Distal-vessel fractional flow reserve by computed tomography to monitor epicardial coronary artery disease.

AIMS: Coronary computed tomography angiography (CTA) and fractional flow reserve by computed tomography (FFR-CT) are increasingly utilized to characterize coronary artery disease (CAD). We evaluated the feasibility of distal-vessel FFR-CT as an integrated measure of epicardial CAD that can be followed serially, assessed the CTA parameters that correlate with distal-vessel FFR-CT, and determined the combination of clinical and CTA parameters that best predict distal-vessel FFR-CT and distal-vessel FFR-CT changes. METHODS AND RESULTS: Patients (n = 71) who underwent serial CTA scans at ≥2 years interval (median = 5.2 years) over a 14-year period were included in this retrospective study. Coronary arteries were analysed blindly using artificial intelligence-enabled quantitative coronary CTA. Two investigators jointly determined the anatomic location and corresponding distal-vessel FFR-CT values at CT1 and CT2. A total of 45.3% had no significant change, 27.8% an improvement, and 26.9% a worsening in distal-vessel FFR-CT at CT2. Stepwise multiple logistic regression analysis identified a four-parameter model consisting of stenosis diameter ratio, lumen volume, low density plaque volume, and age, that best predicted distal-vessel FFR-CT ≤ 0.80 with an area under the curve (AUC) = 0.820 at CT1 and AUC = 0.799 at CT2. Improvement of distal-vessel FFR-CT was captured by a decrease in high-risk plaque and increases in lumen volume and remodelling index (AUC = 0.865), whereas increases in stenosis diameter ratio, medium density calcified plaque volume, and total cholesterol presaged worsening of distal-vessel FFR-CT (AUC = 0.707). CONCLUSION: Distal-vessel FFR-CT permits the integrative assessment of epicardial atherosclerotic plaque burden in a vessel-specific manner and can be followed serially to determine changes in global CAD.

Harnessing imaging biomarkers to refine individualized cardiovascular disease risk: a case-based discussion.

Traditional models of cardiovascular risk assessment rely on population-level risk factors and may not accurately capture individualized risk. Imaging biomarkers such as plaque characterization and pericoronary fat inflammation may offer refined risk prediction and allow physicians to personalize care-plans for cardiovascular disease prevention. The integration of plaque morphology and pericoronary inflammation into clinical care is highlighted using a case-based discussion. This article reviews the existing body of evidence supporting the use of novel biomarkers in an individualized comprehensive risk assessment algorithm.

Performance and Integration of Smartphone Wireless ECG Monitoring into the Enterprise Electronic Health Record: First Clinical Experience.

INTRODUCTION: Patient initiated, remote cardiac monitoring has proved to be a significant advance in the diagnosis and management of arrhythmias. Further improvements in ease of use and access to results will further improve health outcomes and cost-effectiveness. Here we describe a proof-of-concept evaluation to assess the feasibility of successfully implementing a cloud-based management system using KardiaPro (KP) for remote electrocardiogram (ECG) monitoring to interface into EPIC, an enterprise electronic health record (EHR) system. METHODS: The KP management system was embedded using hypertext markup language (HTML) code directly into the EHR. Encrypted credentials and patient data were bundled with an application programming interface key allowing linkage of remote monitoring from patients' smartphones. During the time of implementation, a total of 322 patients and 32 179 ECGs were recorded. RESULTS: The KP-EHR interface provided full functionality, allowing detection, interpretation and documentation of atrial fibrillation (AF), flutter events, ventricular tachycardia, and complete heart block. Our study focused on KP's detection of AF, and 16.7% of tracings were classified as probable AF with only 2.3% of tracings not analyzed by the KP algorithm because of tracings that were too noisy or truncated. Enhanced management was facilitated with clinical information immediately accessible. Blinded physician ECG review validated the KP proprietary algorithm interpretation and ECGs. CONCLUSIONS: Direct integration of KP into EHR was successful and practical. It allows for historical, point of care and immediate retrieval of remote ambulatory monitoring data and documentation into the electronic health record. KP EHR integration warrants further study as it has the potential to improve cost-effectiveness and clinical diagnostic value, leading to improvements in delivery of patient care.

