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Cardiovascular disease (CVD), a global health concern, particularly coronary artery disease (CAD), poses a significant threat to well-being. Seeking safer and cost-effective diagnostic alternatives to invasive coronary angiography, noninvasive coronary computed tomography angiography (CCTA) gains prominence. This study employed OpenFOAM, an open-source Computational Fluid Dynamics (CFD) software, to analyze hemodynamic parameters in coronary arteries with serial stenoses. Patient-specific three-dimensional (3D) models from CCTA images offer insights into hemodynamic changes. OpenFOAM breaks away from traditional commercial software, validated against the FDA benchmark nozzle model for reliability. Applying this refined methodology to seventeen coronary arteries across nine patients, the study evaluates parameters like fractional flow reserve computed tomography simulation (FFRCTS), fluid velocity, and wall shear stress (WSS) over time. Findings include FFRCTS values exceeding 0.8 for grade 0 stenosis and falling below 0.5 for grade 5 stenosis. Central velocity remains nearly constant for grade 1 stenosis but increases 3.4-fold for grade 5 stenosis. This research innovates by utilizing OpenFOAM, departing from previous reliance on commercial software. Combining qualitative stenosis grading with quantitative FFRCTS and velocity measurements offers a more comprehensive assessment of coronary artery conditions. The study introduces 3D renderings of wall shear stress distribution across stenosis grades, providing an intuitive visualization of hemodynamic changes for valuable insights into coronary stenosis diagnosis.

Cardiovascular-kidney-metabolic (CKM) syndrome is a novel construct recently defined by the American Heart Association in response to the high prevalence of metabolic and kidney disease. Epidemiological data demonstrate higher absolute risk of both atherosclerotic cardiovascular disease (CVD) and heart failure as an individual progresses from CKM stage 0 to stage 3, but optimal strategies for risk assessment need to be refined. Absolute risk assessment with the goal to match type and intensity of interventions with predicted risk and expected treatment benefit remains the cornerstone of primary prevention. Given the growing number of therapies in our armamentarium that simultaneously address all 3 CKM axes, novel risk prediction equations are needed that incorporate predictors and outcomes relevant to the CKM context. This should also include social determinants of health, which are key upstream drivers of CVD, to more equitably estimate and address risk. This scientific statement summarizes the background, rationale, and clinical implications for the newly developed sex-specific, race-free risk equations: PREVENT (AHA Predicting Risk of CVD Events). The PREVENT equations enable 10- and 30-year risk estimates for total CVD (composite of atherosclerotic CVD and heart failure), include estimated glomerular filtration rate as a predictor, and adjust for competing risk of non-CVD death among adults 30 to 79 years of age. Additional models accommodate enhanced predictive utility with the addition of CKM factors when clinically indicated for measurement (urine albumin-to-creatinine ratio and hemoglobin A1c) or social determinants of health (social deprivation index) when available. Approaches to implement risk-based prevention using PREVENT across various settings are discussed.

Importance: The Million Hearts Model paid health care organizations to assess and reduce cardiovascular disease (CVD) risk. Model effects on long-term outcomes are unknown., Objective: To estimate model effects on first-time myocardial infarctions (MIs) and strokes and Medicare spending over a period up to 5 years., Design, Setting, and Participants: This pragmatic cluster-randomized trial ran from 2017 to 2021, with organizations assigned to a model intervention group or standard care control group. Randomized organizations included 516 US-based primary care and specialty practices, health centers, and hospital-based outpatient clinics participating voluntarily. Of these organizations, 342 entered patients into the study population, which included Medicare fee-for-service beneficiaries aged 40 to 79 years with no previous MI or stroke and with high or medium CVD risk (a 10-year predicted probability of MI or stroke [ie, CVD risk score] ≥15%) in 2017-2018., Intervention: Organizations agreed to perform guideline-concordant care, including routine CVD risk assessment and cardiovascular care management for high-risk patients. The Centers for Medicare & Medicaid Services paid organizations to calculate CVD risk scores for Medicare fee-for-service beneficiaries. CMS further rewarded organizations for reducing risk among high-risk beneficiaries (CVD risk score ≥30%)., Main Outcomes and Measures: Outcomes included first-time CVD events (MIs, strokes, and transient ischemic attacks) identified in Medicare claims, combined first-time CVD events from claims and CVD deaths (coronary heart disease or cerebrovascular disease deaths) identified using the National Death Index, and Medicare Parts A and B spending for CVD events and overall. Outcomes were measured through 2021., Results: High- and medium-risk model intervention beneficiaries (n = 130 578) and standard care control beneficiaries (n = 88 286) were similar in age (median age, 72-73 y), sex (58%-59% men), race (7%-8% Black), and baseline CVD risk score (median, 24%). The probability of a first-time CVD event within 5 years was 0.3 percentage points lower for intervention beneficiaries than control beneficiaries (3.3% relative effect; adjusted hazard ratio [HR], 0.97 [90% CI, 0.93-1.00]; P = .09). The 5-year probability of combined first-time CVD events and CVD deaths was 0.4 percentage points lower in the intervention group (4.2% relative effect; HR, 0.96 [90% CI, 0.93-0.99]; P = .02). Medicare spending for CVD events was similar between the groups (effect estimate, -$1.83 per beneficiary per month [90% CI, -$3.97 to -$0.30]; P = .16), as was overall Medicare spending including model payments (effect estimate, $2.11 per beneficiary per month [90% CI, -$16.66 to $20.89]; P = .85)., Conclusions and Relevance: The Million Hearts Model, which encouraged and paid for CVD risk assessment and reduction, reduced first-time MIs and strokes. Results support guidelines to use risk scores for CVD primary prevention., Trial Registration: ClinicalTrials.gov Identifier: NCT04047147.

Background: Computational fluid dynamics (CFD) is an important tool for predicting cardiovascular device performance. The FDA developed a benchmark nozzle model in which experimental and CFD data were compared, however, the studies were limited by steady flows and Newtonian models., Objective: Newtonian and non-Newtonian blood models will be compared under steady and pulsatile flows to evaluate their influence on hemodynamics in the FDA nozzle., Methods: CFD simulations were validated against the FDA data for steady flow with a Newtonian model. Further simulations were performed using Newtonian and non-Newtonian models under both steady and pulsatile flows., Results: CFD results were within the experimental standard deviations at nearly all locations and Reynolds numbers. The model differences were most evident at Re = 500, in the recirculation regions, and during diastole. The non-Newtonian model predicted blunter upstream velocity profiles, higher velocities in the throat, and differences in the recirculation flow patterns. The non-Newtonian model also predicted a greater pressure drop at Re = 500 with minimal differences observed at higher Reynolds numbers., Conclusions: An improved modeling framework and validation procedure were used to further investigate hemodynamics in geometries relevant to cardiovascular devices and found that accounting for blood's non-Newtonian and pulsatile behavior can lead to large differences in predictions in hemodynamic parameters.

