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Objectives: We examined mortality in relation to coronary artery disease (CAD) as assessed by ≥64-detector row coronary computed tomography angiography (CCTA). Background: Although CCTA has demonstrated high diagnostic performance for detection and exclusion of obstructive CAD, the prognostic findings of CAD by CCTA have not, to date, been examined for age- and sex-specific outcomes. Methods: We evaluated a consecutive cohort of 24,775 patients undergoing ≥64-detector row CCTA between 2005 and 2009 without known CAD who met inclusion criteria. In these patients, CAD by CCTA was defined as none (0% stenosis), mild (1% to 49% stenosis), moderate (50% to 69% stenosis), or severe (≥70% stenosis). CAD severity was judged on a per-patient, per-vessel, and per-segment basis. Time to mortality was estimated using multivariable Cox proportional hazards models. Results: At a 2.3 ± 1.1-year follow-up, 404 deaths had occurred. In risk-adjusted analysis, both per-patient obstructive (hazard ratio [HR]: 2.60; 95% confidence interval [CI]: 1.94 to 3.49; p < 0.0001) and nonobstructive (HR: 1.60; 95% CI: 1.18 to 2.16; p = 0.002) CAD conferred increased risk of mortality compared with patients without evident CAD. Incident mortality was associated with a dose-response relationship to the number of coronary vessels exhibiting obstructive CAD, with increasing risk observed for nonobstructive (HR: 1.62; 95% CI: 1.20 to 2.19; p = 0.002), obstructive 1-vessel (HR: 2.00; 95% CI: 1.43 to 2.82; p < 0.0001), 2-vessel (HR: 2.92; 95% CI: 2.00 to 4.25; p < 0.0001), or 3-vessel or left main (HR: 3.70; 95% CI: 2.58 to 5.29; p < 0.0001) CAD. Importantly, the absence of CAD by CCTA was associated with a low rate of incident death (annualized death rate: 0.28%). When stratified by age <65 years versus ≥65 years, younger patients experienced higher hazards for death for 2-vessel (HR: 4.00; 95% CI: 2.16 to 7.40; p < 0.0001 vs. HR: 2.46; 95% CI: 1.51 to 4.02; p = 0.0003) and 3-vessel (HR: 6.19; 95% CI: 3.43 to 11.2; p < 0.0001 vs. HR: 3.10; 95% CI: 1.95 to 4.92; p < 0.0001) CAD. The relative hazard for 3-vessel CAD (HR: 4.21; 95% CI: 2.47 to 7.18; p < 0.0001 vs. HR: 3.27; 95% CI: 1.96 to 5.45; p < 0.0001) was higher for women as compared with men. Conclusions: Among individuals without known CAD, nonobstructive and obstructive CAD by CCTA are associated with higher rates of mortality, with risk profiles differing for age and sex. Importantly, absence of CAD is associated with a very favorable prognosis. [Copyright &y& Elsevier]

Objectives: This study identified the incidence and predictors of conversion of a normal to abnormal coronary artery calcium (CAC) scan during serial CAC scanning over 5 years. Background: Although a normal CAC scan signifies absence of significant atherosclerosis and is used to identify individuals at low clinical risk, the “warranty period” of a normal CAC scan relative to its ability to predict sustained absence of coronary atherosclerosis remains unknown. Methods: We assessed frequency of and time to progression, as well as proportional increase of CAC in 422 individuals with normal CAC scan (CAC = 0) undergoing annual CAC scanning for 5 years. Results were compared with those of a referent cohort of 621 individuals with baseline CAC scan (CAC >0). Results: A total of 106 (25.1%) patients with CAC = 0 developed CAC during follow-up at a mean time to conversion of 4.1 ± 0.9 years. Incidence of conversion to CAC >0 was nonlinear and was highest in the fifth year. In multivariable analysis, progression to CAC >0 was associated with age, diabetes, and smoking (p < 0.01 for all). Among the 621 individuals with baseline CAC >0, only the presence of CAC itself, rather than CAD risk factors, was predictive of CAC progression. Among propensity score-matched individuals with CAC >0 versus CAC = 0, baseline CAC >0 emerged as the strongest predictor of CAC progression (hazard ratio [HR]: 12.50, 95% confidence interval [CI]: 9.31 to 16.77), followed by diabetes (HR: 2.07, 95% CI: 1.47 to 2.90) and smoking (HR: 1.29, 95% CI: 1.02 to 1.63, p < 0.05 for all). Conclusions: Among individuals with CAC = 0, conversion to CAC >0 is nonlinear and occurs at low frequency before 4 years. No clinical factor seems to mandate earlier repeat CAC scanning. [Copyright &y& Elsevier]

