Text Messages to Promote Physical Activity in Patients With Cardiovascular Disease: A Micro-Randomized Trial of a Just-In-Time Adaptive Intervention.

BACKGROUND: Text messages may enhance physical activity levels in patients with cardiovascular disease, including those enrolled in cardiac rehabilitation. However, the independent and long-term effects of text messages remain uncertain. METHODS: The VALENTINE study (Virtual Application-supported Environment to Increase Exercise) was a micro-randomized trial that delivered text messages through a smartwatch (Apple Watch or Fitbit Versa) to participants initiating cardiac rehabilitation. Participants were randomized 4× per day over 6-months to receive no text message or a message encouraging low-level physical activity. Text messages were tailored on contextual factors (eg, weather). Our primary outcome was step count 60 minutes following a text message, and we used a centered and weighted least squares mean method to estimate causal effects. Given potential measurement differences between devices determined a priori, data were assessed separately for Apple Watch and Fitbit Versa users over 3 time periods corresponding to the initiation (0-30 days), maintenance (31-120 days), and completion (121-182 days) of cardiac rehabilitation. RESULTS: One hundred eight participants were included with 70 552 randomizations over 6 months; mean age was 59.5 (SD, 10.7) years with 36 (32.4%) female and 68 (63.0%) Apple Watch participants. For Apple Watch participants, text messages led to a trend in increased step count by 10% in the 60-minutes following a message during days 1 to 30 (95% CI, -1% to +20%), with no effect from days 31 to 120 (+1% [95% CI, -4% to +5%]), and a significant 6% increase during days 121 to 182 (95% CI, +0% to +11%). For Fitbit users, text messages significantly increased step count by 17% (95% CI, +7% to +28%) in the 60-minutes following a message in the first 30 days of the study with no effect subsequently. CONCLUSIONS: In patients undergoing cardiac rehabilitation, contextually tailored text messages may increase physical activity, but this effect varies over time and by device. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04587882.

Using Artificial Intelligence to Semi-Quantitate Coronary Calcium as an 'Incidentaloma' on Non-Gated, Non-Contrast CT Scans, A Single-Center Descriptive Study in West Michigan.

INTRODUCTION: Non-gated, non-contrast computed tomography (CT) scans are commonly ordered for a variety of non-cardiac indications, but do not routinely comment on the presence of coronary artery calcium (CAC)/atherosclerotic cardiovascular disease (ASCVD) which is known to correlate with increased cardiovascular risk. Artificial intelligence (AI) algorithms can help detect and quantify CAC/ASCVD which can lead to early treatment and improved outcomes. METHODS: Using an FDA-approved algorithm (NANOX AI) to measure coronary artery calcium (CAC) on non-gated, non-contrast CT chest, 536 serial scans were evaluated in this single-center retrospective study. Scans were categorized by Agatston scores as normal-mild (<100), moderate (100-399), or severe (≥400). AI results were validated by cardiologist's overread. Patient charts were retrospectively analyzed for clinical characteristics. RESULTS: Of the 527 patients included in this analysis, a total of 258 (48.96%) had moderate-severe disease; of these, 164 patients (63.57%, p< 0.001) had no previous diagnosis of CAD. Of those with moderate-severe disease 135 of 258 (52.33% p=0.006) were not on aspirin and 96 (37.21% p=0.093) were not on statin therapy. Cardiologist interpretation demonstrated 88.76% agreement with AI classification. DISCUSSION/CONCLUSION: Machine learning utilized in CT scans obtained for non-cardiac indications can detect and semi-quantitate CAC accurately. Artificial intelligence algorithms can accurately be applied to non-gated, non-contrast CT scans to identify CAC/ASCVD allowing for early medical intervention and improved clinical outcomes.

A randomized trial of a mobile health intervention to augment cardiac rehabilitation.

