Publications by authors named "Christopher G Scott"

220 Publications

Incorporating Robustness to Imaging Physics into Radiomic Feature Selection for Breast Cancer Risk Estimation.

Cancers (Basel) 2021 Nov 1;13(21). Epub 2021 Nov 1.

Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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 < 0.005 for the difference among the quartiles.
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http://dx.doi.org/10.3390/cancers13215497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582675PMC
November 2021

Natural language processing of implantable cardioverter-defibrillator reports in hypertrophic cardiomyopathy: A paradigm for longitudinal device follow-up.

Cardiovasc Digit Health J 2021 Oct 20;2(5):264-269. Epub 2021 May 20.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

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.
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http://dx.doi.org/10.1016/j.cvdhj.2021.05.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562689PMC
October 2021

Escalating incidence of infective endocarditis in Europe in the 21st century.

Open Heart 2021 Oct;8(2)

Taunton and Somerset NHS Foundation Trust, Taunton, UK.

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.
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http://dx.doi.org/10.1136/openhrt-2021-001846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529987PMC
October 2021

Impact of aortic valve replacement for severe aortic stenosis on organic and functional mitral regurgitation.

ESC Heart Fail 2021 Oct 15. Epub 2021 Oct 15.

Department of Cardiovascular Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN, USA.

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 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 ), 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 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 [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 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.
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http://dx.doi.org/10.1002/ehf2.13649DOI Listing
October 2021

Fully Automated Volumetric Breast Density Estimation from Digital Breast Tomosynthesis.

Radiology 2021 12 14;301(3):561-568. Epub 2021 Sep 14.

From the Department of Radiology, University of Pennsylvania, 3700 Hamilton Walk, Richards Bldg, Room D702, Philadelphia, PA 19104 (A.G., L.P., E.A.C., A.D.A.M., E.F.C., D.K.); and the Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minn (C.G.S., F.F.W., S.J.W., M.R.J., C.M.V.).

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 (), 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 ( = 0.32-0.75; all < .001) were observed. Volumetric density estimates calculated from DBT (OR, 2.3 [95% CI: 1.6, 3.4] per SD for VPD%) were more strongly associated with breast cancer than DM-derived density for both APD% (OR, 1.3 [95% CI: 0.9, 1.9] [ < .001] and 1.7 [95% CI: 1.2, 2.3] [ = .004] per SD for LIBRA raw and processed data, respectively) and VPD% (OR, 1.6 [95% CI: 1.1, 2.4] [ = .01] and 1.7 [95% CI: 1.2, 2.6] [ = .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 See also the editorial by Yaffe in this issue.
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http://dx.doi.org/10.1148/radiol.2021210190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608738PMC
December 2021

Prevalence of Transthyretin Amyloid Cardiomyopathy in Heart Failure With Preserved Ejection Fraction.

JAMA Cardiol 2021 Nov;6(11):1267-1274

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

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.
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http://dx.doi.org/10.1001/jamacardio.2021.3070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387947PMC
November 2021

Sex Differences in Outcomes of Patients With Chronic Aortic Regurgitation: Closing the Mortality Gap.

Mayo Clin Proc 2021 08;96(8):2145-2156

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN. Electronic address:

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 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 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.
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http://dx.doi.org/10.1016/j.mayocp.2020.11.033DOI Listing
August 2021

Sex-specific cut-off values for soluble suppression of tumorigenicity 2 (ST2) biomarker increase its cardiovascular prognostic value in the community.

Biomarkers 2021 Nov 29;26(7):639-646. Epub 2021 Jul 29.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.

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 (<0.001; preserved ejection fraction (EF) <0.001, reduced EF =0.23), MACE (=0.003) and mortality (<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).
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http://dx.doi.org/10.1080/1354750X.2021.1956590DOI Listing
November 2021

High Prevalence of Severe Aortic Stenosis in Low-Flow State Associated With Atrial Fibrillation.

Circ Cardiovasc Imaging 2021 07 12;14(7):e012453. Epub 2021 Jul 12.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (S.A., S.K., S.V.P., J.J.T., E.A.E.-A., K.M., D.O., S.A.L., R.P., C.E.L., R.B.M., P.A.P., J.K.O., V.T.N.).

