Showing papers by "Leslee J. Shaw published in 2017"

Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary Angiography Is Associated With Severely Impaired Coronary Flow Reserve, Not Obstructive Disease

Abstract: Background:Cardiovascular disease (CVD) fatality rates are higher for women than for men, yet obstructive coronary artery disease (CAD) is less prevalent in women. Coronary flow reserve (CFR), an i...

Implications of Coronary Artery Calcium Testing for Treatment Decisions Among Statin Candidates According to the ACC/AHA Cholesterol Management Guidelines: A Cost-Effectiveness Analysis.

Abstract: This review evaluates the cost-effectiveness of using coronary artery calcium (CAC) to guide long-term statin therapy compared with treating all patients eligible for statins according to 2013 American College of Cardiology/American Heart Association cholesterol management guidelines for atherosclerotic cardiovascular disease. The authors used a microsimulation model to compare costs and effectiveness from a societal perspective over a lifetime horizon. Both strategies resulted in similar costs and quality-adjusted life years (QALYs). CAC resulted in increased costs (+$81) and near-equal QALY (+0.01) for an incremental cost-effectiveness ratio of $8,100/QALY compared with the treat-all strategy. For 10,000 patients, the treat-all strategy would theoretically avert 21 atherosclerotic cardiovascular disease events, but would add 47,294 person-years of statins. With CAC costs

Marital Status and Outcomes in Patients With Cardiovascular Disease.

Abstract: BackgroundBeing unmarried is associated with decreased survival in the general population. Whether married, divorced, separated, widowed, or never‐married status affects outcomes in patients with c...

Inflammatory biomarkers as predictors of heart failure in women without obstructive coronary artery disease: A report from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE)

Abstract: Background Women with signs and symptoms of ischemia, no obstructive coronary artery disease (CAD) and preserved left ventricular ejection fraction (EF) often have diastolic dysfunction and experience elevated rates of major adverse cardiac events (MACE), including heart failure (HF) hospitalization with preserved ejection fraction (HFpEF). We evaluated the predictive value of inflammatory biomarkers for long-term HF hospitalization and all-cause mortality in these women. Methods We performed a cross-sectional analysis to investigate the relationships between inflammatory biomarkers [serum interleukin-6 (IL-6), C-reactive protein (hs-CRP) and serum amyloid A (SAA)] and median of 6 years follow-up for all-cause mortality and HF hospitalization among women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF. Multivariable Cox regression analysis tested associations between biomarker levels and adverse outcomes. Results Among 390 women, mean age 56 ± 11 years, median follow up of 6 years, we observed that there is continuous association between IL-6 level and HF hospitalization (adjusted hazard ratio [AHR] 2.5 [1.2–5.0], p = 0.02). In addition, we found significant association between IL-6, SAA levels and all-cause mortality AHR (1.8 [1.1–3.0], p = 0.01) (1.5 [1.0–2.1], p = 0.04), respectively. Conclusion In women with signs and symptoms of ischemia, non-obstructive CAD and preserved EF, elevated IL-6 predicted HF hospitalization and all-cause mortality, while SAA level was only associated with all-cause mortality. These results suggest that inflammation plays a role in the pathogenesis of development of HFpEF, as well all-cause mortality.

Progenitor Cells and Clinical Outcomes in Patients With Heart Failure.

Abstract: BackgroundEndogenous regenerative capacity, assessed as circulating progenitor cell (PC) numbers, is an independent predictor of adverse outcomes in patients with cardiovascular disease. However, t...

Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study.

Abstract: BackgroundSudden cardiac death (SCD) is often the first presentation of ischemic heart disease; however, there is limited information on SCD among women with and without obstructive coronary artery...

Comparative Effectiveness Trials of Imaging-Guided Strategies in Stable Ischemic Heart Disease

Abstract: The evaluation of patients with suspected stable ischemic heart disease is among the most common diagnostic evaluations with nearly 20 million imaging and exercise stress tests performed annually in the United States. Over the past decade, there has been an evolution in imaging research with an ever-increasing focus on larger registries and randomized trials comparing the effectiveness of varying diagnostic algorithms. The current review highlights recent randomized trial evidence with a particular focus comparing the effectiveness of cardiac imaging procedures within the stable ischemic heart disease evaluation for coronary artery disease detection, angina, and other quality of life measures, and major clinical outcomes. Also highlighted are secondary analyses from these trials on the economic findings related to comparative cost differences across diagnostic testing strategies.

Defining Quality in Cardiovascular Imaging: A Scientific Statement From the American Heart Association.

