Journal: J Am Soc Echocardiogr

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Abstract

Prognostic value of the MAGGIC score, HFPEF score and HFA-PEFF algorithm in patients with exertional dyspnea and the incremental value of exercise echocardiography.

Przewlocka-Kosmala M, Butler J, Donal E, Ponikowski P, Kosmala W
Background
The strategies for improving outcomes in heart failure with preserved ejection fraction (HFpEF) are insufficiently defined, which affects the optimal patient management. The aim of the study was to compare the prognostic value of previously validated the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score with two approaches primarily dedicated to diagnosing HFpEF: the H2FPEF score (Heavy, 2 or more Hypertensive drugs, atrial Fibrillation, Pulmonary hypertension [pulmonary artery systolic pressure>35 mm Hg], Elder age>60, elevated Filling pressures [E/e\'>9]) and the HFA-PEFF algorithm (Heart Failure Association - Pre-test assessment; Echocardiography and Natriuretic Peptide Score; Functional testing; Final aetiology) in patients with exertional dyspnea categorized as HFpEF.
Methods
Clinical and biochemical variables, and echocardiographic resting and exercise data from 201 enrollees were retrospectively analyzed. Participants were followed for 48 (24-60) months for HF hospitalization and cardiovascular death.
Results
Seventy-four patients (36.8%) met the study outcome. In sequential Cox analysis, the addition of each of the following: MAGGIC risk score, H2FPEF score, and HFA-PEFF step 2 (including only resting echocardiographic evaluation) and step 3 (including also exercise diastolic data) algorithm to the base model comprising BNP and peak VO2 improved the predictive power for the study endpoint. The Harrel\'s c-statistic showed a greater predictive ability for the HFA-PEFF step 3 algorithm than each of the other scores (c-index 0.715 vs. 0.637, 0.644 and 0.638 for MAGGIC, H2FPEF and HFA-PEFF step 2, respectively, all p<0.05). No significant differences were found for other between-score comparisons.
Conclusions
In patients with exertional dyspnea and a possible HFpEF, the H2FPEF score and HFA-PEFF algorithm limited to resting echocardiography provide prognostic value comparable to the MAGGIC risk score. Extending the HFA-PEFF algorithm with exercise diastolic data is associated with a significant improvement in risk stratification.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 20 May 2022; epub ahead of print
Przewlocka-Kosmala M, Butler J, Donal E, Ponikowski P, Kosmala W
J Am Soc Echocardiogr: 20 May 2022; epub ahead of print | PMID: 35605894
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Abstract

A Novel Approach for Semi Automated 3D Quantification of Mitral Regurgitant Volume Reflects a More Physiologic Approach to MR.

Singh A, Su J, This A, Allaire S, ... Lang RM, Bonnefous O
Background
Quantification of mitral regurgitation (MR) by echocardiography is an integral to assessing lesion severity, and entails integration of multiple Doppler-based parameters. These methods are primarily founded upon the principle of PISA (proximal isovelocity surface area), a 2D method known to employ several assumptions regarding MR jet characteristics. We analyzed the results of a semi-automated method of 3D-based RV estimation which accounts for jet behavior throughout the cardiac cycle, and compared it to conventional 2D PISA methods for MR.
Methods
A total of 50 patients referred for transesophageal echocardiogram (TEE) for evaluation of primary (n= 25) and secondary MR (n=25) were included for analysis. 3D full volume color data sets were acquired, along with standard 2D methods for PISA calculation. 3D semi-automated MR flow quantification algorithm was applied offline to calculate 3D regurgitant volume (RVol), with simultaneous temporal curves generated from the 3D dataset. 3DRvol was compared to 2DRVol. 3D vena contracta area was also performed in all cases.
Results
There was a modest correlation between 2DRVol and 3DRVol (r = 0.60). The semi-automated 3D approach resulted in significantly lower RV values compared to 2D PISA. Real-time and dynamic flow curve patterns were used for integral estimates of 3DRVol over the cardiac cycle, with a distinct bimodal pattern in functional MR, and brief and solitary peak in primary.
Conclusions
Using a semi-automated 3D software for quantification of mitral regurgitation allows for simultaneous calculation of 3D RVol with an automated generation of dynamic flow curves characteristic of the underlying MR mechanism. Our flow curve pattern results highlight well-known differences between MR flow dynamics in degenerative MR compared to functional MR.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 20 May 2022; epub ahead of print
Singh A, Su J, This A, Allaire S, ... Lang RM, Bonnefous O
J Am Soc Echocardiogr: 20 May 2022; epub ahead of print | PMID: 35605896
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Abstract