Mobile health (mHealth) interventions may enhance positive health behaviors, but randomized trials evaluating their efficacy are uncommon. Our goal was to determine if a mHealth intervention augmented and extended benefits of center-based cardiac rehabilitation (CR) for physical activity levels at 6-months. We delivered a randomized clinical trial to low and moderate risk patients with a compatible smartphone enrolled in CR at two health systems. All participants received a compatible smartwatch and usual CR care. Intervention participants received a mHealth intervention that included a just-in-time-adaptive intervention (JITAI) as text messages. The primary outcome was change in remote 6-minute walk distance at 6-months stratified by device type. Here we report the results for 220 participants enrolled in the study (mean [SD]: age 59.6 [10.6] years; 67 [30.5%] women). For our primary outcome at 6 months, there is no significant difference in the change in 6 min walk distance across smartwatch types (Intervention versus control: +31.1 meters Apple Watch, -7.4 meters Fitbit; p = 0.28). Secondary outcomes show no difference in mean step counts between the first and final weeks of the study, but a change in 6 min walk distance at 3 months for Fitbit users. Amongst patients enrolled in center-based CR, a mHealth intervention did not improve 6-month outcomes but suggested differences at 3 months in some users.

Understanding Baseline Physical Activity in Cardiac Rehabilitation Enrollees Using Mobile Health Technologies.

BACKGROUND: Baseline physical activity in patients when they initiate cardiac rehabilitation is poorly understood. We used mobile health technology to understand baseline physical activity of patients initiating cardiac rehabilitation within a clinical trial to potentially inform personalized care. METHODS: The VALENTINE (Virtual Application-Supported Environment to Increase Exercise During Cardiac Rehabilitation Study) is a prospective, randomized-controlled, remotely administered trial designed to evaluate a mobile health intervention to supplement cardiac rehabilitation for low- and moderate-risk patients. All participants receive a smartwatch and usual care. Baseline physical activity was assessed remotely after enrollment and included (1) 6-minute walk distance, (2) daily step count, and (3) daily exercise minutes, both over 7 days and for compliant days, defined by >8 hours of watch wear time. Multivariable linear regression identified patient-level features associated with these 3 measures of baseline physical activity. RESULTS: From October 2020 to March 2022, 220 participants enrolled in the study. Participants are mostly White (184 [83.6%]); 67 (30.5%) are female and 84 (38.2%) are >65 years old. Most participants enrolled in cardiac rehabilitation after percutaneous coronary intervention (105 [47.7%]) or coronary artery bypass surgery (39 [17.7 %]). Clinical diagnoses include coronary artery disease (78.6%), heart failure (17.3%), and valve repair or replacement (26.4%). Baseline mean 6-minute walk distance was 489.6 (SD, 143.4) meters, daily step count was 6845 (SD, 3353), and exercise minutes was 37.5 (SD, 33.5). In a multivariable model, 6-minute walk distance was significantly associated with age and sex, but not cardiac rehabilitation indication. Sex but not age or cardiac rehabilitation indication was significantly associated with daily step count and exercise minutes. CONCLUSIONS: Baseline physical activity varies substantially in low- and moderate-risk patients enrolled in cardiac rehabilitation. Future studies are warranted to explore whether personalizing cardiac rehabilitation programs using mobile health technologies could optimize recovery. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04587882.

Virtual AppLication-supported Environment To INcrease Exercise (VALENTINE) during cardiac rehabilitation study: Rationale and design.

BACKGROUND: In-person, exercise-based cardiac rehabilitation improves physical activity and reduces morbidity and mortality for patients with cardiovascular disease. However, activity levels may not be optimized and decline over time after patients graduate from cardiac rehabilitation. Scalable interventions through mobile health (mHealth) technologies have the potential to augment activity levels and extend the benefits of cardiac rehabilitation. METHODS: The VALENTINE Study is a prospective, randomized-controlled, remotely-administered trial designed to evaluate an mHealth intervention to supplement cardiac rehabilitation for low- and moderate-risk patients (ClinicalTrials.gov NCT04587882). Participants are randomized to the control or intervention arms of the study. Both groups receive a compatible smartwatch (Fitbit Versa 2 or Apple Watch 4) and usual care. Participants in the intervention arm of the study additionally receive a just-in-time adaptive intervention (JITAI) delivered as contextually tailored notifications promoting low-level physical activity and exercise throughout the day. In addition, they have access to activity tracking and goal setting through the mobile study application and receive weekly activity summaries via email. The primary outcome is change in 6-minute walk distance at 6-months and, secondarily, change in average daily step count. Exploratory analyses will examine the impact of notifications on immediate short-term smartwatch-measured step counts and exercise minutes. CONCLUSIONS: The VALENTINE study leverages innovative techniques in behavioral and cardiovascular disease research and will make a significant contribution to our understanding of how to support patients using mHealth technologies to promote and sustain physical activity.