In the past 5 years since the introduction of 64-detector row cardiac computed tomography angiography (CCTA), there has been an exponential growth in the quantity of scientific evidence to support the feasibility of its use in the clinical evaluation of individuals with suspected coronary artery disease (CAD). Since then, there has been considerable debate as to where CCTA precisely fits in the algorithm of evaluation of individuals with suspected CAD. Proponents of CCTA contend that the quality and scope of the available evidence to date support the replacement of conventional methods of CAD evaluation by CCTA, whereas critics assert that clinical use of CCTA is not yet adequately proven and should be restricted, if used at all. Coincident with the scientific debate underlying the clinical utility of CCTA, there has developed a perception by many that the rate of growth in cardiac imaging is disproportionately high and unsustainable. In this respect, all noninvasive imaging modalities and, in particular, more newly introduced ones, have undergone a higher level of scrutiny for demonstration of clinical and economic effectiveness. We herein describe the latest available published evidence supporting the potential clinical and cost efficiency of CCTA, drawing attention not only to the significance but also the limitations of such studies. These points may trigger discussion as to what future studies will be both necessary and feasible for determining the exact role of CCTA in the workup of patients with suspected CAD. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to assess whether African-American women are at increased risk of having peripartum cardiomyopathy. Background: Peripartum cardiomyopathy is a heart disease of unknown cause that affects young women, often with devastating consequences. The frequency of peripartum cardiomyopathy varies markedly between African and non-African regions. Methods: A case-control study was performed at a regional center that provides medical care to a racially heterogeneous population. For each case, 3 healthy control patients were randomly selected who delivered babies within the same month. Results: African-American women had a 15.7-fold higher relative risk of peripartum cardiomyopathy than non–African Americans (odds ratio [OR]: 15.7, 95% confidence interval [CI]: 3.5 to 70.6). Other significant univariate risk factors were hypertension (OR: 10.8, 95% CI: 2.6 to 44.4), being unmarried (OR: 4.2, 95% CI: 1.4 to 12.3), and having had >2 previous pregnancies (OR: 2.9, 95% CI: 1.1 to 7.4). African-American ethnicity remained a significant risk factor for peripartum cardiomyopathy when other risk factors were considered in multivariable (OR: 31.5, 95% CI: 3.6 to 277.6) and stratified analyses (OR: 12.9 to 29.1, p < 0.001). Although the frequency of peripartum cardiomyopathy (185 of 100,000 deliveries) at this center was higher than in previous U.S. reports, it was comparable to the frequency in countries with more women of African descent (100 to 980 of 100,000). Analysis of other U.S. studies confirmed that the frequency of peripartum cardiomyopathy was significantly higher among African-American women. Conclusions: African-American women have significantly higher odds of having peripartum cardiomyopathy that could not be explained by several other factors. Further research will be necessary to determine the potential environmental and/or genetic factors associated with African descent that confer this risk. [Copyright &y& Elsevier]

Objectives: We prospectively evaluated procedural costs and resource consumption patterns in the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study after coronary calcium (CAC) measurements. Background: Controversy surrounds expansion of cardiovascular disease (CVD) screening to include atherosclerosis imaging as the result of concern whether induced costs will outweigh any benefit. Methods: Detailed risk factor and CAC measurements with 4-year follow-up for CVD death or myocardial infarction and procedures were performed. Costs were estimated with the use of Medicare reimbursement rates (discounted and inflation corrected). Cox survival analysis was used to estimate procedures and events. Results: CAC scores varied widely but were skewed toward low scores with 56.7% of screened subjects having CAC scores ≤10 and only 8.2% having CAC scores ≥400. Noninvasive testing was infrequent and medical costs were low among subjects with low CAC scores, both rising progressively with increasing CAC scores (p < 0.001), particularly in the 31 (2.2% of subjects) that had CAC scores ≥1,000. Similarly, invasive coronary angiography rose progressively with increasing scores (p < 0.001) but occurred exclusively among subjects first undergoing noninvasive testing and overall, was performed in only 19.4% of subjects with CAC scores ≥1,000. Conclusions: CAC scanning is associated with a marked differential in downstream frequency of medical tests and costs, ranging from a very low frequency of testing and invasive procedures among a predominantly large percentage of subjects with low CAC scores, to selectively concentrated testing and procedures among a small number of subjects with CAC scores >400. Thus, CAC scanning appears to foster efficient selective testing patterns among asymptomatic individuals at risk for CVD. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to examine the association of all-cause death with the coronary computed tomographic angiography (CCTA)-defined extent and severity of coronary artery disease (CAD). Background: The prognostic value of identifying CAD by CCTA remains undefined. Methods: We examined a single-center consecutive cohort of 1,127 patients ≥45 years old with chest symptoms. Stenosis by CCTA was scored as minimal (<30%), mild (30% to 49%), moderate (50% to 69%), or severe (≥70%) for each coronary artery. Plaque was assessed in 3 ways: 1) moderate or obstructive plaque; 2) CCTA score modified from Duke coronary artery score; and 3) simple clinical scores grading plaque extent and distribution. A 15.3 ± 3.9-month follow-up of all-cause death was assessed using Cox proportional hazards models adjusted for pretest CAD likelihood and risk factors. Deaths were verified by the Social Security Death Index. Results: The CCTA predictors of death included proximal left anterior descending artery stenosis and number of vessels with ≥50% and ≥70% stenosis (all p < 0.0001). A modified Duke CAD index, an angiographic score integrating proximal CAD, plaque extent, and left main (LM) disease, improved risk stratification (p < 0.0001). Patients with <50% stenosis had the highest survival at 99.7%. Survival worsened with higher-risk Duke scores, ranging from 96% survival for 1 stenosis ≥70% or 2 stenoses ≥50% (p = 0.013) to 85% survival for ≥50% LM artery stenosis (p < 0.0001). Clinical scores measuring plaque burden and distribution predicted 5% to 6% higher absolute death rate (6.6% vs. 1.6% and 8.4% vs. 2.5%; p = 0.05 for both). Conclusions: In patients with chest pain, CCTA identifies increased risk for all-cause death. Importantly, a negative CCTA portends an extremely low risk for death. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to evaluate the incidence and prognostic implication of diastolic dysfunction (DD) occurring in the first year after transplant. Background: Diastolic dysfunction is a recognized complication in heart transplant recipients, but its true incidence and natural history has been poorly characterized. We studied the prognostic implication of DD, as defined by elevated filling pressures with normal systolic function, occurring in the first year after transplant. Methods: Between June 1992 and June 2002, all patients who underwent heart transplantation at a single institution were included in the study (231 at 6 weeks and 250 at 6 months and 1 year). Diastolic dysfunction was defined as right atrial pressure (RAP) ≥15 mm Hg (right ventricular [RV] DD) or pulmonary capillary wedge pressure ≥18 mm Hg (left ventricular [LV] DD) with normal systolic function by echocardiogram and without severe mitral or tricuspid insufficiency. In addition, RV DD was defined by a RAP/stroke volume (SV) ratio. Results: The incidence of DD was 22%, 8%, and 12% at 6 weeks, 6 months, and 1 year, respectively. The incidence of LV DD was more frequent than that of RV DD at any time point (p < 0.0001). By multivariable analysis RV DD, as manifested by an elevated RAP/SV, but not LV DD was a strong predictor of cardiac mortality at all time points. Conclusions: Diastolic dysfunction is common early after transplant, and its incidence decreases during the first year. Right ventricular DD, as measured by an elevated RAP/SV ratio, but not LV DD is a strong predictor of cardiac mortality. Further studies are needed to evaluate the functional status of patients with RV or LV DD and whether aggressive medical therapy for early DD could alter outcome. [Copyright &y& Elsevier]

