Publications

BACKGROUND: While large scientific and medical evidence has demonstrated the increased risk of death and cardiovascular mortality in patients with severe AS, the independent contribution of moderate AS to an increased risk of death remains uncertain.

METHODS AND FINDINGS: We conducted a multicenter study including a cohort of 30,865 US patients and another cohort of 217,599 Australian patients with equivalent echocardiographic and aortic valve profiling over the same period (2003-2017). During a median 5.2 years (US) and 4.4 years (Australian) follow-up, the risk of death (hazard ratio) of patients with moderate AS as compared to those without AS was 1.66 (95%CI 1.52-1.80) and 1.37 (95%CI 1.34-1.41) in the US and Australian cohorts, even after adjusting this analysis for age and sex. This increased risk of death and cardiovascular mortality (odds ratio) in patients with moderate AS was consistent also across subgroups of left ventricular ejection fraction (LVEF) (subgroups of LVEF < 40%, 40-49%, 50-59%, and ≥ 60%: OR of moderate AS for CV mortality 2.0 [95%CI 1.4-2.7], 1.7 [95%CI 1.2-2.4], 1.5 [95%CI 1.1-1.9], and 1.4 [95%CI 1.2-1.6], respectively).

CONCLUSIONS: The findings of this study suggest that patients with moderate AS have a potential increased risk of death and cardiovascular mortality, regardless of age, sex, and LVEF. Hence, these data suggest the need to develop specific strategies to detect and treat individuals with moderate AS.

BACKGROUND: As automated echocardiographic analysis is increasingly utilized, continued evaluation within hospital settings is important to further understand its potential value. The importance of cardiac involvement in patients hospitalized with COVID-19 provides an opportunity to evaluate the feasibility and clinical relevance of automated analysis applied to limited echocardiograms.

METHODS: In this multisite US cohort, the feasibility of automated AI analysis was evaluated on 558 limited echocardiograms in patients hospitalized with COVID-19. Reliability of automated assessment of left ventricular (LV) volumes, ejection fraction (EF), and LV longitudinal strain (LS) was assessed against clinically obtained measures and echocardiographic findings. Automated measures were evaluated against patient outcomes using ROC analysis, survival modeling, and logistic regression for the outcomes of 30-day mortality and in-hospital sequelae.

RESULTS: Feasibility of automated analysis for both LVEF and LS was 87.5% (488/558 patients). AI analysis was performed with biplane method in 300 (61.5%) and single plane apical 4- or 2-chamber analysis in 136 (27.9%) and 52 (10.7%) studies, respectively. Clinical LVEF was assessed using visual estimation in 192 (39.3%), biplane in 163 (33.4%), and single plane or linear methods in 104 (21.2%) of the 488 studies; 29 (5.9%) studies did not have clinically reported LVEF. LV LS was clinically reported in 80 (16.4%). Consistency between automated and clinical values demonstrated Pearson's R, root mean square error (RMSE) and intraclass correlation coefficient (ICC) of 0.61, 11.3% and 0.72, respectively, for LVEF; 0.73, 3.9% and 0.74, respectively for LS; 0.76, 24.4ml and 0.87, respectively, for end-diastolic volume; and 0.82, 12.8 ml, and 0.91, respectively, for end-systolic volume. Abnormal automated measures of LVEF and LS were associated with LV wall motion abnormalities, left atrial enlargement, and right ventricular dysfunction. Automated analysis was associated with outcomes, including survival.

CONCLUSION: Automated analysis was highly feasible on limited echocardiograms using abbreviated protocols, consistent with equivalent clinically obtained metrics, and associated with echocardiographic abnormalities and patient outcomes.

BACKGROUND: Despite improvements in the safety of transcatheter aortic valve implantation (TAVI),  4% of patients experience a procedure-related stroke. Understanding long-term health and healthcare implications of these events may motivate the development and adoption of preventative strategies.  Aims: We aimed to assess the association of TAVI-related ischaemic stroke with subsequent clinical outcomes and healthcare utilisation.

METHODS: We used Medicare fee-for-service claims to identify patients who underwent their first TAVI between January 2012 and December 2017. Previously used ICD-9-CM and ICD-10-CM codes were used to identify TAVI-related ischaemic stroke. Among those with and without TAVI-related ischaemic stroke, we compared the risk of a composite endpoint that included all-cause mortality, acute myocardial infarction, and subsequent stroke using inverse probability treatment weighted Cox regression. We also performed a difference-in-difference analysis to compare 1-year Medicare expenditures and days spent at home during the first year after TAVI.

