Objectives:To identify unique echocardiographic signatures associated with TTR+ carrier status preceding onset of cardiac amyloidosis. Background:Carrier status for the most common pathogenic TTR variant in the United States, Val142Ile (V142I), found in 4% of African Americans (AA) and 1% of Hispanic/Latino (H/L) individuals, confers a 40-60% lifetime risk of developing variant transthyretin amyloidosis (ATTRv), including cardiac amyloidosis (CA) and heart failure (HF). Myocardial amyloid deposition is believed to progress over many years. Genomic screening programs and familial cascade genetic testing are increasingly uncovering pre-symptomatic TTR+ carriers, yet no guidelines exist to pragmatically risk stratify these individuals for CA. Methods:V142I+ carriers (cases) without prior diagnoses of amyloidosis or HF were identified among BioMe biobank participants with available exome sequencing data linked to electronic health records (EHRs) including at least one available echocardiogram. Controls were biobank participants with normal TTR sequencing who were age-, sex- and ancestry- matched to cases. Speckle-tracking echocardiography (STE) was applied to images and conventional and strain measurements were evaluated by univariate analyses. A random forest model was trained using a minimal redundancy maximal relevance (mRMR, applied to mitigate overfitting) feature set and evaluated by 5-fold cross-validation to minimize optimism bias. Discriminatory performance was assessed using the area under the receiver operating characteristic curve (AUC). Results:49 TTR+ (100% V142I, median age 61 years, 69.4% female) and 45 matched TTR- biobank participants were included in the model development cohort. STE generated approximately 200 features. Univariate analyses revealed no significant differences between carriers and controls on any individual strain or conventional echocardiographic measurements including global longitudinal, right ventricular and left atrial strain. mRMR feature selection resulted in a set of 15 features retained for all downstream modeling, integrating global amyloid signatures, regional inferolateral strain abnormalities, layer-specific deformation, and mechanical timing heterogeneity. Using this feature set, the model achieved good discrimination (AUC=0.76). Feature importance analysis highlighted relative apical sparing, inferolateral strain reduction, and basal-apical timing gradients as key contributors to model performance. External validation (n=115) confirmed good model discrimination (AUC=0.781, 95% CI: 0.688-0.869, sensitivity 0.983). Conclusions:Machine learning applied to routinely acquired echocardiographic data can identify subtle myocardial abnormalities associated with TTR V142I carrier status prior to development of CA. Key model features are physiologically relevant to known echocardiographic characteristics of overt CA. Genotype-guided echocardiographic surveillance may be a scalable strategy for early detection of CA risk.

The objective of this study is to describe the prevalence of inflammatory cardiopulmonary findings in a prospective cohort of long coronavirus disease (LC) patients. Methods: Subjects with a history of coronavirus disease 2019 infection, persistent cardiopulmonary symptoms 9-12 mo after initial infection, and a clinical assessment compatible with LC underwent cardiopulmonary 18F-FDG PET/MRI, dual-energy CT (DECT) of the lungs, and plasma protein analysis (subgroup). A control group that included subjects with a history of acute severe acute respiratory syndrome coronavirus 2 infection but without cardiopulmonary symptoms at recruitment was also characterized. Results: Ninety-eight patients (median age, 48.5 y; 47% men) were enrolled. The most common LC symptom was shortness of breath (80%), and 27% of participants were hospitalized. Of the subjects, 90% presented abnormalities in DECT, with 67% and 59% of participants demonstrating pulmonary infiltrates and abnormal perfusion, respectively. PET/MRI was abnormal for 57% of subjects: 24% showed cardiac involvement suggestive of myocarditis, 22% presented uptake reminiscent of pericarditis, 11% showed periannular uptake, and 30% showed vascular uptake (aortic or pulmonary). There was no myocardial, pericardial, periannular, or pulmonary uptake on the PET/MRI scans of the control group (n = 9). Analysis of plasma protein concentrations showed significant differences between the LC and the control groups. Lastly, the plasma protein profile was significantly different among LC patients with abnormal and normal PET/MRI. Conclusion: In LC subjects evaluated up to a year after coronavirus disease 2019 infection, our results indicate a high prevalence of abnormalities on PET/MRI and DECT, as well as significant differences in the peripheral biomarker profile, which might warrant further monitoring to exclude the development of complications such as pulmonary hypertension and valvular disease.