Midway through the 20th century, direct open-heart operations were not yet a reality, awaiting safe methods to support the cardiopulmonary circulation during cardiac surgery. The scientific advancements collectively leading to safe cardiopulmonary bypass are considered some of the most impactful advances of modern medicine. Stimulated by the work of physiologists and engineers in the late 19th century, primitive pump and oxygenator designs were the forerunners of major work by DeBakey and others in roller pump design and by Gibbon in oxygenator development. Following Gibbon's historic successful closure of an atrial septal defect in 1953 with his heart-lung machine, it was left to Lillehei and Kirklin to first successfully repair large series of cardiac malformations. The history leading to these historic events and the subsequent evolution of cardiopulmonary bypass machines for short- and longer-term support is filled with engineering and surgical brilliance, daring innovations, and serendipity. [ABSTRACT FROM AUTHOR]

Background: Detection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined.Objectives: The authors sought to identify markers of LMD as detected on coronary computed tomography angiography (CTA), using clinical and stress testing parameters.Methods: This was a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, the authors identified predictors of LMD, first without and then with stress testing parameters.Results: Among 5,146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (P < 0.001), male sex (P < 0.01), absence of prior myocardial infarction (P < 0.009), transient ischemic dilation of the left ventricle on stress echocardiography (P = 0.05), magnitude of ST-segment depression on ETT (P = 0.004), and peak metabolic equivalents achieved on ETT (P = 0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684).Conclusions: In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522). [ABSTRACT FROM AUTHOR]

The current paper details the recommendations arising from an NIH-NHLBI/NCI-sponsored symposium held in November 2012, aiming to identify key components of a radiation accountability framework fostering patient-centered imaging and shared decision-making in cardiac imaging. Symposium participants, working in 3 tracks, identified key components of a framework to target critical radiation safety issues for the patient, the laboratory, and the larger population of patients with known or suspected cardiovascular disease. The use of ionizing radiation during an imaging procedure should be disclosed to all patients by the ordering provider at the time of ordering, and reinforced by the performing provider team. An imaging protocol with effective dose ≤3mSv is considered very low risk, not warranting extensive discussion or written informed consent. However, a protocol effective dose >20mSv was proposed as a level requiring particular attention in terms of shared decision-making and either formal discussion or written informed consent. Laboratory reporting of radiation dosimetry is a critical component of creating a quality laboratory fostering a patient-centered environment with transparent procedural methodology. Efforts should be directed to avoiding testing involving radiation, in patients with inappropriate indications. Standardized reporting and diagnostic reference levels for computed tomography and nuclear cardiology are important for the goal of public reporting of laboratory radiation dose levels in conjunction with diagnostic performance. The development of cardiac imaging technologies revolutionized cardiology practice by allowing routine, noninvasive assessment of myocardial perfusion and anatomy. It is now incumbent upon the imaging community to create an accountability framework to safely drive appropriate imaging utilization. [Copyright &y& Elsevier]

Background: A revised definition of right heart failure (RHF) for the Society of Thoracic Surgeons Intermacs database of left ventricular assist devices (LVADs) was introduced in June 2014.Objectives: The purpose of this study was to determine the prevalence and severity of RHF over time and the association of RHF status at 3 months with 12-month outcomes after LVAD.Methods: All patients in Society of Thoracic Surgeons Intermacs with follow-up and supported at least 3 months with a continuous flow LVAD implanted between June 2, 2014 and March 31, 2017 without a simultaneous RVAD. RHF was defined as both documentation and manifestations of elevated central venous pressures.Results: There were 6,118 patients included with an incidence of RHF at 3, 6, and 12 months postimplant categorized as mild in 5%, 6%, and 6% and moderate in 5%, 3%, and 3%, respectively. For those with no RHF at 3 months, there was a low incidence of subsequent RHF at 6 and 12 months. The lack of RHF at 3 months, compared with mild and moderate RHF, was associated with a lower 12-month cumulative incidence of mortality (6.9% vs 16.7% vs 28.1%; P < 0.0001) and a lower 12-month cumulative incidence of stroke (7.4% vs 9.5% vs 11.0%; P = 0.0095), gastrointestinal bleeding (14.8% vs 24.2% vs 23.6%; P < 0.0001), and rehospitalization (65.2% vs 73.2% vs 71.2%; P < 0.0001).Conclusions: In patients surviving 3 months with LVAD support alone, mild or moderate RHF occurred in nearly 1 of 10 patients at 12 months. Patients with late RHF had worse survival and a higher cumulative incidence of major adverse events. [ABSTRACT FROM AUTHOR]

