Evaluation of Women and Underrepresented Racial and Ethnic Group Representation in a General Cardiology Fellowship After a Systematic Recruitment Initiative.

Importance: The proportion of women and underrepresented racial and ethnic groups (UREGs) matriculating into general cardiology fellowships remains low. Objective: To assess a systematic recruitment initiative aimed at ensuring adequate matriculation of women and UREGs in a general cardiology fellowship. Design, Setting, and Participants: This quality improvement study took place at a large, tertiary academic medical center and associated Accreditation Council for Graduate Medical Education Cardiovascular Disease fellowship. Participants included cardiology fellowship and divisional leadership and general cardiology fellow applicants to the Duke Cardiovascular Disease Fellowship Program from 2017 to 2019. Data analysis was performed from December 2019 to May 2020. Exposure: Multipronged initiative that created an environment committed to ensuring equity of opportunity. This included the creation of a fellowship diversity and inclusivity task force that drafted recommendations, which included reorganization of the fellowship recruitment committee, and changes to the applicant screening process, the interview day, applicant ranking process, and postmatch interventions. Main Outcomes and Measures: The percentage of matriculating and overall women and UREGs before and after the interventions were recorded. Results: The fellowship received a mean (SD) of 462 (55) applications annually before the interventions (2006-2016) and 611 (27) applications annually after the interventions (2017-2019). Between the 10-year period before the interventions and the 3-year period during the interventions, there was a significant increase in the annual mean (SD) percentage of women (22.4% [2.9%] vs 26.4% [0.07%]; P < .001) and UREG applicants (10.5% [1.1%] vs 12.5% [1.9%]; P = .01) to the program. Among applicants interviewed, the percentage of women increased from 20.0% to 33.5% (P = .01) and that of and UREGs increased from 14.0% to 20.0% (P = .01). Before the interventions, a mean (SD) of 23.2% (16.2%) women and 9.7% (7.8%) UREGs matriculated as first-year fellows, whereas after the interventions, a mean (SD) of 54.2% (7.2%) women and 33.3% (19.0%) UREGs matriculated as first-year fellows. The proportion of the entire fellowship who were women increased from a 5-year mean (SD) of 27.0% (8.8%) to 54.2% (7.2%) after 3 years of interventions, and that of UREGs increased from 5.6% (4.6%) to 33.3% (19.0%). Overall, the proportion of applicants in the entire population who were either women or from UREGs increased from 27.8% to 66.7%. Conclusions and Relevance: After implementing interventions to promote equity of opportunity in the cardiovascular disease fellowship, the percentage of women and UREGs significantly increased in the fellowship over a 3-year time period. These interventions may be applicable to other cardiovascular disease fellowships seeking to diversify training programs.

Resolution and Speckle Reduction in Cardiac Imaging.

Cardiac imaging depends on clear visualization of several different structural and functional components to determine left ventricular and overall cardiac health. Ultrasound imaging is confounded by the characteristic speckle texture resulting from subwavelength scatterers in tissues, which is similar to a multiplicative noise on underlying tissue structure. Reduction of this texture can be achieved through physical means, such as spatial or frequency compounding, or through adaptive image processing. Techniques in both categories require a tradeoff of resolution for speckle texture reduction, which together contribute to overall image quality and diagnostic value. We evaluate this tradeoff for cardiac imaging tasks using spatial compounding as an exemplary speckle reduction method. Spatial compounding averages the decorrelated speckle patterns formed by views of a target from multiple subaperture positions to reduce the texture at the expense of active aperture size (and, in turn, lateral resolution). We demonstrate the use of a novel synthetic aperture focusing technique to decompose harmonic backscattered data from focused beams to their aperture-domain spatial frequency components to enable combined transmit and receive compounding. This tool allows the evaluation of matched data sets from a single acquisition over a wide range of spatial compounding conditions. We quantified the tradeoff between resolution and texture reduction in an imaging phantom and demonstrated improved lesion detectability with increasing levels of spatial compounding. We performed a cardiac ultrasound on 25 subjects to evaluate the degree of compounding useful for diagnostic imaging. Of these, 18 subjects were included in both qualitative and quantitative analysis. We found that compounding improved detectability of the endocardial border according to the generalized contrast-to-noise ratio in all cases, and more aggressive compounding made further improvements in ten out of 18 cases. Three expert reviewers evaluated the images for their usefulness in several diagnostic tasks and ranked four compounding conditions ("none," "low," "medium," and "high"). Contrary to the quantitative metrics that suggested the use of high levels of compounding, the reviewers determined that "low" was usually preferred (77.9%), while "none" or "medium" was selected in 21.2% of cases. We conclude with a brief discussion of the generalization of these results to other speckle reduction methods using the imaging phantom data.