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 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 ≤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, =0.001), not different in AF-LGAS (2399 arbitrary units; IQR1817-2810, =0.47), and lower in SR-LGAS (1593 arbitrary units; IQR945-1832, <0.001); AVCS in AF-LGAS were higher when HS were present (=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], <0.001) and AF-LGAS with HS (hazard ratio=1.54 [1.04-2.26], =0.03) but not different in AF-LGAS without HS or SR-LGAS (both =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.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.012453DOI Listing
July 2021

Prognostic Value of Urinary and Plasma C-Type Natriuretic Peptide in Acute Decompensated Heart Failure.

JACC Heart Fail 2021 09 7;9(9):613-623. Epub 2021 Jul 7.

Cardiorenal Research Laboratory, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jchf.2021.04.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419026PMC
September 2021

Risk Prediction in Women With Congenital Long QT Syndrome.

J Am Heart Assoc 2021 07 9;10(14):e021088. Epub 2021 Jul 9.

Division of Cardiology Clinical Cardiovascular Research Center University of Rochester Medical Center Rochester NY.

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.
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http://dx.doi.org/10.1161/JAHA.121.021088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483453PMC
July 2021

Mammographic Variation Measures, Breast Density, and Breast Cancer Risk.

AJR Am J Roentgenol 2021 08 23;217(2):326-335. Epub 2021 Jun 23.

Department of Quantitative Health Sciences, Division of Epidemiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905.

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 and p [a normalized version of P], 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. 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. 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, and 1.51 [95% CI, 1.33-1.72] for p). 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. Variation measures were significantly associated with breast cancer risk (comparable to the volumetric density measures) but were independent of the DV.
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http://dx.doi.org/10.2214/AJR.20.22794DOI Listing
August 2021

Artificial Intelligence-Augmented Electrocardiogram Detection of Left Ventricular Systolic Dysfunction in the General Population.

Mayo Clin Proc 2021 Oct 10;96(10):2576-2586. Epub 2021 Jun 10.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN. Electronic address:

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.
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http://dx.doi.org/10.1016/j.mayocp.2021.02.029DOI Listing
October 2021

Cardiac Involvement in Facioscapulohumeral Muscular Dystrophy (FSHD).

Front Neurol 2021 24;12:668180. Epub 2021 May 24.

Department of Neurology, Mayo Clinic, Rochester, MN, United States.

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. We reviewed cardiac, neurological and genetic findings of 104 patients with genetically confirmed FSHD. 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. 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.
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http://dx.doi.org/10.3389/fneur.2021.668180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181417PMC
May 2021

Recurrence of Pathologically Proven Papillary Fibroelastoma.

Ann Thorac Surg 2021 May 19. Epub 2021 May 19.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address:

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.
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http://dx.doi.org/10.1016/j.athoracsur.2021.03.114DOI Listing
May 2021

Progression of Preclinical Heart Failure: A Description of Stage A and B Heart Failure in a Community Population.

Circ Cardiovasc Qual Outcomes 2021 05 6;14(5):e007216. Epub 2021 May 6.

Department of Cardiovascular Diseases (K.A.Y., R.J.R., H.H.C.), Mayo Clinic, Rochester, MN.

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]; <0.001). NT-proBNP correlated with progression for Stage B (=0.01), but not for Stage A (=0.39). A multivariate model found female sex (odds ratio, 1.65 [95% CI, 1.05-2.58]; =0.03), increased E/e' (odds ratio, 1.13 [95% CI, 1.02-1.26], =0.02), and beta blocker use (odds ratio, 2.19 [95% CI, 1.25-3.82], =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 (=0.06 for Stage A and =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.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.120.007216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137558PMC
May 2021

Effectiveness of a Weight Loss Program Using Digital Health in Adolescents and Preadolescents.

Child Obes 2021 07 6;17(5):311-321. Epub 2021 Apr 6.

Department of Cardiovascular Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.

To identify an efficacious intervention on treating adolescents with overweight and obesity, this might result in health benefits. 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 -test (continuous variables) were used to compare subjects. 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 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, 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 ( < 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. 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.
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http://dx.doi.org/10.1089/chi.2020.0317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236388PMC
July 2021

Aortic Stenosis Progression, Cardiac Damage, and Survival: Comparison Between Bicuspid and Tricuspid Aortic Valves.

