R. Jay Widmer

Digital Health Interventions for the Prevention of Cardiovascular Disease: A Systematic Review and Meta-Analysis

OBJECTIVE To assess the potential benefit of digital health interventions (DHIs) on cardiovascular disease (CVD) outcomes (CVD events, all-cause mortality, hospitalizations) and risk factors compared with non-DHIs. PATIENTS AND METHODS We conducted a systematic search of PubMed, MEDLINE, EMBASE, Web of Science, Ovid, CINHAL, ERIC, PsychINFO, Cochrane, and Cochrane Central Register of Controlled Trials for articles published from January 1, 1990, through January 21, 2014. Included studies examined any element of DHI (telemedicine, Web-based strategies, e-mail, mobile phones, mobile applications, text messaging, and monitoring sensors) and CVD outcomes or risk factors. Two reviewers independently evaluated study quality utilizing a modified version of the Cochrane Collaboration risk assessment tool. Authors extracted CVD outcomes and risk factors for CVD such as weight, body mass index, blood pressure, and lipid levels from 51 full-text articles that met validity and inclusion criteria. RESULTS Digital health interventions significantly reduced CVD outcomes (relative risk, 0.61; 95% CI, 0.46-0.80; P<.001; I(2)=22%). Concomitant reductions in weight (-2.77 lb [95% CI, -4.49 to -1.05 lb]; P<.002; I(2)=97%) and body mass index (-0.17 kg/m(2) [95% CI, -0.32 kg/m(2) to -0.01 kg/m(2)]; P=.03; I(2)=97%) but not blood pressure (-1.18 mm Hg [95% CI, -2.93 mm Hg to 0.57 mm Hg]; P=.19; I(2)=100%) were found in these DHI trials compared with usual care. In the 6 studies reporting Framingham risk score, 10-year risk percentages were also significantly improved (-1.24%; 95% CI, -1.73% to -0.76%; P<.001; I(2)=94%). Results were limited by heterogeneity not fully explained by study population (primary or secondary prevention) or DHI modality. CONCLUSION Overall, these aggregations of data provide evidence that DHIs can reduce CVD outcomes and have a positive impact on risk factors for CVD.

Severe Pulmonary Vein Stenosis Resulting From Ablation for Atrial Fibrillation: Presentation, Management, and Clinical Outcomes.

Background: The frequency of pulmonary vein stenosis (PVS) after ablation for atrial fibrillation has decreased, but it remains a highly morbid condition. Although treatment strategies including pulmonary vein dilation and stenting have been described, the long-term impacts of these interventions are unknown. We evaluated the presentation of severe PVS, and examined the risk for restenosis after intervention using either balloon angioplasty (BA) alone or BA with stenting. Methods: This was a prospective, observational study of 124 patients with severe PVS evaluated between 2000 and 2014. Results: All 124 patients were identified as having severe PVS by computed tomography in 219 veins. One hundred two patients (82%) were symptomatic at diagnosis. The most common symptoms were dyspnea (67%), cough (45%), fatigue (45%), and decreased exercise tolerance (45%). Twenty-seven percent of patients experienced hemoptysis. Ninety-two veins were treated with BA, 86 were treated with stenting, and 41 veins were not treated. A 94% acute procedural success rate was observed and did not differ by initial management. Major procedural complications occurred in 4 of the 113 patients (3.5%) who underwent invasive assessment, and minor complications occurred in 15 patients (13.3%). Overall, 42% of veins developed restenosis including 27% of veins (n=23) treated with stenting and 57% of veins (n=52) treated with BA. The 3-year overall rate of restenosis was 37%, with 49% of BA-treated veins and 25% of stented veins developing restenosis (hazard ratio, 2.77; 95% confidence interval, 1.72–4.45; P<0.001). After adjustment for age, CHA2DS2-VASc score, hypertension, and the time period of the study, there was still a significant difference in the risk of restenosis for BA versus stenting (hazard ratio, 2.46; 95% confidence interval, 1.47–4.12; P<0.001). Conclusions: The diagnosis of PVS is challenging because of nonspecific symptoms and the need for dedicated pulmonary vein imaging. There is no difference in acute success by type of initial intervention; however, stenting significantly reduces the risk of subsequent pulmonary vein restenosis in comparison with BA.