Perceptions on Diversity in Cardiology: A Survey of Cardiology Fellowship Training Program Directors.

Background The lack of diversity in the cardiovascular physician workforce is thought to be an important driver of racial and sex disparities in cardiac care. Cardiology fellowship program directors play a critical role in shaping the cardiology workforce. Methods and Results To assess program directors' perceptions about diversity and barriers to enhancing diversity, the authors conducted a survey of 513 fellowship program directors or associate directors from 193 unique adult cardiology fellowship training programs. The response rate was 21% of all individuals (110/513) representing 57% of US general adult cardiology training programs (110/193). While 69% of respondents endorsed the belief that diversity is a driver of excellence in health care, only 26% could quote 1 to 2 references to support this statement. Sixty-three percent of respondents agreed that "our program is diverse already so diversity does not need to be increased." Only 6% of respondents listed diversity as a top 3 priority when creating the cardiovascular fellowship rank list. Conclusions These findings suggest that while program directors generally believe that diversity enhances quality, they are less familiar with the literature that supports that contention and they may not share a unified definition of "diversity." This may result in diversity enhancement having a low priority. The authors propose several strategies to engage fellowship training program directors in efforts to diversify cardiology fellowship training programs.

Cardiac remodeling after large ST-elevation myocardial infarction in the current therapeutic era.

BACKGROUND: The evolution and clinical impact of cardiac remodeling after large ST-elevation myocardial infarction (STEMI) is not well delineated in the current therapeutic era. METHODS: The PRESERVATION I trial longitudinally assessed cardiac structure and function in STEMI patients receiving primary percutaneous coronary intervention (PCI). Echocardiograms were performed immediately post-PCI and at 1, 3, 6 and 12 months after STEMI. The extent of cardiac remodeling was assessed in patients with ejection fraction (EF) ≤ 40% after PCI. Patients were stratified by the presence or absence of reverse remodeling, defined as an increase in end-diastolic volume (EDV) of ≤10 mL or decrease in EDV at 1 month, and evaluated for an association with adverse events at 1 year. RESULTS: Of the 303 patients with large STEMI enrolled in PRESERVATION I, 225 (74%) had at least moderately reduced systolic function (mean EF 32 ±â€¯5%) immediately after primary PCI. In the following year, there were significant increases in EF and LV volumes, with the greatest magnitude of change occurring in the first month. At 1 month, 104 patients (46%) demonstrated reverse remodeling, which was associated with a significantly lower rate of death, recurrent myocardial infarction and repeat cardiovascular hospitalization at 1 year (HR 0.44; 95% CI: 0.19-0.99). CONCLUSION: Reduced EF after large STEMI and primary PCI is common in the current therapeutic era. The first month following primary reperfusion is a critical period during which the greatest degree of cardiac remodeling occurs. Patients demonstrating early reverse remodeling have a significantly lower rate of adverse events in the year after STEMI.

Improved Visualization in Difficult-to-Image Stress Echocardiography Patients Using Real-Time Harmonic Spatial Coherence Imaging.

Stress echocardiography is used to detect myocardial ischemia by evaluating cardiovascular function both at rest and at elevated heart rates. Stress echocardiography requires excellent visualization of the left ventricle (LV) throughout the cardiac cycle. However, LV endocardial border visualization is often negatively impacted by high levels of clutter associated with patient obesity, which has risen dramatically worldwide in recent decades. Short-lag spatial coherence (SLSC) imaging has demonstrated reduced clutter in several applications. In this work, a computationally efficient formulation of SLSC was implemented into an object-oriented graphics processing unit-based software beamformer, enabling real-time (>30 frames per second) SLSC echocardiography on a research ultrasound scanner. The system was then used to image 15 difficult-to-image stress echocardiography patients in a comparison study of tissue harmonic imaging (THI) and harmonic spatial coherence imaging (HSCI). Video clips of four standard stress echocardiography views acquired with either THI or HSCI were provided in random shuffled order to three experienced readers. Each reader rated the visibility of 17 LV segments as "invisible," "suboptimally visualized," or "well visualized," with the first two categories indicating a need for contrast agent. In a symmetry test unadjusted for patientwise clustering, HSCI demonstrated a clear superiority over THI ( ). When measured on a per-patient basis, the median total score significantly favored HSCI with . When collapsing the ratings to a two-level scale ("needs contrast" versus "well visualized"), HSCI once again showed an overall superiority over THI, with by McNemar test adjusted for clustering.

Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial.

Importance: The appropriate duration of antibiotics for staphylococcal bacteremia is unknown. Objective: To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events. Design, Setting, and Participants: A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization. Interventions: Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care. Main Outcomes and Measures: Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia. Results: Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, -6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, -3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, -1.8 days [95% CI, -3.1 to -0.6]). Conclusions and Relevance: Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm. Trial Registration: ClinicalTrials.gov Identifier: NCT01191840.

Crowdsourcing consensus: proposal of a novel method for assessing accuracy in echocardiography interpretation.

Quality in stress echocardiography interpretation is often gauged against coronary angiography (CA) data but anatomic obstructive coronary disease on CA is an imperfect gold standard for a stress induced wall motion abnormality. We examined the utility of crowd-sourcing a "majority-vote" consensus as an alternative 'gold standard' against which to evaluate the accuracy of an individual echocardiographer's interpretation of stress echocardiography studies. Participants independently interpreted baseline and post-exercise stress echocardiographic images of cases that had undergone follow up CA within 3 months of the stress echo in two surveys, 2 years apart. We examined the agreement of consensus on survey (survey participant response (> 60%) for one decision) with the stress echocardiography clinical read and with CA results. In the first survey, 29 participants reviewed and independently interpreted 14 stress echo cases. Consensus was reached in all 14 cases. There was good agreement between clinical and consensus (kappa = 0.57), survey participant response and consensus (kappa = 0.68) and consensus and CA results (kappa = 0.40). In the validation survey, the agreement between clinical reads and consensus (kappa = 0.75) and survey participant response and consensus (kappa = 0.81) remained excellent. Independent consensus is achievable and offers a fair comparison for stress echocardiographic interpretation. Future validation work, in other laboratories, and against hard outcomes, is necessary to test the feasibility and effectiveness of this approach.

Two-dimensional global longitudinal strain is superior to left ventricular ejection fraction in prediction of outcome in patients with left-sided infective endocarditis.

BACKGROUND: Impaired cardiac function is the main predictor of poor outcome in infective endocarditis (IE). Global longitudinal strain (GLS) derived from two-dimensional strain echocardiography has proven superior in prediction of long-term outcome as compared to left ventricular ejection fraction (LVEF) in valvular disease and heart failure in general. Whether measurements of cardiac deformation can predict survival in patients with IE has not previously been investigated. METHODS: The study included consecutive patients with Duke definite IE who underwent transthoracic and transesophageal echocardiography within 7 days. Clinical and echocardiographic markers associated with 1-year survival were identified using a Cox-proportional hazards model that included propensity adjustment for surgery. Reclassification statistics including receiver operating characteristic curves and net reclassification improvement were applied to LVEF and GLS, respectively. RESULTS: A cohort of 190 patients met eligibility criteria. LVEF and GLS were both prognostic markers of mortality. Independent markers of 1-year mortality were S. aureus IE (HR:2.02; 95%CI 1.11-5.72, p = .022), diabetes (HR:2.05; 95%CI 1.12-3.75, p = .020), embolic stroke (HR:3.95; 95%CI 1.93-8.10, p < .001) and LVEF<45% (HR: 3.02; 95% CI 1.70-5.38, p < .001), GLS> -15.4% (HR:2.95; 95%CI 1.52-5.72, p < .001). Adding LVEF<45% to a model with known risk factors of IE did not significantly improve risk classification, whereas addition of GLS to the model resulted in significant increase (AUC = 0.763, p < .001). CONCLUSIONS: When treatment was taken into account, LVEF<45% and GLS > -15.4% were both associated with adverse long-term outcome in left-sided IE. GLS >-15.4 % was significantly associated with 1-year mortality in the multivariate analysis. Further, GLS was superior to LVEF in risk prediction and risk discrimination of long-term outcome in patients with left-sided IE.