Abstract: The aims of the current statement are to refine the definition of quality in cardiovascular imaging and to propose novel methodological approaches to inform the demonstration of quality in imaging in future clinical trials and registries. We propose defining quality in cardiovascular imaging using an analytical framework put forth by the Institute of Medicine whereby quality was defined as testing being safe, effective, patient-centered, timely, equitable, and efficient. The implications of each of these components of quality health care are as essential for cardiovascular imaging as they are for other areas within health care. Our proposed statement may serve as the foundation for integrating these quality indicators into establishing designations of quality laboratory practices and developing standards for value-based payment reform for imaging services. We also include recommendations for future clinical research to fulfill quality aims within cardiovascular imaging, including clinical hypotheses of improving patient outcomes, the importance of health status as an end point, and deferred testing options. Future research should evolve to define novel methods optimized for the role of cardiovascular imaging for detecting disease and guiding treatment and to demonstrate the role of cardiovascular imaging in facilitating healthcare quality.

Can Functional Testing for Ischemia and Viability Guide Revascularization

Abstract: Cardiac imaging procedures are a cornerstone of the diagnosis and management of patients with cardiac disease. The optimal management of the patient with stable ischemic heart disease or ischemic heart failure often rests on the totality of symptom burden, patient risk, and disease severity, whether assessed anatomically or functionally. Recent trials have demonstrated the power of flow measurements to direct revascularization as well as the strengths and limitations of ischemia and viability/hibernation imaging as markers of risk to direct interventions. They have also highlighted the challenges in evaluating imaging or functional testing to direct therapies, because imaging does not directly affect outcome itself, rather it affects the management decisions that may result in a positive outcome. Ongoing studies with randomized designs, such as FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation), ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), and AIMI-HF (Alternative Imaging Modalities in Ischemic Heart Failure) (IMAGE-HF [Imaging Modalities to Assist with Guiding Therapy in The Evaluation of Patients with Heart Failure]), will provide the highest level of evidence to support practice changes that may further clarify the role of cardiac imaging in the evaluation of these patients and result in improved patient outcomes.

Coronary revascularization vs. medical therapy following coronary-computed tomographic angiography in patients with low-, intermediate- and high-risk coronary artery disease: results from the CONFIRM long-term registry.

Abstract: Aims: To identify the effect of early revascularization on 5-year survival in patients with CAD diagnosed by coronary-computed tomographic angiography (CCTA). Methods and results: We examined 5544 stable patients with suspected CAD undergoing CCTA who were followed a median of 5.5 years in a large international registry. Patients were categorized as having low-, intermediate-, or high-risk CAD based on CCTA findings. Two treatment groups were defined: early revascularization within 90 days of CCTA (n = 1171) and medical therapy (n = 4373). To account for the non-randomized referral to revascularization, we developed a propensity score by logistic regression. This score was incorporated into Cox proportional hazard models to calculate the effect of revascularization on all-cause mortality. Death occurred in 363 (6.6%) patients and was more frequent in medical therapy. In multivariable models, when compared with medical therapy, the mortality benefit of revascularization varied significantly over time and by CAD risk (P for interaction 0.04). In high-risk CAD, revascularization was significantly associated with lower mortality at 1 year (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.11-0.47) and 5 years (HR 0.31, 95% CI 0.18-0.54). For intermediate-risk CAD, revascularization was associated with reduced mortality at 1 year (HR 0.45, 95% CI 0.22-0.93) but not 5 years (HR 0.63, 95% CI 0.33-1.20). For low-risk CAD, there was no survival benefit at either time point. Conclusions: Early revascularization was associated with reduced 1-year mortality in intermediate- and high-risk CAD detected by CCTA, but this association only persisted for 5-year mortality in high-risk CAD.

Patient and Provider Attitudes on Appropriate Use Criteria for Myocardial Perfusion Imaging.

Abstract: Appropriate use criteria (AUC) have been developed for a variety of cardiovascular tests and services. AUC are based on the best available evidence with the goal of identifying which clinical scenarios are likely to result in net patient benefit or harm. Little is known about how well physicians on

Perceptions of patients and providers on myocardial perfusion imaging for asymptomatic patients, choosing wisely, and professional liability