BACKGROUND:Ultrasound enhancing agents (UEAs) are a commonly used tool to enhance the diagnostic quality of echocardiographic studies. Although serious allergic reactions are rare, they have been documented. CASE SUMMARY:A 39-year-old woman with NYHA functional class I heart failure developed a severe allergic reaction to UEA with decompensation into Society for Cardiovascular Angiography & Interventions stage D cardiogenic shock. Serial echocardiography demonstrated abrupt decrease in left ventricular ejection fraction from a baseline of 45% to 20%, which recovered to 35% before discharge. DISCUSSION:Higher rates of adverse drug reactions (ADRs) are reported in observational studies of contemporary practice compared with previously published data. Cardiogenic shock as a consequence of an anaphylactic reaction to Lumason has not been previously described in the literature. TAKE-HOME MESSAGES:Observational data have shown that ADR to UEA has become more prevalent in the past several years, with higher rates with Lumason vs Definity. It is important to monitor patients who have ADRs to UEA and who are treated with epinephrine, especially those with underlying cardiomyopathy, as there is potential for a transition from anaphylaxis to stress cardiomyopathy and cardiogenic shock. Given the risk for significant ADR, UEA should be used selectively and only as needed.

BACKGROUND:18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/magnetic resonance (MR) can identify inflammation and fibrosis, which are high-risk features in cardiac sarcoidosis. OBJECTIVE:The purpose of this study was to evaluate whether the involvement of certain myocardial segments is associated with higher risk compared to others. METHODS:One hundred twenty-four patients with suspected clinical sarcoidosis underwent 18F-FDG-PET/MR. Late gadolinium enhancement (LGE) and focal 18F-FDG uptake were evaluated globally and in the 16 myocardial segments. Presence of LGE was defined when the percentage of LGE exceeded 5.7% globally (relative to myocardial volume) and in each myocardial segment. Patients were followed up for 5.5 years. Events were defined as ventricular arrhythmia (VA) (including sustained ventricular tachycardia, ventricular fibrillation, and appropriate implantable cardioverter-defibrillator discharge), heart failure hospitalization, or all-cause death. RESULTS:Mean age was 57.1 ± 8.9 years, and 39.5% were female. Twenty-two patients (17.6%) had an event during follow-up, and 9 (7.2%) presented with VA. LGE and 18F-FDG uptake were more frequent in patients with than without events (36.4% vs 7.8%, P = .001). Presence of LGE and 18F-FDG in the basal anterior segment were independent predictors for events after adjustment for left ventricular ejection fraction and relative enhanced volume (LGE: odds ratio [1.2-92.4], P = .034;18F-FDG: odds ratio 5.5 [1.1-27.5], P = .038). LGE presence in basal to mid-anterior, mid-anteroseptal, and basal to mid-inferoseptal segments was an independent predictor of VA. Presence of 18F-FDG in basal to mid-anterior, mid-inferoseptal and mid-inferior segments was an independent predictor of VA. CONCLUSION:Involvement of specific myocardial segments, particularly basal to mid-anterior and mid-septal segments, is associated with higher rates of events in patients with suspected cardiac sarcoidosis.