Hospital and Operator Variation in Cardiac Rehabilitation Referral and Participation After Percutaneous Coronary Intervention: Insights From Blue Cross Blue Shield of Michigan Cardiovascular Consortium.

BACKGROUND: Despite its established benefit and strong endorsement in international guidelines, cardiac rehabilitation (CR) use remains low. Identifying determinants of CR referral and use may help develop targeted policies and quality improvement efforts. We evaluated the variation in CR referral and use across percutaneous coronary intervention (PCI) hospitals and operators. METHODS: We performed a retrospective observational cohort study of all patients who underwent PCI at 48 nonfederal Michigan hospitals between January 1, 2012 and March 31, 2018 and who had their PCI clinical registry record linked to administrative claims data. The primary outcomes included in-hospital CR referral and CR participation, defined as at least one outpatient CR visit within 90 days of discharge. Bayesian hierarchical regression models were fit to evaluate the association between PCI hospital and operator with CR referral and use after adjusting for patient characteristics. RESULTS: Among 54 217 patients who underwent PCI, 76.3% received an in-hospital referral for CR, and 27.1% attended CR within 90 days after discharge. There was significant hospital and operator level variation in in-hospital CR referral with median odds ratios of 3.88 (95% credible interval [CI], 3.06-5.42) and 1.64 (95% CI, 1.55-1.75), respectively, and in CR participation with median odds ratios of 1.83 (95% CI, 1.63-2.15) and 1.40 (95% CI, 1.35-1.47), respectively. In-hospital CR referral was significantly associated with an increased likelihood of CR participation (adjusted odds ratio, 1.75 [95% CI, 1.52-2.01]), and this association varied by treating PCI hospital (odds ratio range, 0.92-3.75) and operator (odds ratio range, 1.26-2.82). CONCLUSIONS: In-hospital CR referral and 90-day CR use after PCI varied significantly by hospital and operator. The association of in-hospital CR referral with downstream CR use also varied across hospitals and less so across operators suggesting that specific hospitals and operators may more effectively translate CR referrals into downstream use. Understanding the factors that explain this variation will be critical to developing strategies to improve CR participation overall.

Multimodality Intracoronary Imaging With Near-Infrared Spectroscopy and Intravascular Ultrasound in Asymptomatic Individuals With High Calcium Scores.

BACKGROUND: This study sought to determine the frequency of large lipid-rich plaques (LRP) in the coronary arteries of individuals with high coronary artery calcium scores (CACS) and to determine whether the CACS correlates with coronary lipid burden. METHODS AND RESULTS: Combined near-infrared spectroscopy and intravascular ultrasound was performed in 57 vessels in 20 asymptomatic individuals (90% on statins) with no prior history of coronary artery disease who had a screening CACS ≥300 Agatston units. Among 268 10-mm coronary segments, near-infrared spectroscopy images were analyzed for LRP, defined as a bright yellow block on the near-infrared spectroscopy block chemogram. Lipid burden was assessed as the lipid core burden index (LCBI), and large LRP were defined as a maximum LCBI in 4 mm ≥400. Vessel plaque volume was measured by quantitative intravascular ultrasound. Vessel-level CACS significantly correlated with plaque volume by intravascular ultrasound (r=0.69; P<0.0001) but not with LCBI by near-infrared spectroscopy (r=0.24; P=0.07). Despite a high CACS, no LRP was detected in 8 (40.0%) subjects. Large LRP having a maximum LCBI in 4 mm ≥400 were infrequent, found in only 5 (25.0%) of 20 subjects and in only 5 (1.9%) of 268 10-mm coronary segments analyzed. CONCLUSIONS: Among individuals with a CACS ≥300 Agatston units mostly on statins, CACS correlated with total plaque volume but not LCBI. This observation may have implications on coronary risk among individuals with a high CACS considering that it is coronary LRP, rather than calcification, that underlies the majority of acute coronary events.

Collaborative quality improvement vs public reporting for percutaneous coronary intervention: A comparison of percutaneous coronary intervention in New York vs Michigan.