Hemolysis in medical devices and implants has been a primary concern over the past fifty years. Turbulent flow in particular can cause cell trauma and hemolysis in such devices. In this work, the effects of turbulence on red blood cell (RBC) damage are examined by simulating the flow field through a centrifugal blood pump that has been identified as a case study through the critical path initiative of the US Food and Drug Administration (FDA). In this study, a new model was employed to predict hemolysis in the turbulent flow environment in the pump selected for the FDA critical path initiative. The operating conditions for a centrifugal blood pump were specified by the FDA for rotational speeds of 2500 and 3500 rpm. The model is based on the analysis of the smaller eddies within the turbulent flow field, since it is assumed that turbulent flow eddies with sizes comparable to the dimensions of the RBCs lead to cell trauma. The Kolmogorov length scale of the velocity field is used to identify such small eddies. Using model parameters obtained in prior work through comparisons to capillary and jet flow, it is found that hemolysis for the 2500-rpm pump was predicted well, while hemolysis for the 3500-rpm pump was overpredicted. Results indicate refinement of the model and empirical constants with better experimental data is needed., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the present study, the effect of physical and operational uncertainties on the hydrodynamic and hemocompatibility characteristics of a centrifugal blood pump designed by the U.S. food and drug administration is investigated. Physical uncertainties include the randomness in the blood density and viscosity, while the operational uncertainties are composed of the pump rotational speed, mass flow rate, and turbulence intensity. The non-intrusive polynomial chaos expansion has been employed to conduct the uncertainty quantification analysis. Additionally, to assess each stochastic parameter's influence on the quantities of interest, the sensitivity analysis is utilized through the Sobol' indices. For numerical simulation of the pump's blood flow, the SST [Formula: see text] turbulence model and a power-law model of hemolysis were employed. The pump's velocity field is profoundly affected by the rotational speed in the bladed regions and the mass flow rate in other zones. Furthermore, the hemolysis index is dominantly sensitive to blood viscosity. According to the results, pump hydraulic characteristics (i.e., head and efficiency) show a more robust behavior than the hemocompatibility characteristics (i.e., hemolysis index) regarding the operational and physical uncertainties. Finally, it was found that the probability distribution function of the hemolysis index covers the experimental measurements., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Although cardiovascular toxicity from traditional chemotherapies has been well recognized for decades, the recent explosion of effective novel targeted cancer therapies with cardiovascular sequelae has driven the emergence of cardio-oncology as a new clinical and research field. Cardiovascular toxicity associated with cancer therapy can manifest as a broad range of potentially life-threatening complications, including heart failure, arrhythmia, myocarditis, and vascular events. Beyond toxicology, the intersection of cancer and heart disease has blossomed to include discovery of genetic and environmental risk factors that predispose to both. There is a pressing need to understand the underlying molecular mechanisms of cardiovascular toxicity to improve outcomes in patients with cancer. Preclinical cardiovascular models, ranging from cellular assays to large animals, serve as the foundation for mechanistic studies, with the ultimate goal of identifying biologically sound biomarkers and cardioprotective therapies that allow the optimal use of cancer treatments while minimizing toxicities. Given that novel cancer therapies target specific pathways integral to normal cardiovascular homeostasis, a better mechanistic understanding of toxicity may provide insights into fundamental pathways that lead to cardiovascular disease when dysregulated. The goal of this scientific statement is to summarize the strengths and weaknesses of preclinical models of cancer therapy-associated cardiovascular toxicity, to highlight overlapping mechanisms driving cancer and cardiovascular disease, and to discuss opportunities to leverage cardio-oncology models to address important mechanistic questions relevant to all patients with cardiovascular disease, including those with and without cancer.

The Food and Drug Administration's (FDA) benchmark nozzle model has been studied extensively both experimentally and computationally. Although considerable efforts have been made on validations of a variety of numerical models against available experimental data, the transitional flow cases are still not fully resolved, especially with regards to detailed comparison of predicted turbulence quantities with experimental measurements. This study aims to fill this gap by conducting large-eddy simulations (LES) of flow through the FDA's benchmark model, at a transitional Reynolds number of 2000. Numerical results are compared to previous interlaboratory experimental results, with an emphasis on turbulence characteristics. Our results show that the LES methodology can accurately capture laminar quantities throughout the model. In the pre-jet breakdown region, predicted turbulence quantities are generally larger than high resolution experimental data acquired with laser Doppler velocimetry. In the jet breakdown regions, where maximum Reynolds stresses occur, Reynolds shear stresses show excellent agreement. Differences of up to 4% and 20% are observed near the jet core in the axial and radial normal Reynolds stresses, respectively. Comparisons between viscous and Reynolds shear stresses show that peak viscous shear stresses occur in the nozzle throat reaching a value of 18 Pa in the boundary layer, whilst peak Reynolds shear stresses occur in the jet breakdown region reaching a maximum value of 87 Pa. Our results highlight the importance in considering both laminar and turbulent contributions towards shear stresses and that neglecting the turbulence effect can significantly underestimate the total shear force exerted on the fluid., (© 2020 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Million Hearts and partners have been committed to raising national cardiac rehabilitation participation rates to a goal of 70%. Quality improvement tools, resources, and surveillance models have been developed in support. Efforts to enhance research programs and collaborative initiatives have created momentum to accelerate implementation of new care models.

In order to simulate hemodynamics within centrifugal blood pumps and to predict pump hemolysis, CFD simulations must be thoroughly validated against experimental data. They must also account for and accurately model the specific working fluid in the pump, whether that is a blood-analog solution to match an experimental PIV study or animal blood in a hemolysis experiment. Therefore, the Food and Drug Administration (FDA) benchmark centrifugal blood pump and its database of experimental PIV and hemolysis data were used to thoroughly validate CFD simulations of the same blood pump. A Newtonian blood model was first used to compare to the PIV data with a blood analog fluid while hemolysis data were compared using a power-law hemolysis model fit to porcine blood data. A viscoelastic blood model was then incorporated into the CFD solver to investigate the importance of modeling blood's viscoelasticity in centrifugal pumps. The established computational framework, including a dynamic rotating mesh, animal blood-specific fluid properties and hemolysis modeling, and a k-ω SST turbulence model, was shown to more accurately predict pump pressure heads, velocity fields, and hemolysis compared to previously published CFD studies of the FDA centrifugal pump. The CFD simulations were able to match the FDA pressure and hemolysis data for multiple pump operating conditions, with the CFD results being within the standard deviations of the experimental results. While CFD radial velocity profiles between the impeller blades also compared well to the PIV velocity results, more work is still needed to address the large variability among both experimental and computational predictions of velocity in the diffuser outlet jet. Small differences were observed between the Newtonian and viscoelastic blood models in pressure head and hemolysis at the higher flow rate cases (FDA Conditions 4 and 5) but were more significant at lower flow rate and pump impeller speeds (FDA Condition 1). These results suggest that the importance of accounting for blood's viscoelasticity may be dependent on the specific blood pump operating conditions. This detailed computational framework with improved modeling techniques and an extensive validation procedure will be used in future CFD studies of centrifugal blood pumps to aid in device design and predictions of their biological responses., (© 2020 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background Nocturnal hypertension, defined by a mean asleep systolic blood pressure (SBP)/diastolic blood pressure (BP) ≥120/70 mm Hg, and nondipping SBP, defined by an awake-to-asleep decline in SBP <10%, are each associated with increased risk for cardiovascular disease. Methods and Results We developed predictive equations to identify adults with a high probability of having nocturnal hypertension or nondipping SBP using data from the CARDIA (Coronary Artery Risk Development in Young Adults) study (n=787), JHS (Jackson Heart Study) (n=1063), IDH (Improving the Detection of Hypertension) study (n=395), and MHT (Masked Hypertension) study (n=772) who underwent 24-hour ambulatory BP monitoring. Participants were randomized to derivation (n=2511) or validation (n=506) data sets. The prevalence rates of nocturnal hypertension and nondipping SBP were 39.7% and 44.9% in the derivation data set, respectively, and 36.6% and 44.5% in the validation data set, respectively. The predictive equation for nocturnal hypertension included age, race/ethnicity, smoking status, neck circumference, height, high-density lipoprotein cholesterol, albumin/creatinine ratio, and clinic SBP and diastolic BP. The predictive equation for nondipping SBP included age, sex, race/ethnicity, waist circumference, height, alcohol use, high-density lipoprotein cholesterol, and albumin/creatinine ratio. Concordance statistics (95% CI) for nocturnal hypertension and nondipping SBP predictive equations in the validation data set were 0.84 (0.80-0.87) and 0.73 (0.69-0.78), respectively. Compared with reference models including antihypertensive medication use and clinic SBP and diastolic BP as predictors, the continuous net reclassification improvement (95% CI) values for the nocturnal hypertension and nondipping SBP predictive equations were 0.52 (0.35-0.69) and 0.51 (0.34-0.69), respectively. Conclusions These predictive equations can direct ambulatory BP monitoring toward adults with high probability of having nocturnal hypertension and nondipping SBP.