RESULTS:  Among 129,628 primary TAVI patients, 5,549 (4.3%) had a procedure-related stroke. These patients were more likely to be female and have had prior stroke, peripheral vascular disease, ischaemic heart disease, or renal failure. After adjustment, TAVI-related ischaemic stroke was associated with a higher risk of the 1-year composite outcome (HR 1.67, 95% CI: 1.56-1.78), higher 1-year Medicare expenditures (difference $9,245 [standard error 790], p<0.001), and fewer days at home during the first year (difference 16 days [standard error 1], p<0.001).

CONCLUSIONS: Among Medicare beneficiaries undergoing TAVI, procedure-related ischaemic stroke was associated with worse outcomes, increased Medicare expenditures, and less time spent at home. Procedure-related ischaemic stroke during TAVI remains a critically important and potentially preventable source of patient mortality, morbidity and healthcare utilisation.

The present CEUS Cardiac Exam Protocols represent the first effort to promulgate a standard set of protocols for optimal administration of ultrasound enhancing agents (UEAs) in echocardiography, based on more than two decades of experience in the use of UEAs for cardiac imaging. The protocols reflect current clinical CEUS practice in many modern echocardiography laboratories throughout the world. Specific attention is given to preparation and dosing of three UEAs that have been approved by the United States Food and Drug Administration (FDA) and additional regulatory bodies in Europe, the Americas and Asia-Pacific. Consistent with professional society guidelines (J Am Soc Echocardiogr 31:241-274, 2018; J Am Soc Echocardiogr 27:797-810, 2014; Eur Heart J Cardiovasc Imaging 18:1205, 2017), these protocols cover unapproved "off-label" uses of UEAs-including stress echocardiography and myocardial perfusion imaging-in addition to approved uses. Accordingly, these protocols may differ from information provided in product labels, which are generally based on studies performed prior to product approval and may not always reflect state of the art clinical practice or guidelines.

BACKGROUND: Aortic stenosis is the most common cardiac valve disorder requiring clinical management. However, there is little evidence on the societal cost of progressive aortic stenosis. We sought to quantify the societal burden of premature mortality associated with progressively worse aortic stenosis.

METHODS: In this observational clinical cohort study, we examined echocardiograms on native aortic valves of 98 565 men and 99 357 women aged 65 years or older across 23 sites in Australia, from Jan 1, 2003, to Dec 31, 2017. Individuals were grouped according to their peak aortic valve velocity in 0·50 m/s increments up to 4·00 m/s or more (severe aortic stenosis), using 1·00-1·99 m/s (no aortic stenosis) as the reference group. Sex-specific premature mortality and years of life lost during a 5-year follow-up were calculated, along with willingness-to-pay to regain quality-adjusted life years (QALYs).

FINDINGS: Overall, 20 701 (21·0%) men and 18 576 (18·7%) women had evidence of mild-to-severe aortic stenosis. The actual 5-year mortality in men with normal aortic valves was 32·1% and in women was 26·1%, increasing to 40·9% (mild aortic stenosis) and 52·2% (severe aortic stenosis) in men and to 35·9% (mild aortic stenosis) and 55·3% (severe aortic stenosis) in women. Overall, the estimated societal cost of premature mortality associated with aortic stenosis was AU$629 million in men and $735 million in women. Per 1000 men and women investigated, aortic stenosis was associated with eight more premature deaths in men resulting in 32·5 more QALYs lost (societal cost of $1·40 million) and 12 more premature deaths in women resulting in 57·5 more QALYs lost (societal cost of $2·48 million) when compared with those without aortic stenosis.

INTERPRETATION: Any degree of aortic stenosis in older individuals is associated with premature mortality and QALYs. In this context, there is a crucial need for cost-effective strategies to promptly detect and optimally manage this common condition within our ageing populations.

FUNDING: Edwards LifeSciences, National Health and Medical Research Council of Australia, and the National Heart, Lung, and Blood Institute.

PURPOSE OF REVIEW: Ultrasound enhancing agents (UEAs), microbubbles which are composed of lipid or albumin shells containing high molecular weight gases with nonlinear acoustic properties in the ultrasound field, are important components of the diagnostic armamentarium in echocardiography. This review highlights the substantial value of UEAs in delineating endocardial border definition and influencing downstream decision-making in cardiovascular ultrasound.