INTRODUCTION: Public reporting (PR) is a policy mechanism that may improve clinical outcomes for percutaneous coronary intervention (PCI). However, prior studies have shown that PR may have an adverse impact on patient selection. It is unclear whether alternatives to PR, such as collaborative quality improvement (CQI), may drive improvements in quality of care and outcomes for patients receiving PCI without the unintended consequences seen with PR. METHODS: Using National Cardiovascular Data Registry CathPCI Registry data from January 2011 through September 2012, we evaluated patients who underwent PCI in New York (NY), a state with PR (N = 51,983), to Michigan, a state with CQI (N = 53,528). We compared patient characteristics, the quality of care delivered, and clinical outcomes. RESULTS: Patients undergoing PCI in NY had a lower-risk profile, with a lower proportion of patients with ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, or cardiogenic shock, compared with Michigan. Quality of care was broadly similar in the 2 states; however, outcomes were better in NY. In a propensity-matched analysis, patients in NY were less likely to be referred for emergent, urgent, or salvage coronary artery bypass surgery (odds ratio [OR] 0.67, 95% CI 0.51-0.88, P < .0001) and to receive blood transfusion (OR 0.7, 95% CI 0.61-0.82, P < .0001), and had lower in-hospital mortality (OR 0.72, 95% CI 0.63-0.83, P < .0001). CONCLUSIONS: Public reporting of PCI data is associated with fewer high-risk patients undergoing PCI compared with CQI. However, in comparable samples of patients, PR is also associated with a lower risk of mortality and adverse events. The optimal quality improvement method may involve combining these 2 strategies to protect access to care while still driving improvements in patient outcomes.

Effectiveness of cardiac rehabilitation among older patients after acute myocardial infarction.

BACKGROUND: Guidelines recommend cardiac rehabilitation after acute myocardial infarction, yet little is known about the impact of cardiac rehabilitation on medication adherence and clinical outcomes among contemporary older adults. The optimal number of cardiac rehabilitation sessions is not clear. METHODS: We linked patients 65years or older enrolled in the Acute Coronary Treatment Intervention Outcomes Network Registry-Get With the Guidelines (ACTION Registry-GWTG) from January 2007 to December 2010 to Medicare longitudinal claims data to obtain 1 year follow-up. RESULTS: A total of 11,862 patients participated in cardiac rehabilitation after acute myocardial infarction, attending a median number of 26 sessions. Patients attending ≥26 sessions were more likely to be male, had lesser prevalence of comorbid conditions and prior revascularization, and were more likely to present with ST-segment elevation myocardial infarction, compared with patients attending 1 to 25 sessions. Among patients with Medicare Part D prescription coverage, increasing number of cardiac rehabilitation sessions was associated with improvement in adherence to secondary prevention medications such as P2Y12 inhibitors and ß-blockers. Each 5-session increase in participation was associated with lower mortality (adjusted hazard ratio [HR] 0.87, 95% CI 0.83-0.92) and lower overall risk of major adverse cardiac event (adjusted HR 0.69, 95% CI 0.65-0.73) and death/readmission (adjusted HR 0.79, 95% CI 0.76-0.83). CONCLUSIONS: In this older patient population, number of cardiac rehabilitation sessions attended was associated with improved medication adherence and lower downstream cardiovascular risk in a dose-response relationship. This provides support for the continued use of cardiac rehabilitation for older adults and encourages efforts to maximize attendance.

Predictors of early and late enrollment in cardiac rehabilitation, among those referred, after acute myocardial infarction.