Purpose of Review: To review the cardiac surgical simulation experience with a focus on data supporting its use., Recent Findings: Simulators have been used to improve trainee performance across multiple surgical domains. Few cardiac surgery residency programs have incorporated the use of simulation individually and Boot Camp programs in the United States and Canada have also introduced surgical simulation early in cardiac surgical training. Simulation curricula have some common elements: component tasks, deliberate practice, progressive operative responsibility, and coaching by an experienced surgeon. Cardiac surgical simulators can range from inexpensive, low-fidelity models for the practice of isolated skills to high-fidelity, operating room-scenarios. Multiple small studies have consistently demonstrated that the use of simulation improves qualitative and quantitative performance measures as well as overall resident confidence in clinical settings. To our knowledge, no study has demonstrated that use of simulation has led to improved quantitative performance measures in the operating room or patient outcomes. The barriers to wider use of surgical simulators include perceived lack of time and resources, the need for sustained practice and the lack of high-quality data to demonstrate clinical benefit., Summary: Incorporation of cardiac surgery simulation has been slow in most residency programs. There is consistent data demonstrating that simulation improves resident performance measures of simulation-based tasks but whether this will lead to improved patient outcomes remains an open question.

Hemolysis is a major concern in blood-circulating devices, which arises due to hydrodynamic loading on red blood cells from ambient flow environment. Hemolysis estimation models have often been used to aid hemocompatibility design. The preponderance of hemolysis models was formulated on the basis of laminar flows. However, flows in blood-circulating devices are rather complex and can be laminar, transitional or turbulent. It is an extrapolation to apply these models to turbulent flows. For the commonly used power-law models, effective stress has often been represented using Reynolds stresses for estimating hemolysis in turbulent flows. This practice tends to overpredict hemolysis. This study focused on the representation of effective stress in power-law models. Through arithmetic manipulations from Navier-Stokes equation, we showed that effective stress can be represented in terms of energy dissipation, which can be readily obtained from CFD simulations. Three cases were tested, including a capillary tube, the FDA benchmark cases of nozzle model and blood pump. The results showed that the representation of effective stress in terms of energy dissipation greatly improved the prediction of hemolysis for a wide range of flow conditions. The improvement increases as Reynolds number increases; the overprediction of hemolysis was reduced by up to two orders of magnitude.

Objective- Increased Lp(a) [lipoprotein(a)] is associated with coronary heart disease risk, but links with stroke are less consistent. Blacks have higher Lp(a) levels and stroke incidence than whites but have been underrepresented in studies. We hypothesized that Lp(a) is a risk factor for ischemic stroke and that risk differs by race. Approach and Results- REGARDS (Reasons for Geographic and Racial Differences in Stroke) recruited 30 239 black and white US adults aged ≥45 in 2003-2007 to study regional and racial differences in stroke mortality. We measured baseline Lp(a) by immunonephelometric assay in 572 cases of incident ischemic stroke and a 967-person cohort random sample. The hazard ratio of stroke by baseline Lp(a) was calculated using Cox proportional hazards models, stratified by race. Lp(a) was modeled in sex- and race-specific quartiles, given known differences in distributions by race and sex. Interactions were tested by including interaction terms in the proportional hazards models, with P<0.10 considered statistically significant. After adjustment for age, sex, and stroke risk factors, being in the fourth versus the first Lp(a) quartile was weakly associated with ischemic stroke overall, hazard ratio, 1.45 (95% CI, 0.96-2.19). In blacks, the hazard ratio was 1.96 (95% CI, 1.10-3.46), whereas in whites HR was 1.14 (95% CI, 0.64-2.04); P interaction=0.12. Lp(a) was lower in men than women, but associations with stroke in men and women were similar. Conclusions- We confirm that Lp(a) is a risk factor for ischemic stroke. Further research is needed to confirm the role of racial differences of the Lp(a) risk multiplier in ischemic stroke.

Purpose: The United States' Food and Drug Administration (FDA) recommends that device manufacturers demonstrate 10 years of equivalent life duration for endovascular stents. Yet since the early 2000s clinical evidence of stent strut fracture defies the recommendations for these FDA approved devices. Stent strut fracture has been correlated with a higher incidence of adverse clinical events, such as in-stent thrombosis and in-stent restenosis., Methods: This paper reviews the current clinical evidence, computational modelling relating to fatigue lifetimes, experimental testing of coronary stents, and the related regulatory guidance and standards., Results: The scale of stent fracture is evident from the clinical data reviewed. In terms of model setups, either physical or computational the loadings, in particular, dictate the durability response., Conclusions: The full scale of stent fracture is most likely under-reported and its assessment is dependent on detection time and detection resolution. Within the event of SF it is not necessarily consequential; further research is warranted to distinguish when the event negatively impacts the patient.

Purpose: A credible computational fluid dynamics (CFD) model can play a meaningful role in evaluating the safety and performance of medical devices. A key step towards establishing model credibility is to first validate CFD models with benchmark experimental datasets to minimize model-form errors before applying the credibility assessment process to more complex medical devices. However, validation studies to establish benchmark datasets can be cost prohibitive and difficult to perform. The goal of this initiative sponsored by the U.S. Food and Drug Administration is to generate validation data for a simplified centrifugal pump that mimics blood flow characteristics commonly observed in ventricular assist devices., Methods: The centrifugal blood pump model was made from clear acrylic and included an impeller, with four equally spaced, straight blades, supported by mechanical bearings. Particle Image Velocimetry (PIV) measurements were performed at several locations throughout the pump by three independent laboratories. A standard protocol was developed for the experiments to ensure that the flow conditions were comparable and to minimize systematic errors during PIV image acquisition and processing. Velocity fields were extracted at the pump entrance, blade passage area, back gap region, and at the outlet diffuser regions. A Newtonian blood analog fluid composed of sodium iodide, glycerin, and water was used as the working fluid. Velocity measurements were made for six different pump flow conditions, with the blood-equivalent flow rate ranging between 2.5 and 7 L/min for pump speeds of 2500 and 3500 rpm., Results: Mean intra- and inter-laboratory variabilities in velocity were ~ 10% at the majority of the measurement locations inside the pump. However, the inter-laboratory variability increased to more than ~ 30% in the exit diffuser region. The variability between the three laboratories for the peak velocity magnitude in the diffuser region ranged from 5 to 25%. The bulk velocity field near the impeller changed proportionally with the rotational speed but was relatively unaffected by the pump flow rate. In contrast, flow in the exit diffuser region was sensitive to both the flow rate and the rotational speed. Specifically, at 3500 rpm, the exit jet tilted toward the inner wall of the diffuser at a flow rate of 2.5 L/min, but the jet tilted towards the outer wall when the flow rate was 7 L/min., Conclusions: Inter-laboratory experimental mean velocity data (and the corresponding variance) were obtained for the FDA pump model and are available for download at https://nciphub.org/wiki/FDA&#95;CFD . Experimental datasets from the inter-laboratory characterization of benchmark flow models, including the blood pump model presented herein and our previous nozzle model, can be used for validating future CFD studies and to collaboratively develop guidelines on best practices for verification, validation, uncertainty quantification, and credibility assessment of CFD simulations in the evaluation of medical devices (e.g. ASME V&V 40 standards working group).