JACC Cardiovasc Imaging 2021 06 17;14(6):1113-1126. Epub 2021 Mar 17.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jcmg.2021.01.017DOI Listing
June 2021

Association of Daily Alcohol Intake, Volumetric Breast Density, and Breast Cancer Risk.

JNCI Cancer Spectr 2021 Apr 4;5(2):pkaa124. Epub 2021 Feb 4.

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

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  = .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  > .10 for all). Dense volume mediated 25.0% (95% CI = 5.5% to 44.4%) of the alcohol-BC association (2-sided  = .01), suggesting alcohol may partially increase BC risk by increasing fibroglandular tissue.
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http://dx.doi.org/10.1093/jncics/pkaa124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952225PMC
April 2021

Usability of a Digital Registry to Promote Secondary Prevention for Peripheral Artery Disease Patients.

Mayo Clin Proc Innov Qual Outcomes 2021 Feb 28;5(1):94-102. Epub 2020 Nov 28.

Department of Cardiovascular Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN.

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,  = .002). Completion of CKS tasks required 34 clicks compared with 148 clicks for the EHR (median,  = .002). Keystrokes for CKS task completion was 8 compared with 72 for EHR (median,  = .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.
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http://dx.doi.org/10.1016/j.mayocpiqo.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930799PMC
February 2021

Cardiac Abnormalities in COVID-19 and Relationship to Outcome.

Mayo Clin Proc 2021 04 19;96(4):932-942. Epub 2021 Jan 19.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN. Electronic address:

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.
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http://dx.doi.org/10.1016/j.mayocp.2021.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816643PMC
April 2021

Ceramide Scores Predict Cardiovascular Risk in the Community.

Arterioscler Thromb Vasc Biol 2021 04 18;41(4):1558-1569. Epub 2021 Feb 18.

Department of Laboratory Medicine and Pathology (V.C.V., J.W.M., L.J.D., A.S.J.), Mayo Clinic College of Medicine, Rochester, MN.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.120.315530DOI Listing
April 2021

A Novel Assessment Using Projected Transmitral Gradient Improves Diagnostic Yield of Doppler Hemodynamics in Rheumatic and Calcific Mitral Stenosis.

JACC Cardiovasc Imaging 2021 03 10;14(3):559-570. Epub 2021 Feb 10.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA. Electronic address:

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, 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.
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http://dx.doi.org/10.1016/j.jcmg.2020.12.013DOI Listing
March 2021

Predicting Quality of Clinical Performance From Cardiology Fellowship Applications.

Tex Heart Inst J 2020 08;47(4):258-264

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota 55905.

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.
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http://dx.doi.org/10.14503/THIJ-18-6851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819435PMC
August 2020

Association of mammographic density measures and breast cancer "intrinsic" molecular subtypes.

Breast Cancer Res Treat 2021 May 4;187(1):215-224. Epub 2021 Jan 4.

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN, 55905, USA.

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.
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http://dx.doi.org/10.1007/s10549-020-06049-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216504PMC
May 2021

Prognostic value of peak stress cardiac power in patients with normal ejection fraction undergoing exercise stress echocardiography.

Eur Heart J 2021 02;42(7):776-785

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA.

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.
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http://dx.doi.org/10.1093/eurheartj/ehaa941DOI Listing
February 2021

Conversion of left atrial volume to diameter for automated estimation of sudden cardiac death risk in hypertrophic cardiomyopathy.

Echocardiography 2021 02 16;38(2):183-188. Epub 2020 Dec 16.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.

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 . 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.
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http://dx.doi.org/10.1111/echo.14943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986336PMC
February 2021

Association of Left Ventricular Volume in Predicting Clinical Outcomes in Patients with Aortic Regurgitation.

J Am Soc Echocardiogr 2021 04 27;34(4):352-359. Epub 2020 Nov 27.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota. Electronic address:

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 had lower survival and a higher prevalence of symptoms than those with volumes < 45 mL/m.

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 was associated with worse outcomes.
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http://dx.doi.org/10.1016/j.echo.2020.11.014DOI Listing
April 2021

Association of Echocardiographic Left Ventricular End-Systolic Volume and Volume-Derived Ejection Fraction With Outcome in Asymptomatic Chronic Aortic Regurgitation.

JAMA Cardiol 2021 Feb;6(2):189-198

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

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.
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http://dx.doi.org/10.1001/jamacardio.2020.5268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643045PMC
February 2021
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