Dark-Blood Delayed Enhancement Cardiac Magnetic Resonance of Myocardial Infarction.

OBJECTIVES: This study introduced and validated a novel flow-independent delayed enhancement technique that shows hyperenhanced myocardium while simultaneously suppressing blood-pool signal. BACKGROUND: The diagnosis and assessment of myocardial infarction (MI) is crucial in determining clinical management and prognosis. Although delayed enhancement cardiac magnetic resonance (DE-CMR) is an in vivo reference standard for imaging MI, an important limitation is poor delineation between hyperenhanced myocardium and bright LV cavity blood-pool, which may cause many infarcts to become invisible. METHODS: A canine model with pathology as the reference standard was used for validation (n = 22). Patients with MI and normal controls were studied to ascertain clinical performance (n = 31). RESULTS: In canines, the flow-independent dark-blood delayed enhancement (FIDDLE) technique was superior to conventional DE-CMR for the detection of MI, with higher sensitivity (96% vs. 85%, respectively; p = 0.002) and accuracy (95% vs. 87%, respectively; p = 0.01) and with similar specificity (92% vs, 92%, respectively; p = 1.0). In infarcts that were identified by both techniques, the entire length of the endocardial border between infarcted myocardium and adjacent blood-pool was visualized in 33% for DE-CMR compared with 100% for FIDDLE. There was better agreement for FIDDLE-measured infarct size than for DE-CMR infarct size (95% limits-of-agreement, 2.1% vs. 5.5%, respectively; p < 0.0001). In patients, findings were similar. FIDDLE demonstrated higher accuracy for diagnosis of MI than DE-CMR (100% [95% confidence interval [CI]: 89% to 100%] vs. 84% [95% CI: 66% to 95%], respectively; p = 0.03). CONCLUSIONS: The study introduced and validated a novel CMR technique that improves the discrimination of the border between infarcted myocardium and adjacent blood-pool. This dark-blood technique provides diagnostic performance that is superior to that of the current in vivo reference standard for the imaging diagnosis of MI.

The Role for Cardiovascular Remodeling in Cardiovascular Outcomes.

PURPOSE OF REVIEW: Ischemic and non-ischemic injury to the heart causes deleterious changes in ventricular size, shape, and function. This adverse remodeling is mediated by neurohormonal and hemodynamic alterations and is reflected in non-invasive measures of left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV). These measures are closely linked to cardiovascular outcomes and have become key surrogate endpoints for evaluating the therapeutic efficacy of contemporary treatments for heart failure with reduced ejection fraction (HFrEF). In this review, we critically evaluate recent published data (2015-2016) from randomized clinical trials (RCTs) and observational studies of HFrEF therapies to assess the role of ventricular remodeling on outcomes. RECENT FINDINGS: These data highlight the benefits of certain guideline-directed medical therapies (GDMT) such as cardiac resynchronization therapy, surgical revascularization, and mechanical circulatory support on remodeling, while revealing the limitations of other therapies-routine mitral valve repair for patients with moderate ischemic mitral regurgitation and adjuncts to percutaneous coronary intervention in patients with ST elevation myocardial infarction (cyclosporine A and bioabsorbable cardiac matrix). The new angiotensin receptor blocker/neprilysn inhibitor, sacubitril/valsartan, demonstrates convincing improvements in clinical outcomes with a study of remodeling parameters to follow; the new cardiac myosin activator, omecamtiv mecarbil, demonstrates improvement in remodeling parameters without a clear early clinical benefit. The concepts and contemporary trials reviewed in this paper reinforce the value of non-invasive measures of ventricular remodeling (LVEF, LVESV, and LVEDV) as important metrics across a range of cardiovascular therapies. Global non-invasive measures of cardiovascular remodeling have roughly paralleled or preceded hard clinical outcomes. Additionally, the capacity for reverse remodeling in HFrEF with GDMT motivates continued research in the fields of implementation science, diagnostic imaging, and gene-based therapeutics.

Efficient Strategies for Estimating the Spatial Coherence of Backscatter.