BACKGROUND: Cardiac rehabilitation (CR) after acute myocardial infarction (AMI) is a Class I recommendation. Although referral to CR after an AMI has recently become a performance measure, many patients may not participate. To illuminate potential barriers to participation, we examined the prevalence of, and patient-related factors associated with, CR participation within 1 and 6 months after an AMI. METHODS AND RESULTS: We studied 2096 AMI patients enrolled from 19 US sites in the Prospective Registry Evaluating outcomes after Myocardial Infarction: Events and Recovery (PREMIER) registry. Analyses were limited to those patients referred for CR at the time of AMI hospitalization. A multivariable, conditional logistic regression model, stratified by hospital, was used to identify sociodemographic, comorbidity, and clinical factors independently associated with CR participation within 1 and 6 months of AMI hospital discharge. Only 29% (419/1450) and 48.25% (650/1347) of AMI patients who received referral for CR participated within 1 and 6 months after discharge, respectively. Women (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.44-0.86), uninsured (OR, 0.39; 95% CI, 0.21-0.71), and patients with hypertension (OR, 0.58; 95% CI, 0.43-0.78) and peripheral arterial disease (OR, 0.43; 95% CI, 0.22-0.85) were less likely to participate at 1 month. At 6 months after AMI, older patients (OR, 0.85 for each 10-year increment; 95% CI, 0.74-0.97), smokers (OR, 0.59; 95% CI, 0.44-0.80), and patients with economic burden (OR, 0.56; 95% CI, 0.38-0.81) were less likely to participate. Caucasians (OR, 1.73; 95% CI, 1.16-2.58) and educated patients (OR, 1.81; 95% CI, 1.42-2.30) were more likely to participate at 6 months. Patients with previous percutaneous interventions were less likely to participate at both 1 and 6 months post-AMI. CONCLUSIONS: Among patients referred for CR post-AMI, participation remains low both at 1 and 6 months after AMI. Because CR is associated with beneficial changes in cardiovascular risk factors and better outcomes after AMI, more aggressive efforts are needed to increase CR participation after referral.

The ezetimibe controversy: implications for clinical practice.

Low-density lipoprotein cholesterol (LDL-C) remains the primary target of lipid-lowering therapy. Achieving LDL-C goals as outlined by the National Cholesterol Education Program Adult Treatment Panel III can be difficult with statins alone; therefore, adjunctive therapy is often indicated to reduce cardiovascular risk. Ezetimibe, a potent inhibitor of intestinal cholesterol absorption, has been shown to be safe, tolerable and effective at lowering LDL-C, non-high-density lipoprotein cholesterol and apolipoprotein B, each of which has been correlated with improved clinical outcomes, alone or in combination with a statin. However, because of randomized trials that demonstrated mixed results about atherosclerotic plaque regression via carotid intima-media thickness and a concern about cancer risk, ezetimibe's role in lipid therapy has been questioned. Currently, a large randomized controlled trial is in progress to answer if ezetimibe improves clinical outcomes in patients with high-risk acute coronary syndrome. A smaller trial in patients with chronic kidney disease demonstrated reduced clinical events, including myocardial infarction, stroke and revascularization for patients taking the combination of ezetimibe and simvastatin versus those taking statin or placebo alone. In this paper, we review the trials that have led to the ezetimibe controversy and then discuss the possible role of ezetimibe in specific patient populations until the results of ongoing clinical trials are known.

Comparative safety and efficacy of a sirolimus-eluting versus paclitaxel-eluting stent: a meta-analysis.

BACKGROUND: Drug-eluting stents have emerged as the favored device for percutaneous coronary intervention. It is not clear if there are differences in the currently available drug-eluting stents. We performed a meta-analysis to systematically evaluate currently available data comparing sirolimus-eluting stents (SESs) with paclitaxel-eluting stents (PESs) in patients with coronary artery disease. METHODS: We searched the MEDLINE, Embase, ISI Web of Knowledge, Current Contents, and International Pharmaceutical Abstracts databases, and the Cochrane Central Register of Controlled Trials, as well as scientific meeting abstracts up to November 30, 2006. All randomized controlled trials comparing SES with PES and providing follow-up data of > or = 6 months were eligible for inclusion in our analysis. RESULTS: Data from 12 trials (number of patients 7455) were pooled. There was no difference in death (summary odds ratio [OR] 0.88, 95% CI 0.61-1.25, P = .46), myocardial infarction (summary OR 0.92, 95% CI, 0.71-1.19, P = .51), or stent thrombosis (summary OR 0.75, 95% CI 0.40-1.40, P = .37) between SES and PES. The use of SES was associated with a significant reduction in angiographic restenosis (summary OR 0.64, 95% CI 0.52-0.78, P < .001), target vessel revascularization (5.66% vs 7.70%, summary OR 0.72, 95% CI 0.59-0.88, P = .002), or target lesion revascularization (summary OR 0.67, 95% CI 0.53-0.84, P = .001). CONCLUSIONS: Patients treated with SES appear to have a significantly lower risk of restenosis and need for target vessel revascularization compared with those treated with PES. There is no significant difference between the 2 stents with respect to mortality, myocardial infarction, or early stent thrombosis.