Coronary computed tomography angiography (CTA) has emerged as a noninvasive method for direct visualization of coronary artery disease, with previous studies demonstrating high diagnostic performance of CTA compared with invasive coronary angiography. However, CTA assessment of coronary stenoses tends toward overestimation, and even among CTA-identified severe stenosis confirmed at the time of invasive coronary angiography, only a minority are found to be ischemia causing. Recent advances in computational fluid dynamics and image-based modeling now permit determination of rest and hyperemic coronary flow and pressure from CTA scans, without the need for additional imaging, modification of acquisition protocols, or administration of medications. These techniques have been used to noninvasively compute fractional flow reserve (FFR), which is the ratio of maximal coronary blood flow through a stenotic artery to the blood flow in the hypothetical case that the artery was normal, using CTA images. In the recently reported prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) study and the DeFACTO (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography) trial, FFR derived from CTA was demonstrated as superior to measures of CTA stenosis severity for determination of lesion-specific ischemia. Given the significant interest in this novel method for determining the physiological significance of coronary artery disease, we herein present a review on the scientific principles that underlie this technology. [Copyright &y& Elsevier]

Background: Survival, functional outcomes, and quality of life after left ventricular assist device (LVAD) are ill-defined in elderly patients, and with new-generation devices.Objectives: This study sought to evaluate survival, functional outcomes, and quality of life after LVAD in contemporary practice.Methods: Adults receiving durable LVADs between January 1, 2010, and March 1, 2020, were identified from the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) database. The primary outcome was adjusted survival; secondary outcomes included quality of life rated using a visual analogue scale (where 0 represents "worst health" and 100 "best health"); 6-minute walk distance; stroke; device malfunction; and rehospitalization, stratified by patient age. Median follow-up was 15 months (IQR: 6-32 months).Results: The cohort comprised 68.9% (n = 16,808) patients aged <65 years, 26.3% (n = 6,418) patients aged 65-75 years, and 4.8% (n = 1,182) patients aged >75 years, who were predominantly male (n = 19,119, 78%) and on destination therapy (n = 12,425, 51%). Competing outcomes analysis demonstrated mortality (70% CIs) of 34% (33%-34%), 54% (54%-55%), and 66% (64%-68%) for patients aged <65, 65-75, and >75 years, respectively, which improved during the study in patients aged >75 years. Newer-generation devices were associated with reduced late mortality (HR: 0.35; 95% CI: 0.25-0.49). Stroke, device malfunction or thrombosis, and rehospitalizations decreased with increasing age (all P < 0.01). Median 6-minute walk distance increased from 0 feet (IQR: 0-665 feet) to 1,065 feet (IQR: 642-1,313 feet) (P < 0.001), and quality of life improved from 40 (IQR: 15-60) to 75 (IQR: 60-90) (P < 0.001) after LVAD in all age groups.Conclusions: In elderly patients, LVADs are associated with increased functional capacity, similar improvements in quality of life, and fewer complications compared with younger patients. [ABSTRACT FROM AUTHOR]

: ObjectivesWe sought to study the effect of long-term statin use on psychometric measures in an adult population with underlying coronary artery disease (CAD).: BackgroundPrevious studies have suggested associations between cholesterol lowering and psychological well-being.: MethodsStudy subjects were recruited from an outpatient cardiology clinic. Psychological well-being was assessed at baseline and annually during follow-up. The exposure of interest was long-term statin use and the outcomes of interest were depression, anxiety, and hostility. We estimated the odds ratios (ORs) and 95% confidence intervals (CI) that represented the strength of association between statin use (vs. no use of any cholesterol-lowering drug) and the risk of having abnormal depression, anxiety, and hostility scores.: ResultsStudy subjects had an average follow-up of four years and maximum of seven years. Comparing the 140 patients who had continuous use of statins with the 231 patients who did not use any cholesterol-lowering drugs, statin use was associated with lower risk of abnormal depression scores (OR 0.63, 95% CI 0.43 to 0.93), anxiety (OR 0.69, 95% CI 0.47 to 0.99), and hostility (OR 0.77, 95% CI 0.58 to 0.93) after adjustment for the propensity for statin use and potential confounders. The beneficial psychological effects of the statins appeared to be independent of the drugs'' cholesterol-lowering effects.: ConclusionsLong-term use of statins among patients with CAD appeared to be associated with reduced risk of anxiety, depression, and hostility. [Copyright &y& Elsevier]

: ObjectivesThis study compared a biphasic waveform with a conventional monophasic waveform for cardioversion of atrial fibrillation (AF).: BackgroundBiphasic shock waveforms have been demonstrated to be superior to monophasic shocks for termination of ventricular fibrillation, but data regarding biphasic shocks for conversion of AF are still emerging.: MethodsIn an international, multicenter, randomized, double-blind clinical trial, we compared the effectiveness of damped sine wave monophasic versus impedance-compensated truncated exponential biphasic shocks for the cardioversion of AF. Patients received up to five shocks, as necessary for conversion: 100 J, 150 J, 200 J, a fourth shock at maximum output for the initial waveform (200 J biphasic, 360 J monophasic) and a final cross-over shock at maximum output of the alternate waveform.: ResultsAnalysis included 107 monophasic and 96 biphasic patients. The success rate was higher for biphasic than for monophasic shocks at each of the three shared energy levels (100 J: 60% vs. 22%, p < 0.0001; 150 J: 77% vs. 44%, p < 0.0001; 200 J: 90% vs. 53%, p < 0.0001). Through four shocks, at a maximum of 200 J, biphasic performance was similar to monophasic performance at 360 J (91% vs. 85%, p = 0.29). Biphasic patients required fewer shocks (1.7 ± 1.0 vs. 2.8 ± 1.2, p < 0.0001) and lower total energy delivered (217 ± 176 J vs. 548 ± 331 J, p < 0.0001). The biphasic shock waveform was also associated with a lower frequency of dermal injury (17% vs. 41%, p < 0.0001).: ConclusionsFor the cardioversion of AF, a biphasic shock waveform has greater efficacy, requires fewer shocks and lower delivered energy, and results in less dermal injury than a monophasic shock waveform. [Copyright &y& Elsevier]

