Search

Objective: To evaluate the prevalence and natural history of mitral annulus calcification (MAC) and associated mitral valve dysfunction (MVD) in patients undergoing clinically indicated echocardiography., Methods: A retrospective review was conducted of all adults who underwent echocardiography in 2015. Mitral valve dysfunction was defined as mitral regurgitation or mitral stenosis (MS) of moderate or greater severity. All-cause mortality during 3.0 (0.4 to 4.2) years of follow-up was compared between groups stratified according to the presence of MAC or MVD., Results: Of 24,414 evaluated patients, 5502 (23%) had MAC. Patients with MAC were older (75±10 years vs 60±16 years; P<.001) and more frequently had MVD (MS: 6.6% vs 0.5% [P<.001]; mitral regurgitation without MS: 9.5% vs 6.1% [P<.001]). Associated with MS in patients with MAC were aortic valve dysfunction, female sex, chest irradiation, renal dysfunction, and coronary artery disease. Kaplan-Meier 1-year survival was 76% in MAC+/MVD+, 87% in MAC+/MVD-, 86% in MAC-/MVD+, and 92% in MAC-/MVD-. Adjusted for age, diabetes, renal dysfunction, cancer, chest irradiation, ejection fraction below 50%, aortic stenosis, tricuspid regurgitation, and pulmonary hypertension, MAC was associated with higher mortality during follow-up (adjusted hazard ratio, 1.40; 95% CI, 1.31 to 1.49; P<.001); MVD was associated with even higher mortality in patients with MAC (adjusted hazard ratio, 1.79; 95% CI, 1.58 to 2.01; P<.001). There was no significant interaction between MAC and MVD for mortality (P=.10)., Conclusion: In a large cohort of adults undergoing echocardiography, the prevalence of MAC was 23%. Mitral valve dysfunction was more than twice as prevalent in patients with MAC. Adjusted mortality was increased in patients with MAC and worse with both MAC and MVD., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: To compare breast density assessments between C-View ™ and Intelligent 2D ™ , different generations of synthesized mammography (SM) from Hologic., Methods: In this retrospective study, we identified a subset of females between March 2017 and December 2019 who underwent screening digital breast tomosynthesis (DBT) with C-View followed by DBT with Intelligent 2D. Clinical Breast Imaging Reporting and Database System breast density was obtained along with volumetric breast density measures (including density grade, breast volume, percentage volumetric density, dense volume) using Volpara TM . Differences in density measures by type of synthesized image were calculated using the pairwise t -test or McNemar's test, as appropriate., Results: 67 patients (avg age 62.7; range 40-84) were included with an average of 13.3 months between the two exams. No difference was found in Breast Imaging Reporting and Database System density between the SM reconstructions ( p = 0.74). Similarly, there was no difference in Volpara TM mean density grade ( p = 0.71), mean breast volume ( p = 0.48), mean dense volume ( p = 0.43) or mean percent volumetric density ( p = 0.12) between the exams., Conclusion: We found no significant differences in clinical and automated breast density assessments between these two versions of SM., Advances in Knowledge: Lack of differences in density estimates between the two SM reconstructions is important as density assignment impacts risk stratification and adjunct screening recommendations.

Objectives: To determine incidence trends of Staphylococcus aureus bacteremia (SAB) from population-based studies from multiple countries., Methods: A contemporary systematic review was conducted using Ovid Cochrane Central Register of Controlled Trials (1991+), Ovid Embase (1974+), Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE) (1946+ including epub ahead of print, in-process & other non-indexed citations), and Web of Science Core Collection (Science Citation Index Expanded 1975+ and Emerging Sources Citation Index 2015+). Two authors (J.R.H. and J.A.Q.M.) independently reviewed all studies and included those that reported population-based incidence of SAB in patients aged 18 years and older., Results: Twenty-six studies met inclusion criteria with the highest number (n=6) of studies conducted in Canada. The incidence of SAB ranged from 9.3 to 65 cases/100,000/year. The median age of patients with SAB ranged from 62 to 72 years and SAB cases were more commonly observed in men than in women. The most common infection sources were intravascular catheters and skin and soft tissue infections. SAB incidence trends demonstrated high variability for geographic regions and calendar years. Overall, there was no change in the incidence trend across all studies during the past two decades., Conclusion: Multiple factors, both pros, and cons are likely responsible for the overall stable SAB incidence in countries included in this systematic review. Some of these factors vary in geographic location and prompt additional investigations from countries not included in the current review so that a more global characterization is defined., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2022, Hindy et al.)

Objectives: To compare all-cause mortality in patients with mitral annulus calcification (MAC) and severe mitral valve dysfunction (MVD) who received standard mitral intervention versus no intervention., Background: Patients with MAC often have high surgical risk due to advanced age, comorbidities, and technical challenges related to calcium. The impact of a mitral intervention on outcomes of patients with MAC and severe MVD is not well known., Methods: Retrospective review of patients with MAC by transthoracic echocardiography (TTE) in 2015 at a single institution. Patients with severe mitral stenosis (MS) or regurgitation (MR) were analyzed and stratified into two groups: surgical or transcatheter intervention performed <1 year after the index TTE, and no or later intervention. The primary endpoint was all-cause mortality., Results: Of 5502 patients with MAC, 357 had severe MVD (MS = 27%, MR = 73%). Of those, 108 underwent mitral intervention (surgery = 87; transcatheter = 21). They were younger (73 ± 11 vs. 76 ± 11 years, p < 0.01) and less frequently had cardiovascular diseases compared with no-intervention. Frequency in women was similar (45% vs. 50%, p = 0.44). During median follow-up of 3.2 years, the intervention group had higher estimated survival than those without intervention (80% vs. 72% at 1 year and 55% vs. 35% at 4 year, p < 0.01). Adjusted for age, eGFR, LVEF < 50%, and pulmonary hypertension, mitral intervention was an independent predictor of lower mortality (hazard ratio = 0.66, 95% confidence interval 0.43-0.99, p = 0.046)., Conclusion: Patients with MAC and severe MVD who underwent mitral intervention <1 year from index TTE had lower mortality than those without intervention. Mitral intervention was independently associated with lower mortality., (© 2022 Wiley Periodicals LLC.)

Background: Papillary fibroelastoma (PFE) is the most common primary benign cardiac tumor. Because PFEs have the potential to embolize, they often are surgically excised. Prior studies have suggested that postoperative recurrence of PFE is rare or does not occur. We aimed to determine the rate at which PFEs recurred after surgical removal and to identify any risk factors associated with recurrence., Methods: We retrospectively identified all patients from a single center with pathologically proven PFE, treated from January 1995 through December 2018. Patients were included in the study if they had an echocardiographic examination at least 1 year after surgery. We compared echocardiographic images obtained intraoperatively (after excision) and at dismissal with those of the most recent examination to assess the possibility of PFE recurrence., Results: We included 98 patients in the study. The mean duration of follow-up was 5.4 (SD 3.7) years (range, 1 to 17); the median duration of follow-up was 4.3 years (interquartile range, 1.9 to 7.7). Twelve patients (12.2%) had echocardiographically supported PFE recurrence. Three patients had the recurrent lesion surgically reexcised, and pathologic analysis showed that two were recurrent PFEs and one was a Lambl excrescence. Initial clinical presentation of stroke or transient ischemic attack was more common for the recurrence group (for the first PFE) than for the nonrecurrence group (83% vs 26%; P < .001)., Conclusions: Contrary to findings from previous studies, PFEs do recur after surgical excision. These findings emphasize the importance of postoperative follow-up with transesophageal echocardiography for identifying recurrent masses., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Most work on the validity of clinical assessments for measuring learner performance in graduate medical education has occurred at the residency level. Minimal research exists on the validity of clinical assessments for measuring learner performance in advanced subspecialties. We sought to determine validity characteristics of cardiology fellows' assessment scores during subspecialty training, which represents the largest subspecialty of internal medicine. Validity evidence included item content, internal consistency reliability, and associations between faculty-of-fellow clinical assessments and other pertinent variables., Methods: This was a retrospective validation study exploring the domains of content, internal structure, and relations to other variables validity evidence for scores on faculty-of-fellow clinical assessments that include the 10-item Mayo Cardiology Fellows Assessment (MCFA-10). Participants included 7 cardiology fellowship classes. The MCFA-10 item content included questions previously validated in the assessment of internal medicine residents. Internal structure evidence was assessed through Cronbach's α. The outcome for relations to other variables evidence was overall mean of faculty-of-fellow assessment score (scale 1-5). Independent variables included common measures of fellow performance., Findings: Participants included 65 cardiology fellows. The overall mean ± standard deviation faculty-of-fellow assessment score was 4.07 ± 0.18. Content evidence for the MCFA-10 scores was based on published literature and core competencies. Cronbach's α was 0.98, suggesting high internal consistency reliability and offering evidence for internal structure validity. In multivariable analysis to provide relations to other variables evidence, mean assessment scores were independently associated with in-training examination scores (beta = 0.088 per 10-point increase; p = 0.05) and receiving a departmental or institutional award (beta = 0.152; p = 0.001). Assessment scores were not associated with educational conference attendance, compliance with completion of required evaluations, faculty appointment upon completion of training, or performance on the board certification exam. R 2 for the multivariable model was 0.25., Conclusions: These findings provide sound validity evidence establishing item content, internal consistency reliability, and associations with other variables for faculty-of-fellow clinical assessment scores that include MCFA-10 items during cardiology fellowship. Relations to other variables evidence included associations of assessment scores with performance on the in-training examination and receipt of competitive awards. These data support the utility of the MCFA-10 as a measure of performance during cardiology training and could serve as the foundation for future research on the assessment of subspecialty learners., (© 2022. The Author(s).)