Background: Previously proposed algorithms to predict the ventricular tachycardia (VT) exit site have been based on diverse left ventricular models, but none of them identify the precise region of origin in the electroanatomic map. Moreover, no electrocardiographic (ECG) algorithm has been tested to predict the region of origin of scar-related VTs in patients with nonischemic cardiomyopathy., Objective: The purpose of this study was to validate a simple ECG algorithm to identify the segment of origin (SgO) of VT relative to the 17-segment American Heart Association model in patients with structural heart disease (SHD)., Methods: The study included 108 consecutive patients with documented VT and SHD [77 (71%) with coronary artery disease]. A novel frontal plane axis-based ECG algorithm (highest positive or negative QRS voltage) together with the polarity in leads V 3 and V 4 was used to predict the SgO of VT. The actual SgO of VT was obtained from the analysis of the electroanatomic map during the procedure. Conventional VT mapping techniques were used to identify the VT exit., Results: In total, 149 12-lead ECGs of successfully ablated VT were analyzed. The ECG-suggested SgO matched with the actual SgO in 122 of the 149 VTs (82%). In 21 of the 27 mismatched ECG-suggested SgOs (77.8%), the actual SgO was adjacent to the segment suggested by the ECG. There were no differences in the accuracy of the algorithm based on the SgO or the type of SHD., Conclusion: This novel QRS axis-based algorithm accurately identifies the SgO of VT in the 17-segment American Heart Association model in patients with SHD., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve replacement (TAVR) has become an acceptable therapy for patients with severe aortic valve stenosis at high or prohibitive surgical risk. Attempts are ongoing to validate risk prediction models for in-hospital mortality after TAVR. Our aim was to define modifiable risk factors predictive of in-hospital mortality after TAVR., Methods: We identified patients who underwent TAVR from the 2012 database of the National Inpatient Sample. Patients who died during the index hospitalization were compared to those that were successfully discharged. The predictors of in-hospital mortality were analyzed using multivariate logistic regression., Results: A total of 1,360 patients (mean age 81 ± 8.8 years, whites 80.1%, blacks 3.5%) had TAVR and 68 (5%) died during hospitalization (χ 2 [1, n = 1,360] = 1,101.6, P < 0.001). The average length of hospital stay was 8.33 ± 6.7 days. The positive predictors of in-hospital mortality in the unadjusted model were comorbidities such as congestive heart failure, coagulopathy, fluid and electrolyte disorder, weight loss and history of drug abuse. Hypertension was a negative predictor of in-hospital mortality. Following multivariate analysis and adjustment for possible confounders, fluid and electrolyte disorder was the only significant positive predictor of in-hospital mortality (odds ratio = 1.89, CI: 1.11-3.22, P = 0.019). The odds of in-hospital mortality were reduced in patients with hypertension (odds ratio = 0.45, CI: 0.26-0.78, P = 0.004)., Conclusions: Fluid and electrolyte disturbance could be a modifiable predictor of in-hospital mortality following TAVR. Efforts should be geared towards reducing its occurrence in this patient population., (Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Induced pluripotent stem cells (iPSCs) offer an unprece-dented opportunity to study human physiology and disease at the cellular level. They also have the potential to be leveraged in the practice of precision medicine, for example, personalized drug testing. This statement comprehensively describes the provenance of iPSC lines, their use for cardiovascular disease modeling, their use for precision medicine, and strategies through which to promote their wider use for biomedical applications. Human iPSCs exhibit properties that render them uniquely qualified as model systems for studying human diseases: they are of human origin, which means they carry human genomes; they are pluripotent, which means that in principle, they can be differentiated into any of the human body's somatic cell types; and they are stem cells, which means they can be expanded from a single cell into millions or even billions of cell progeny. iPSCs offer the opportunity to study cells that are genetically matched to individual patients, and genome-editing tools allow introduction or correction of genetic variants. Initial progress has been made in using iPSCs to better understand cardiomyopathies, rhythm disorders, valvular and vascular disorders, and metabolic risk factors for ischemic heart disease. This promising work is still in its infancy. Similarly, iPSCs are only just starting to be used to identify the optimal medications to be used in patients from whom the cells were derived. This statement is intended to (1) summarize the state of the science with respect to the use of iPSCs for modeling of cardiovascular traits and disorders and for therapeutic screening; (2) identify opportunities and challenges in the use of iPSCs for disease modeling and precision medicine; and (3) outline strategies that will facilitate the use of iPSCs for biomedical applications. This statement is not intended to address the use of stem cells as regenerative therapy, such as transplantation into the body to treat ischemic heart disease or heart failure., (© 2018 American Heart Association, Inc.)

Background: The influence of prolonged and repeated water immersions on heart rate variability (HRV) and complexity was examined in 10 U.S. Navy divers who completed six-hour resting dives on five consecutive days. Pre-dive and during-dive measures were recorded daily., Methods: Dependent variables of interest were average heart rate (HR), time-domain measures of HRV [root mean square of successive differences of the normal RR (NN) interval (RMSSD), standard deviation of the NN interval (SDNN)], frequency-domain measures of HRV [low-frequency power spectral density (psd) (LFpsd), low-frequency normalized (LFnu), high-frequency psd (HFpsd), high-frequency normalized (HFnu), low-frequency/ high-frequency ratio (LF/HF)], and non-linear dynamics of HRV [approximate entropy (ApEn)]. A repeated-measures ANOVA was performed to examine pre-dive measure differences among baseline measures. Hierarchical linear modeling (HLM) was performed to test the effects of prolonged and repeated water immersion on the dependent variables., Results: Pre-dive HR (P=0.005) and RMSSD (P⟨0.001) varied significantly with dive day while changes in SDNN approached significance (P=0.055). HLM indicated that HR decreased during daily dives (P=0.001), but increased across dive days (P=0.011); RMSSD increased during daily dives (P=0.018) but decreased across dive days (P⟨0.001); SDNN increased during daily dives (P⟨0.001); LF measures increased across dive days (LFpsd P⟨0.001; LFnu P⟨0.001), while HF measures decreased across dive days (HFpsd P⟨0.001; HFnu P⟨0.001); LF/HF increased across dive days (P⟨0.001); ApEn decreased during daily dives (P⟨0.02) and across dive days (P⟨0.001)., Conclusions: These data suggest that the cumulative effect of repeated dives across five days results in decreased vagal tone and a less responsive cardiovascular system., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission.

Mitochondrial biology is the sum of diverse phenomena from molecular profiles to physiological functions. A mechanistic understanding of mitochondria in disease development, and hence the future prospect of clinical translations, relies on a systems-level integration of expertise from multiple fields of investigation. Upon the successful conclusion of a recent National Institutes of Health, National Heart, Lung, and Blood Institute initiative on integrative mitochondrial biology in cardiovascular diseases, we reflect on the accomplishments made possible by this unique interdisciplinary collaboration effort and exciting new fronts on the study of these remarkable organelles., (© 2015 American Heart Association, Inc.)