Evaluation of coronary artery disease (CAD) using coronary computed tomography angiography (CCTA) has seen a paradigm shift in the last decade. Evidence increasingly supports the clinical utility of CCTA across various stages of CAD, from the detection of early subclinical disease to the assessment of acute chest pain. Additionally, CCTA can be used to noninvasively quantify plaque burden and identify high-risk plaque, aiding in diagnosis, prognosis, and treatment. This is especially important in the evaluation of CAD in immune-driven conditions with increased cardiovascular disease prevalence. Emerging applications of CCTA based on hemodynamic indices and plaque characterization may provide personalized risk assessment, affect disease detection, and further guide therapy. This review provides an update on the evidence, clinical applications, and emerging technologies surrounding CCTA as highlighted at the 2019 National Heart, Lung and Blood Institute CCTA Summit. [ABSTRACT FROM AUTHOR]

Background: Coronary lesions with low fractional flow reserve (FFR) that are treated medically are associated with higher revascularization rates. High wall shear stress (WSS) has been linked with increased plaque vulnerability.Objectives: This study investigated the prognostic value of WSS measured in the proximal segments of lesions (WSSprox) to predict myocardial infarction (MI) in patients with stable coronary artery disease (CAD) and hemodynamically significant lesions. The authors hypothesized that in patients with low FFR and stable CAD, higher WSSprox would predict MI.Methods: Among 441 patients in the FAME II (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation II) trial with FFR ≤0.80 who were randomized to medical therapy alone, 34 (8%) had subsequent MI within 3 years. Patients with vessel-related MI and adequate angiograms for 3-dimensional reconstruction (n = 29) were propensity matched to a control group with no MI (n = 29) by using demographic and clinical variables. Coronary lesions were divided into proximal, middle, and distal, along with 5-mm upstream and downstream segments. WSS was calculated for each segment.Results: Median age was 62 years, and 46 (79%) were male. In the marginal Cox model, whereas lower FFR showed a trend (hazard ratio: 0.084; p = 0.064), higher WSSprox (hazard ratio: 1.234; p = 0.002, C-index = 0.65) predicted MI. Adding WSSprox to FFR resulted in a significant increase in global chi-square for predicting MI (p = 0.045), a net reclassification improvement of 0.69 (p = 0.005), and an integrated discrimination index of 0.11 (p = 0.010).Conclusions: In patients with stable CAD and hemodynamically significant lesions, higher WSS in the proximal segments of atherosclerotic lesions is predictive of MI and has incremental prognostic value over FFR. [ABSTRACT FROM AUTHOR]

Background: Pediatric ventricular assist device (VAD) use has evolved dramatically over the last 2 decades.Objectives: This study sought to describe the evolution of VAD support to heart transplantation (HTx) in children in a large international multicenter cohort.Methods: Using data from the Pediatric Heart Transplant Study, comparisons were made between children (<18 years) supported to HTx (January 1, 1993 to December 31, 2015) with VAD or extracorporeal membrane oxygenation (ECMO) to VAD support.Results: Of 7,135 listed patients, 5,145 underwent HTx; 995 (19.3%) were supported by a VAD (113 with congenital heart disease [CHD]). Patients with a VAD as their first device (n = 821) were older, larger, and more likely to have cardiomyopathy (80%) than patients transitioned from ECMO to VAD (n = 164). In the VAD-only cohort, 79% underwent HTx and 14% died, compared with 69% and 24% in the ECMO-to-VAD cohort, respectively. Patients with cardiomyopathy achieved HTx 84% of the time, with a 9% waitlist mortality rate compared with 55% and 36%, respectively, for CHD. Among VAD-treated patients, 79% were age >10 years in the earliest era, a percentage decreasing to 34% more recently, though neonates still represent <1%. Overall, survival at 2 and 20 years showed no difference between VAD and no support (2 years: 75% vs. 80%; 20 years: 55% vs. 54%). Post-HTx outcomes were better for durable versus temporary VADs (p < 0.01) and for continuous versus pulsatile VADs (p < 0.01) from 2005 onward; timing of VAD had no impact on post-HTx survival (p = 0.65).Conclusions: For one-quarter of a century, major advances have occurred in mechanical support technology for children, thereby expanding the capability to bridge to HTx without compromising post-HTx outcomes. Significant challenges remain, especially for neonates and patients with CHD, but ongoing innovation portends improved methods of support during the next decade. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) imparts a heavy economic burden on the U.S. health care system. Evidence regarding the long-term costs after comprehensive CVD screening is limited.Objectives: This study calculated 10-year health care costs for 6,814 asymptomatic participants enrolled in MESA (Multi-Ethnic Study of Atherosclerosis), a registry sponsored by the National Heart, Lung, and Blood Institute, National Institutes of Health.Methods: Cumulative 10-year costs for CVD medications, office visits, diagnostic procedures, coronary revascularization, and hospitalizations were calculated from detailed follow-up data. Costs were derived by using Medicare nationwide and zip code-specific costs, inflation corrected, discounted at 3% per year, and presented in 2014 U.S. dollars.Results: Risk factor prevalence increased dramatically and, by 10 years, diabetes, hypertension, and dyslipidemia was reported in 19%, 57%, and 53%, respectively. Self-reported symptoms (i.e., chest pain or shortness of breath) were common (approximately 40% of enrollees). At 10 years, approximately one-third of enrollees reported having an echocardiogram or exercise test, whereas 7% underwent invasive coronary angiography. These utilization patterns resulted in 10-year health care costs of $23,142. The largest proportion of costs was associated with CVD medication use (78%). Approximately $2 of every $10 were spent for outpatient visits and diagnostic testing among the elderly, obese, those with a high-sensitivity C-reactive protein level >3 mg/l, or coronary artery calcium score (CACS) ≥400. Costs varied widely from <$7,700 for low-risk (Framingham risk score <6%, 0 CACS, and normal glucose measurements at baseline) to >$35,800 for high-risk (persons with diabetes, Framingham risk score ≥20%, or CACS ≥400) subgroups. Among high-risk enrollees, CVD costs accounted for $74 million of the $155 million consumed by MESA participants.Conclusions: Longitudinal patterns of health care resource use after screening revealed new evidence on the economic burden of treatment and testing patterns not previously reported. Maintenance of a healthy population has the potential to markedly reduce the economic burden of CVD among asymptomatic individuals. [ABSTRACT FROM AUTHOR]