The spatial coherence of ultrasound backscatter has been proposed to reduce clutter in medical imaging, to measure the anisotropy of the scattering source, and to improve the detection of blood flow. These techniques rely on correlation estimates that are obtained using computationally expensive strategies. In this paper, we assess the existing spatial coherence estimation methods and propose three computationally efficient modifications: a reduced kernel, a downsampled receive aperture, and the use of an ensemble correlation coefficient. The proposed methods are implemented in simulation and in vivo studies. Reducing the kernel to a single sample improved computational throughput and improved axial resolution. Downsampling the receive aperture was found to have negligible effect on estimator variance, and improved computational throughput by an order of magnitude for a downsample factor of 4. The ensemble correlation estimator demonstrated lower variance than the currently used average correlation. Combining the three methods, the throughput was improved 105-fold in simulation with a downsample factor of 4- and 20-fold in vivo with a downsample factor of 2.

Critical Review of Current Approaches for Echocardiographic Reproducibility and Reliability Assessment in Clinical Research.

BACKGROUND: There is no broadly accepted standard method for assessing the quality of echocardiographic measurements in clinical research reports, despite the recognized importance of this information in assessing the quality of study results. METHODS: Twenty unique clinical studies were identified reporting echocardiographic data quality for determinations of left ventricular (LV) volumes (n = 13), ejection fraction (n = 12), mass (n = 9), outflow tract diameter (n = 3), and mitral Doppler peak early velocity (n = 4). To better understand the range of possible estimates of data quality and to compare their utility, reported reproducibility measures were tabulated, and de novo estimates were then calculated for missing measures, including intraclass correlation coefficient (ICC), 95% limits of agreement, coefficient of variation (CV), coverage probability, and total deviation index, for each variable for each study. RESULTS: The studies varied in approaches to reproducibility testing, sample size, and metrics assessed and values reported. Reported metrics included mean difference and its SD (n = 7 studies), ICC (n = 5), CV (n = 4), and Bland-Altman limits of agreement (n = 4). Once de novo estimates of all missing indices were determined, reasonable reproducibility targets for each were identified as those achieved by the majority of studies. These included, for LV end-diastolic volume, ICC > 0.95, CV < 7%, and coverage probability > 0.93 within 30 mL; for LV ejection fraction, ICC > 0.85, CV < 8%, and coverage probability > 0.85 within 10%; and for LV mass, ICC > 0.85, CV < 10%, and coverage probability > 0.60 within 20 g. CONCLUSIONS: Assessment of data quality in echocardiographic clinical research is infrequent, and methods vary substantially. A first step to standardizing echocardiographic quality reporting is to standardize assessments and reporting metrics. Potential benefits include clearer communication of data quality and the identification of achievable targets to benchmark quality improvement initiatives.

Echocardiographic agreement in the diagnostic evaluation for infective endocarditis.

Echocardiography is essential for the diagnosis and management of infective endocarditis (IE). However, the reproducibility for the echocardiographic assessment of variables relevant to IE is unknown. Objectives of this study were: (1) To define the reproducibility for IE echocardiographic variables and (2) to describe a methodology for assessing quality in an observational cohort containing site-interpreted data. IE reproducibility was assessed on a subset of echocardiograms from subjects enrolled in the International Collaboration on Endocarditis registry. Specific echocardiographic case report forms were used. Intra-observer agreement was assessed from six site readers on ten randomly selected echocardiograms. Inter-observer agreement between sites and an echocardiography core laboratory was assessed on a separate random sample of 110 echocardiograms. Agreement was determined using intraclass correlation (ICC), coverage probability (CP), and limits of agreement for continuous variables and kappa statistics (κweighted) and CP for categorical variables. Intra-observer agreement for LVEF was excellent [ICC = 0.93 ± 0.1 and all pairwise differences for LVEF (CP) were within 10 %]. For IE categorical echocardiographic variables, intra-observer agreement was best for aortic abscess (κweighted = 1.0, CP = 1.0 for all readers). Highest inter-observer agreement for IE categorical echocardiographic variables was obtained for vegetation location (κweighted = 0.95; 95 % CI 0.92-0.99) and lowest agreement was found for vegetation mobility (κweighted = 0.69; 95 % CI 0.62-0.86). Moderate to excellent intra- and inter-observer agreement is observed for echocardiographic variables in the diagnostic assessment of IE. A pragmatic approach for determining echocardiographic data reproducibility in a large, multicentre, site interpreted observational cohort is feasible.

An Approach to Improve the Negative Predictive Value and Clinical Utility of Transthoracic Echocardiography in Suspected Native Valve Infective Endocarditis.