Abstract: Despite efforts by professional societies to reduce low value care, many reports indicate that unnecessary tests, such as nuclear myocardial perfusion imaging (MPI), are commonly used in contemporary practice. The degree to which lack of awareness and professional liability concerns drive these behaviors warrants further study. We sought to investigate patient and provider perceptions about MPI in asymptomatic patients, the Choosing Wisely (CW) campaign, and professional liability concerns. We administered an anonymous, paper-based survey with both discrete and open-response queries to subjects in multiple outpatient settings at our facilities. The survey was completed by 456 respondents including 342 patients and 114 physicians and advanced practice providers between May and August 2014. Our outcome was to compare patient and provider perceptions about MPI in asymptomatic patients and related factors. Patients were more likely than providers to report that MPI was justified for asymptomatic patients (e.g. asymptomatic with family history of heart disease 75% versus 9.2%, p < 0.0001). In free responses to the question “What would be an inappropriate reason for MPI?” many responses echoed the goals of CW (for example, “If you don’t have symptoms”, “If the test is too risky”, “For screening or in asymptomatic patients”). A minority of providers were aware of CW while even fewer patients were aware (37.2% versus 2.7%, p < 0.0001). Over one third of providers (38.9%) admitted to ordering MPI out of concern for professional liability including 48.3% of VA affiliated providers. While some patients and providers are aware of the low value of MPI in patients without symptoms, others are enthusiastic to use it for a variety of scenarios. Concerns about professional liability likely contribute, even in the VA setting. Awareness of the Choosing Wisely campaign is low in both groups.

Imaging Registries and Single-Center Series.

Abstract: Randomized controlled trials are often regarded as the pinnacle of research designs, valued for their rigor and internal validity. However, their high costs and selected patient populations limit their applicability, and complementary study designs are needed to guide evidence. In the realm of cardiovascular imaging, research designs using single-center series and registries have contributed key foundational insights into diagnosis, resource use and cost patterns, and prognosis as derived from practical, “real-world” settings. This review highlights the strengths and limitations of these study designs, provides notable examples, and indicates future directions for research.

Typical angina is associated with greater coronary endothelial dysfunction but not abnormal vasodilatory reserve.

Abstract: Background Typical angina (TA) is defined as substernal chest pain precipitated by physical exertion or emotional stress and relieved with rest or nitroglycerin. Women and elderly patients are usually have atypical symptoms both at rest and during stress, often in the setting of nonobstructive coronary artery disease (CAD). Hypothesis To further understand this, we performed subgroup analysis comparing subjects who presented with TA vs nontypical angina (NTA) using baseline data of patients with nonobstructive CAD and coronary microvascular dysfunction (CMD) enrolled in a clinical trial. Methods 155 subjects from the RWISE study were divided into 2 groups based on angina characteristics: TA (defined as above) and NTA (angina that does not meet criteria for TA). Coronary reactivity testing (responses to adenosine, acetylcholine, and nitroglycerin), cardiac magnetic resonance–determined myocardial perfusion reserve index (MPRI), baseline Seattle Angina Questionnaire (SAQ), and Duke Activity Status Index (DASI) scores were evaluated. Results The mean age was 55 ± 10 years; Overall, 30% of subjects had TA. Baseline shortness of breath, invasively assessed acetylcholine-mediated coronary endothelial function, and SAQ score were worse in the TA group (all P < 0.05), whereas adenosine-mediated coronary flow reserve, MPRI, and DASI score were similar to the NTA group. Conclusions Among subjects with CMD and no obstructive CAD, those with TA had more angina pectoris, shortness of breath, and worse quality of life, as well as more severe coronary endothelial dysfunction. Typical angina in the setting of CMD is associated with worse symptom burden and coronary endothelial dysfunction. These results indicate that TA CMD subjects represent a relatively new CAD phenotype for future study and treatment trials.

Nuclear Cardiology Practices and Radiation Exposure in the Oceania Region: Results From the IAEA Nuclear Cardiology Protocols Study (INCAPS)

Abstract: Background There is concern about radiation exposure with radionuclide myocardial perfusion imaging (MPI). This sub-study of the International Atomic Energy Agency (IAEA) Nuclear Cardiology Protocols Study reports radiation doses from MPI, and use of dose-optimisation protocols in Australia and New Zealand (ANZ), and compares them with data from the rest of the world. Methods Data were collected from 7911 MPI studies performed in 308 laboratories worldwide in one week in 2013, including 439 MPI studies from 34 ANZ laboratories. For each laboratory, effective radiation dose (ED) and a quality index (QI) score (out of 8) based on pre-specified “best practices” was determined. Results In ANZ patients, ED ranged from 0.9-17.9 milliSievert (mSv). Median ED was similar in ANZ compared with the rest of the world (10.0 (IQR: 6.5-11.7) vs. 10.0 (IQR 6.4-12.6, P=0.15), as were mean QI scores (5.5±0.7 vs. 5.4±1.3, P=0.84). Use of stress-only imaging (17.6% vs. 31.8% of labs, P=0.09) and weight-based dosing of technetium-99m (14.7% vs. 30.3%, P=0.07) was lower in ANZ compared with the rest of the world but this difference was not statistically significant. Median ED was significantly lower in metropolitan versus non-metropolitan laboratories (10.1 mSv vs. 11.6 mSv, P Conclusion Across ANZ, there is variability in ED from MPI, and use of radiation safety practices, particularly between metropolitan and non-metropolitan laboratories. Overall, ANZ laboratories have a similar median ED to laboratories in the rest of the world.