HomeCirculation: Cardiovascular ImagingVol. 16, No. 11Beware Before Mitral Balloon Valvuloplasty: Parachute Mitral Valve Can Mimic Rheumatic Mitral Stenosis No AccessCase ReportRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessCase ReportRequest AccessFull TextBeware Before Mitral Balloon Valvuloplasty: Parachute Mitral Valve Can Mimic Rheumatic Mitral Stenosis Sarah Goldman, Hartzell Schaff, Kimberly Capustin, Annapoorna Kini, Samin Sharma, David Power, Waqas Malick, Jose Meller, Steve Liao, Lori Croft and Martin Goldman Sarah GoldmanSarah Goldman Correspondence to: Sarah Goldman, MD, Zucker School of Medicine at Hofstra Northwell, Department of Internal Medicine, Lenox Hill Hospital New York, NY 917-446-4860. Email E-mail Address: [email protected] https://orcid.org/0009-0009-1227-2074 Zucker School of Medicine at Hofstra Northwell, Department of Internal Medicine, Lenox Hill Hospital New York (S.G.). , Hartzell SchaffHartzell Schaff https://orcid.org/0000-0003-0994-027X Department of Cardiovascular Surgery, Mayo Clinic, Rochester, MN (H.S.). , Kimberly CapustinKimberly Capustin The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (K.C., A.K., S.S., D.P., W.M., J.M., S.L., L.C., M.G.). , Annapoorna KiniAnnapoorna Kini https://orcid.org/0000-0002-7189-3307 The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (K.C., A.K., S.S., D.P., W.M., J.M., S.L., L.C., M.G.). , Samin SharmaSamin Sharma https://orcid.org/0000-0002-1888-0793 The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (K.C., A.K., S.S., D.P., W.M., J.M., S.L., L.C., M.G.). , David PowerDavid Power https://orcid.org/0000-0002-5409-1943 The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (K.C., A.K., S.S., D.P., W.M., J.M., S.L., L.C., M.G.). , Waqas MalickWaqas Malick The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (K.C., A.K., S.S., D.P., W.M., J.M., S.L., L.C., M.G.). , Jose MellerJose Meller The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (K.C., A.K., S.S., D.P., W.M., J.M., S.L., L.C., M.G.). , Steve LiaoSteve Liao The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (K.C., A.K., S.S., D.P., W.M., J.M., S.L., L.C., M.G.). , Lori CroftLori Croft The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (K.C., A.K., S.S., D.P., W.M., J.M., S.L., L.C., M.G.). and Martin GoldmanMartin Goldman The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (K.C., A.K., S.S., D.P., W.M., J.M., S.L., L.C., M.G.). Originally published10 Oct 2023https://doi.org/10.1161/CIRCIMAGING.123.015483Circulation: Cardiovascular Imaging. 2023;16FootnotesFor Sources of Funding and Disclosures, see page 928.Correspondence to: Sarah Goldman, MD, Zucker School of Medicine at Hofstra Northwell, Department of Internal Medicine, Lenox Hill Hospital New York, NY 917-446-4860. Email sgoldman7@northwell.eduREFERENCES1. Hakim FA, Kendall CB, Alharthi M, Mancina JC, Tajik JA, Mookadam FSO. Parachute mitral valve in adults - a systematic overview.Echocardiogr. 2010; 27:581–586. doi: 10.1111/j.1540-8175.2009.01143.xCrossrefMedlineGoogle Scholar2. Suraci N, Goldman H, Baruqui D, Santana O. Parachute mitral valve.Ann Card Anesthesia. 2021; 24:75–76. doi: 10.4103/aca.ACA_82_19CrossrefMedlineGoogle Scholar3. Casavecchia G, Gravina M, Zicchino S, Capalbo S, Di Biase M, Brunetti ND. Parachute mitral valve assessed by cardiac magnetic resonance.Interv Med Appl Sci. 2019; 11:65–67. doi: 10.1556/1646.11.2019.03CrossrefMedlineGoogle Scholar4. Yuan SM. Parachute mitral valve: morphology and surgical management.Turk Gogus Kalp Damar Cerrahisi Derg. 2020; 28:219–226. doi: 10.5606/tgkdc.dergisi.2020.18041CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails November 2023Vol 16, Issue 11 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.123.015483PMID: 37814885 Originally publishedOctober 10, 2023 Keywordschildhoodechocardiogramfeverheart ratepalpitationsPDF download Advertisement SubjectsEchocardiographyMagnetic Resonance Imaging (MRI)Nuclear Cardiology and PETRheumatic Heart DiseaseValvular Heart Disease