Objective: Currently, no quantitative guidelines have been established for treatment of left pulmonary artery (LPA) stenosis. This study aims to quantify the effects of LPA stenosis on postoperative hemodynamics for single-ventricle patients undergoing stage II superior cavopulmonary connection (SCPC) surgery, using a multiscale computational approach., Methods: Image data from 6 patients were segmented to produce 3-dimensional models of the pulmonary arteries before stage II surgery. Pressure and flow measurements were used to tune a 0-dimensional model of the entire circulation. Postoperative geometries were generated through stage II virtual surgery; varying degrees of LPA stenosis were applied using mesh morphing and hemodynamics assessed through coupled 0-3-dimensional simulations. To relate metrics of stenosis to clinical classifications, pediatric cardiologists and surgeons ranked the degrees of stenosis in the models. The effects of LPA stenosis were assessed based on left-to-right pulmonary artery flow split ratios, mean pressure drop across the stenosis, cardiac pressure-volume loops, and other clinically relevant parameters., Results: Stenosis of >65% of the vessel diameter was required to produce a right pulmonary artery:LPA flow split <30%, and/or a mean pressure drop of >3.0 mm Hg, defined as clinically significant changes., Conclusions: The effects of <65% stenosis on SCPC hemodynamics and physiology were minor and may not justify the increased complexity of adding LPA arterioplasty to the SCPC operation. However, in the longer term, pulmonary augmentation may affect outcomes of the Fontan completion surgery, as pulmonary artery distortion is a risk factor that may influence stage III physiology., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Several groups report electrical rotors or focal sources that sustain atrial fibrillation (AF) after it has been triggered. However, it is difficult to separate stable from unstable activity in prior studies that examined only seconds of AF. We applied phase-based focal impulse and rotor mapping (FIRM) to study the dynamics of rotors/sources in human AF over prolonged periods of time., Methods: We prospectively mapped AF in 260 patients (169 persistent, 61 ± 12 years) at 6 centers in the FIRM registry, using baskets with 64 contact electrodes per atrium. AF was phase mapped (RhythmView, Topera, Menlo Park, CA, USA). AF propagation movies were interpreted by each operator to assess the source stability/dynamics over tens of minutes before ablation., Results: Sources were identified in 258 of 260 of patients (99%), for 2.8 ± 1.4 sources/patient (1.8 ± 1.1 in left, 1.1 ± 0.8 in right atria). While AF sources precessed in stable regions, emanating activity including spiral waves varied from collision/fusion (fibrillatory conduction). Each source lay in stable atrial regions for 4,196 ± 6,360 cycles, with no differences between paroxysmal versus persistent AF (4,290 ± 5,847 vs. 4,150 ± 6,604; P = 0.78), or right versus left atrial sources (P = 0.26)., Conclusions: Rotors and focal sources for human AF mapped by FIRM over prolonged time periods precess ("wobble") but remain within stable regions for thousands of cycles. Conversely, emanating activity such as spiral waves disorganize and collide with the fibrillatory milieu, explaining difficulties in using activation mapping or signal processing analyses at fixed electrodes to detect AF rotors. These results provide a rationale for targeted ablation at AF sources rather than fibrillatory spiral waves., (© 2014 Wiley Periodicals, Inc.)

Background: Although left ventricular cardiac geometric indices such as size and sphericity characterize adverse remodeling and have prognostic value in symptomatic patients, little is known of shape distributions in subclinical populations. We sought to quantify shape variation across a large number of asymptomatic volunteers, and examine differences among sub-cohorts., Methods: An atlas was constructed comprising 1,991 cardiovascular magnetic resonance (CMR) cases contributed from the Multi-Ethnic Study of Atherosclerosis baseline examination. A mathematical model describing regional wall motion and shape was used to establish a coordinate map registered to the cardiac anatomy. The model was automatically customized to left ventricular contours and anatomical landmarks, corrected for breath-hold mis-registration between image slices. Mathematical techniques were used to characterize global shape distributions, after removal of translations, rotations, and scale due to height. Differences were quantified among ethnicity, sex, smoking, hypertension and diabetes sub-cohorts., Results: The atlas construction process yielded accurate representations of global shape (errors between manual and automatic surface points in 244 validation cases were less than the image pixel size). After correction for height, the dominant shape component was associated with heart size, explaining 32% of the total shape variance at end-diastole and 29% at end-systole. After size, the second dominant shape component was sphericity at end-diastole (13%), and concentricity at end-systole (10%). The resulting shape components distinguished differences due to ethnicity and risk factors with greater statistical power than traditional mass and volume indices., Conclusions: We have quantified the dominant components of global shape variation in the adult asymptomatic population. The data and results are available at cardiacatlas.org. Shape distributions were principally explained by size, sphericity and concentricity, which are known correlates of adverse outcomes. Atlas-based global shape analysis provides a powerful method for quantifying left ventricular shape differences in asymptomatic populations., Trial Registration: ClinicalTrials.gov NCT00005487.

Background: Limited brachial artery (BA) flow-mediated dilation during brachial artery reactivity testing (BART) has been linked to increased cardiovascular risk. We report on the phenomenon of BA constriction (BAC) following hyperemia., Objectives: To determine whether BAC predicts adverse CV outcomes and/or mortality in the women's ischemic Syndrome Evaluation Study (WISE). Further, as a secondary objective we sought to determine the risk factors associated with BAC., Methods: We performed BART on 377 women with chest pain referred for coronary angiography and followed for a median of 9.5 years. Forearm ischemia was induced with 4 minutes occlusion by a cuff placed distal to the BA and inflated to 40mm Hg > systolic pressure. BAC was defined as >4.8% artery constriction following release of the cuff. The main outcome was major adverse events (MACE) including all-cause mortality, non-fatal MI, non-fatal stroke, or hospitalization for heart failure., Results: BA diameter change ranged from -20.6% to +44.9%, and 41 (11%) women experienced BAC. Obstructive CAD and traditional CAD risk factors were not predictive of BAC. Overall, 39% of women with BAC experienced MACE vs. 22% without BAC (p=0.004). In multivariate Cox proportional hazards regression, BAC was a significant independent predictor of MACE (p=0.018) when adjusting for obstructive CAD and traditional risk factors., Conclusions: BAC predicts almost double the risk for major adverse events compared to patients without BAC. This risk was not accounted for by CAD or traditional risk factors. The novel risk marker of BAC requires further investigation in women.