Aims: Concurrent mitral regurgitation (MR) influences treatment considerations in patients with severe aortic stenosis (sAS). Limited information exists regarding haemodynamic effects of sAS on MR severity and outcome of these patients. We assessed the impact of aortic valve replacement (AVR) on MR according to mechanism in patients with sAS and MR., Methods and Results: In patients with sAS who received surgical or transcatheter AVR from 2008 to 2017, those with effective mitral regurgitant orifice area (ERO) ≥ 10 mm 2 prior to AVR were evaluated. The change in MR after AVR was considered significant when there was at least one grade difference. We compared the all-cause mortality of patients with and without improvement in MR. Of 234 patients with sAS and MR (age 80 ± 9 years, 52% male, ERO 19 ± 7 mm 2 ), organic and functional MR were present in 166 (71%) and 68 (29%), respectively. MR improved in 136 (58%); improvement occurred with similar frequency in organic versus functional MR (59% and 57%, P = 0.88). Associated determinants were absence of atrial fibrillation in organic MR [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.00-4.37; P = 0.049] and indexed aortic valve area (iAVA) ≤ 0.40 cm 2 in functional MR (OR 3.28, 95% CI 1.13-9.47; P = 0.028). In the overall cohort, mitral annulus diameter < 3 cm (OR 1.74, 95% CI 1.02-2.97; P = 0.041) and QRS duration < 115 ms (OR 1.73, 95% CI 1.00-2.98; P = 0.049) were independently associated with improvement in MR. During median follow-up of 3.5 years, lack of improvement in MR was not associated with higher mortality in the overall cohort of patients with ERO ≥ 20 mm 2 [adjusted hazard ratio (HR) 1.71, 95% CI 0.90-3.27; P = 0.10, adjusted for age, New York Heart Association III or IV, diabetes, and creatinine ≥ 2.0 mg/dL]. Lack of improvement in organic MR was associated with higher mortality (adjusted HR 3.36, 95% CI 1.40-8.05; P < 0.01). In patients with functional MR, change in MR was not associated with mortality (HR 1.24, 95% CI 0.44-3.47; P = 0.68)., Conclusions: In nearly 60% of patients with sAS and MR, MR improved after AVR, even in the majority of patients with organic MR. Absence of atrial fibrillation in organic MR, iAVA ≤ 0.40 cm 2 in functional MR, and mitral annulus diameter < 3 cm and QRS duration < 115 ms in the overall population were associated with MR improvement. Post-operative improvement in organic MR was associated with better survival., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background While digital breast tomosynthesis (DBT) is rapidly replacing digital mammography (DM) in breast cancer screening, the potential of DBT density measures for breast cancer risk assessment remains largely unexplored. Purpose To compare associations of breast density estimates from DBT and DM with breast cancer. Materials and Methods This retrospective case-control study used contralateral DM/DBT studies from women with unilateral breast cancer and age- and ethnicity-matched controls (September 19, 2011-January 6, 2015). Volumetric percent density (VPD%) was estimated from DBT using previously validated software. For comparison, the publicly available Laboratory for Individualized Breast Radiodensity Assessment software package, or LIBRA, was used to estimate area-based percent density (APD%) from raw and processed DM images. The commercial Quantra and Volpara software packages were applied to raw DM images to estimate VPD% with use of physics-based models. Density measures were compared by using Spearman correlation coefficients ( r ), and conditional logistic regression was performed to examine density associations (odds ratios [OR]) with breast cancer, adjusting for age and body mass index. Results A total of 132 women diagnosed with breast cancer (mean age ± standard deviation [SD], 60 years ± 11) and 528 controls (mean age, 60 years ± 11) were included. Moderate correlations between DBT and DM density measures ( r = 0.32-0.75; all P < .001) were observed. Volumetric density estimates calculated from DBT (OR, 2.3 [95% CI: 1.6, 3.4] per SD for VPD% DBT ) were more strongly associated with breast cancer than DM-derived density for both APD% (OR, 1.3 [95% CI: 0.9, 1.9] [ P < .001] and 1.7 [95% CI: 1.2, 2.3] [ P = .004] per SD for LIBRA raw and processed data, respectively) and VPD% (OR, 1.6 [95% CI: 1.1, 2.4] [ P = .01] and 1.7 [95% CI: 1.2, 2.6] [ P = .04] per SD for Volpara and Quantra, respectively). Conclusion The associations between quantitative breast density estimates and breast cancer risk are stronger for digital breast tomosynthesis compared with digital mammography. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Yaffe in this issue.

Digital mammography has seen an explosion in the number of radiomic features used for risk-assessment modeling. However, having more features is not necessarily beneficial, as some features may be overly sensitive to imaging physics (contrast, noise, and image sharpness). To measure the effects of imaging physics, we analyzed the feature variation across imaging acquisition settings (kV, mAs) using an anthropomorphic phantom. We also analyzed the intra-woman variation (IWV), a measure of how much a feature varies between breasts with similar parenchymal patterns-a woman's left and right breasts. From 341 features, we identified "robust" features that minimized the effects of imaging physics and IWV. We also investigated whether robust features offered better case-control classification in an independent data set of 575 images, all with an overall BI-RADS ® assessment of 1 (negative) or 2 (benign); 115 images (cases) were of women who developed cancer at least one year after that screening image, matched to 460 controls. We modeled cancer occurrence via logistic regression, using cross-validated area under the receiver-operating-characteristic curve (AUC) to measure model performance. Models using features from the most-robust quartile of features yielded an AUC = 0.59, versus 0.54 for the least-robust, with p < 0.005 for the difference among the quartiles.

Background: Suppression of tumorigenicity 2 (ST2) has important cardiovascular prognostic value in community patients; however, previous analyses have utilized non-sex specific cut-off values. We assessed whether sex-specific ST2 cut-off values would improve the prognostic utility of ST2 in the asymptomatic community., Methods: A total of 2042 participants underwent clinical assessment and echocardiographic evaluation. Baseline measurements of high sensitivity troponin, natriuretic peptides and ST2 were obtained in 1681 individuals. ST2, cardiac biomarkers and associated co-morbidities were evaluated by sex-specific ST2 quartile analysis. ST2 concentrations were also analysed as dichotomous variables defined as being above the sex-specific cut-off for each the outcomes of heart failure (HF), major adverse cardiac event (MACE) and mortality., Results: Median ST2 concentration was 29.4 ng/mL in male subjects and 24.1 ng/mL in female subjects. Higher ST2 concentrations were associated with incident HF ( p <0.001; preserved ejection fraction (EF) p <0.001, reduced EF p =0.23), MACE ( p =0.003) and mortality ( p <0.001) across sex-specific quartiles. Event-based, hazard ratio (HR) analysis revealed sex-specific ST2 cut-offs were significantly more predictive of incident HF, MACE and mortality compared to non-sex-specific analysis even following adjustment for cardiac co-morbidities and traditional biomarkers., Conclusions: These data suggest that sex-specific cut-offs, greater than non-sex specific cut-offs, significantly impact the prognostic value of the biomarker ST2 in the asymptomatic community cohort.Clinical SignificanceSuppression of tumorigenicity 2 (ST2) is a biomarker which has known associations with heart failure (HF), major adverse cardiac events (MACEs) and mortality in the general population.Recent data support the concept of sex-specific cut off values and individualized approaches based on sex to predict cardiovascular disease. Given the difference in pathobiology between the sexes, the fact that such approaches improve risk stratification is understandable. Thus, when sex-specific treatments are developed, this may similarly lead to improved outcomes.The use of sex-specific ST2 cut-off values significantly improved the prognostic value in predicting HF, MACE, and mortality in an asymptomatic community. This prognostication was particularly strong for HF with preserved ejection fraction and remained clinically significant following adjustment for cardiac co-morbidities and other traditional cardiac biomarkers (NTproBNP and hscTnI).

Importance: Heart failure (HF) with preserved ejection fraction (HFpEF) is common, is frequently associated with ventricular wall thickening, and has no effective therapy. Transthyretin amyloid cardiomyopathy (ATTR-CM) can cause the HFpEF clinical phenotype, has highly effective therapy, and is believed to be underrecognized., Objective: To examine the prevalence of ATTR-CM without and with systematic screening in patients with HFpEF and ventricular wall thickening., Design, Setting, and Participants: This population-based cohort study assessed ATTR-CM prevalence in 1235 consecutive patients in southeastern Minnesota with HFpEF both without (prospectively identified cohort study) and with (consenting subset of cohort study, n = 286) systematic screening. Key entry criteria included validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In this community cohort of 1235 patients, 884 had no known ATTR-CM, contraindication to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in the screening study. Of these 884 patients, 295 consented and 286 underwent scanning between October 5, 2017, and March 9, 2020 (community screening cohort)., Exposures: Medical record review or technetium Tc 99m pyrophosphate scintigraphy and reflex testing for ATTR-CM diagnosis., Main Outcomes and Measures: The ATTR-CM prevalence by strategy (clinical diagnosis or systematic screening), age, and sex., Results: A total of 1235 patients participated in the study, including a community cohort (median age, 80 years; interquartile range, 72-87 years; 630 [51%] male) and a community screening cohort (n = 286; median age, 78 years; interquartile range, 71-84 years; 149 [52%] male). In the 1235 patients in the community cohort without screening group, 16 patients (1.3%; 95% CI, 0.7%-2.1%) had clinically recognized ATTR-CM. The prevalence was 2.5% (95% CI, 1.4%-4.0%) in men and 0% (95% CI, 0.0%-0.6%) in women. In the 286 patients in the community screening cohort, 18 patients (6.3%; 95% CI, 3.8%-9.8%) had ATTR-CM. Prevalence increased with age from 0% in patients 60 to 69 years of age to 21% in patients 90 years and older (P < .001). Adjusting for age, ATTR-CM prevalence differed by sex, with 15 of 149 men (10.1%; 95% CI, 5.7%-16.1%) and 3 of 137 women (2.2%; 95% CI, 0.4%-6.3%) having ATTR-CM (P = .002)., Conclusions and Relevance: In this cohort study based in a community-based setting, ATTR-CM was present in a substantial number of cases of HFpEF with ventricular wall thickening, particularly in older men. These results suggest that systematic evaluation can increase the diagnosis of ATTR-CM, thereby providing therapeutically relevant phenotyping of HFpEF.