RECENT FINDINGS: In this article, we review recent updates to the clinical applications of UEAs, special circumstances regarding use, the impact of use on downstream testing and cost-effectiveness, and recommended approaches for optimizing workflow in the echocardiography laboratory with UEAs.

SUMMARY: In multiple studies, UEAs have been identified as a useful tool in echocardiography, improving study accuracy and reader confidence, while reducing downstream testing and procedures and resulting in significant changes in clinical management. Despite their proven efficacy and cost-effectiveness, recent studies have suggested utilization remains low, in part due to perceived concerns and workflow issues that impair uptake. With an increasingly broader list of indications for echocardiography, UEAs will continue to play an important role in the diagnosis and management of patients with cardiovascular and noncardiovascular diseases.

BACKGROUND: Administrative claims for aortic stenosis (AS) regurgitation may be useful, but their accuracy and ability to identify individuals at risk for valve-related outcomes have not been well characterized.

METHODS: Using echocardiographic (transthoracic echocardiogram [TTE]) reports linked to US Medicare claims, 2017 to 2018, the performance of candidate International Classification of Diseases, Tenth Revision claims to ascertain AS/aortic regurgitation was evaluated. The optimal performing algorithm was tested against outcomes at 1-year after TTE in a separate 100% sample of US Medicare claims, 2017 to 2019.

RESULTS: Of those included in the derivation (N=5497, mean age 74.4±11.0 years, 49.7% female), any AS or aortic regurgitation was present in 24% and 38.8%, respectively. The sensitivity and specificity of International Classification of Diseases, Tenth Revision code I35.0 for identification of any AS was 53.1% and 94.8%, respectively. Among those with an I35.0 code, 40.3% had severe AS. Claims were unable to distinguish disease severity (ie, severe versus nonsevere) or subtype (eg, bicuspid or rheumatic AS), and were insensitive and nonspecific for aortic regurgitation of any severity. Among all beneficiaries who received a TTE (N=4 033 844), adjusting for age, sex, and 27 comorbidities, those with an I35.0 code had a higher adjusted risk of all-cause mortality (adjusted hazard ratio, 1.33 [95% CI, 1.31-1.34]), heart failure hospitalization (adjusted hazard ratio, 1.37 [95% CI, 1.34-1.41]), and aortic valve replacement (adjusted hazard ratio, 34.96 [95% CI, 33.74-36.22]).

CONCLUSIONS: Among US Medicare beneficiaries receiving a TTE, International Classification of Diseases, Tenth Revision claims, though identifying a population at significant greater risk of valve-related outcomes, failed to identify nearly half of individuals with AS and were unable to distinguish disease severity or subtype. These results argue against the widespread use of International Classification of Diseases, Tenth Revision claims to screen for patients with AS and suggests the need for improved coding algorithms and alternative systems to extract TTE data for quality improvement and hospital benchmarking.

The association of mitral regurgitation (MR) severity and mortality in heart failure with preserved ejection fraction (HFpEF) is uncertain. We sought to evaluate the relation between MR severity on transthoracic echocardiography (TTE) and subsequent all-cause mortality in Medicare beneficiaries with HFpEF. We linked 57,608 patients referred for TTE at Beth Israel Deaconess Medical Center to Medicare inpatient claims from 2003 to 2017. In those with a history of HF and a physician-reported left ventricular ejection fraction ≥50%, we evaluated the relation of MR severity and time to the primary end point of all-cause mortality using Kaplan-Meier methods. A total of 7,778 individuals (14.5%) met inclusion criteria (mean age 75.5 years ± 11.9, 55.9% female). Over a median follow-up of 8.1 years, 2,016 (25.9%) died at a median (interquartile range) of 1.7 (0.3 to 4.1) years. At 1 year, 15.8% with 3 to 4+ MR had died versus 10.5% with 0 to 2+ MR (hazard ratio 1.54, 95% confidence interval 1.22 to 1.95, p <0.001). After multivariable adjustment, 3 to 4+ MR continued to be associated with increased all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.14 to 1.94, p = 0.004) except in the subset with atrial fibrillation (interaction p = 0.03) or recent (<3 months) HF hospitalization (p = 0.54). In conclusion, in this large, single-institution retrospective study of Medicare beneficiaries with HFpEF who underwent TTE, moderate-to-severe and severe MR were significantly associated with an increased risk of all-cause mortality after multivariable adjustment, except in those with atrial fibrillation or recent HF. Prospective studies are needed to assess the role of MR reduction in mitigating this risk.