Effects of exercise training on cellular mechanisms of endothelial nitric oxide synthase regulation in coronary arteries after chronic occlusion

Exercise training enhances agonist-mediated relaxation in both control and collateral-dependent coronary arteries of hearts subjected to chronic occlusion, an enhancement that is mediated in part by nitric oxide. The purpose of the present study was to elucidate exercise training-induced adaptations in specific cellular mechanisms involved in the regulation of endothelial nitric oxide synthase (eNOS) in coronary arteries of ischemic hearts. Ameroid constrictors were surgically placed around the proximal left circumflex coronary artery (LCX) of adult female Yucatan miniature swine. Eight weeks postoperatively, animals were randomized into sedentary (pen-confined) or exercise training (treadmill run; 5 days/wk; 14 wk) protocols. Coronary artery segments ( approximately 1.0 mm luminal diameter) were isolated from collateral-dependent (LCX) and control (nonoccluded left anterior descending) arteries 22 wk after ameroid placement. Endothelial cells were enzymatically dissociated, and intracellular Ca(2+) responses (fura 2) to bradykinin stimulation were studied. Immunofluorescence and laser scanning confocal microscopy were used to quantify endothelial cell eNOS and caveolin-1 cellular distribution under basal and bradykinin-stimulated conditions. Immunoblot analysis was used to determine eNOS, phosphorylated (p)-eNOS, protein kinase B (Akt), pAkt, and caveolin-1 protein levels. Bradykinin-stimulated nitrite plus nitrate (NOx; nitric oxide metabolites) levels were assessed via HPLC. Exercise training resulted in significantly enhanced bradykinin-mediated increases in endothelial Ca(2+) levels, NOx levels, and the distribution of eNOS-to-caveolin-1 ratio at the plasma membrane in endothelial cells of control and collateral-dependent arteries. Exercise training also significantly increased total eNOS and phosphorylated levels of eNOS (pSer(1179)) in collateral-dependent arteries. Total eNOS protein levels were also significantly increased in collateral-dependent arteries of sedentary animals. These data provide new insights into exercise training-induced adaptations in cellular mechanisms of nitric oxide regulation in collateral-dependent coronary arteries of chronically occluded hearts that contribute to enhanced nitric oxide production.

The Association between Circulating MicroRNA Levels and Coronary Endothelial Function

Human microRNAs (miRs) have been implicated in human diseases presumably through the downregulation and silencing of targeted genes via post-translational modifications. However, their role in the early stage of coronary atherosclerosis is not known. The aim of this study was to test the hypothesis that patients with early atherosclerosis and coronary endothelial dysfunction (CED) have alterations in transcoronary miR gradients. Patients underwent coronary angiography and endothelial function testing in the cardiac catheterization laboratory. Patients were divided into abnormal (n = 26) and normal (n = 22) microvascular coronary endothelial function based on intracoronary response to infused acetylcholine measured as a percent change in coronary blood flow (CBF) and arterial diameter. Blood samples were obtained simultaneously from the aorta and coronary sinus at the time of catheterization for RNA isolation, and miR subsequently assessed. Baseline characteristics were similar in both groups. Patients with microvascular CED displayed transcoronary gradients significantly elevated in miR-92a and miR-133 normalized to C-elegans-39 miR. Percent change in CBF and the transcoronary gradient of miR-133 displayed a significant inverse correlation (r2 = 0.11, p = 0.03). Thus, we present novel data whereupon selected miRs demonstrate elevated transcoronary gradients in patients with microvascular CED. The current findings support further studies on the mechanistic role of miRs in coronary atherosclerosis and in humans.