Coronary artery plaque progression and cardiovascular risk scores in men with and without HIV-infection.

OBJECTIVE: The aim of this study was to assess the association of cardiovascular disease (CVD) risk scores and coronary artery plaque (CAP) progression in HIV-infected participants. METHODS: We studied men with and without HIV-infection enrolled in the Multicenter AIDS Cohort Study (MACS) CVD study. CAP at baseline and follow-up was assessed with cardiac computed tomography angiography (CCTA). We examined the association between baseline risk scores including pooled cohort equation (PCE), Framingham risk score (FRS), and Data collect of Adverse effects of anti-HIV drugs equation (D:A:D) and CAP progression. RESULTS: We studied 495 men (211 HIV-uninfected, 284 HIV-infected). The adjusted odds ratio (aOR) of total plaque volume (TPV) and noncalcified plaque volume (NCPV) progression in the highest relative to lowest tertile was 9.4 [95% confidence interval (95% CI) 2.4-12.1, P < 0.001)] and 7.7 (95% CI 3.1-19.1, P < 0.001) times greater, respectively, among HIV-uninfected men in the PCE atherosclerotic cardiovascular disease (ASCVD) high vs. low-risk category. Among HIV-infected men, the association for TPV and NCPV progression for the same PCE risk categories, odds ratio (OR) 2.8 (95% CI 1.4-5.8, P < 0.01) and OR 2.4 (95% CI 1.2-4.8, P < 0.05), respectively (P values for interaction by HIV = 0.02 and 0.08, respectively). Similar results were seen for the FRS risk scores. Among HIV-uninfected men, PCE high risk category identified the highest proportion of men with plaque progression in the highest tertile, although in HIV-infected men, high-risk category by D:A:D identified the greatest percentage of men with plaque progression albeit with lower specificity than FRS and PCE. CONCLUSION: PCE and FRS categories predict CAP progression better in HIV-uninfected than in HIV-infected men. Improved CVD risk scores are needed to identify high-risk HIV-infected men for more aggressive CVD risk prevention strategies.

Intraventricular Flow Patterns in Patients Treated with Left Ventricular Assist Devices.

The success of left ventricular assist device (LVAD) therapy is hampered by complications such as thrombosis and bleeding. Understanding blood flow interactions between the heart and the LVAD might help optimize treatment and decrease complication rates. We hypothesized that LVADs modify shear stresses and blood transit in the left ventricle (LV) by changing flow patterns and that these changes can be characterized using 2D echo color Doppler velocimetry (echo-CDV). We used echo-CDV and custom postprocessing methods to map blood flow inside the LV in patients with ongoing LVAD support (Heartmate II, N = 7). We compared it to healthy controls (N = 20) and patients with dilated cardiomyopathy (DCM, N = 20). We also analyzed intraventricular flow changes during LVAD ramp tests (baseline ± 400 rpm). LVAD support reversed the increase in blood stasis associated with DCM, but it did not reduce intraventricular shear exposure. Within the narrow range studied, the ventricular flow was mostly insensitive to changes in pump speed. Patients with significant aortic insufficiency showed abnormalities in blood stasis and shear indices. Overall, this study suggests that noninvasive flow imaging could potentially be used in combination with standard clinical methods for adjusting LVAD settings to optimize flow transport and minimize stasis on an individual basis.

Feasibility of measuring pericoronary fat from precontrast scans: Effect of iodinated contrast on pericoronary fat attenuation.