Background: Atherosclerotic plaque characteristics may affect downstream myocardial perfusion, as well as coronary lesion severity.Objectives: This study sought to evaluate the association between quantitative plaque burden and plaque morphology obtained using coronary computed tomography angiography (CTA) and quantitative myocardial perfusion obtained using [15O]H2O positron emission tomography (PET), as well as fractional flow reserve (FFR) derived invasively.Methods: Two hundred eight patients (63% men; age 58 ± 8.7 years) with suspected coronary artery disease were prospectively included. All patients underwent 256-slice coronary CTA, [15O]H2O PET, and invasive FFR measurements. Coronary CTA-derived plaque burden and morphology were assessed using commercially available software and compared with PET perfusion and FFR.Results: Atherosclerotic plaques were present in 179 patients (86%) and 415 of 610 (68%) evaluable coronary arteries. On a per-vessel basis, traditional coronary plaque burden indexes, such as plaque length and volume, minimal lumen area, and stenosis percentage, were significantly associated with impaired hyperemic myocardial blood flow (MBF) and FFR. In addition, morphological features, such as partially calcified plaques, positive remodeling (PR), and low attenuation plaque, displayed a negative impact on hyperemic MBF and FFR. Multivariable analysis revealed that the morphological feature of PR was independently related to impaired hyperemic MBF as well as an unfavorable FFR (p = 0.004 and p = 0.007, respectively), next to stenosis percentage (p = 0.001 and p < 0.001, respectively) and noncalcified plaque volume (p < 0.001 and p = 0.010, respectively).Conclusions: PR and noncalcified plaque volume are associated with detrimental downstream hyperemic myocardial perfusion and FFR, independent of lesion severity. [ABSTRACT FROM AUTHOR]

Background: Patients with acute myocardial infarction (AMI) complicated by acute heart failure or cardiogenic shock have high mortality with conventional management.Objectives: This study evaluated outcomes of patients with AMI who received durable ventricular assist devices (VAD).Methods: Patients in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry who underwent VAD placement in the setting of AMI were included and compared with patients who received VAD for non-AMI indications.Results: VAD were implanted in 502 patients with AMI: 443 left ventricular assist devices; 33 biventricular assist devices; and 26 total artificial hearts. Median age was 58.3 years, and 77.1% were male. At implantation, 66% were INTERMACS profile 1. A higher proportion of AMI than non-AMI patients had pre-operative intra-aortic balloon pumps (57.6% vs. 25.3%; p < 0.01), intubation (58% vs. 8.3%; p < 0.01), extracorporeal membrane oxygenation (17.9% vs. 1.7%, p < 0.01), cardiac arrest (33.5% vs. 3.3%, p < 0.01), and higher-acuity INTERMACS profiles. At 1 month post-VAD, 91.8% of AMI patients were alive with ongoing device support, 7.2% had died on device, and 1% had been transplanted. At 1-year post-VAD, 52% of AMI patients were alive with ongoing device support, 25.7% had been transplanted, 1.6% had left VAD explanted for recovery, and 20.7% had died on device. The AMI group had higher unadjusted early phase hazard (hazard ratio [HR]: 1.24; p = 0.04) and reduced late-phase hazard of death (HR: 0.57; p = 0.04) than the non-AMI group did. After accounting for established risk factors, the AMI group no longer had higher early mortality hazard (HR: 0.89; p = 0.30), but it had lower late mortality hazard (HR: 0.55; p = 0.02).Conclusions: Patients with AMI who receive VAD have outcomes similar to other VAD populations, despite being more critically ill pre-implantation. VAD therapy is an effective strategy for patients with AMI and acute heart failure or shock in whom medical therapy is failing. [ABSTRACT FROM AUTHOR]