Lesion-Specific Ischemia With Noninvasive Computed Tomographic Angiography: Superior to Conventional Stress Testing?

Abstract: For many decades, stress testing has been at the core of the diagnostic evaluation algorithm for detection of obstructive coronary artery disease (CAD) for the patient presenting with stable, suspected ischemic heart disease.1 The underlying rationale for stress testing is based on the principle of demand ischemia, whereby above a patientspecific exercise workload, myocardial ischemia may be induced in the setting of a functionally limited stenosis. Since the early days of the Master step test, graded exercise with observation of an ischemic threshold has been undertaken to corroborate the patient’s presenting suspected cardiac symptoms and, if positive, to guide anti-ischemic therapy and invasive coronary angiography (ICA) use. The exercise test and knowledge of a given ischemic threshold are fundamental to guiding referral to cardiac rehabilitation, as a basis for exercise prescription, and to guide prescription of anti-ischemic therapies. Depending on the severity of inducible ischemia, the evaluation algorithm may also include referral to ICA and consideration of coronary revascularization, as appropriate.1 For this culminating step in the diagnostic work-up, sufficient inducible ischemia is necessary and forms the basis for ischemia-guided management of stable chest pain. Although straightforward in concept, today’s symptomatic populations are often unable to exercise sufficiently, have a lower prevalence of functionally significant CAD, and often present with atypical symptoms. More than half of referred patients require nonexercise approaches to elucidate ischemia (ie, pharmacologic stress). Obesity and lung disease can impair accurate visualization of ischemia, with image artifact, and may reduce diagnostic accuracy. Moreover, despite the abundant imaging technology to apply during stress testing, localization of ischemia with precise identification of coronary artery stenosis within a given epicardial vessel remains problematic. These factors complicate the diagnostic evaluation and render identification of true ischemia, in the setting of a flow-limiting coronary stenosis, a challenge that requires mastery by the cardiac imager. Over the past decade, noninvasive coronary computed tomographic angiography (CTA) has emerged, with abundant high-quality evidence supporting strong concordance with ICA findings of normal, nonobstructive, and obstructive CAD, and similar clinical effectiveness when compared with functional stress testing.2-4 The randomized trial evidence demonstrate that CTA has a higher diagnostic accuracy when compared with stress testing, often with sensitivity measures more than 90%.1,5 Using CTA-guided management, a large proportion of symptomatic patients without CAD or nonobstructive coronary atherosclerosis do not require additional follow-up. The detection of atherosclerosis serves as a prominent motivator for patients and is associated with improved adherence to cardiovascular preventive care.6,7 This finding has resulted in the UK National Institute for Health and Care Excellence now recommending CTA as the first-line investigation for symptomatic patients, regardless of their pretest CAD likelihood.8 Estimated savings of ~ $20 million US dollars annually were projected following index CTA use within the National Health Services due to the confident exclusion of CAD with CTA and limiting (more costly) stress imaging only to those with obstructive CAD.9 Index evaluation with CTA is, however, challenged by the lack of ischemia evidence and, thus, must currently be coupled selectively with stress testing (in the setting of an intermediate or high grade stenosis). That index CTA testing may lead to prompt referral to ICA without knowledge of provocative ischemia is concerning. Elimination of ischemia testing following CTA is problematic as this evidence guides interventional and medical therapy decisions.1 Ischemia testing, however, may be performed outside of the stress testing laboratory. Intracoronary pressure-derived measurement of fractional flow reserve (FFR) has a robust evidence base in determining lesion-specific ischemia and guiding percutaneous coronary intervention (PCI).10 Based on several clinical trials, selective PCI for stenoses associated with a reduced FFR improves major CAD events when compared with an anatomic-guided interventional approach.11,12 More recent technology now allows for a noninvasive calculation of FFR with CTA (FFR-CT) based on complex computational fluid dynamic modeling to simulate physiologic conditions upon which lesion-specific ischemia may be estimated.13 The controlled clinical trial evidence to date supports a relatively high degree of concordance between invasive and CT-based FFR.14 In this issue of the journal, Cook and colleagues15 provide a systematic review (n = 5 reports in 536 patients) of the FFR-CT evidence with the 82% (overall) diagnostic accuracy threshold met for values of FFR-CT lower than 0.63 or above 0.83. The extremes of FFR-CT values were highly accurate to rule-out (ie, >0.90) or rule-in (ie, ≤0.60) ischemia, as confirmed with Editor's Note

