR and brachial FMD that improved after 3 months of nCPAP. These findings suggest that relief of apnea in OSA may improve microvascular disease and endothelial dysfunction, which may prevent the development of overt cardiovascular disease. Further study in a larger patient population may be warranted.

Background: Previously published reports show that there is significant intraobserver, interobserver, and interinstitutional variability in the determination of left ventricular (LV) ejection fraction (EF) by echocardiography. With the increased deployment of echocardiography (eg, handheld devices), there exists a need for developing a simple, intuitive approach for evaluating LVEF that allows a wider range of physicians to accurately and rapidly determine LVEF., Objective: We sought to create a system for assessing LVEF that relies on recognition and matching of patterns, rather than on mathematic calculations and geometric assumptions., Methods: A library of videoclips of cardiac function was compiled from 54 patients who spanned the spectrum of LVEF. LVEFs were calculated for these patients using standard echocardiographic methods, with further validation of a subsample using cardiac magnetic resonance imaging measurement of LVEF. The library of images was used to create a software tool for assessing LVEF on the basis of a "template-matching" approach. The software tool was then tested on medical students (N=13) to determine whether it enabled relatively untrained individuals to make accurate LVEF estimates., Results: Using a template-matching approach for interpretation of echocardiograms, medical students were able to accurately estimate LVEF after only a limited introduction to echocardiography. Their LVEF estimates showed good correlation and agreement with gold standard (r = 0.88, standard square of the estimate = 6.0, limits of agreement = +12.0%, -15.6%)., Conclusions: A new visual approach for assessing cardiac function using template matching can accurately estimate LVEF. With minimal training, medical students can make LVEF estimates that correlate well with gold standard. The application of this new approach includes allowing for the interpretation of LVEF from echocardiograms to be performed by a broader spectrum of physicians.

Magnetic resonance coronary angiography (MRCA) has witnessed tremendous technical advances over the past decade. Although high-quality images of the coronary arteries have been demonstrated, this imaging modality is not performed routinely today. The fundamental properties of the coronary arteries deterring noninvasive imaging are well known. This article provides an overview of the developmental efforts to overcome these challenges, and highlights key technical and clinical advances. The future prospect of MRCA depends on clinical implementation of the technique. In order to meet this challenge, the following issues must be addressed: contrast- and signal-to-noise ratio, temporal and spatial resolution, and scan protocol.