Background: Right ventricular (RV) function is important in the evaluation of cardiac function, but its assessment using standard transthoracic echocardiography (TTE) remains challenging. Cardiac magnetic resonance imaging (CMR) is considered the gold standard. The American Society of Echocardiography recommends surrogate measures of RV function and RV ejection fraction (RVEF) by TTE, including fractional area change (FAC), free wall strain (FWS), and tricuspid annular planar systolic excursion (TAPSE), but they require technical expertise in acquisition and quantification.Methods: The aim of this study was to evaluate the sensitivity, specificity, and positive and negative predictive values of FAC, FWS, and TAPSE derived using a rapid, novel artificial intelligence (AI) software (LVivoRV) from a single-plane transthoracic echocardiographic apical four-chamber, RV-focused view without ultrasound enhancing agents for detecting abnormal RV function compared with CMR-derived RVEF. RV dysfunction was defined as RVEF < 50% and RVEF < 40% on CMR.Results: TTE and CMR were performed within a median of 10 days (interquartile range, 2-32 days) of each other in 225 consecutive patients without interval procedural or pharmacologic intervention. The sensitivity and negative predictive value to detect CMR-defined RV dysfunction when all three AI-derived parameters (FAC, FWS, and TAPSE) were abnormal were 91% and 96%, while those of expert physician reads were 91% and 97%. Specificity and positive predictive value were lower (50% and 32%) compared with expert physician-read echocardiograms (82% and 56%).Conclusions: AI-derived measurements of FAC, FWS, and TAPSE had excellent sensitivity and negative predictive value for ruling out significant RV dysfunction (CMR RVEF < 40%), comparable with that of expert physician readers, but lower specificity. Thus AI, using American Society of Echocardiography guidelines, may serve as a useful screening tool for rapid bedside assessment to exclude significant RV dysfunction.

BACKGROUND:Sustained ventricular tachycardia and sudden cardiac death due to degenerative mitral valve prolapse (MVP) can occur in the absence of severe mitral regurgitation (MR). A significant percentage of patients with MVP-related sudden death do not have any evidence of replacement fibrosis, suggesting other unrecognized proarrhythmic factors may place these patients at risk. OBJECTIVES:This study aims to characterize myocardial fibrosis/inflammation and ventricular arrhythmia complexity in patients with MVP and only mild or moderate MR. METHODS:Prospective observational study of patients with MVP and only mild or moderate MR underwent ventricular arrhythmia characterization and hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI). Coregistered hybrid 18F-fluorodeoxyglucose (18F-FDG)-PET and MRI late gadolinium enhancement images were assessed and categorized. Recruitment occurred in the cardiac electrophysiology clinic. RESULTS:In 12 patients with degenerative MVP with only mild or moderate MR, of which a majority had complex ventricular ectopy (n = 10, 83%), focal (or focal-on-diffuse) uptake of 18F-FDG (PET-positive) was detected in 83% (n = 10) of patients. Three-quarters of the patients (n = 9, 75%) had FDG uptake that coexisted with areas of late gadolinium enhancement (PET/MRI-positive). Abnormal T1, T2 and extracellular volume (ECV) values were observed in 58% (n = 7), 25% (n = 3), and 16% (n = 2), respectively. CONCLUSIONS:Most patients with degenerative MVP, ventricular ectopy, and mild or moderate MR show myocardial inflammation that is concordant with myocardial scar. Further study is needed to determine whether these findings contribute to the observation that most MVP-related sudden deaths occur in patients with less than severe MR.

Introduction: Patients (pts) with pulmonary embolism (PE) and right ventricular (RV) dysfunction have a worse prognosis. We previously validated a real-time artificial intelligence software (AI, LVivoRV®) which calculates RV fractional area changes (FAC), free wall strain (FWS), and tricuspid annular planar systolic excursion (TAPSE) from a single unedited, non-ultrasound agent-enhanced apical 4-chamber (A4C) TTE view. Hypothesis: AI-calculated TTE parameters of RV function will accurately identify pts with intermediate-high and high-risk PE that would otherwise have been identified by comprehensive physician assessment of all TTE parameters, physical exam and biomarkers (“physician assessment”). Methods: We retrospectively identified pts in whom both a TTE (60.7% with ultrasound contrast) and chest CTA were performed for PE evaluation (median 1 day between studies). Based on comprehensive physician assessments, pts were stratified by the 2019 ESC guidelines from low-risk to high-risk for PE mortality. The accuracy of AI-TTE thresholds for RV dysfunction (previously defined) to identify physician-assessed high-risk PE was examined. Results: Of the 107 pts, 66 (61.7%) had confirmed PE on CTA. By physician assessment, 28 of these 66 cases were classified as intermediate-high/high-risk PE. Across all AI-TTE parameters, the sensitivities and negative predictive values for intermediate-high/high-risk PE (n=28) ranged from 79-86% and 83-87% respectively (Table). In contrast, the specificities and positive predictive values ranged from 30-56% and 29-38%. Conclusions: A simple to use, fully automated, AI-based TTE assessment of RV dysfunction at the bedside identified ~85% of all cases that would otherwise have been identified as intermediate-high and high-risk PE by comprehensive physician assessment (although the false positive rate was high). Further studies are warranted to examine how best to integrate this AI into clinical care pathways.