Background: The follow-up of implantable cardioverter-defibrillators (ICDs) generates large amounts of valuable structured and unstructured data embedded in device interrogation reports., Objective: We aimed to build a natural language processing (NLP) model for automated capture of ICD-recorded events from device interrogation reports using a single-center cohort of patients with hypertrophic cardiomyopathy (HCM)., Methods: A total of 687 ICD interrogation reports from 247 HCM patients were included. Using a derivation set of 480 reports, we developed a rule-based NLP algorithm based on unstructured (free-text) data from the interpretation field of the ICD reports to identify sustained atrial and ventricular arrhythmias, and ICD therapies. A separate model based on structured numerical tabulated data was also developed. Both models were tested in a separate set of the 207 remaining ICD reports. Diagnostic performance was determined in reference to arrhythmia and ICD therapy annotations generated by expert manual review of the same reports., Results: The NLP system achieved sensitivity 0.98 and 0.99, and F1-scores 0.98 and 0.92 for arrhythmia and ICD therapy events, respectively. In contrast, the performance of the structured data model was significantly lower with sensitivity 0.33 and 0.76, and F1-scores 0.45 and 0.78, for arrhythmia and ICD therapy events, respectively., Conclusion: An automated NLP system can capture arrhythmia events and ICD therapies from unstructured device interrogation reports with high accuracy in HCM. These findings demonstrate the feasibility of an NLP paradigm for the extraction of data for clinical care and research from ICD reports embedded in the electronic health record.

Aim: To provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe., Methods: A systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence., Results: Of 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%., Conclusion: Based on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase., Trial Registeration Number: CRD42020191196., Competing Interests: Competing interests: LMB, M.D. reports Boston Scientific, consultant duties; UpToDate, royalty payments (authorship duties); Botanix Pharmaceuticals, consulting duties; Roivant Sciences, consultant duties. MRS, M.D. reports receiving funds from TYRX and Medtronic for prior research unrelated to this study administered according to a sponsored research agreement between Mayo Clinic and study sponsor that prospectively defined the scope of the research effort and corresponding budget; and honoraria/consulting fees from Medtronic, Philips and Aziyo Biologics. Research Grant: Medtronic. MJD, M.B.B.S. reports payments from Biotronik unrelated to this study. IMT, M.D. reports UpToDate, royalty payments (authorship duties). The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To validate an artificial intelligence-augmented electrocardiogram (AI-ECG) algorithm for the detection of preclinical left ventricular systolic dysfunction (LVSD) in a large community-based cohort., Methods: We identified a randomly selected community-based cohort of 2041 subjects age 45 years or older in Olmsted County, Minnesota. All participants underwent a study echocardiogram and ECG. We first assessed the performance of the AI-ECG to identify LVSD (ejection fraction ≤40%). After excluding participants with clinical heart failure, we further assessed the AI-ECG to detect preclinical LVSD among all patients (n=1996) and in a high-risk subgroup (n=1348). Next we modelled an imputed screening program for preclinical LVSD detection where a positive AI-ECG triggered an echocardiogram. Finally, we assessed the ability of the AI-ECG to predict future LVSD. Participants were enrolled between January 1, 1997, and September 30, 2000; and LVSD surveillance was performed for 10 years after enrollment., Results: For detection of LVSD in the total population (prevalence, 2.0%), the area under the receiver operating curve for AI-ECG was 0.97 (sensitivity, 90%; specificity, 92%); in the high-risk subgroup (prevalence 2.7%), the area under the curve was 0.97 (sensitivity, 92%; specificity, 93%). In an imputed screening program, identification of one preclinical LSVD case would require 88.3 AI-ECGs and 8.7 echocardiograms in the total population and 65.7 AI-ECGs and 5.5 echocardiograms in the high-risk subgroup. The unadjusted hazard ratio for a positive AI-ECG for incident LVSD over 10 years was 2.31 (95% CI, 1.32 to 4.05; P=.004)., Conclusion: Artificial intelligence-augmented ECG can identify preclinical LVSD in the community and warrants further study as a screening tool for preclinical LVSD., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to characterize urinary and plasma C-type natriuretic peptide (CNP) in acute decompensated heart failure (ADHF) to define their relationship with clinical variables and to determine whether urinary and plasma CNP together add prognostic value., Background: CNP is a protective hormone that is synthesized in the kidney and endothelium and possesses antiremodeling properties. Urinary and plasma CNP levels are elevated in pathophysiological conditions; however, their regulation and prognostic value in heart failure (HF) is unclear., Methods: Urinary and plasma CNP were measured in 109 healthy subjects and 208 patients with ADHF; the 95th percentile of CNP values from healthy subjects established the normal contemporary cutoffs. Patients with ADHF were stratified based on urinary and plasma CNP levels for clinical characterization and the assessment of risk for adverse outcomes., Results: There was no significant correlation between urinary and plasma CNP in both cohorts. Urinary and plasma CNP were significantly elevated in patients with ADHF, and both increased with disease severity and were positively correlated with plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP). Of the patients with ADHF, 23% had elevations in both urinary and plasma CNP, whereas 24% had normal CNP levels. During a median follow-up of 3 years, patients with elevated urinary and plasma CNP had a significantly higher risk of rehospitalization and/or death (HR: 1.79; P = 0.03) and rehospitalization (HR: 2.16; P = 0.01) after adjusting for age, sex, left ventricular ejection fraction, renal function, and plasma NT-proBNP. The C-statistic and integrated discrimination analyses further supported that the addition of urinary and plasma CNP to established risk models improved the prediction of adverse outcomes in patients with ADHF., Conclusions: Urinary and plasma CNP are differentially regulated in ADHF, and elevations in both provided independent prognostic value for predicting adverse outcomes., Competing Interests: Funding Support and Funding Disclosures This work was supported by National Heart, Lung and Blood Institute grants R01 HL36634 (to Dr Burnett) and R01 HL132854 (to Dr Sangaralingham). This work was also supported by the Division of Circulatory Failure, Department of Cardiovascular Medicine at Mayo Clinic and the Mayo Foundation. Drs Ma, Y. Chen, H. Chen, Burnett, and Sangaralingham, and the Mayo Foundation have issued or filed patents for assessing the use of CNP as well as for natriuretic peptide-based or particulate guanylyl cyclase enhancing therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To examine contemporary clinical differences between men and women with hemodynamically significant chronic aortic regurgitation (AR)., Patients and Methods: We retrospectively identified 1072 consecutive patients with moderate to severe or severe AR diagnosed between February 21, 2004, and April 29, 2019. Echocardiographic data, aortic valve surgical intervention (AVS), and all-cause death were analyzed., Results: At baseline, the 189 women in the study group were older than the 883 men (mean ± SD age, 64±18 years vs 58±17 years), had more advanced symptoms, and had larger left ventricular end-systolic dimension index (LVESDi) (all P<.001) despite similar AR severity. An LVESDi of greater than 20 mm/m 2 was noted in 60 of 92 asymptomatic women (65%) vs 225 of 559 asymptomatic men (40%) (P<.001). Median follow-up was 5.6 years (interquartile range, 2.5 to 10.0 years). Female sex was associated with less AVS (P=.009), and overall 10-year survival was better in men (76%±2%) than in women (64%±5%) (P=.004). However, 10-year post-AVS survival was similar between the sexes (P=.86), and women had better left ventricular reverse remodeling than men regarding end-diastolic dimension (P=.02). Multivariable independent predictors of death were age, advanced symptoms, LVESDi, ejection fraction, and AVS (all P≤.03) but not female sex. When compared with the age-matched US population, women exhibited a 1.3-fold increased relative risk of death (P=.0383) while men had similar survival (P=.11)., Conclusion: In contemporary practice, women with AR continue to exhibit an overall survival penalty not related to female sex but to late referral markers, including more advanced symptoms, larger LVESDi, and less AVS. Nonetheless, women in our study exhibited outstanding post-AVS left ventricular remodeling and had good post-AVS survival, a step forward toward closing the sex-related mortality gap. The high percentage of LVESDi of 20 mm/m 2 or greater in asymptomatic women represents a window of opportunity for advanced-symptom prevention and timely AR surgical correction that may close the mortality gap., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

OBJECTIVE. Our previous work showed that variation measures, which represent breast architecture derived from mammograms, were significantly associated with breast cancer. For replication purposes, we examined the association of three variation measures (variation [V], which is measured in the image domain, and P 1 and p 1 [a normalized version of P 1 ], which are derived from restricted regions in the Fourier domain) with breast cancer risk in an independent population. We also compared these measures to volumetric density measures (volumetric percent density [VPD] and dense volume [DV]) from a commercial product. MATERIALS AND METHODS. We examined 514 patients with breast cancer and 1377 control patients from a screening practice who were matched for age, date of examination, mammography unit, facility, and state of residence. Spearman rank-order correlation was used to evaluate the monotonic association between measures. Breast cancer associations were estimated using conditional logistic regression, after adjustment for age and body mass index. Odds ratios were calculated per SD increment in mammographic measure. RESULTS. These variation measures were strongly correlated with VPD (correlation, 0.68-0.80) but not with DV (correlation, 0.31-0.48). Similar to previous findings, all variation measures were significantly associated with breast cancer (odds ratio per SD: 1.30 [95% CI, 1.16-1.46] for V, 1.55 [95% CI, 1.35-1.77] for P 1 , and 1.51 [95% CI, 1.33-1.72] for p 1 ). Associations of volumetric density measures with breast cancer were similar (odds ratio per SD: 1.54 [95% CI, 1.33-1.78] for VPD and 1.34 [95% CI, 1.20-1.50] for DV). When DV was included with each variation measure in the same model, all measures retained significance. CONCLUSION. Variation measures were significantly associated with breast cancer risk (comparable to the volumetric density measures) but were independent of the DV.