Background: The Framingham Global Cardiovascular Disease (FRS-CVD) risk assessment is a proposed alternative for the assessment of hard coronary heart disease (FRS-CHD) event risk. Beyond heart attack and death, FRS-CVD risk adds the end points of cerebrovascular disease, angina, heart failure, and peripheral vascular disease., Objective: We sought to estimate the population impact of using FRS-CVD instead of FRS-CHD risk prediction on U.S. adults., Methods: We analyzed FRS-CHD and FRS-CVD risk in men age 45-74 and women age 55-74 without cardiovascular disease or diabetes, using the National Health and Nutrition Examination Survey 2005-2006. We stratified the population into 10-year risk categories: low: <6%, moderate ≥ 6 to <10%, moderate high ≥ 10 to <20%, and high ≥ 20% by both risk models, and assessed change in risk category distribution and achievement of lipid goals., Results: We analyzed 1020 subjects who statistically represent approximately 50 million U.S. adults. When the FRS-CVD was used, we found that 63% of men and 74% of women increase at least one risk category compared with when the FRS-CHD is used. Overall, the low-risk population decreases from 52% to 16% and the high-risk group increases from 4% to 20%. Of the subjects changing risk categories, 30% will now fail to meet their new corresponding lipid goals., Conclusions: FRS-CVD end points are more comprehensive, yet the population implications of such a change may be profound. The use of a FRS-CVD risk model significantly increases the intermediate and high-risk groups, thus increasing the number of individuals eligible for novel risk assessment tools such as high-sensitivity C-reactive protein, coronary calcium scoring, and more frequent use of pharmacotherapy., (Copyright © 2011 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

In this work we present an enhanced medical workflow and a decision support system for atherosclerotic risk assessment and treatment, that is based both on existing medical guidelines and on patient specific multiscale data. The medical expert that uses the system is able to apply both existing medical guidelines as well as to take into account additional information for the patient by inspecting the 3D geometry of an arterial segment or the arterial tree, model the blood flow in the patient specific arterial model and predict the progression of the plaque. Moreover, the user is able to apply plaque characterization techniques in Intravascular Ultrasound images (IVUS) and Tomography Images (CT). The combination of the medical guidelines with the patient specific multiscale data provides a detailed view in the patient status for risk assessment and treatment suggestion.

Cardiac arrest occurs when organized cardiac contractility ceases and circulation stops. During cardiac arrest, electrical activity may be abnormal or absent, and the rhythm documented can be ventricular fibrillation, pulseless ventricular tachycardia, pulseless electrical activity, or asystole. It has been estimated that 300 000 sudden cardiac arrests occur each year in the United States, with 75% (225,000) occurring out-of-hospital and 25% (75,000) occurring in-hospital. A similar number occur in Europe each year. The 3-phase model of cardiac arrest, which proposes that a cardiac arrest progresses through distinct phases as time elapses, helps inform research and clinical care by providing a framework for improving outcomes from cardiac arrest. Early in an arrest, during the electrical phase, defibrillation is paramount. The circulatory phase begins after 4 to 5 minutes, and interventions to optimize circulation become of primary importance. When an arrest is prolonged, lasting for ≥10 minutes, the patient passes into the metabolic phase, in which significant metabolic derangements have accrued and start to dominate arrest physiology. If return of spontaneous circulation occurs during this phase, significant injury to diverse organs may have occurred, producing a critical illness known as post-cardiac arrest syndrome. The post-cardiac arrest syndrome has been recognized as a unique entity requiring unique therapies for successful management. Recent advances in cardiac arrest care include cardiocerebral resuscitation and the use of therapeutic hypothermia to treat comatose survivors of cardiac arrest.

Background: Sodium consumption raises blood pressure, increasing the risk for heart attack and stroke. Several countries, including the United States, are considering strategies to decrease population sodium intake., Objective: To assess the cost-effectiveness of 2 population strategies to reduce sodium intake: government collaboration with food manufacturers to voluntarily cut sodium in processed foods, modeled on the United Kingdom experience, and a sodium tax., Design: A Markov model was constructed with 4 health states: well, acute myocardial infarction (MI), acute stroke, and history of MI or stroke., Data Sources: Medical Panel Expenditure Survey (2006), Framingham Heart Study (1980 to 2003), Dietary Approaches to Stop Hypertension trial, and other published data., Target Population: U.S. adults aged 40 to 85 years., Time Horizon: Lifetime., Perspective: Societal., Outcome Measures: Incremental costs (2008 U.S. dollars), quality-adjusted life-years (QALYs), and MIs and strokes averted., Results of Base-Case Analysis: Collaboration with industry that decreases mean population sodium intake by 9.5% averts 513 885 strokes and 480 358 MIs over the lifetime of adults aged 40 to 85 years who are alive today compared with the status quo, increasing QALYs by 2.1 million and saving $32.1 billion in medical costs. A tax on sodium that decreases population sodium intake by 6% increases QALYs by 1.3 million and saves $22.4 billion over the same period., Results of Sensitivity Analysis: Results are sensitive to the assumption that consumers have no disutility with modest reductions in sodium intake., Limitation: Efforts to reduce population sodium intake could result in other dietary changes that are difficult to predict., Conclusion: Strategies to reduce sodium intake on a population level in the United States are likely to substantially reduce stroke and MI incidence, which would save billions of dollars in medical expenses., Primary Funding Source: Department of Veterans Affairs, Stanford University, and National Science Foundation.

Objective: The purpose of our study was to measure the radiation dose from ECG-gated CT coronary angiography in children and to estimate the cancer risk associated with the radiation dose., Materials and Methods: Organ doses were measured with a 5-year-old pediatric phantom and thermoluminescent dosimeters on a 64-MDCT scanner. Four retrospectively ECG-gated CT coronary angiography protocols with four simulated heart rates and the corresponding pitches were studied. The lifetime attributable risk of cancer incidence was estimated for children in the United States and Hong Kong according to the National Academies Biologic Effects of Ionizing Radiation VII report., Results: The effective doses were 16.45, 12.17, 11.97, and 11.81 mSv for the four protocols, respectively. The corresponding lifetime attributable risks estimated for 5-year-old U.S. boys and girls were 0.14%-0.20% and 0.43%-0.60%, respectively, and for 5-year-old Hong Kong boys and girls were 0.22%-0.33% and 0.61%-0.85%. In relation to the total cancer incidence (baseline cancer incidence plus lifetime attributable risk), lifetime attributable risk from radiation exposure contributed up to 0.99% and 3.51% for Hong Kong boys and girls and up to 0.46% and 1.57% for U.S. boys and girls., Conclusion: Our results suggest that radiation dose and cancer risk of CT coronary angiography to pediatric patients are not negligible, more so in Hong Kong children than in U.S. children. Therefore, these examinations should be well justified clinically.

Objective: People with diabetes have an increased risk of coronary artery disease (CAD). An unanswered question is what portion of CAD can be attributed to insulin resistance, related metabolic variables, and other known CAD risk factors., Research Design and Methods: The Archimedes model was used to estimate the proportion of myocardial infarctions that would be prevented by maintaining insulin resistance and other risk factors at healthy levels. Person-specific data from the National Health and Nutrition Examination Survey 1998-2004 were used to create a simulated population representative of young adults in the U.S. This population was then entered into a series of simulated clinical trials designed to explore the effects of each risk factor. Each trial had a control arm (all risk factors were allowed to progress without interventions) and a treatment arm (a risk factor was held to its value in young healthy adults). The trials continued for 60 years. The effects of these hypothetical "cures" of each risk factor provide estimates of their impact on CAD., Results: In young adults, preventing insulin resistance would prevent approximately 42% of myocardial infarctions. The next most important determinant of CAD is systolic hypertension, prevention of which would reduce myocardial infarctions by approximately 36%. Following systolic blood pressure, the most important determinants are HDL cholesterol (31%), BMI (21%), LDL cholesterol (16%), triglycerides (10%), fasting plasma glucose and smoking (both approximately 9%), and family history (4%)., Conclusions: Insulin resistance is likely the most important single cause of CAD. A better understanding of its pathogenesis and how it might be prevented or cured could have a profound effect on CAD.