Training and Service Provision in Cardiovascular CT: International Challenges and Solutions

Abstract: This manuscript identifies international challenges in cardiovascular CT that may prevent it from becoming a mainstream cardiovascular investigation. It offers potential solutions and a vision to overcome these barriers. The acceptance of cardiovascular CT as a mainstream investigation now mandates a root and branch review of how we deliver a technology that is no longer emerging but recommended for mainstream clinical practice. The main challenges include investment in equipment and personnel and a substantial uplift in educational and training opportunities available. This requires revision of existing structures for training and accreditation and a broadening of these opportunities to include radiographers/technologists. The evidence for cardiovascular CT is overwhelming; the same energy and investment witnessed in driving the evidence base for this technology is now required in education and training. Failure to do so risks undermining the academic investment made over the last decade.

Can a Machine Learn Better Than Humans

Abstract: O ver the past several decades, we have seen explosive growth in the power of computing that has significantly impacted the field of cardiovascular imaging in terms of imaging resolution, efficiencies, and diverse capabilities for disease detection. Recently, the term “predictive analytics” has been applied to many areas, including medical imaging, to identify actionable intelligence to improve many aspects of patient care. Machine learning is one example of the new analytical approaches that may be applied to risk and disease prediction. In this issue of iJACC, a group from Cedars-Sinai Medical Center, led by Betancur et al. (1), published results of a prognostic analysis based on stress myocardial perfusion imaging data using machine learning techniques. This is part of a growing series of papers from this group on estimation of prognosis in cardiac imaging using machine learning as the primary analytical technique (2–4). These new methodologic approaches appear to have unbounded applications, including data extraction and prediction from imaging metadata (e.g., radiomics) to using electronic health records. An appropriate question is whether this is more than a fad or does this research represent a clear advantage in terms of actionable intelligence that improves patient care. In other words, is machine learning lots of hope or lots of hype? At first glance, it appears that much of the findings from machine learning are similar to prognostic findings published using Cox regression modeling. However, Cox models, as in most standard statistical models, are based on simple linear relationships. That is, how many events occur over time within a given set of variables? The analysis examines variable

Aortic flow conditions predict ejection efficiency in the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE).

Abstract: Background: The Windkessel model of the cardiovascular system, both in its original wind-chamber and flow-pipe form, and in its electrical circuit analog has been used for over a century to modeled left ventricular ejection conditions. Using parameters obtained from aortic flow we formed a Flow Index that is proportional to the impedance of such a “circuit”. We show that the impedance varies with ejection fraction (EF) in a manner characteristic of a resonant circuit with multiple resonance points, with each resonance point centrally located in a small range of EF values, i.e., corresponding to multiple contiguous EF bands. Methods: Two target populations were used: (I) a development group comprising male and female subjects (n=112) undergoing cardiovascular magnetic resonance (CMR) imaging for a variety of cardiac conditions. The Flow Index was developed using aortic flow data and its relationship to left ventricular EF was shown. (II) An illustration group comprised of female subjects from the Women’s Ischemia Syndrome Evaluation (WISE) (n=201) followed for 5 years for occurrence of major adverse cardiovascular events (MACE). Flow data was not available in this group but since the Flow Index was related to the EF we noted the MACE rate with respect to EF. Results: The EFs of the development population covered a wide range (9%–76%) traversing six Flow Index resonance bands. Within each Flow Index resonance band the impedance varied from highly capacitive at the lower range of EF through minimal impedance at resonance, to highly inductive at the higher range of EF, which is characteristic of a resonant circuit. When transitioning from one EF band to a higher band, the Flow Index made a sudden transition from highly inductive to capacitive impedance modes. MACE occurred in 26 (13%) of the WISE (illustration) population. Distance in EF units (Delta center ) from the central location between peaks of MACE activity was derived from EF data and was predictive of MACE rate with an area under the receiver operator curve of 0.73. Of special interest, Delta center was highly predictive of MACE in the sub-set of women with EF >60% (AUC 0.79) while EF was no more predictive than random chance (AUC 0.48). Conclusions: A Flow Index that describes impedance conditions of left ventricular ejection can be calculated using data obtained completely from the ascending aorta. The Flow Index exhibits a periodic variation with EF, and in a separate illustration population the occurrence of MACE was observed to exhibit a similar periodic variation with EF, even in cases of normal EF.