BACKGROUND: Pericoronary adipose tissue (PCAT) attenuation has been identified as a marker for cardiovascular risk. The effect of contrast enhancement on fat attenuation is unknown. We aim to compare precontrast coronary scans to postcontrast CCTA for quantification of pericoronary fat volume and attenuation. METHODS: Thin slice pre- and post-contrast studies obtained at 120 kVp, heart rate <60, with no plaque or artifact in the right coronary artery (RCA) were selected. Analysis was limited to pixels -30 Hounsfield units (HU) to -190 HU and from 10 mm to 50 mm distal to the RCA origin at a radial distance equal to the vessel diameter. A subgroup with no plaque across all coronaries was also analyzed. RESULTS: Of 119 study pairs, the average RCA diameter was highly correlated at 3.85 mm (postcontrast) and 3.84 mm (precontrast), r = 0.97, p < 0.0001. The mean attenuation of pre- and postcontrast images was also highly correlated at -87.02 ±â€¯7.15 HU and -82.74 ±â€¯6.54 HU, respectively (r = 0.65, p < 0.0001). Pericoronary fat volume in the -190 to -30 HU range was 396 mm³ lower in the post contrast versus pre-contrast, consistent with higher attenuation (less negative) voxels postcontrast (p < 0.0001). Inter- and intra-reader agreement ranged 95-100% and 90% for precontrast and 85-90% for postcontrast studies, respectively. Subgroup analysis revealed precontrast attenuation -85.59 ±â€¯7.53 HU and postcontrast -82.21 ±â€¯7.15 HU were highly correlated r = 0.67, p < 0.0001. CONCLUSION: Pericoronary fat enhances with iodinated contrast, potentially explaining some of its risk-predictive capabilities. Fat attenuation and volume can be reliably measured from precontrast calcium scans, with volume quantification showing particularly strong correlation. Excellent inter- and intra-reader agreement is also demonstrated.

Aged garlic extract reduces low attenuation plaque in coronary arteries of patients with diabetes: A randomized, double-blind, placebo-controlled study.

Several previous studies have demonstrated that aged garlic extract (AGE) inhibits the progression of coronary artery calcification and non-calcified plaque (NCP) in the general population. However, its effects on plaque progression in patients with diabetes have not yet been investigated, at least to the best of our knowledge. This study investigated whether AGE reduces the coronary plaque volume measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). A total of 80 participants with DM with a median age of 57 years were prospectively assigned to consume 2,400 mg AGE/day (after completion, 37 participants) or placebo (after completion, 29 participants) orally. Both groups underwent CCTA at baseline and follow-up 365 days apart. In total, 66 participants completed the study. Coronary plaque volume, including total plaque (TP), dense calcium (DC), fibrous, fibro-fatty and low-attenuation plaque (LAP) volumes were measured based upon pre-defined intensity cut-off values using semi-automated software (QAngio CT). Changes in various plaque types were normalized to the total coronary artery length. The non-parametric Wilcoxon rank-sum test was performed to examine the differences in plaque formation between the 2 groups. No significant differences were found in the baseline characteristics between the AGE and placebo groups. Compared with the placebo group, the AGE group exhibited a statistically significant regression in normalized LAP [median and standard deviation (SD) -0.2 (18.8) vs. 2.5 (69.3), P=0.0415]. No differences were observed in TP, fibrous, or fibrofatty plaque volumes between the AGE and placebo group. On the whole, this study indicated that the %LAP change in the AGE group was significantly greater than that in the placebo group in patients with diabetes. However, further studies are warranted to evaluate whether AGE has the ability to stabilize vulnerable plaque and decrease adverse cardiovascular events.

Aged garlic extract reduces left ventricular myocardial mass in patients with diabetes: A prospective randomized controlled double-blind study.

Increased left ventricular myocardial mass (LVM) is a well known prognostic marker of poor cardiac outcomes. Decreases in LVM have been shown to decrease the cardiovascular risk. Aged garlic extract (AGE) has been shown to have an overall favorable effect on cardiac health; however, to the best of our knowledge, no study to date has specifically examined its effects on left ventricular mass. This study investigated whether AGE can affect LVM measured by cardiac computed tomography angiography (CCTA) in patients with diabetes mellitus (DM). This is a double-blind, placebo controlled randomized trial. In total, 65 participants with DM with a mean age of 58 years were prospectively assigned to consume 2,400 mg AGE/day or the placebo orally. Both groups underwent CCTA at baseline and follow-up at 1 year apart. LVM was measured using automated software. The baseline characteristics did not differ between the AGE and placebo groups. There was a trend towards a significant reduction in LVM at follow-up as compared to baseline in the AGE group (119.30±34.77 vs. 121.0±34.70, P=0.059). No change was observed in LVM in the placebo group at 1-year follow-up as compared to baseline (124.6±37.33 vs. 124.6±35.13, P=0.9). On the whole, this study indicated that AGE may decrease or stabilize LVM. Further studies however, with a larger sample size and longer follow-up times are required to evaluate the effects of AGE on hypertension and LVM.