Background We aimed to provide personalized risk estimates for cardiac events (CEs) and life-threatening events in women with either type 1 or type 2 long QT. Methods and Results The prognostic model was derived from the Rochester Long QT Syndrome Registry, comprising 767 women with type 1 long QT (n=404) and type 2 long QT (n=363) from age 15 through 60 years. The risk prediction model included the following variables: genotype/mutation location, QTc-specific thresholds, history of syncope, and β-blocker therapy. A model was developed with the end point of CEs (syncope, aborted cardiac arrest, or long QT syndrome-related sudden cardiac death), and was applied with the end point of life-threatening events (aborted cardiac arrest, sudden cardiac death, or appropriate defibrillator shocks). External validation was performed with data from the Mayo Clinic Genetic Heart Rhythm Clinic (N=467; type 1 long QT [n=286] and type 2 long QT [n=181]). The cumulative follow-up duration among the 767 enrolled women was 22 243 patient-years, during which 323 patients (42%) experienced ≥1 CE. Based on genotype-phenotype data, we identified 3 risk groups with 10-year projected rates of CEs ranging from 15%, 29%, to 51%. The corresponding 10-year projected rates of life-threatening events were 2%, 5%, and 14%. C statistics for the prediction model for the 2 respective end points were 0.68 (95% CI 0.65-0.71) and 0.71 (95% CI 0.66-0.76). Corresponding C statistics for the model in the external validation Mayo Clinic cohort were 0.65 (95% CI 0.60-0.70) and 0.77 (95% CI 0.70-0.84). Conclusions This is the first risk prediction model that provides absolute risk estimates for CEs and life-threatening events in women with type 1 or type 2 long QT based on personalized genotype-phenotype data. The projected risk estimates can be used to guide female-specific management in long QT syndrome.

Objective: To identify an efficacious intervention on treating adolescents with overweight and obesity, this might result in health benefits. Methods: Adolescents with overweight or obesity aged 10-17 years with BMI percentile ≥85th were included in this historical observational analysis. Subjects used an entirely remote weight loss program combining mobile applications, frequent self-weighing, and calorie restriction with meal replacement. Body weight changes were evaluated at 42, 60, 90, and 120 days using different metrics including absolute body weight, BMI, and BMI z-score. Chi-square or Fisher exact tests (categorical variables) and Student's t -test (continuous variables) were used to compare subjects. Results: In total, 2,825 participants, mean age 14.4 ± 2.2 years, (54.8% girls), were included from October 27, 2016, to December 31, 2017, in mainland China; 1355 (48.0%) had a baseline BMI percentile ≥97th. Mean BMI and BMI z-score were 29.20 ± 4.44 kg/m 2 and 1.89 ± 0.42, respectively. At day 120, mean reduction in body weight, BMI, and BMI z-score was 8.6 ± 0.63 kg, 3.13 ± 0.21 kg/m 2 , and 0.42 ± 0.03; 71.4% had lost ≥5% body weight, 69.4% of boys and 73.2% of girls, respectively. Compared with boys, girls achieved greater reduction on BMI z-score at all intervals ( p  < 0.004 for all comparisons). Higher BMI percentile at baseline and increased frequency of use of the mobile application were directly associated with more significant weight loss. Conclusions: An entirely remote digital weight loss program is effective in facilitating weight loss in adolescents with overweight or obesity in the short term and mid term.

Background: Atrial fibrillation (AF) is a low-flow state and may underestimate aortic stenosis (AS) severity. Single-high Doppler signals (HS) consistent with severe AS (peak velocity ≥4 m/s or mean gradient ≥40 mm Hg) are averaged down in current practice. The objective for the study was to determine the significance of HS in AF low-gradient AS (LGAS)., Methods: One thousand five hundred forty-one patients with aortic valve area ≤1 cm 2 and left ventricular ejection fraction ≥50% were identified and classified as high-gradient AS (HGAS) (≥40 mm Hg) and LGAS (<40 mm Hg), and AF versus sinus rhythm (SR). Available computed tomography aortic valve calcium scores (AVCS) were retrieved from the medical record. Outcomes were assessed., Results: Mean age was 76±11 years, female 47%. Mean gradient was 51±12 in SR-HGAS, 48±10 in AF-HGAS, 31±5 in SR-LGAS, and 29±7 mm Hg in AF-LGAS, all P ≤0.001 versus SR-HGAS; HS were present in 33% of AF-LGAS. AVCS were available in 34%. Compared with SR-HGAS (2409 arbitrary units; interquartile range, 1581-3462) AVCS were higher in AF-HGAS (2991 arbitrary units; IQR1978-4229, P =0.001), not different in AF-LGAS (2399 arbitrary units; IQR1817-2810, P =0.47), and lower in SR-LGAS (1593 arbitrary units; IQR945-1832, P <0.001); AVCS in AF-LGAS were higher when HS were present ( P =0.048). Compared with SR-HGAS, the age-, sex-, comorbidity index-, and time-dependent aortic valve replacement-adjusted mortality risk was higher in AF-HGAS (hazard ratio=1.82 [1.40-2.36], P <0.001) and AF-LGAS with HS (hazard ratio=1.54 [1.04-2.26], P =0.03) but not different in AF-LGAS without HS or SR-LGAS (both P =not significant)., Conclusions: Severe AS was common in AF-LGAS. AVCS in AF-LGAS were not different from SR-HGAS. AVCS were higher and mortality worse in AF-LGAS when HS were present.

Objectives: This study sought to compare aortic stenosis (AS) progression rates, AS-related cardiac damage (AS-CD) indicator incidence and determinants, and survival between patients with tricuspid aortic valve (TAV)-AS and those with bicuspid aortic valve (BAV)-AS., Background: Differences in AS progression and AS-CD between patients with BAV and patients with TAV are unknown., Methods: We retrospectively studied consecutive patients with baseline peak aortic valve velocity (peakV) ≥2.5 m/s and left ventricular ejection fraction ≥50%. Follow-up echocardiograms (n = 4,818) provided multiparametric AS progression rates and AS-CD., Results: The study included 330 BAV (age 54 ± 14 years) and 581 patients with TAV (age 72 ± 11 years). At last echocardiogram (median: 5.9 years; interquartile range: 3.9 to 8.5 years), BAV-AS exhibited similar peakV and mean pressure gradient (MPG) as TAV-AS, but larger calculated aortic valve area due to larger aortic annulus (p < 0.0001). Multiparametric progression rates were similar between BAV-AS and TAV-AS (all p ≥ 0.08) and did not predict age-/sex-adjusted survival (p ≥ 0.45). Independent determinants of rapid progression were male sex and baseline AS severity for TAV (all p ≤ 0.024), and age, baseline AS severity, and cardiac risk factors (age interaction: p = 0.02) for BAV (all p ≤ 0.005). At 12 years, patients with TAV-AS had a higher incidence of AS-CD than BAV-AS patients (p < 0.0001), resulting in significantly worse survival compared to BAV-AS (p < 0.0001). AS-CD were independently determined by multiple factors (MPG, age, sex, comorbidities, cardiac function; all p ≤ 0.039), and BAV was independently protective of most AS-CD (all p ≤ 0.05)., Conclusions: In this cohort, TAV-AS and BAV-AS progression rates were similar. Rapid progression did not affect survival and was determined by cardiac risk factors for BAV-AS (particularly in patients with BAV <60 years of age) and unmodifiable factors for TAV-AS. AS-CD and mortality were significantly higher in TAV-AS. Independent determinants of AS-CD were multifactorial, and BAV morphology was AS-CD protective. Therefore, the totality of AS burden (cardiac damage) is clinically crucial for TAV-AS, whereas attention to modifiable risk factors may be preventive for BAV-AS., Competing Interests: Funding Support and Author Disclosures Internal funding has been received from the Mayo Clinic Department of Cardiovascular Medicine. All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To comprehensively explore contemporary differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with chronic haemodynamically significant aortic regurgitation (AR)., Methods: Consecutive patients with chronic ≥moderate-severe AR from a tertiary referral centre (2006-2017) were included. All-cause mortality, surgical indications and aortic valve surgery (AVS) were analysed., Results: Of 798 patients (296 BAV-AR, age 46±14 years; 502 TAV-AR, age 67±14 years, p<0.0001) followed for 5.5 (IQR: 2.9-9.2) years, 403 underwent AVS (repair in 96) and 154 died during follow-up. The 8-year AVS incidence was 60%±3% versus 53%±3% for BAV-AR and TAV-AR, respectively (p=0.014). The unadjusted (real-life) 8-year total survival was 93%±7% versus 71%±2% for BAV-AR and TAV-AR, respectively (p<0.0001), and became statistically insignificant after sole adjustment for age (p=0.14). The within-group relative risk of death in BAV-AR patients demonstrated a large age-dependent increase (two fold at 50-55 years, up to 10-fold at 70 years). The presence of baseline symptoms was significantly associated with death for both BAV-AR (p=0.039) and TAV-AR (p<0.0001), but the strength of the association decreased with age adjustment for BAV-AR (age-adjusted HR 2.43 (0.92-6.39), p=0.07) and not for TAV-AR (age-adjusted HR, 2.3 (1.6-3.3), p<0.0001). As compared with general population, TAV-AR exhibited baseline excess risk which further increased at left ventricular ejection fraction (LVEF) <60% and left ventricular end-systolic dimension index (LVESDi) >20 mm/m 2 ; similar thresholds were observed for BAV-AR patients., Conclusion: BAV-AR patients were two decades younger than TAV-AR and underwent AVS more frequently, resulting in a considerable real-life survival advantage for BAV-AR that was determined primarily by age and not valve anatomy. Pragmatically, regardless of valve anatomy, patients with haemodynamically significant AR and age >50-55 years require a low-threshold for surgical referral to prevent symptom development where LVEF <60% and LVESDi >20 mm/m 2 seem appropriate referral thresholds., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and predominantly affects facial and shoulder girdle muscles. Previous case reports and cohort studies identified minor cardiac abnormalities in FSHD patients, but their nature and frequency remain incompletely characterized. Methods: We reviewed cardiac, neurological and genetic findings of 104 patients with genetically confirmed FSHD. Results: The most common conduction abnormality was complete (7%) or incomplete (5%) right bundle branch block (RBBB). Bifascicular block, left anterior fascicular block, complete atrioventricular block, and 2:1 atrioventricular block each occurred in 1% of patients. Atrial fibrillation or flutter were seen in 5% of patients. Eight percent of patients had heart failure with reduced ejection fraction and 25% had valvular disease. The latter included aortic stenosis in 6% (severe in 4% and moderate in 2%) and moderate aortic regurgitation in 8%. Mitral valve prolapse (MVP) was present in 9% of patients without significant mitral regurgitation. There were no significant associations between structural or conduction abnormalities and age, degree of muscle weakness, or size of the 4q deletion. Conclusions: Both structural and conduction abnormalities can occur in FSHD. The most common abnormalities are benign (RBBB and MVP), but more significant cardiac involvement was also observed. The presence of cardiac abnormalities cannot be predicted from the severity of the neurological phenotype, nor from the genotype., Competing Interests: GL has received fees from the Pfizer Speaker's bureau. However, there was no involvement in this study in any way. VKS has served as a consultant to U-Health, GlaxoSmithKline, Price Waterhouse Coopers, Rhonda Gray, Dane Garvin, Philips, ResMed, Sorin Inc., and is working with Mayo Health Solutions and their industry partners on intellectual property related to sleep and cardiovascular disease. The Mayo Foundation has received a gift from the Philips Respironics Foundation for the study of sleep and cardiovascular disease. MM receives an honorarium to serve as associate editor of Neurology Genetics. However, none of these entities were involved in this study in any way. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ducharme-Smith, Nicolau, Chahal, Ducharme-Smith, Rehman, Jaliparthy, Khan, Scott, St Louis, Liewluck, Somers, Lin, Brady and Milone.)