Several challenges exist with respect to training the current and next generation of vascular specialists. Current advances in technology have led to changes in the length and type of training required to master new endovascular techniques. At the same time, the number of open surgical cases being provided to trainees may not be sufficient to allow them to manage complex open procedures. This growth is occurring at a time when increased external pressures are being applied to shorten training programs. Finally, the next generation of vascular specialists will come from medical students who are accruing a large educational debt during their course of training. Vascular specialists outside the US have already begun to successfully deal with many of these issues, and insight can be gained from their successes and difficulties. In this article, we review the current status of training for vascular and endovascular specialists and discuss the need for changes in current US training paradigms. While this will touch on initiatives in other specialties, including cardiology, vascular medicine, and interventional and neuroradiology, we will focus primarily on changes that are occurring with respect to the training of surgical specialists who manage vascular disease.

Orthogonal recursive bisection (ORB) algorithm can be used as data decomposition strategy to distribute a large data set of a cardiac model to a distributed memory supercomputer. It has been shown previously that good scaling results can be achieved using the ORB algorithm for data decomposition. However, the ORB algorithm depends on the distribution of computational load of each element in the data set. In this work we investigated the dependence of data decomposition and load balancing on different rotations of the anatomical data set to achieve optimization in load balancing. The anatomical data set was given by both ventricles of the Visible Female data set in a 0.2 mm resolution. Fiber orientation was included. The data set was rotated by 90 degrees around x, y and z axis, respectively. By either translating or by simply taking the magnitude of the resulting negative coordinates we were able to create 14 data set of the same anatomy with different orientation and position in the overall volume. Computation load ratios for non - tissue vs. tissue elements used in the data decomposition were 1:1, 1:2, 1:5, 1:10, 1:25, 1:38.85, 1:50 and 1:100 to investigate the effect of different load ratios on the data decomposition. The ten Tusscher et al. (2004) electrophysiological cell model was used in monodomain simulations of 1 ms simulation time to compare performance using the different data sets and orientations. The simulations were carried out for load ratio 1:10, 1:25 and 1:38.85 on a 512 processor partition of the IBM Blue Gene/L supercomputer. Th results show that the data decomposition does depend on the orientation and position of the anatomy in the global volume. The difference in total run time between the data sets is 10 s for a simulation time of 1 ms. This yields a difference of about 28 h for a simulation of 10 s simulation time. However, given larger processor partitions, the difference in run time decreases and becomes less significant. Depending on the processor partition size, future work will have to consider the orientation of the anatomy in the global volume for longer simulation runs.

A number of revolutionary techniques have been developed for cardiac electrophysiology research to better study the various arrhythmia mechanisms that can enhance ablating strategies for cardiac arrhythmias. Once the three-dimensional high resolution cardiac optical imaging data is acquired, it is time consuming to manually go through them and try to identify the patterns associated with various arrhythmia symptoms. In this paper, we present an interactive computer wizard that helps cardiac electrophysiology researchers to visualize and analyze the high resolution cardiac optical imaging data. The wizard provides a file interface that accommodates different file formats. A series of analysis algorithms output waveforms, activation and action potential maps after spatial and temporal filtering, velocity field and heterogeneity measure. The interactive GUI allows the researcher to identify the region of interest in both the spatial and temporal domain, thus enabling them to study different heart chamber at their choice.

High performance computing is required to make feasible simulations of whole organ models of the heart with biophysically detailed cellular models in a clinical setting. Increasing model detail by simulating electrophysiology and mechanical models increases computation demands. We present scaling results of an electro - mechanical cardiac model of two ventricles and compare them to our previously published results using an electrophysiological model only. The anatomical data-set was given by both ventricles of the Visible Female data-set in a 0.2 mm resolution. Fiber orientation was included. Data decomposition for the distribution onto the distributed memory system was carried out by orthogonal recursive bisection. Load weight ratios for non-tissue vs. tissue elements used in the data decomposition were 1:1, 1:2, 1:5, 1:10, 1:25, 1:38.85, 1:50 and 1:100. The ten Tusscher et al. (2004) electrophysiological cell model was used and the Rice et al. (1999) model for the computation of the calcium transient dependent force. Scaling results for 512, 1024, 2048, 4096, 8192 and 16,384 processors were obtained for 1 ms simulation time. The simulations were carried out on an IBM Blue Gene/L supercomputer. The results show linear scaling from 512 to 16,384 processors with speedup factors between 1.82 and 2.14 between partitions. The most optimal load ratio was 1:25 for on all partitions. However, a shift towards load ratios with higher weight for the tissue elements can be recognized as can be expected when adding computational complexity to the model while keeping the same communication setup. This work demonstrates that it is potentially possible to run simulations of 0.5 s using the presented electro-mechanical cardiac model within 1.5 hours.

Little is known about the impact of the total cavopulmonary connection (TCPC) on resting and exercise hemodynamics in a single ventricle (SV) circulation. The aim of this study was to elucidate this mechanism using a lumped parameter model of the SV circulation. Pulmonary vascular resistance (1.96+/-0.80 WU) and systemic vascular resistances (18.4+/-7.2 WU) were obtained from catheterization data on 40 patients with a TCPC. TCPC resistances (0.39+/-0.26 WU) were established using computational fluid dynamic simulations conducted on anatomically accurate three-dimensional models reconstructed from MRI (n=16). These parameters were used in a lumped parameter model of the SV circulation to investigate the impact of TCPC resistance on SV hemodynamics under resting and exercise conditions. A biventricular model was used for comparison. For a biventricular circulation, the cardiac output (CO) dependence on TCPC resistance was negligible (sensitivity=-0.064 l.min(-1).WU(-1)) but not for the SV circulation (sensitivity=-0.88 l.min(-1).WU(-1)). The capacity to increase CO with heart rate was also severely reduced for the SV. At a simulated heart rate of 150 beats/min, the SV patient with the highest resistance (1.08 WU) had a significantly lower increase in CO (20.5%) compared with the SV patient with the lowest resistance (50%) and normal circulation (119%). This was due to the increased afterload (+35%) and decreased preload (-12%) associated with the SV circulation. In conclusion, TCPC resistance has a significant impact on resting hemodynamics and the exercise capacity of patients with a SV physiology.

The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of cardiologists, cardiac electrophysiologists, cell biophysicists, and computational modelers on August 20 and 21, 2007, in Washington, DC, to advise the NHLBI on new research directions needed to develop integrative approaches to elucidate human cardiac function. The workshop strove to identify limitations in the use of data from nonhuman animal species for elucidation of human electromechanical function/activity and to identify what specific information on ion channel kinetics, calcium handling, and dynamic changes in the intracellular/extracellular milieu is needed from human cardiac tissues to develop more robust computational models of human cardiac electromechanical activity. This article summarizes the workshop discussions and recommendations on the following topics: (1) limitations of animal models and differences from human electrophysiology, (2) modeling ion channel structure/function in the context of whole-cell electrophysiology, (3) excitation-contraction coupling and regulatory pathways, (4) whole-heart simulations of human electromechanical activity, and (5) what human data are currently needed and how to obtain them. The recommendations can be found on the NHLBI Web site at http://www.nhlbi.nih.gov/meetings/workshops/electro.htm.