Workplace Digital Health Is Associated with Improved Cardiovascular Risk Factors in a Frequency-Dependent Fashion: A Large Prospective Observational Cohort Study.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the US. Emerging employer-sponsored work health programs (WHP) and Digital Health Intervention (DHI) provide monitoring and guidance based on participants’ health risk assessments, but with uncertain success. DHI–mobile technology including online and smartphone interventions–has previously been found to be beneficial in reducing CVD outcomes and risk factors, however its use and efficacy in a large, multisite, primary prevention cohort has not been described to date. We analyzed usage of DHI and change in intermediate markers of CVD over the course of one year in 30,974 participants of a WHP across 81 organizations in 42 states between 2011 and 2014, stratified by participation log-ins categorized as no (n = 14,173), very low (<12/yr, n = 12,260), monthly (n = 3,360), weekly (n = 651), or semi-weekly (at least twice per week). We assessed changes in weight, waist circumference, body mass index (BMI), blood pressure, lipids, and glucose at one year, as a function of participation level. We utilized a Poisson regression model to analyze variables associated with increased participation. Those with the highest level of participation were slightly, but significantly (p<0.0001), older (48.3±11.2 yrs) than non-participants (47.7±12.2 yr) and more likely to be females (63.7% vs 37.3% p<0.0001). Significant improvements in weight loss were demonstrated with every increasing level of DHI usage with the largest being in the semi-weekly group (-3.39±1.06 lbs; p = 0.0013 for difference from weekly). Regression analyses demonstrated that greater participation in the DHI (measured by log-ins) was significantly associated with older age (p<0.001), female sex (p<0.001), and Hispanic ethnicity (p<0.001). The current study demonstrates the success of DHI in a large, community cohort to modestly reduce CVD risk factors in individuals with high participation rate. Furthermore, participants previously underrepresented in WHPs (females and Hispanics) and those with an increased number of CVD risk factors including age and elevated BMI show increased adherence to DHI, supporting the use of this low-cost intervention to improve CVD health.

MicroRNAs: small molecule, big potential for coronary artery disease.

This editorial refers to ‘Transcoronary gradients of vascular miRNAs and coronary atherosclerotic plaque characteristics’, by D.M. Leistner et al . on doi:10.1093/eurheartj/ehw047 MicroRNAs (miRs), the diminutive epigenetic silencing phenomena only recently discovered, are moving tantalizing close to becoming a realizable diagnostic and therapeutic focus for coronary artery disease (CAD), and the results presented in this issue of the journal just may have provided supportive data allowing that work to begin in earnest intent on achieving that goal. These small non-coding nucleotide sequences that repress protein translation by binding to competing sequences have been shown to be contributory to pathologies from renal and neural diseases to obesity and alcoholism.1,2 In their manuscript, Leistner et al . present a noteworthy contribution to a potential link between tenuous coronary pathology and miRs.3 Notably, the authors describe associations between the overall plaque burden in addition to gradients from the arterial to venous aspects of the coronary circulation with respect to miR-126-3p, miR-145-5p, miR-155-5p, and miR-29b-3p. Furthermore, the authors also demonstrate the predictive power of these transcoronary gradients of miR-126-3p, miR-126-5p, miR-145-5p, miR-15-5p, and miR-29-b-3p in detecting potentially vulnerable plaques as indicated by thin-cap fibroatheromas (TCFAs) by integrating optical coherence tomograpy (OCT), a novel intracoronary imaging modality. Although the data are cross-sectional in nature, and the usual miR methodological concerns should be heeded, these authors have provided hypothesis-generating data for a potential link between the pathophysiology of vulnerable plaques and miRs. Importantly, the authors use a physiological approach by gathering transcoronary gradients of the miRs in patients appropriately undergoing coronary angiography coupled with the anatomic advantages offered by OCT to image atherosclerotic plaques. The resultant data are …

Clinical usefulness of nonhyperemic baseline Pd/Pa as a hybrid baseline Pd/Pa-fractional flow reserve strategy.