Does gadolinium-based angiography protect against contrast-induced nephropathy?: a systematic review of the literature.

UNLABELLED: We evaluated the incidence of contrast-induced nephropathy (CIN) in patients exposed to gadolinium for diagnostic or therapeutic procedures. BACKGROUND: CIN with iodinated contrast agents is a leading cause of acute renal failure. Gadolinium is often used as an alternative to iodinated contrast in patients at increased risk of CIN. The safety of gadolinium in patients at increased risk of CIN has not been established. METHODS AND RESULTS: The authors performed a systematic review by searching MEDLINE, ISI Web of Knowledge, Current Contents, Embase, and the Cochrane Central Register of Controlled Trials to identify relevant studies evaluating gadolinium and its associated incidence of CIN. They identified 17 studies that reported both favorable and negative results with regard to the association of gadolinium and CIN. The differences in the results appeared to be dose related. When gadolinium was used in doses of 0.4 mmol/kg or higher, there appeared to be an increased incidence of ARF particularly in patients with preexisting renal insufficiency. CONCLUSIONS: Although the evidence base is limited, gadolinium does not appear to be safer than iodinated contrast in patients at risk of CIN. Given the lack of randomized data to support its safety, gadolinium in lieu of iso-osmolar iodinated contrast cannot be advocated in patients at high risk of contrast nephropathy.

Meta-analysis of randomized trials of drug-eluting stents versus bare metal stents in patients with diabetes mellitus.

Diabetes mellitus is a major risk factor for restenosis in patients undergoing percutaneous coronary intervention. Randomized controlled trials comparing drug-eluting stents (DESs) with bare metal stents (BMSs) showed a marked decrease in in-stent restenosis and target lesion revascularization with DESs in the total patient population enrolled in the studies, including patients with diabetes. However, it remains unclear whether the antirestenotic benefit of DESs is preserved in the high-risk diabetic subgroup. MEDLINE, EMBASE, ISI Web of Knowledge, Current Contents, International Pharmaceutical Abstracts, and recent Scientific Sessions databases were searched to identify relevant clinical trials comparing DESs with BMSs. A randomized controlled trial was included if it provided outcome data for patients with diabetes for > or =1 of the following: late lumen loss, in-stent restenosis, or target lesion revascularization. Data were combined using fixed-effects models, and standard tests for heterogeneity were performed. Eight studies with 1,520 patients with diabetes were identified that reported > or =1 outcome of interest. Mean late lumen losses (7 studies) were 0.93 mm (95% confidence interval [CI] 0.510 to 1.348) with BMSs and 0.18 mm (95% CI -0.088 to +0.446) with DESs. For patients receiving a DES, this translated into a marked decrease in in-stent restenosis (7 studies, RR 0.14, 95% CI 0.10 to 0.22, p <0.001) and target lesion revascularization (8 studies, RR 0.34, 95% CI 0.26 to 0.45, p <0.001). DES use is associated with a marked decrease in in-stent restenosis and target lesion revascularization in patients with diabetes. In conclusion, the analysis supports the current widespread use of DESs in these high-risk patients.

The pollination biology of Calypso bulbosa var. Americana (Orchidaceae): Initial deception of bumblebee visitors.

The orchid Calypso bulbosa var. americana has deceptive flowers that provide no rewards for visitors. Near Banff, Alberta, the flowering period of this species is synchronized with the emergence of its pollinators, large bumblebee queens, in late spring. Calypso flowers appear to rely on the initial attraction and deception of newly-emerged naive bumblebees for pollination. Indirect evidence suggests that individual bees subsequently learn to avoid these flowers and that avoidance is learned quite rapidly. Avoidance behavior by pollinators is obviously detrimental to sexual reproduction in Calypso. This negative effect appears to be offset by the large number of seeds produced in plants which are effectively pollinated. A test of the hypothesis that Calypso flowers mimic flowers of the shooting star, Dodecatheon radicatum (Primulaceae) failed to provide evidence for mimicry.