BACKGROUND: In patients with suspected native valve infective endocarditis, current guidelines recommend initial transthoracic echocardiography (TTE) followed by transesophageal echocardiography (TEE) if clinical suspicion remains. The guidelines do not account for the quality of initial TTE or other findings that may alter the study's diagnostic characteristics. This may lead to unnecessary TEE when initial TTE was sufficient to rule out vegetation. METHODS: The objective of this study was to determine if the use of a strict definition of negative results on TTE would improve the performance characteristics of TTE sufficiently to exclude vegetation. A retrospective analysis of patients at a single institution with suspected native valve endocarditis who underwent TTE followed by TEE within 7 days between January 1, 2007, and February 28, 2014, was performed. Negative results on TTE for vegetation were defined by either the standard approach (no evidence of vegetation seen on TTE) or by applying a set of strict negative criteria incorporating other findings on TTE. Using TEE as the gold standard for the presence of vegetation, the diagnostic performance of the two transthoracic approaches was compared. RESULTS: In total, 790 pairs of TTE and TEE were identified. With the standard approach, 661 of the transthoracic studies had negative findings (no vegetation seen), compared with 104 studies with negative findings using the strict negative approach (meeting all strict negative criteria). The sensitivity and negative predictive value of TTE for detecting vegetation were substantially improved using the strict negative approach (sensitivity, 98% [95% CI, 95%-99%] vs 43% [95% CI, 36%-51%]; negative predictive value, 97% [95% CI, 92%-99%] vs 87% [95% CI, 84%-89%]). CONCLUSIONS: The ability of TTE to exclude vegetation in patients is excellent when strict criteria for negative results are applied. In patients at low to intermediate risk with strict negative results on TTE, follow-up TEE may be unnecessary.

Choice of agreement indices for assessing and improving measurement reproducibility in a core laboratory setting.

Clinical core laboratories, such as Echocardiography core laboratories, are increasingly used in clinical studies with imaging outcomes as primary, secondary, or surrogate endpoints. While many factors contribute to the quality of measurements of imaging variables, an essential step in ensuring the value of imaging data includes formal assessment and control of reproducibility via intra-observer and inter-observer reliability. There are many different agreement/reliability indices in the literature. However, different indices may lead to different conclusions and it is not clear which index is the preferred choice as an overall indication of data quality and a tool for providing guidance on improving quality and reliability in a core lab setting. In this paper, we pre-specify the desirable characteristics of an agreement index for assessing and improving reproducibility in a core lab setting; we compare existing agreement indices in terms of these characteristics to choose a preferred index. We conclude that, among the existing indices reviewed, the coverage probability for assessing agreement is the preferred agreement index on the basis of computational simplicity, its ability for rapid identification of discordant measurements to provide guidance for review and retraining, and its consistent evaluation of data quality across multiple reviewers, populations, and continuous/categorical data.

Echocardiographic Findings Predict In-Hospital and 1-Year Mortality in Left-Sided Native Valve Staphylococcus aureus Endocarditis: Analysis From the International Collaboration on Endocarditis-Prospective Echo Cohort Study.

BACKGROUND: Staphylococcus aureus left-sided native valve infective endocarditis (LNVIE) has higher complication and mortality rates compared with endocarditis from other pathogens. Whether echocardiographic variables can predict prognosis in S aureus LNVIE is unknown. METHODS AND RESULTS: Consecutive patients with LNVIE, enrolled between January 2000 and September 2006, in the International Collaboration on Endocarditis were identified. Subjects without S aureus IE were matched to those with S aureus IE by the propensity of having S aureus. Survival differences were determined using log-rank significance tests. Independent echocardiographic predictors of mortality were identified using Cox-proportional hazards models that included inverse probability of treatment weighting and surgery as a time-dependent covariate. Of 727 subjects with LNVIE and 1-year follow-up, 202 had S aureus IE. One-year survival rates were significantly lower for patients with S aureus IE overall (57% S aureus IE versus 80% non-S aureus IE; P<0.001) and in the propensity-matched cohort (59% S aureus IE versus 68% non-S aureus IE; P<0.05). Intracardiac abscess (hazard ratio, 2.93; 95% confidence interval, 1.52-5.40; P<0.001) and left ventricular ejection fraction <40% (odds ratio, 3.01; 95% confidence interval, 1.35-6.04; P=0.004) were the only independent echocardiographic predictors of in-hospital mortality in S aureus LNVIE. Valve perforation (hazard ratio, 2.16; 95% confidence interval, 1.21-3.68; P=0.006) and intracardiac abscess (hazard ratio, 2.25; 95% confidence interval, 1.26-3.78; P=0.004) were the only independent predictors of 1-year mortality. CONCLUSIONS: S aureus is an independent predictor of 1-year mortality in subjects with LNVIE. In S aureus LNVIE, intracardiac abscess and left ventricular ejection fraction <40% independently predicted in-hospital mortality and intracardiac abscess and valve perforation independently predicted 1-year mortality.