Background Recent guidelines recommend assessment of systolic function and filling pressures to augment angiographic grading of cardiac allograft vasculopathy (CAV); however, no data exist on the utility of these guidelines. Objectives The aims of this study were to evaluate whether the assessment of systolic and diastolic graft function, in addition to angiography, improves recognition of patients at high risk of graft loss and to assess the ability of adult filling-pressure thresholds to discriminate graft dysfunction in pediatric patients. Methods This study reviewed Pediatric Heart Transplant Study data from 1993 to 2009. Graft dysfunction was defined as significant systolic dysfunction (ejection fraction [EF] <45%) or the presence of restrictive hemodynamic features. Additional pediatric hemodynamic cutpoints of right atrial pressure (RAP) >12 mm Hg or pulmonary capillary wedge pressure (PCWP) >15 mm Hg were analyzed. Results In the study, 8,122 angiograms were performed in 3,120 patients, and 70% of patients had at least 1 angiogram. Angiographic incidence of CAV was 5%, 15%, and 28% at 2, 5, and 10 years, respectively, and most disease was mild. The presence of graft dysfunction identified patients at greater risk for graft loss even in children with mild angiographic vasculopathy (p < 0.0001). An RAP >12 mm Hg or a PCWP >15 mm Hg was sufficient to detect patients at high risk of graft loss even with mild angiographic disease. Conclusions Patients with only mild angiographic CAV have significantly better outcomes than do patients with moderate or severe disease. The presence of an EF <45%, an RAP >12 mm Hg, or a PCWP >15 mm Hg identifies children at increased risk of graft loss even in the presence of only mild angiographic vasculopathy. [ABSTRACT FROM AUTHOR]

Functional capacity is a robust predictor of clinical outcomes, and stress testing is used in current practice paradigms to guide referral to invasive coronary angiography. However, invasive coronary angiography is driven by ongoing symptoms, as well as risk of adverse outcomes. The limitations of current functional testing-based paradigms might be avoided by using coronary computed tomographic angiography (CCTA) for exclusion of obstructive coronary artery disease. The growth of CCTA has been supported by comparative prognostic evidence with CCTA and functional testing, as well as radiation dose reduction. Use of CCTA for physiological evaluation of coronary lesion-specific ischemia may facilitate evaluation of moderate stenoses, designation of the culprit lesion, and prediction of benefit from revascularization. The potential of CCTA to serve as an effective gatekeeper to invasive coronary angiography will depend, in part, on the adoption of these new developments, as well as definition of the benefit of detecting high-risk plaque for guiding the management of selected patients. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the current analysis was to compare sex differences in the prognostic accuracy of stress myocardial perfusion rubidum-82 (Rb-82) positron emission tomography (PET). Background: The diagnostic evaluation of women presenting with suspected cardiac symptoms is challenging with reported reduced accuracy, attenuation artifact, and more recent concerns regarding radiation safety. Stress myocardial perfusion Rb-82 PET is a diagnostic alternative with improved image quality and radiation dosimetry. Currently, the prognostic accuracy of stress Rb-82 PET in women has not been established. Methods: A total of 6,037 women and men were enrolled in the PET Prognosis Multicenter Registry. Patients were followed for the occurrence of coronary artery disease (CAD) mortality, with a median follow-up of 2.2 years. Cox proportional hazards modeling was used to estimate CAD mortality. The net re-classification improvement index (NRI) was calculated. Results: The 5-year CAD mortality was 3.7% for women and 6.0% for men (p < 0.0001). Unadjusted CAD mortality ranged from 0.9% to 12.9% for women (p < 0.0001) and from 1.5% to 17.4% for men (p < 0.0001) for 0% to ≥15% abnormal myocardium at stress. In multivariable models, the percentage of abnormal stress myocardium was independently predictive of CAD mortality in women and men. An interaction term of sex by the percentage of abnormal stress myocardium was nonsignificant (p = 0.39). The categorical NRI when Rb-82 PET data was added to a clinical risk model was 0.12 for women and 0.17 for men. Only 2 cardiac deaths were reported in women <55 years of age; accordingly the percentage of abnormal myocardium at stress was of borderline significance (p = 0.063), but it was highly significant for women ≥55 years of age (p < 0.0001), with an increased NRI of 0.21 (95% confidence interval: 0.09 to 0.34), including 17% of CAD deaths and 3.9% of CAD survivors that were correctly re-classified in this older female subset. Conclusions: Stress Rb-82 PET provides significant and clinically meaningful effective risk stratification of women and men, supporting this modality as an alternative to comparative imaging modalities. Rb-82 PET findings were particularly helpful at identifying high-risk, older women. [Copyright &y& Elsevier]

Objectives: This study examined the performance of percent aggregate plaque volume (%APV), which represents cumulative plaque volume as a function of total vessel volume, by coronary computed tomography angiography (CTA) for identification of ischemic lesions of intermediate stenosis severity. Background: Coronary lesions of intermediate stenosis demonstrate significant rates of ischemia. Coronary CTA enables quantification of luminal narrowing and %APV. Methods: We identified 58 patients with intermediate lesions (30% to 69% diameter stenosis) who underwent invasive angiography and fractional flow reserve. Coronary CTA measures included diameter stenosis, area stenosis, minimal lumen diameter (MLD), minimal lumen area (MLA) and %APV. %APV was defined as the sum of plaque volume divided by the sum of vessel volume from the ostium to the distal portion of the lesion. Fractional flow reserve ≤0.80 was considered diagnostic of lesion-specific ischemia. Area under the receiver operating characteristic curve and net reclassification improvement (NRI) were also evaluated. Results: Twenty-two of 58 lesions (38%) caused ischemia. Compared with nonischemic lesions, ischemic lesions had smaller MLD (1.3 vs. 1.7 mm, p = 0.01), smaller MLA (2.5 vs. 3.8 mm2, p = 0.01), and greater %APV (48.9% vs. 39.3%, p < 0.0001). Area under the receiver operating characteristic curve was highest for %APV (0.85) compared with diameter stenosis (0.68), area stenosis (0.66), MLD (0.75), or MLA (0.78). Addition of %APV to other measures showed significant reclassification over diameter stenosis (NRI 0.77, p < 0.001), area stenosis (NRI 0.63, p = 0.002), MLD (NRI 0.62, p = 0.001), and MLA (NRI 0.43, p = 0.01). Conclusions: Compared with diameter stenosis, area stenosis, MLD, and MLA, %APV by coronary CTA improves identification, discrimination, and reclassification of ischemic lesions of intermediate stenosis severity. [Copyright &y& Elsevier]