Background: There are currently no clear guidelines regarding the use of ultrasound enhancing agents (UEAs) with transthoracic echocardiography (TTE) for patients hospitalized with Covid-19. We investigated whether the performance of TTE with UEAs provides more diagnostic information and allows for shorter acquisition time compared to unenhanced TTE imaging in this patient population. Methods: We analyzed the TTEs of 107 hospitalized Covid-19 patients between April and June 2020 who were administered UEAs (Definity (R), Lantheus). The time to acquire images with and without UEAs was calculated. A level III echocardiographer determined if new, clinically significant findings were visualized with the addition of UEAs. Results: There was a mean of 11.84 +/- 3.59 UEA cineloops/study vs 20.74 +/- 8.10 non-UEA cineloops/study (p < 0.0001). Mean time to acquire UEA cineloop images was 72.28 +/- 28.18 s/study compared to 188.07 +/- 86.04 s/ study for non-UEA cineloop images (p < 0.0001). Forty-eight patients (45%) had at least one new finding on UEA imaging, with a total of 62 new findings seen. New information gained with UEAs was more likely to be found in patients with acute respiratory distress syndrome (21 vs 9, p < 0.001) and in those on mechanical ventilation (21 vs 15, p = 0.046). Conclusions: TTE with UEAs required less time and fewer cineloop images compared to non-UEA imaging in patients hospitalized with Covid-19. Additionally, Covid-19 patients with severe respiratory disease benefited most with regard to new diagnostic information. Health care personnel should consider early use of UEAs in select hospitalized Covid-19 patients in order to reduce exposure and optimize diagnostic yield.

Mitral valve prolapse (MVP) has been associated with ventricular arrhythmias and sudden cardiac death (SCD). A majority of MVP-related SCD occurs in patients with only mild or moderate MR. Replacement fibrosis, which is known to occur in the absence of severe MR, may be preceded and accompanied by an inflammatory response. We previously reported on a series of patients with severe MR planned for elective mitral valve surgery who underwent Hybrid PET-MRI imaging, and demonstrated that >90% of those patients with complex ventricular ectopy had evidence of FDG uptake, suggestive of ongoing subclinical inflammation.

BACKGROUND:Quantification of left ventricular ejection fraction (LVEF) by transthoracic echocardiography (TTE) is operator-dependent, time-consuming, and error-prone. LVivoEF by DIA is a new artificial intelligence (AI) software, which displays the tracking of endocardial borders and rapidly quantifies LVEF. We sought to assess the accuracy of LVivoEF compared to cardiac magnetic resonance imaging (cMRI) as the reference standard and to compare LVivoEF to the standard-of-care physician-measured LVEF (MD-EF) including studies with ultrasound enhancing agents (UEAs).METHODS:In 273 consecutive patients, we compared MD-EF and AI-derived LVEF to cMRI. AI-derived LVEF was obtained from a non-UEA four-chamber view without manual correction. Thirty-one patients were excluded: 25 had interval interventions or incomplete TTE or cMRI studies and six had uninterpretable non-UEA apical views.RESULTS:In the 242 subjects, the correlation between AI and cMRI was r = .890, similar to MD-EF and cMRI with r = .891 (p = 0.48). Of the 126 studies performed with UEAs, the correlation of AI using the unenhanced four-chamber view was r = .89, similar to MD-EF with r = .90. In the 116 unenhanced studies, AI correlation was r = .87, similar to MD-EF with r = .84. From Bland-Altman analysis, LVivoEF underreported the LVEF with a bias of 3.63 ± 7.40% EF points compared to cMRI while MD-EF to cMRI had a bias of .33 ± 7.52% (p = 0.80).CONCLUSIONS:Compared to cMRI, LVivoEF can accurately quantify LVEF from a standard apical four-chamber view without manual correction. Thus, LVivoEF has the ability to improve and expedite LVEF quantification.