Purpose: We evaluated the association of percent mammographic density (PMD), absolute dense area (DA), and non-dense area (NDA) with risk of "intrinsic" molecular breast cancer (BC) subtypes., Methods: We pooled 3492 invasive BC and 10,148 controls across six studies with density measures from prediagnostic, digitized film-screen mammograms. We classified BC tumors into subtypes [63% Luminal A, 21% Luminal B, 5% HER2 expressing, and 11% as triple negative (TN)] using information on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. We used polytomous logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CI) for density measures (per SD) across the subtypes compared to controls, adjusting for age, body mass index and study, and examined differences by age group., Results: All density measures were similarly associated with BC risk across subtypes. Significant interaction of PMD by age (P = 0.001) was observed for Luminal A tumors, with stronger effect sizes seen for younger women < 45 years (OR = 1.69 per SD PMD) relative to women of older ages (OR = 1.53, ages 65-74, OR = 1.44 ages 75 +). Similar but opposite trends were seen for NDA by age for risk of Luminal A: risk for women: < 45 years (OR = 0.71 per SD NDA) was lower than older women (OR = 0.83 and OR = 0.84 for ages 65-74 and 75 + , respectively) (P < 0.001). Although not significant, similar patterns of associations were seen by age for TN cancers., Conclusions: Mammographic density measures were associated with risk of all "intrinsic" molecular subtypes. However, findings of significant interactions between age and density measures may have implications for subtype-specific risk models.

BACKGROUND. Background parenchymal uptake (BPU) on molecular breast imaging (MBI) was identified in a case-control study as a breast cancer risk factor beyond mammographic density. To our knowledge, this finding has not yet been confirmed in a cohort study. OBJECTIVE. The objectives of this study were to examine the association of BPU with breast cancer and to estimate the absolute risk and discriminatory accuracy of BPU in a cohort study. METHODS. A retrospective cohort was established that included women without a history of breast cancer who underwent MBI from 2004 to 2015. Radiologists who were blinded to future breast cancer diagnoses assessed BPU on baseline MBI examinations as low (photopenic or minimal) or elevated (mild, moderate, or marked). Associations of BPU with breast cancer were estimated using multivariable Cox proportional hazards models of the time to diagnosis. The 5-year absolute risk was calculated for study subgroups. The discriminatory accuracy of BPU was also assessed. RESULTS. Among 2992 women (mean age, 56.3 years; SD, 10.6 years) who underwent MBI, breast cancer events occurred in 144 women (median follow-up, 7.3 years). Median time to diagnosis after MBI was 4.2 years (range, 0.5-11.6 years). Elevated BPU was associated with a greater breast cancer risk (hazard ratio [HR], 2.39; 95% CI, 1.68-3.41; p ≤ .001). This association remained in postmenopausal women (HR, 3.50; 95% CI, 2.31-5.31; p < .001) but was not significant in premenopausal women (HR, 1.29; 95% CI, 0.72-2.32; p = .39). The 5-year absolute risk of breast cancer was 4.3% (95% CI, 2.9-5.7%) for women with elevated BPU versus 2.5% (95% CI, 1.8-3.1%) for those with low BPU. Postmenopausal women with dense breasts and elevated BPU had a 5-year absolute risk of 8.1% (95% CI, 4.3-11.8%) versus 2.8% (1.8-3.8%) for those with low BPU. Among postmenopausal women, discriminatory accuracy for invasive cancer was improved with the addition of BPU versus use of the Gail risk score alone (C statistic, 65.1 vs 59.1; p = .04) or use of the Breast Cancer Surveillance Consortium risk score alone (C statistic, 66.4 vs 60.4; p = .04). CONCLUSION. BPU on MBI is an independent risk factor for breast cancer, with the strongest association observed among postmenopausal women with dense breasts. In postmenopausal women, BPU provides incremental discrimination in predicting breast cancer when combined with either the Gail model or the Breast Cancer Surveillance Consortium model. CLINICAL IMPACT. Observation of elevated BPU on MBI may identify a subset of women with dense breasts who would benefit most from supplemental screening or preventive options.

Background: The aims of this study are to evaluate the rate of progression of preclinical (Stage A and B) heart failure, identify associated characteristics, and evaluate long-term outcomes., Methods: Retrospective review of the Olmsted County Heart Function Study. Individuals categorized as Stage A or B heart failure at initial visit that returned for a second visit 4 years later were included. Logistic regression analyses evaluated group differences with adjustment for age and sex., Results: At visit 1, 413 (32%) individuals were classified as Stage A and 413 (32%) as Stage B. By visit 2, 146 (35%) individuals from Stage A progressed with the vast majority (n=142) progressing to Stage B. In comparison, a total of 23 (6%) individuals progressed from Stage B. A greater rate of progression was seen for Stage A compared with Stage B (8.7 per 100 person-years [95% CI, 7.4-10.2] versus 1.4 per 100 person-years [95% CI, 0.9-2.1]; P <0.001). NT-proBNP correlated with progression for Stage B ( P =0.01), but not for Stage A ( P =0.39). A multivariate model found female sex (odds ratio, 1.65 [95% CI, 1.05-2.58]; P =0.03), increased E/e' (odds ratio, 1.13 [95% CI, 1.02-1.26], P =0.02), and beta blocker use (odds ratio, 2.19 [95% CI, 1.25-3.82], P =0.006) were associated with progression for Stage A. There was a signal that cardiovascular mortality was higher in individuals who progressed, although not statistically significant ( P =0.06 for Stage A and P =0.05 for Stage B)., Conclusions: There is significant progression of preclinical heart failure in a community population, with progression rates higher for Stage A. NT-proBNP correlated with progression for Stage B, but not for Stage A. No statistically significant differences in long-term outcomes were seen. Study results have clinical implications important to help guide future heart failure screening and prevention strategies.

Background: We have demonstrated that a neural network is able to predict a person's age from the electrocardiogram (ECG) [artificial intelligence (AI) ECG age]. However, some discrepancies were observed between ECG-derived and chronological ages. We assessed whether the difference between AI ECG and chronological age (Age-Gap) represents biological ageing and predicts long-term outcomes., Methods and Results: We previously developed a convolutional neural network to predict chronological age from ECGs. In this study, we used the network to analyse standard digital 12-lead ECGs in a cohort of 25 144 subjects ≥30 years who had primary care outpatient visits from 1997 to 2003. Subjects with coronary artery disease, stroke, and atrial fibrillation were excluded. We tested whether Age-Gap was correlated with total and cardiovascular mortality. Of 25 144 subjects tested (54% females, 95% Caucasian) followed for 12.4 ± 5.3 years, the mean chronological age was 53.7 ± 11.6 years and ECG-derived age was 54.6 ± 11 years ( R 2 = 0.79, P < 0.0001). The mean Age-Gap was small at 0.88 ± 7.4 years. Compared to those whose ECG-derived age was within 1 standard deviation (SD) of their chronological age, patients with Age-Gap ≥1 SD had higher all-cause and cardiovascular disease (CVD) mortality. Conversely, subjects whose Age-Gap was ≤1 SD had lower all-cause and CVD mortality. Results were unchanged after adjusting for CVD risk factors and other survival influencing factors., Conclusion: The difference between AI ECG and chronological age is an independent predictor of all-cause and cardiovascular mortality. Discrepancies between these possibly reflect disease independent biological ageing., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Aortic regurgitation (AR) is a common valvular lesion associated with increased mortality once the left ventricle enlarges significantly or develops systolic dysfunction (ejection fraction < 50%). Valve guidelines recommend aortic valve repair or replacement (AVR) for left ventricular (LV) linear end-systolic dimension ≥ 50 mm or end-diastolic dimension ≥ 65 mm. However, chamber quantification guidelines recommend using LV volume for LV size determination because linear measurements may not accurately reflect LV remodeling. The aim of this study was to evaluate the correlation of LV volumes with linear dimensions, interobserver variability in the estimation of volumes, and the association of volumes with outcomes in patients with AR., Methods: A total of 1,100 consecutive patients with chronic moderate to severe and severe AR on echocardiography between 2004 and 2019 were retrospectively analyzed. The modified Simpson disk summation method was used for LV volume estimation. The primary outcome was all-cause mortality; the secondary outcome was mortality censored at AVR., Results: Patients' age was 60 ± 17 years, and 198 were women (18%). Volumes were measured using the biplane method in 939 patients (85%) and the monoplane method in 161 (15%); end-systolic volume was normal in 169 (11%). Correlations between volumes and linear dimensions were 0.5 for end-diastolic volume and 0.6 for end-systolic volume. At median follow-up of 5.4 years (interquartile range, 2.4-10.0 years), 216 patients had died and 539 had undergone AVR. Indexed LV end-systolic volume (iLVESV) and indexed left ventricular end-systolic dimension were both associated with mortality and symptoms, but the association of iLVESV was stronger. iLVESV, age, male gender, Charlson comorbidity index, New York Heart Association functional class III or IV, and time-dependent AVR were independently associated with all-cause mortality. Interobserver variability in the estimation of LV volumes in 200 patients included intraclass coefficients of 0.94 (95% CI, 0.92-0.95) for end-diastolic volume and 0.88 (95% CI, 0.78-0.93) for end-systolic volume. Patients with iLVESV ≥ 45 mL/m 2 had lower survival and a higher prevalence of symptoms than those with volumes < 45 mL/m 2 ., Conclusions: Echocardiographic LV volume assessment had good reproducibility in patients with moderate to severe and severe AR. The correlation between linear dimensions and volumes was limited. Both iLVESV and indexed left ventricular end-systolic dimension were associated with worse outcomes, but the association of iLVESV was stronger. iLVESV ≥ 45 mL/m 2 was associated with worse outcomes., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

[Figure: see text].