Effect of 5-lipoxygenase inhibitor, VIA-2291 (Atreleuton), on epicardial fat volume in patients with recent acute coronary syndrome.

BACKGROUND AND AIMS: The association between inflammation and atherosclerosis has been well described in the literature. There is now mounting evidence in support of adipose tissue as a reservoir for inflammatory markers. Epicardial adipose tissue (EAT) has been shown to associate with coronary atherosclerosis and found to be a predictor of future adverse cardiovascular events. This study, VIA-EAT, assesses the change in epicardial fat volume (EFV) after treatment with an investigational anti-inflammatory agent (VIA-2291) in a cohort of post-acute coronary syndrome (ACS) patients. METHODS: This study is derived from a post-hoc analysis of a previously conducted randomized clinical trial (NCT00358826). Patients were recruited for a prospective, double-blind, multi-center randomized trial of a 5-lipooxygenase inhibitor or placebo in a 3:1 randomization, including doses of placebo, and 25 mg, 50 mg and 100 mg of active treatment. Cardiac computed tomography was performed at baseline and at 24 weeks after treatment with VIA-2291. EAT and pericardial adipose tissue (PAT) were measured using previously published methodology. A Pearson correlation test was used to determine the relationship between change in epicardial fat and change in plaque composition. RESULTS: We analyzed 54 pre- and post-treatment scans. There were no major differences between traditional cardiovascular risk factors among the 4 randomized study arms. There was a significant decrease in EAT and PAT in patients in the treatment arms vs. placebo, -3.0 ± 8.2mm3 and -3.9 ± 10.9mm3 vs. 1.7 ± 7.5mm3 and 1.4 ± 10.7mm3 (p = 0.001), respectively. The changes in EAT and PAT were more pronounced in patients taking 100 mg of the drug vs. placebo: 4.2 ± 9.6mm3, -7.6 ± 8.5mm3, p = 0.0001, respectively. In a subgroup analysis, reduction in epicardial fat volume correlated with reduction in total atherosclerotic plaque volume across all VIA treatment groups, r = 0.52 (p = 0.004). CONCLUSIONS: After adjustment for traditional cardiovascular risk factors including age, gender, body mass index, dyslipidemia and smoking, VIA-2291 decreases EAT and PAT in individuals with recent ACS. Treatment with the drug also appears to alter plaque volume and composition.

Biomarkers and Noncalcified Coronary Artery Plaque Progression in Older Men Treated With Testosterone.

OBJECTIVE: Recent results from the Cardiovascular Trial of the Testosterone Trials showed that testosterone treatment of older men with low testosterone was associated with greater progression of noncalcified plaque (NCP). We evaluated the effect of anthropometric measures and cardiovascular biomarkers on plaque progression in individuals in the Testosterone Trial. METHODS: The Cardiovascular part of the trial included 170 men aged 65 years or older with low testosterone. Participants received testosterone gel or placebo gel for 12 months. The primary outcome was change in NCP volume from baseline to 12 months, as determined by coronary computed tomography angiography (CCTA). We assayed several markers of cardiovascular risk and analyzed each marker individually in a model as predictive variables and change in NCP as the dependent variable. RESULTS: Of 170 enrollees, 138 (73 testosterone, 65 placebo) completed the study and were available for the primary analysis. Of 10 markers evaluated, none showed a significant association with the change in NCP volume, but a significant interaction between treatment assignment and waist-hip ratio (WHR) (P = 0.0014) indicated that this variable impacted the testosterone effect on NCP volume. The statistical model indicated that for every 0.1 change in the WHR, the testosterone-induced 12-month change in NCP volume increased by 26.96 mm3 (95% confidence interval, 7.72-46.20). CONCLUSION: Among older men with low testosterone treated for 1 year, greater WHR was associated with greater NCP progression, as measured by CCTA. Other biomarkers and anthropometric measures did not show statistically significant association with plaque progression.