Introduction: Cardiac MRI (CMR) is the gold standard for right ventricular function (RVF) because echo assessment is limited. Potential echo parameters to assess RVF include RV fractional area change (FAC), RV free wall strain (FWS), and tricuspid annular plane systolic excursion (TAPSE) on apical 4-chamber (A4C) view. We compared a new Artificial Intelligence method that tracks the RV almost instantaneously in a single 4-chamber view (AI, LVivo RV®, DiA Imaging, Figure) to quantify RVF vs CMR. Methods: We compared AI RVF against CMR in 125 pts. Abnormal LVEF and RVEF were defined as <57% and <49% respectively. Echo closest to CMR date was analyzed with AI RV to obtain FAC, FWS, and TAPSE. We defined abnormal RVF by DiA Imaging’s predetermined thresholds. Sensitivities and specificities for abnormal RVF and chi-square (χ 2 ) tests were calculated for each variable against CMR RVEF. Results: Of the 125 pts, 55 (44%) were female with median age 55 [Q1 44, Q3 67] years. Thirty pts (24%) had abnormal RVEF and 78 (62.4%) had abnormal LVEF by CMR. All pts with abnormal RVEF had abnormal LVEF. Compared to CMR, AI RV sensitivities and specificities for abnormal RVEF were: FAC 87% and 60%, FWS 80% and 61%, TAPSE 77% and 54%, any 2 criteria 83% and 61%, and all 3 criteria 63% and 69%. AI RV χ 2 values were: FAC 19.9 (p<0.001), FWS 15.4 (p<0.001), TAPSE 8.4 (p=0.004), any 2 criteria 18.0 (p<0.001), and all 3 criteria 10.4 (p=0.001). Conclusions: This is the first validation of a novel AI method (LVivo RV®) that can detect RV dysfunction using 3 standard RV measurements from a single A4C view with good sensitivity and specificity compared to volumetric CMR as the gold standard.

Objectives: To identify echocardiographic signatures featuring left ventricular longitudinal strain (LS) associated with genetic risk for cardiac amyloidosis (CA) due to the TTR Val142Ile (V142I) variant in African American (AA) and Hispanic/Latinx (H/L) individuals. Background: Hereditary transthyretin amyloidosis (hATTR) can cause CA in 60-70% of older V142I carriers, but amyloid deposition progresses over many years. Disease-modifying therapy for CA is now available and early initiation is a priority for improving outcomes. Genomic screening programs and familial cascade genetic testing uncover pre-symptomatic V142I carriers, yet no guidelines exist for early CA detection. Methods: Exome sequencing data linked to electronic health records (EHRs) of BioMe biobank participants were queried for AA or H/L TTR- and TTR+ (V142I) subjects without hATTR diagnoses and with prior echocardiograms suitable for retrospective LS analysis. Systemic red flag features of ATTR were extracted from EHRs of TTR+ subjects. Speckle tracking echocardiography was retrospectively applied to determine global (GLS) and segmental LS. Relative apical sparing (RAS) was calculated. Results: 57 TTR+ and 46 TTR- age- and ancestry-matched subjects were included. GLS declined with age in females but not males, and was abnormal (<16%) in 18 (31.6%) TTR+ and 7 (15.2%) TTR- subjects (p = 0.066). Apical sparing was observed in 13 (22.8%) TTR+ and 11 (23.9%) TTR- subjects (p = 1.0). After adjusting for relevant demographic and echocardiographic covariates, neither GLS nor RAS was associated with TTR+ V142I status. Red flag features were not associated with GLS or RAS in TTR+ subjects. Conclusions: Neither GLS nor RAS were significantly different between TTR+ and TTR- subjects. Since >50% of TTR+ subjects were [≥] 60 years old, penetrance of CA by echocardiography among unselected V142I carriers may be lower than previously estimated. These findings indicate that surveillance for CA in individuals at increased genetic risk due to V142I should not rely solely on echocardiography, even with LS.

Pathogenic gene variants in transthyretin ( TTR ) can cause heritable amyloidosis (hATTR) and confer a 60% risk of heart failure. Echocardiography with global longitudinal strain (GLS) discriminates fully manifest cardiac amyloid (CA) but its ability to detect preclinical CA is unknown. We