Objective: To characterize the clinical and transthoracic echocardiographic features and 30-day outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19)., Methods: Retrospective cohort study that included consecutive inpatients with COVID-19 infection who underwent clinically indicated transthoracic echocardiography at 10 sites in the Mayo Clinic Health System between March 10 and August 5, 2020. Echocardiography was performed at bedside by cardiac sonographers according to an abbreviated protocol. Echocardiographic results, demographic characteristics, laboratory findings, and clinical outcomes were analyzed., Results: There were 179 patients, aged 59.8±16.9 years and 111 (62%) men; events within 30 days occurred in 70 (39%) patients, including prolonged hospitalization in 43 (24%) and death in 27 (15%). Echocardiographic abnormalities included left ventricular ejection fraction less than 50% in 29 (16%), regional wall motion abnormalities in 26 (15%), and right ventricular systolic pressure (RVSP) of 35 or greater mm Hg in 44 (44%) of 101 in whom it was measured. Myocardial injury, defined as the presence of significant troponin level elevation accompanied by new ventricular dysfunction or electrocardiographic abnormalities, was present in 13 (7%). Prior echocardiography was available in 36 (20%) patients and pre-existing abnormalities were seen in 28 (78%) of these. In a multivariable age-adjusted model, area under the curve of 0.81, prior cardiovascular disease, troponin level, D-dimer level, and RVSP were related to events at 30 days., Conclusion: Bedside Doppler assessment of RVSP appears promising for short-term risk stratification in hospitalized patients with COVID-19 infection undergoing clinically indicated echocardiography. Pre-existing echocardiographic abnormalities were common; caution should be exercised in attributing such abnormalities to the COVID-19 infection in this comorbid patient population., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objectives: The aims of this study were to: 1) develop a formula for projected transmitral gradient (TMG), expected gradient under normal heart rate (HR), and stroke volume (SV); and 2) assess the prognostic value of projected TMG., Background: In mitral stenosis (MS), TMG is highly dependent on hemodynamics, often leading to discordance between TMG and mitral valve area., Methods: All patients with suspected MS based on echocardiography from 2001 to 2017 were analyzed. Data were randomly split (2:1); projected TMG was modeled in the derivation cohort, then tested in the validation cohort. The composite endpoint was death or mitral valve intervention., Results: Of 4,973 patients with suspected MS, severe and moderate MS, defined as mitral valve area ≤1.5 and >1.5 to 2.0 cm 2 , were present in 437 (9%) and 936 (19%), respectively. In the derivation cohort (n = 3,315; age 73 ± 12 years; 34% male), corresponding gradients were TMG ≥6 and 4 to <6 mm Hg, respectively, under normal hemodynamics. Based on the impact of hemodynamics on TMG, the formula was projected TMG = TMG - 0.07 (HR - 70) - 0.03 (SV - 97) in men and projected TMG = TMG - 0.08 (HR - 72) - 0.04 (SV - 84) in women. In the validation cohort (n = 1,658), projected TMG had better agreement with MS severity than TMG (kappa 0.61 vs. 0.28). Among 281 patients with TMG ≥6 mm Hg, projected TMG ≥6 mm Hg, present in 171 patients (61%), was associated with higher probability of the endpoint versus projected TMG <6 mm Hg (adjusted hazard ratio: 1.8; 95% confidence interval: 1.2 to 2.6; p < 0.01)., Conclusions: The novel concept of projected TMG, constructed using the observed impact of HR and SV on TMG, significantly improved the concordance of gradient and valve area in MS and provided better risk stratification than TMG., Competing Interests: Funding Support and Author Disclosures Dr. Pellikka is supported as the Betty Knight Scripps Professor in Cardiovascular Disease Clinical Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Cardiac power is a measure of cardiac performance that incorporates both pressure and flow components. Prior studies have shown that cardiac power predicts outcomes in patients with reduced left ventricular (LV) ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise cardiac power and power reserve in patients with normal EF., Methods and Results: We performed a retrospective analysis in 24 885 patients (age 59 ± 13 years, 45% females) with EF ≥50% and no significant valve disease or right ventricular dysfunction, undergoing exercise stress echocardiography between 2004 and 2018. Cardiac power and power reserve (developed power with stress) were normalized to LV mass and expressed in W/100 g of LV myocardium. Endpoints at follow-up were all-cause mortality and diagnosis of heart failure (HF). Patients in the higher quartiles of power/mass (rest, peak stress, and power reserve) were younger and had higher peak blood pressure and heart rate, lower LV mass, and lower prevalence of comorbidities. During follow-up [median 3.9 (0.6-8.3) years], 929 patients died. After adjusting for age, sex, metabolic equivalents (METs) achieved, ischaemia/infarction on stress test results, medication, and comorbidities, peak stress power/mass was independently associated with mortality [adjusted hazard ratio (HR), highest vs. lowest quartile, 0.5, 95% confidence interval (CI) 0.4-0.6, P < 0.001] and HF at follow-up [adjusted HR, highest vs. lowest quartile, 0.4, 95% CI (0.3, 0.5), P < 0.001]. Power reserve showed similar results., Conclusion: The assessment of cardiac power during exercise stress echocardiography in patients with normal EF provides valuable prognostic information, in addition to stress test findings on inducible myocardial ischaemia and exercise capacity., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

High alcohol intake and breast density increase breast cancer (BC) risk, but their interrelationship is unknown. We examined whether volumetric density modifies and/or mediates the alcohol-BC association. BC cases (n = 2233) diagnosed from 2006 to 2013 in the San Francisco Bay area had screening mammograms 6 or more months before diagnosis; controls (n = 4562) were matched on age, mammogram date, race or ethnicity, facility, and mammography machine. Logistic regression was used to estimate alcohol-BC associations adjusted for age, body mass index, and menopause; interaction terms assessed modification. Percent mediation was quantified as the ratio of log (odds ratios [ORs]) from models with and without density measures. Alcohol consumption was associated with increased BC risk (2-sided P trend  = .004), as were volumetric percent density (OR = 1.45 per SD, 95% confidence interval [CI] = 1.36 to 1.56) and dense volume (OR = 1.30, 95% CI = 1.24 to 1.37). Breast density did not modify the alcohol-BC association (2-sided P  > .10 for all). Dense volume mediated 25.0% (95% CI = 5.5% to 44.4%) of the alcohol-BC association (2-sided P  = .01), suggesting alcohol may partially increase BC risk by increasing fibroglandular tissue., (© The Author(s) 2021. Published by Oxford University Press.)

Background: A subset of patients with hypertrophic cardiomyopathy (HCM) is at high risk of sudden cardiac death (SCD). Practice guidelines endorse use of a risk calculator, which requires entry of left atrial (LA) diameter. However, American Society of Echocardiography (ASE) guidelines recommend the use of LA volume index (LAVI) for routine quantification of LA size. The aims of this study were to (a) develop a model to estimate LA diameter from LAVI and (b) evaluate whether substitution of measured LA diameter by estimated LA diameter derived from LAVI reclassifies HCM-SCD risk., Methods: The study cohort was comprised of 500 randomly selected HCM patients who underwent transthoracic echocardiography (TTE). LA diameter and LAVI were measured offline using digital clips from TTE. Linear regression models were developed to estimate LA diameter from LAVI. A European Society of Cardiology endorsed equation estimated SCD risk, which was measured using LA diameter and estimated LA diameter derived from LAVI., Results: The mean LAVI was 48.5 ± 18.8 mL/m 2 . The derived LA diameter was 45.1 mm (SD: 5.5 mm), similar to the measured LA diameter (45.1 mm, SD: 7.1 mm). Median SCD risk at 5 years estimated by measured LA diameter was 2.22% (interquartile range (IQR): 1.39, 3.56), while median risk calculated by estimated LA diameter was 2.18% (IQR: 1.44, 3.52). 476/500 (95%) patients maintained the same risk classification regardless of whether the measured or estimated LA diameter was used., Conclusions: Substitution of measured LA diameter by estimated LA diameter in the HCM-SCD calculator did not reclassify risk., (© 2020 The Authors. Echocardiography published by Wiley Periodicals LLC.)

Importance: Volumetric measurements by transthoracic echocardiogram may better reflect left ventricular (LV) remodeling than conventional linear LV dimensions. However, the association of LV volumes with mortality in patients with chronic hemodynamically significant aortic regurgitation (AR) is unknown., Objective: To assess whether LV volumes and volume-derived LV ejection fraction (Vol-LVEF) are determinants of mortality in AR., Design, Setting, and Participants: This cohort study included consecutive asymptomatic patients with chronic moderately severe to severe AR from a tertiary referral center (January 2004 through April 2019)., Exposures: Clinical and echocardiographic data were analyzed retrospectively. Aortic regurgitation severity was graded by comprehensive integrated approach. De novo disk-summation method was used to derive LV volumes and Vol-LVEF., Main Outcome and Measures: Associations between all-cause mortality under medical surveillance and the following LV indexes: linear LV end-systolic dimension index (LVESDi), linear LVEF, LV end-systolic volume index (LVESVi), and Vol-LVEF., Results: Of 492 asymptomatic patients (mean [SD] age, 60 [17] years; 425 men [86%]), ischemic heart disease prevalence was low (41 [9%]), and 453 (92.1%) had preserved linear LVEF (≥50%) with mean (SD) LVESVi of 41 (15) mL/m2. At a median (interquartile range) of 5.4 (2.5-10.1) years, 66 patients (13.4%) died under medical surveillance; overall survival was not different than the age- and sex-matched general population (P = .55). Separate multivariate models, adjusted for age, sex, Charlson Comorbidity Index, and AR severity, demonstrated that in addition to linear LVEF and LVESDi, LVESVi and Vol-LVEF were independently associated with mortality under surveillance (all P < .046) with similar C statistics (range, 0.83-0.84). Spline curves showed that continuous risks of death started to rise for both linear LVEF and Vol-LVEF less than 60%, LVESVi more than 40 to 45 mL/m2, and LVESDi above 21 to 22 mm/m2. As dichotomized variables, patients with LVESVi more than 45 mL/m2 exhibited increased relative death risk (hazard ratio, 1.93; 95% CI, 1.10-3.38; P = .02) while LVESDi more than 20 mm/m2 did not (P = .32). LVESVi more than 45 mL/m2 showed a decreased survival trend compared with expected population survival., Conclusions and Relevance: In this large asymptomatic cohort of patients with hemodynamically significant AR, LVESVi and Vol-LVEF worked equally as well as LVESDi and linear LVEF in risk discriminating patients with excess mortality. A LVESVi threshold of 45 mL/m2 or greater was significantly associated with an increased mortality risk.