Left Main Coronary Artery Thrombus Diagnosed and Managed With Coronary Computed Tomography Angiography and Fractional Flow Reserve Derived From Computed Tomography.

Left main coronary artery thrombus (LMCA-T) is a rare disease state and diagnosed with invasive coronary angiography (ICA). We present a case of LMCA-T diagnosed with coronary computed tomography angiography (CTA) and treated without ICA in a patient who presented to a hospital in the middle of war zone in Erbil, Iraqi Kurdistan. Coronary CTA performed 1 month later demonstrated resolution of the thrombus. Fractional flow reserve computed from computed tomography (FFR-CT; HeartFlow, Redwood City, CA) performed retrospectively confirmed that the clot was not hemodynamically significant at the time of diagnosis. This case demonstrates the diagnostic capabilities of coronary CTA and FFR-CT when ICA is not readily available.

Low short-term and long-term cardiovascular and all-cause mortality in absence of coronary artery calcium: A 22-year follow-up observational study from large cohort.

OBJECTIVES: We sought to evaluate the gender-specific predictive value of coronary artery calcium (CAC) score on all-cause mortality and cardiovascular disease (CVD) mortality in individuals with and without diabetes mellitus (DM). BACKGROUND: CAC score is a robust predictor of CVD and all-cause mortality during long-term follow-up in large cohorts in adults with DM. However, less is known about its sex-specific impact on all-cause mortality in DM. METHODS: We evaluated 25,563 asymptomatic participants with no known history of coronary artery disease (CAD) who underwent clinically indicated CAC. 1999 (7.8%) individuals had diabetes. CAC was characterized as an Agatston score of 0, 1-99, 100-300, and ≫300. We evaluated the association between CAC and all-cause mortality and CVD mortality. RESULTS: Overall, 1345 individuals died (5.3%) from all causes during a mean follow-up of 14.7 ±â€¯3.8 years. CAC score was 0 in 57.5% females and 34.4% of males without DM, while 36.6% females and 20.3% males with DM had CAC-0. The frequency of CAC ≫ 300 was 18% and 36% in females and males with DM, respectively. CAC score of zero was associated with low all-cause mortality event rate in females and males with diabetes (1.7 and 2.5 events per 1000 person-years, respectively). Cardiovascular mortality per 1000 person years was ≪1 in females and males with CAC score of 0 irrespective of their diabetes. Adjusted multivariable analysis, compared to CAC-0, HR for all-cause mortality associated with CAC 1-99, 100-299 and ≫300 were 1.74(95% CI 0.65, 4.63, P-0.20), 5.54(95% CI 2.16, 14.22, P ≪ 0.001) and 5.75(95% CI 2.30, 14.37, P ≪ 0.001) in females with DM respectively; in males with DM HR associated with CAC 1-99, 100-299 and ≫300 were 1.87(95% CI 0.95, 3.66, P-0.06), 2.15(95% CI 1.05, 4.38, P-0.035) and 2.60(95% CI 1.34, 5.0, P-0.004), respectively. CONCLUSION: Presence of subclinical atherosclerosis varies among individuals with DM. The absence of CAC was associated with very low cardiovascular as well as all-cause mortality events in all subgroups during long term follow-up.

Effect of statins on atherosclerotic plaque.

Lipid lowering therapy has been the mainstay of cardiovascular risk reduction and prevention. Statin drugs have been shown to reduce serum cholesterol along with significant reduction in morbidity and mortality of cardiovascular disease. Whether these benefits are purely through lipid lowering or pleiotropic (cholesterol independent) effects has yet to be fully understood. Advances in cardiac imaging, from intravascular ultrasound to multi-detector coronary computed tomography angiography, have furthered our understanding of statin's effect on atherosclerotic plaque. Notably, statins play a role in plaque regression with reduction in lipid content. These drugs further stabilize atherosclerotic plaque with thickened fibrous caps and macrocalcification that serves to stabilize atheromas.