ObjectiveThe ratio of basal distal intracoronary pressure (Pd) and aortic pressure (Pa) is a nonhyperemic index for the severity of coronary artery stenosis. The aim of the current study was to evaluate the clinical usefulness of a hybrid baseline Pd/Pa–fractional flow reserve (FFR) strategy in reducing the need for hyperemia. MethodsIn this study, 570 lesions from 527 consecutive patients who had both baseline Pd/Pa and FFR determined were evaluated retrospectively. To evaluate the hybrid baseline Pd/Pa–FFR approach, patients were categorized into treatment, deferral, and undetermined groups on the basis of their baseline Pd/Pa. Thereafter, patients in the undetermined group were assigned to FFR-guided treatment or deferral on the basis of an FFR cutoff value of 0.80 or lower. Major adverse cardiac events were evaluated in a median of 48.8 months (interquartile range, 35.0–66.4). ResultsA hybrid strategy using a deferral baseline Pd/Pa value of 1.00 (negative predictive value of 100%) and a treatment baseline Pd/Pa value of 0.86 or lower (positive predictive value of 100%), and limiting adenosine to a baseline Pd/Pa value between 0.87 and 0.99 would prevent the need for vasodilator drugs in 14.6% of lesions (14.0% patients), maintaining 100% agreement with an FFR-only strategy. However, adenosine-free lesions are increased to 59.6%, with 91% agreement. There was no difference in the major adverse cardiac event-free survival rate at 5 years between baseline Pd/Pa-guided and FFR-guided treatment patients (70.8 vs. 76.3%, P=0.63), or between baseline Pd/Pa-guided and FFR-guided deferral patients (71.3 vs. 82.4%, P=0.99). ConclusionThe current study reports a range of baseline Pd/Pa values that can predict myocardial ischemia without the need for inducing hyperemia. Adoption of this hybrid baseline Pd/Pa–FFR approach can reduce the need for drug-induced hyperemia.

Online Physician Reviews Do Not Reflect Patient Satisfaction Survey Responses

&NA; Online physician reviews have become increasingly prevalent and are a common means by which patients explore medical options online. Currently, there are no data comparing physicians with negative online reviews and those without negative reviews. We sought to compare industry‐vetted patient satisfaction surveys (PSSs), such as Press Ganey (PG) PSSs, between those physicians with negative online reviews and those without negative reviews. Overall, there were 113 unique individuals with negative online reviews from September 1, 2014, to December 31, 2014, with 8 being nonphysicians. We matched 113 physicians in similar departments/divisions. We obtained PG PSS scores of both groups and compared the mean scores of the 2 groups. Press Ganey PSS scores were available for 98 physicians with negative online reviews compared with 82 matched physicians without negative online reviews. The mean raw PG PSS scores were not different between the 2 groups (4.05; 95% CI, 3.99‐4.11 vs 4.04; 95% CI, 3.97‐4.11; P=.92). We also noted no difference in mean scores on questions related to physician‐patient communication and interaction skills between those with poor online reviews and those without (4.38; 95% CI, 4.32‐4.43 vs 4.41; 95% CI, 4.35‐4.47; P=.42). However, there was a significantly lower non–physician‐specific mean in those with negative online reviews (3.91; 95% CI, 3.84‐3.97) vs those without negative online reviews (4.01; 95% CI, 3.95‐4.09) (P=.02). Here, we provide data indicating that online physician reviews do not correlate to formal institutional PG PSS. Furthermore, physicians with negative online reviews have lower scores on non–physician‐specific variables included in the PG PSSs, emphasizing that these discrepancies can negatively affect overall patient experience, online physician reviews, and physician reputation. It is prudent that an improved mechanism for online ratings be implemented to better inform patients about a physicians online reputation.

Association Between Work‐Related Stress and Coronary Heart Disease: A Review of Prospective Studies Through the Job Strain, Effort‐Reward Balance, and Organizational Justice Models

Work‐related stress is an example of a psychosocial risk factor that has become of interest in todays ever‐demanding, fast‐paced, and globalized society, although its link to adverse health and in particular coronary heart disease (CHD) is incompletely understood. In this review, we will

Social Media Platforms and Heart Failure

With the pervasive use of the internet and social media, the potential applicability toward patients with heart failure (HF) remains understudied. Here, we outline the general use of social media and some early work with the use of social media as well as data from our own Mayo Clinic Center for Social Media experience. Both enterprise-wide social media data as well as those specific to HF-related pages and posts appear to support the preferential use of Facebook and Youtube for potential benefit in patients with HF. Large-scale prospective studies are needed to confirm these anecdotal results, and to ensure we can optimally, yet safely, engage our patients with HF to improve their care.