Aortic stenosis (AS) is associated with significant morbidity and mortality, including sudden cardiac death (SCD). Anemia is a known risk factor for mortality in patients with AS. We sought to understand the prognostic implications between anemia and SCD in severe AS. The Mayo Clinic AS database includes 8,357 adults with severe AS (mean gradient ≥40 mm Hg, aortic valve area ≤1 cm 2 , or peak aortic jet velocity ≥4 m/s) enrolled between January 1, 1995 and April 30, 2015. Survival and cause of death were ascertained from the National Death Index and SCD from medical records. We excluded patients with multiple valvular abnormalities, leaving 7,292 subjects. The median (interquartile range, [IQR]) age was 76 (68, 82) years with 56% male, and median (IQR) hemoglobin level was 12.9 (11.6, 14.1) g/dl. The frequency of anemia (hemoglobin <13.0g/dl for men, <12.0 g/dL for women) was 40%. During median (IQR) follow up of 4.4 (1.8, 8.1) years, 4,056 died (10-year survival 38%) including 225 with SCD (10-year cumulative incidence 5%). In a multivariate model including age, sex, body-mass index, hypertension, diabetes mellitus, myocardial infarction, estimated glomerular filtration rate, and time dependent aortic valve replacement, anemia was associated with increased all-cause mortality (hazard ratios 1.75, 95%CI 1.64, 1.87; p < 0.001) and increased SCD mortality (hazard ratios 1.42, 95%CI 1.07, 1.86; p = 0.01). In conclusions, anemia is a frequent finding in patients with severe AS and independently associated with increased all-cause mortality and SCD. Anemia may be a useful prognostic marker and a modifiable therapeutic target in managing patients with severe AS., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To evaluate usability of a quality improvement tool that promotes guideline-based care for patients with peripheral arterial disease (PAD)., Patients and Methods: The study was conducted from July 19, 2018, to August 21, 2019. We compared the usability of a PAD cohort knowledge solution (CKS) with standard management supported by an electronic health record (EHR). Two scenarios were developed for usability evaluation; the first for the PAD-CKS while the second evaluated standard EHR workflow. Providers were asked to provide opinions about the PAD-CKS tool and to generate a System Usability Scale (SUS) score. Metrics analyzed included time required, number of mouse clicks, and number of keystrokes., Results: Usability evaluations were completed by 11 providers. SUS for the PAD-CKS was excellent at 89.6. Time required to complete 21 tasks in the CKS was 4 minutes compared with 12 minutes for standard EHR workflow (median, P  = .002). Completion of CKS tasks required 34 clicks compared with 148 clicks for the EHR (median, P  = .002). Keystrokes for CKS task completion was 8 compared with 72 for EHR (median, P  = .004). Providers indicated that overall they found the tool easy to use and the PAD mortality risk score useful., Conclusions: Usability evaluation of the PAD-CKS tool demonstrated time savings, a high SUS score, and a reduction of mouse clicks and keystrokes for task completion compared to standard workflow using the EHR. Provider feedback regarding the strengths and weaknesses also created opportunities for iterative improvement of the PAD-CKS tool., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Background: Exercise oscillatory ventilation (EOV) is a consequence of ventilatory control system instability and is commonly observed in patients with advanced heart failure (HF); it is associated with adverse prognosis. The goal of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) on oscillatory ventilation as quantified by a proposed EOV score., Methods and Results: Consecutive patients with HF (N = 35) who underwent clinically indicated CRT, cardiopulmonary exercise testing and carbon dioxide (CO 2 ) chemosensitivity by rebreathe before and 4-6 months after CRT were included in this post hoc analysis. With CRT, EOV scores improved in 22 patients (63%). In these patients, left ventricular ejection fraction, left atrial volume, brain natriuretic peptide concentration, and CO 2 chemosensitivity significantly improved after CRT (P < 0.05). Furthermore, minute ventilation per unit CO 2 production significantly decreased, and end-tidal CO 2 increased at rest and at peak exercise post-CRT. Multiple regression analysis showed only the change of CO 2 chemosensitivity to be significantly associated with the improvement of the EOV score (b = 0.64; F = 11.3; P = 0.004). In the group without EOV score improvement (n = 13), though left ventricular ejection fraction significantly increased with CRT (P = 0.015), no significant changes in ventilation or gas exchange were observed., Conclusion: The EOV score was mitigated by CRT and was associated with decreased CO 2 chemosensitivity., (Copyright © 2020. Published by Elsevier Inc.)

Aims: Right atrial pressure (RAP) provides a composite measure of right ventricular diastolic dysfunction, right atrial compliance, and volume status, and these three variables are typically abnormal in adults with repaired tetralogy of Fallot (TOF). RAP is a well-established prognostic metric in patients with pulmonary hypertension, and recent data suggest that RAP is associated with clinical outcomes in TOF. The purpose of this study was to determine the role of inferior vena cava (IVC) haemodynamics (size and collapsibility) for the assessment of RAP and its potential application for risk stratification and prognostication in the TOF population., Methods and Results: Adult TOF patients with echocardiographic assessment of IVC haemodynamics were divided into patients with (derivation cohort, n = 256) and without (validation cohort, n = 492) cardiac catheterization data. We assessed the correlation between IVC haemodynamics, RAP, and disease severity indices [arrhythmias, peak oxygen consumption (VO 2 ), and heart failure hospitalization] in derivation cohort and compared it with the correlations in the validation cohort. IVC haemodynamics correlated with RAP (r = 0.52, P < 0.001), with disease severity indices {atrial arrhythmias [area under the curve (AUC) 0.81], ventricular arrhythmias [AUC 0.67], heart failure hospitalizations [AUC 0.78], and peak VO 2 [r = 0.53]}, and with transplant-free survival in the derivation cohort. Similar correlations between IVC haemodynamics, disease severity indices, and transplant-free survival were also observed in the validation cohort., Conclusions: These findings suggest that IVC haemodynamics can potentially be used for risk stratification and prognostication in TOF patients and can complement the current risk models that are based predominately on right ventricular volumes and systolic function., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: The safety and diagnostic accuracy of stress testing in anemic patients have not been well studied. Despite a lack of data, significant anemia may be considered a relative contraindication to stress testing because of safety concerns related to insufficient myocardial oxygen supply., Methods: The authors reviewed 28,829 consecutive patients with blood hemoglobin drawn within 48 hours of stress echocardiography (15,624 exercise and 13,205 dobutamine). The associations of blood hemoglobin concentration with arrhythmia and other stress echocardiographic findings were examined. Additionally, the effect of anemia on the positive predictive value of stress echocardiography for the detection of significant coronary artery stenosis (≥50%) was assessed in patients who subsequently underwent coronary angiography., Results: Anemia was present in 6,401 patients (22.2%) and was severe (hemoglobin < 8.0 g/dL) in 52. Stress testing with either exercise or dobutamine was safe, with no significant increase in serious arrhythmia events or need for hospitalization. In the exercise cohort, worsening anemia was associated with reduced treadmill exercise time, lower peak heart rate, peak rate-pressure product, and achieved workload. In the dobutamine stress cohort, worsening anemia was associated with higher resting heart rate, more use of atropine, and fewer patients attaining target heart rate. The positive predictive value of stress echocardiography was higher in patients with moderate anemia compared with those without anemia (71.8% vs 60.2%, P = .01)., Conclusions: This study demonstrates that stress testing is safe in patients with mild and moderately anemia, albeit with a small increase in mild supraventricular arrhythmias with exercise. However, worsening anemia was associated with a significant reduction in exercise capacity. Additionally, worsening anemia was associated with an improvement in the positive predictive value of stress echocardiography. Extrapolation of these data to patients with severe anemia should be performed with caution given the limited number of patients with severe anemia in this study., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Variables in cardiology fellowship applications have not been objectively analyzed against applicants' subsequent clinical performance. We investigated possible correlations in a retrospective cohort study of 65 cardiology fellows at the Mayo Clinic (Rochester, Minn) who began 2 years of clinical training from July 2007 through July 2013. Application variables included the strength of comparative statements in recommendation letters and the authors' academic ranks, membership status in the Alpha Omega Alpha Honor Medical Society, awards earned, volunteer activities, United States Medical Licensing Examination (USMLE) scores, advanced degrees, publications, and completion of a residency program ranked in the top 6 in the United States. The outcome was clinical performance as measured by a mean of faculty evaluation scores during clinical training. The overall mean evaluation score was 4.07 ± 0.18 (scale, 1-5). After multivariable analysis, evaluation scores were associated with Alpha Omega Alpha designation (β=0.13; 95% CI, 0.01-0.25; P=0.03), residency program reputation (β=0.13; 95% CI, 0.05-0.21; P=0.004), and strength of comparative statements in recommendation letters (β=0.08; 95% CI, 0.01-0.15; P=0.02), particularly in letters from residency program directors (β=0.05; 95% CI, 0.01-0.08; P=0.009). Objective factors to consider in the cardiology fellowship application include Alpha Omega Alpha membership, residency program reputation, and comparative statements from residency program directors., (© 2020 by the Texas Heart® Institute, Houston.)