Anomalous coronary sinus communication to the left atrium.

This report highlights an unusual anatomical finding with serious implications in clinical cardiac care. We present a case of a fistula or bridging vein originating from the left atrium (LA) and inserting into the coronary sinus (CS) which courses posteriorly to the right atrium and inserts near the superior vena cava, essentially serving as a left to right shunt in a 64-year-old woman presenting with chest pain. The coronary venous system serves as a vital access point in the placement of cardiac pacemakers and defibrillators. Coronary sinus anomalies are rare and often occur in isolation or in association with other vascular anomalies. The described conduit serves as a functional interatrial shunt, though likely with minimal hemodynamic significance given the low pressure state of the left and right atria. This case highlights the importance of understanding the coronary venous anatomy and its variations in terms of anatomic course, valves, diameter, angulation, relationship to coronary arteries. .

Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors.

UNLABELLED: Given the limited regenerative capacity of the heart, cellular therapy with stem cell-derived cardiac cells could be a potential treatment for patients with heart disease. However, reliable imaging techniques to longitudinally assess engraftment of the transplanted cells are scant. To address this issue, we used ferumoxytol as a labeling agent of human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) to facilitate tracking by magnetic resonance imaging (MRI) in a large animal model. Differentiating hESCs were exposed to ferumoxytol at different time points and varying concentrations. We determined that treatment with ferumoxytol at 300 µg/ml on day 0 of cardiac differentiation offered adequate cell viability and signal intensity for MRI detection without compromising further differentiation into definitive cardiac lineages. Labeled hESC-CPCs were transplanted by open surgical methods into the left ventricular free wall of uninjured pig hearts and imaged both ex vivo and in vivo. Comprehensive T2*-weighted images were obtained immediately after transplantation and 40 days later before termination. The localization and dispersion of labeled cells could be effectively imaged and tracked at days 0 and 40 by MRI. Thus, under the described conditions, ferumoxytol can be used as a long-term, differentiation-neutral cell-labeling agent to track transplanted hESC-CPCs in vivo using MRI. SIGNIFICANCE: The development of a safe and reproducible in vivo imaging technique to track the fate of transplanted human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) is a necessary step to clinical translation. An iron oxide nanoparticle (ferumoxytol)-based approach was used for cell labeling and subsequent in vivo magnetic resonance imaging monitoring of hESC-CPCs transplanted into uninjured pig hearts. The present results demonstrate the use of ferumoxytol labeling and imaging techniques in tracking the location and dispersion of cell grafts, highlighting its utility in future cardiac stem cell therapy trials.

Arrhythmia in stem cell transplantation.

Stem cell regenerative therapies hold promise for treating diseases across the spectrum of medicine. While significant progress has been made in the preclinical stages, the clinical application of cardiac cell therapy is limited by technical challenges. Certain methods of cell delivery, such as intramyocardial injection, carry a higher rate of arrhythmias. Other potential contributors to the arrhythmogenicity of cell transplantation include reentrant pathways caused by heterogeneity in conduction velocities between graft and host as well as graft automaticity. In this article, the arrhythmogenic potential of cell delivery to the heart is discussed.

Can structured data fields accurately measure quality of care? The example of falls.

By automating collection of data elements, electronic health records may simplify the process of measuring the quality of medical care. Using data from a quality improvement initiative in primary care medical groups, we sought to determine whether the quality of care for falls and fear of falling in outpatients aged 75 and older could be accurately measured solely from codable (non-free-text) data in a structured visit note. A traditional medical record review by trained abstractors served as the criterion standard. Among 215 patient records reviewed, we found a structured visit note in 54% of charts within 3 mo of the date patients had been identified as having falls or fear of falling. The reliability of an algorithm based on codable data was at least good (kappa of at least 0.61) compared with full medical record review for three care processes recommended for patients with two falls or one fall with injury in the past year: orthostatic vital signs, vision test/eye examination, and home safety evaluation. However, the automated algorithm routinely underestimated quality of care. Performance standards based on automated measurement of quality of care from electronic health records need to account for documentation occurring in nonstructured form.