Relationship of T2-Weighted MRI Myocardial Hyperintensity and the Ischemic Area-At-Risk.

RATIONALE: After acute myocardial infarction (MI), delineating the area-at-risk (AAR) is crucial for measuring how much, if any, ischemic myocardium has been salvaged. T2-weighted MRI is promoted as an excellent method to delineate the AAR. However, the evidence supporting the validity of this method to measure the AAR is indirect, and it has never been validated with direct anatomic measurements. OBJECTIVE: To determine whether T2-weighted MRI delineates the AAR. METHODS AND RESULTS: Twenty-one canines and 24 patients with acute MI were studied. We compared bright-blood and black-blood T2-weighted MRI with images of the AAR and MI by histopathology in canines and with MI by in vivo delayed-enhancement MRI in canines and patients. Abnormal regions on MRI and pathology were compared by (a) quantitative measurement of the transmural-extent of the abnormality and (b) picture matching of contours. We found no relationship between the transmural-extent of T2-hyperintense regions and that of the AAR (bright-blood-T2: r=0.06, P=0.69; black-blood-T2: r=0.01, P=0.97). Instead, there was a strong correlation with that of infarction (bright-blood-T2: r=0.94, P<0.0001; black-blood-T2: r=0.95, P<0.0001). Additionally, contour analysis demonstrated a fingerprint match of T2-hyperintense regions with the intricate contour of infarcted regions by delayed-enhancement MRI. Similarly, in patients there was a close correspondence between contours of T2-hyperintense and infarcted regions, and the transmural-extent of these regions were highly correlated (bright-blood-T2: r=0.82, P<0.0001; black-blood-T2: r=0.83, P<0.0001). CONCLUSION: T2-weighted MRI does not depict the AAR. Accordingly, T2-weighted MRI should not be used to measure myocardial salvage, either to inform patient management decisions or to evaluate novel therapies for acute MI.

Quality Improvement Implementation: Improving Reproducibility in the Echocardiography Laboratory.

BACKGROUND: Interpretative variability can adversely affect echocardiographic reliability, but there is no widely accepted method to minimize variability and improve reproducibility. METHODS: A continuous quality improvement process was devised that involves testing reproducibility by assessment of measurement differences followed by robust review, retraining, and retesting. Reproducibility was deemed acceptable if ≥80% of all interreader comparisons were within a prespecified acceptable difference. Readers not meeting this standard underwent retraining and retesting until acceptable reproducibility was achieved for the following parameters: left ventricular end-diastolic volume, biplane ejection fraction, mitral and aortic regurgitation, left ventricular outflow tract diameter, peak and mean aortic valve gradients, and aortic valve area. Eight hundred interreader comparisons for evaluation of reproducibility were generated from five readers interpreting 10 echocardiograms per testing cycle. The applicability and efficacy of this method were then evaluated by testing a second larger group of 10 readers and reevaluating reproducibility 1 year later. RESULTS: All readers demonstrated acceptable reproducibility for biplane ejection fraction, mitral regurgitation, and peak and mean aortic valve gradients. Acceptable reproducibility for left ventricular end-diastolic volume, aortic regurgitation, and aortic valve area was achieved by four of five readers. No readers attained acceptable reproducibility on initial evaluation of left ventricular outflow tract diameter. After review and retraining, all readers demonstrated acceptable reproducibility, which was maintained on subsequent testing 1 year later. A second larger group of 10 readers was also evaluated and yielded similar results. CONCLUSIONS: A continuous quality improvement process was devised that successfully reduced interpretative variability in echocardiography and improved reproducibility that was sustained over time.