Background: Etiology, mechanisms, and survival of mitral regurgitation (MR) plus hemodynamically-significant chronic aortic regurgitation (AR) are mostly unknown., Objectives: The purpose of this study was to investigate the prevalence, mechanisms, etiologies, and survival impact of coexistent ≥ moderate MR in AR patients., Methods: Consecutive patients with ≥ moderate-severe AR were retrospectively identified between 2004 and 2019., Results: Of 1,239 eligible patients (61 ± 18 years, 80% men), 1,072 (86%) had pure AR, and 167 (14%) had AR + MR (9% functional mitral regurgitation [FMR] [84% nonischemic] and 5% organic mitral regurgitation [OMR] [62% degenerative]). At baseline transthoracic echocardiogram, pure AR versus AR + OMR versus AR + FMR exhibited differences in age (59 ± 18, 62 ± 16, and 73 ± 14 years, respectively), female sex (18%, 27%, and 39%, respectively), symptoms (36%, 41%, and 64%, respectively), atrial fibrillation (5%, 17%, and 36%, respectively), left ventricular (LV) ejection fraction (59%, 58%, and 46%, respectively), LV end-systolic dimension and volume index, ≥ moderate tricuspid regurgitation (TR) (7%, 35%, and 53%, respectively), and right ventricular systolic pressure (32 ± 11, 45 ± 15, and 50 ± 14 mm Hg, respectively), all p < 0.0001. After a median follow-up of 5.2 years (interquartile range: 2.2 to 10.0 years) and adjusting for demographics, New York Heart Association functional class, aortic valve surgery, LV ejection fraction, LV end-systolic dimension and volume index, presence of FMR was independently associated with all-cause mortality (p ≤ 0.004). Compared with pure AR, AR + MR + TR exhibited the highest adjusted risk of death (2.4-fold; p < 0.0001). When compared with expected population survival, excess mortality risks of pure AR, AR + OMR, and AR + FMR were 1.25-fold, 1.76-fold, and 2.34-fold, respectively (all p ≤ 0.02)., Conclusions: In hemodynamically significant AR, coexistent MR is not uncommon (approximately 14%) and mostly comprises FMR and less commonly OMR. As compared with pure AR, AR + MR + TR exhibit the largest mortality risk. Both AR + OMR and AR + FMR carry a survival penalty compared with the general population, but AR + FMR is associated with the largest excess mortality and represents an advanced stage within the AR clinical spectrum., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background The associations of density measures from the publicly available Laboratory for Individualized Breast Radiodensity Assessment (LIBRA) software with breast cancer have primarily focused on estimates from the contralateral breast at the time of diagnosis. Purpose To evaluate LIBRA measures on mammograms obtained before breast cancer diagnosis and compare their performance to established density measures. Materials and Methods For this retrospective case-control study, full-field digital mammograms in for-processing (raw) and for-presentation (processed) formats were obtained (March 2008 to December 2011) in women who developed breast cancer an average of 2 years later and in age-matched control patients. LIBRA measures included absolute dense area and area percent density (PD) from both image formats. For comparison, dense area and PD were assessed by using the research software (Cumulus), and volumetric PD (VPD) and absolute dense volume were estimated with a commercially available software (Volpara). Density measures were compared by using Spearman correlation coefficients ( r ), and conditional logistic regression (odds ratios [ORs] and 95% confidence intervals [CIs]) was performed to examine the associations of density measures with breast cancer by adjusting for age and body mass index. Results Evaluated were 437 women diagnosed with breast cancer (median age, 62 years ± 17 [standard deviation]) and 1225 matched control patients (median age, 61 years ± 16). LIBRA PD showed strong correlations with Cumulus PD ( r = 0.77-0.84) and Volpara VPD ( r = 0.85-0.90) ( P < .001 for both). For LIBRA, the strongest breast cancer association was observed for PD from processed images (OR, 1.3; 95% CI: 1.1, 1.5), although the PD association from raw images was not significantly different (OR, 1.2; 95% CI: 1.1, 1.4; P = .25). Slightly stronger breast cancer associations were seen for Cumulus PD (OR, 1.5; 95% CI: 1.3, 1.8; processed images; P = .01) and Volpara VPD (OR, 1.4; 95% CI: 1.2, 1.7; raw images; P = .004) compared with LIBRA measures. Conclusion Automated density measures provided by the Laboratory for Individualized Breast Radiodensity Assessment from raw and processed mammograms correlated with established area and volumetric density measures and showed comparable breast cancer associations. © RSNA, 2020 Online supplemental material is available for this article.

Background: Prevalence of calcific mitral stenosis (MS) increases with age; however, its natural history and relation to cardiac symptoms or comorbidities are not well defined., Objectives: This study assessed the prevalence of symptoms, comorbidities, and determinants of all-cause mortality in patients with severe calcific MS., Methods: The authors retrospectively investigated adults with isolated severe calcific MS and mitral valve area ≤1.5 cm 2 from July 2003 to December 2017. Inactivity was defined as requirement for assistance with activities of daily living., Results: Of 491 patients with isolated severe MS, calcific MS was present in 200 (41%; age 78 ± 11 years, 18% men, 32% with atrial fibrillation). Charlson Comorbidity Index was 5.1 ± 1.7 and 14 (7%) were inactive. Mitral valve area and transmitral gradient (TMG) were 1.26 ± 0.19 cm 2 and 8.1 ± 3.8 mm Hg, respectively. Symptoms were present at baseline in 120 (60%); 20 (10%) developed symptoms during follow-up of 2.8 ± 3.0 years. Kaplan-Meier survival at 1 year was 72% without intervention. Inactivity (hazard ratio [HR]: 6.59; 95% confidence interval [CI]: 3.54 to 12.3; p < 0.01), Charlson Comorbidity Index >5 (HR: 1.53; 95% CI: 1.04 to 2.26; p < 0.01), TMG ≥8 mm Hg (HR: 1.68; 95% CI: 1.12 to 2.51; p = 0.012), and right ventricular systolic pressure ≥50 mm Hg (HR: 2.27; 95% CI: 1.50 to 3.43; p < 0.01) were independently associated with mortality. Symptoms were not associated with mortality., Conclusion: Patients with isolated severe calcific MS had a high burden of comorbidities, resulting in high mortality without intervention. Symptoms were reported in 60%, but not associated with mortality. TMG ≥8 mm Hg and right ventricular systolic pressure ≥50 mm Hg were independently associated with mortality., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the incidence of major adverse cardiac events and death among severe aortic stenosis patients with and without aortic valve replacement (AVR) before noncardiac surgery., Patients and Methods: We retrospectively evaluated 491 severe aortic stenosis patients undergoing non-emergency/non-urgent elevated-risk noncardiac surgery between January 1, 2000, and December 31, 2013, including 203 patients (mean age, 74±10 years, 63.5% men) with previous AVR and 288 patients (mean age, 77±12 years, 55.6% men) without prior AVR., Results: The incidence of major adverse cardiac events was significantly lower in the AVR group (5.4% vs 20.5%; P<.001), primarily because of the lower incidence of new or worsening heart failure (2.5% vs 17.7%; P<.001), compared with the non-AVR group. No significant differences were observed between the groups with and without AVR in the incidence of death (2.5% vs 3.5%; P=.56), myocardial infarction (0.5% vs 1.4%; P=.48), ventricular arrhythmia (0.0% vs 0.7%; P=.51), or stroke (0.0% vs 0.7%; P=.51) at 30-days. At a median follow-up of 4.2 (interquartile range,1.3-7.5) years, overall mortality was significantly worse in patients without versus with AVR (5-year rate: 57.0% vs 32.7%; P<.001). Symptomatic patients without AVR (n=35) had the worst outcomes overall, including increased 30-day and overall mortality rates, compared with the AVR-group and asymptomatic non-AVR patients., Conclusion: In patients with severe aortic stenosis, AVR before noncardiac surgery was associated with decreased incidence of heart failure after noncardiac surgery and improved overall survival without differences in 30-day survival, myocardial infarction, ventricular arrhythmia, or stroke. Preoperative AVR should be considered in symptomatic patients for whom the benefit of AVR is greatest., (Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Aims: Right ventricular dysfunction (RVD) is an important determinant of functional status and survival in various diseases states. Data are sparse on the epidemiology and outcome of patients with severe RVD. This study examined the characteristics, aetiology, and survival of patients with severe RVD., Methods and Results: Retrospective study of consecutive patients with severe RVD diagnosed by transthoracic echocardiography (TTE) between 2011 and 2015 in a single tertiary referral institution. Patients with prior cardiac surgery, mechanical assist devices, and congenital heart disease were excluded. Primary endpoint was all-cause mortality. In 64 728 patients undergoing TTE, the prevalence of ≥mild RVD was 21%. This study focused on the cohort of 1299 (4%) patients with severe RVD; age 64 ± 16 years; 61% male. The most common causes of severe RVD were left-sided heart diseases (46%), pulmonary thromboembolic disease (18%), chronic lung disease/hypoxia (CLD; 17%), and pulmonary arterial hypertension (PAH; 11%). After 2 ± 2 years of follow-up, 701 deaths occurred, 66% within the first year of diagnosis. The overall probability of survival at 1- and 5 years for the entire cohort were 61% [95% confidence interval (CI) 58-64%] and 35% (95% CI 31-38%), respectively. In left-sided heart diseases, 1- and 5-year survival rates were 61% (95% CI 57-65%) and 33% (95% CI 28-37%), respectively; vs. 76% (95% CI 68-82%) and 50% (95% CI 40-59%) in PAH, vs. 71% (95% CI 64-76%) and 49% (95% CI 41-58%) in thromboembolic diseases, vs. 42% (95% CI 35-49%) and 8% (95% CI 4-15%) in CLD (log-rank P < 0.0001). Presence of ≥moderate tricuspid regurgitation portended worse survival in severe RVD., Conclusion: One-year mortality of patients with severe RVD was high (∼40%) and dependent on the aetiology of RVD. Left-sided heart diseases is the most common cause of severe RVD but prognosis was worst in CLD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)