Background: We sought to validate the recently developed Mayo Clinic Risk Score model for in-hospital mortality after percutaneous coronary intervention using an independent data set. The Mayo Clinic Risk Score has 7 simple clinical and noninvasive variables, available before coronary angiography, for prediction of in-hospital mortality. External validation using an independent data set would support broader applicability of the model., Methods and Results: In-hospital mortality after percutaneous coronary intervention on 309 351 patients from the National Cardiovascular Data Registry admitted from January 1, 2004, to March, 30, 2006, was studied. Using the Mayo Clinic Risk Score equation, we assigned predicted probabilities of death to each patient. The area under the receiver-operating characteristics curve was 0.884, indicating excellent discrimination overall as well as among subgroups, including gender, diabetes mellitus, renal failure, low ejection fraction, different age groups, and multivessel disease. Ninety-seven percent of patients undergoing percutaneous coronary intervention had a Mayo Clinic Risk Score <10, indicating low to intermediate risk. The Mayo Clinic Risk Score model initially slightly underpredicted event rates when applied in National Cardiovascular Data Registry data (observed 1.23% versus predicted 1.10%), but this underprediction was corrected after recalibration. The recalibrated risk score discriminated (c index=0.885) and calibrated well in an National Cardiovascular Data Registry validation data set consisting of procedures performed between April 1, 2006, and March 30, 2007., Conclusions: Seven variables can be combined into a convenient risk scoring system before coronary angiography is performed to predict in-hospital mortality after percutaneous coronary intervention. This model may be useful for providing patients with individualized, evidence-based estimates of procedural risk as part of the informed consent process before percutaneous coronary intervention.

Objectives: The purpose of this study was to investigate the correspondence between the coronary arterial anatomy and supplied myocardium based on the proposed American Heart Association 17-segment model., Background: Standardized assignment of coronary arteries to specific myocardial segments is currently based on empirical assumptions., Methods: A cardiac magnetic resonance study was performed in 93 subjects following acute myocardial infarction treated with primary percutaneous coronary intervention. Two observers blindly reviewed all angiograms to examine the location of the culprit lesion and coronary dominance. Two additional observers scored for the presence of cardiac magnetic resonance hyperenhancement (HE) on a 17-segment model. Segments were divided based on anatomical landmarks such as the interventricular grooves and papillary muscles., Results: In a per-segment analysis, 23% of HE segments were discordant with the empirically assigned coronary distribution. Presence of HE in the basal anteroseptal, mid-anterior, mid-anteroseptal, or apical anterior wall was 100% specific for left anterior descending artery occlusion. The left anterior descending artery infarcts frequently involved the mid-anterolateral, apical lateral, and apical inferior walls. No segment was 100% specific for right coronary artery or left circumflex artery (LCX) occlusion, although HE in the basal anterolateral wall was highly specific (98%) for LCX occlusion. Combination of HE in the anterolateral and inferolateral walls was 100% specific for a LCX occlusion, and when extended to the inferior wall, was also 100% specific for a dominant or codominant LCX occlusion., Conclusions: Four segments were completely specific for left anterior descending artery occlusion. No segment can be exclusively attributed to the right coronary artery or LCX occlusion. However, analysis of adjacent segments increased the specificity for a given coronary occlusion. These findings bring objective evidence in the appropriate segmentation of coronary arterial perfusion territories and assist accurate assignment of the culprit vessel in various imaging modalities.

Coronary artery calcium (CAC) accumulation, a marker of atherosclerosis burden, differs significantly among patients of different ethnicities. It has been proposed that CAC scores can be used to assess the number of life years lost or gained by an individual with a given amount of coronary artery calcium. Therefore, we sought to develop a method to calculate the coronary age of an individual based on the extent of CAC in this subject compared to that of individuals of the same race, age and sex. We used median CAC scores from previously published data from the Multi-Ethnic Study of Atherosclerosis (MESA) to derive the predicted coronary age of subjects from 4 ethnic groups (White, Black, Hispanic and Chinese) of both sexes. With this method a 50-year-old white man with a CAC score of 40 has a coronary age of a 61-year-old white man; for a black man with a score of 40 the coronary age is 70. This method should allow patients to better understand the prognostic significance of their test results and may ensure a better compliance with preventive regimens.

The continued failure in approving new drugs for treatment of acute stroke has been recently set back by the failure of the NXY-059 (Stroke-Acute Ischemic NXY Treatment (SAINT) II) trial. The disappointment was heightened by the latter study being viewed as a most promising compound for stroke drug development program based on the preclinical data. Since the SAINT I/II development program included many of the STAIR (Stroke Therapy Academic Industry Round table) guidelines, yet have still failed to achieve the expected efficacy, there is a clear need to continue and analyze the path forward for stroke drug discovery. To this end, this review calls for a consortium approach including academia, government (FDA/NIH), and pharmaceutical industry partnerships to define this path. It is also imperative that more attention is given to the evolving discipline of Translational Medicine. A key issue in this respect is the need to devote more attention to the characteristics of the drug candidate nature-target interaction, and its relationship to pharmacodynamic treatment end points. It is equally important that efforts are spent to prove that phenotypic outcomes are linked to the purported mechanism of action of the compound. Development of technologies that allows a better assessment of these parameters, especially in in vivo models are paramount. Finally, rational patient selection and new outcome scales tailored in an adaptive design model must be evaluated.

For a satisfactory computer simulation, a model, which imitates a natural situation, is needed. The Human heart is an irregular 3D object and thus difficult to reproduce. Basic data was taken from Visible Human Dataset (VHD), National Library of Medicine. The heart area was cut out of the original cross-sections and different tissues segmented. All the slices also had to be aligned to assure precise overlapping of the structures. A 3D computer heart model with the resolution of 1mm was designed. The heart model was dedicated to simulations of heat transfer during heart surgery however, it is applicable also to other medical simulations.

This new training method is based on developing a sound understanding of the sequence in which electrical excitation spreads through both the normal and the infarcted myocardium. The student is made aware of the cardiac electrical performance through a series of 3-dimensional pictures during the excitation process. The electrocardiogram 3D Heart 3-dimensional program contains a variety of different activation simulations. Currently, this program enables the user to view the activation simulation for all of the following pathology examples: normal activation; large, medium, and small anterior myocardial infarction (MI); large, medium, and small posterolateral MI; large, medium, and small inferior MI. Simulations relating to other cardiac abnormalities, such as bundle branch block and left ventricular hypertrophy fasicular block, are being developed as part of a National Institute of Health (NIH) Phase 1 Small Business Innovation Research (SBIR) program.

Recent trials of patients with cardiovascular disease (CVD) have provided a wealth of data regarding diagnosis, risk factors, and treatment. Aggressive risk factor management has been shown to improve patient survival, reduce recurrent events and the need for interventional procedures, and improve the quality of life in patients with known CVD. There have been impressive reductions in blood pressure and low-density lipoprotein cholesterol levels, and improved diabetes control. Medical therapy with options such as angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and aspirin has been shown to have positive effects. Patients in current trials are more likely to be receiving appropriate treatment upon study entry than were patients in older trials. Changes in the risk profile of high-risk patients have reduced the overall rates of cardiovascular events and will continue to affect outcomes in randomized clinical trials. Such changes should be considered in the design of new clinical trials and in the interpretation of current data.

Drug-eluting stents (DES) have dramatically transformed the landscape of interventional cardiology largely on the basis of empirical evidence showing profound reduction in angiographic and clinical restenosis without any significant increase in adverse events. Recent data, however, raise questions regarding the increased risk of late stent thrombosis associated with DES in more complex lesions and higher-risk patients than those evaluated in the initial clinical trials or Food and Drug Administration-approved indications, the challenge of continuing long-term antiplatelet therapy, and the danger of early discontinuation of antiplatelet therapy. We herein review the current status of this controversy, describe the additional evidence needed for its resolution, and offer recommendations for regulatory reform and 3 specific recommendations to encourage evidence-based patient management: 1) an emphasis on medical therapies with proven long-term benefit; 2) the use of kinetic modeling to estimate long-term outcomes of therapies based on the available near-term data; and 3) the restructuring of reimbursement incentives to encourage the use of evidence-based clinical management strategies.