Objectives: This study sought to evaluate the impact of a multimodality-appropriate use criteria decision support tool (AUC-DST) on rates of appropriate testing and clinical decision making. Background: AUC have been developed to guide utilization of noninvasive imaging for individuals with suspected coronary artery disease (CAD). The effect of a point-of-order AUC-DST on rates of appropriateness and clinical decision making has not been examined. Methods: We performed a prospective multicenter cohort study evaluating physicians who ordered CAD imaging tests for consecutive patients insured by 1 large private payer. During an 8-month study period, each study site was granted exemption from prior authorization requirements by radiology benefits managers. An AUC-DST was employed to determine appropriateness ratings for myocardial perfusion scintigraphy (MPS), stress echocardiography (STE), or coronary computed tomographic angiography (CCTA), as well as intended downstream testing and therapy. Results: One hundred physicians used the AUC-DST for 472 patients (age 55.6 ± 9.6 years, 61% male, 52% prior known CAD) over 8 months for MPS (72%), STE (24%), and CCTA (5%). The AUC-DST required an average of 137 ± 360 s to determine the appropriateness category that, by American College of Cardiology AUC, was considered appropriate in 241 (51%), uncertain in 96 (20%), inappropriate in 85 (18%), and not addressed in 50 (11%). For tests ordered in the first 2 months compared with the last 2 months, appropriate tests increased from 49% to 61% (p = 0.02), whereas inappropriate tests decreased from 22% to 6% (p < 0.001). During this period, intended changes in medical therapy increased from 11% to 32% (p = 0.001). Conclusions: A point-of-order AUC-DST enabled rapid determination of test appropriateness for CAD evaluation and was associated with increased and decreased testing for appropriate and inappropriate indications, respectively. These changes in test ordering were associated with greater intended changes in post-test medical therapy. [ABSTRACT FROM AUTHOR]

Objectives: This study compared cross-sectional three-dimensional (3D) transesophageal echocardiography (TEE) to two-dimensional (2D) TEE as methods for predicting aortic regurgitation after transcatheter aortic valve replacement (TAVR). Background: Data have shown that TAVR sizing using cross-sectional contrast computed tomography (CT) parameters is superior to 2D-TEE for the prediction of paravalvular aortic regurgitation (AR). Three-dimensional TEE can offer cross-sectional assessment of the aortic annulus but its role for TAVR sizing has been poorly elucidated. Methods: All patients had severe symptomatic aortic stenosis and were treated with balloon-expandable TAVR in a single center. Patients studied had both 2D-TEE and 3D imaging (contrast CT and/or 3D-TEE) of the aortic annulus at baseline. Receiver-operating characteristic curves were generated for each measurement parameter using post-TAVR paravalvular AR moderate or greater as the state variable. Results: For the 256 patients studied, paravalvular AR moderate or greater occurred in 26 of 256 (10.2%) of patients. Prospectively recorded 2D-TEE measurements had a low discriminatory value (area under the curve = 0.52, 95% confidence interval: 0.40 to 0.63, p = 0.75). Average cross-sectional diameter by CT offered a high degree of discrimination (area under the curve = 0.82, 95% confidence interval: 0.73 to 0.90, p < 0.0001) and mean cross-sectional diameter by 3D-TEE was of intermediate value (area under the curve = 0.68, 95% confidence interval: 0.54 to 0.81, p = 0.036). Conclusions: Cross-sectional 3D echocardiographic sizing of the aortic annulus dimension offers discrimination of post-TAVR paravalvular AR that is significantly superior to that of 2D-TEE. Cross-sectional data should be sought from 3D-TEE if good CT data are unavailable for TAVR sizing. [Copyright &y& Elsevier]

Objectives: The primary objective of this multicenter registry was to study the prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) and the improved classification of risk in a large cohort of patients with suspected or known coronary artery disease (CAD). Background: Limited prognostic data are available for MPI with PET. Methods: A total of 7,061 patients from 4 centers underwent a clinically indicated rest/stress rubidium-82 PET MPI, with a median follow-up of 2.2 years. The primary outcome of this study was cardiac death (n = 169), and the secondary outcome was all-cause death (n = 570). Net reclassification improvement (NRI) and integrated discrimination analyses were performed. Results: Risk-adjusted hazard of cardiac death increased with each 10% myocardium abnormal with mildly, moderately, or severely abnormal stress PET (hazard ratio [HR]: 2.3 [95% CI: 1.4 to 3.8; p = 0.001], HR: 4.2 [95% CI: 2.3 to 7.5; p < 0.001], and HR: 4.9 [95% CI: 2.5 to 9.6; p < 0.0001], respectively [normal MPI: referent]). Addition of percent myocardium ischemic and percent myocardium scarred to clinical information (age, female sex, body mass index, history of hypertension, diabetes, dyslipidemia, smoking, angina, beta-blocker use, prior revascularization, and resting heart rate) improved the model performance (C-statistic 0.805 [95% CI: 0.772 to 0.838] to 0.839 [95% CI: 0.809 to 0.869]) and risk reclassification for cardiac death (NRI 0.116 [95% CI: 0.021 to 0.210]), with smaller improvements in risk assessment for all-cause death. Conclusions: In patients with known or suspected CAD, the extent and severity of ischemia and scar on PET MPI provided powerful and incremental risk estimates of cardiac death and all-cause death compared with traditional coronary risk factors. [Copyright &y& Elsevier]