Implementation of Appropriate Use Criteria for Transthoracic Echocardiography in Follow up Care of Pediatric Patients with Congenital Heart Disease.

Patel T, Kelleman M, Pickard S, Miller J, Suthar D, Sachdeva R
Background
Indications for transthoracic echocardiography (TTE) from the 2020 Appropriate Use Criteria (AUC) for congenital heart disease (CHD) were incorporated into our electronic ordering system as a clinical decision support tool. The purpose of this study was to evaluate TTE utilization and factors affecting appropriateness of TTE orders during follow-up care of patients with CHD.
Methods
All TTEs performed during follow-up clinic visits from 5/1/2020 to 11/30/2020 were included. TTE indications were rated appropriate (A), may be appropriate (M), or rarely appropriate (R) based on the AUC, and unclassifiable if indication was not in the document but related to included lesions. CHD was graded as simple, moderate, and complex based on Bethesda classification. Logistic regression was used to determine association of ratings with patient age, insurance status, CHD complexity, clinician experience and specialty.
Results
Of the 5158 studies, 3979 (77.2%) were for CHD included in the AUC document, 322 (8%) were unclassifiable, 37 (0.7%) for CHD not in the document, and 1142 (22.1%) for non-CHD indications. Of the 3657 TTEs to which AUC ratings could be applied, 95.6% were A, 2.4% M, and 2.0% R. The highest utilization of TTE was for follow-up of ventricular septal defects, left ventricular outflow tract obstruction, and single ventricles; 46% for unrepaired CHD; 78% for routine surveillance and the remaining for a change in clinical status. On multivariable analysis, the only significant factor associated with M/R ratings was simple CHD [OR 11.58 (95% CI 5.36 - 24.98), p<0.001].
Conclusions
Three-quarters of the TTEs ordered during follow-up care in pediatric cardiology clinics are for indications related to CHD. Most TTEs for follow-up of CHD were for routine surveillance and indications rated A. TTE orders for M/R ratings were associated with simple CHD. Though the 2020 AUC document successfully stratifies majority of indications related to CHD, future documents should consider the unclassifiable CHD indications and the non-CHD indications.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 11 May 2022; epub ahead of print
Patel T, Kelleman M, Pickard S, Miller J, Suthar D, Sachdeva R
J Am Soc Echocardiogr: 11 May 2022; epub ahead of print | PMID: 35568251
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Abstract

Visualization and Quantification of the Unrepaired Complete Atrioventricular Canal Valve using Open-Source Software.

Nam HH, Herz C, Lasso A, Cianciulli A, ... Glatz AC, Jolley MA
Background
Repair of complete atrioventricular canal (CAVC) is often complicated by residual left atrioventricular valve regurgitation (AVVR). The structure of the mitral and tricuspid valves in biventricular hearts has previously been shown to be associated with valve dysfunction. However, the three-dimensional (3D) structure of the entire unrepaired CAVC valve has not been quantified. Understanding the 3D structure of the CAVC may inform optimized repair.
Methods
We created novel open-source workflows in SlicerHeart for the modeling and quantification of CAVC valves based upon 3D echocardiogram (3DE) images. We applied these methods to model the annulus, leaflets, and papillary muscle structure of 35 patients (29 with Trisomy 21) with CAVC using transthoracic 3D echocardiograms. The mean leaflet and annular shapes were calculated and visualized using shape analysis. Metrics of the complete native CAVC valve structure were compared to normal mitral valves, using the Mann-Whitney U test. Associations between CAVC structure and AVVR were analyzed.
Results
CAVC leaflet metrics vary throughout systole. Compared to normal mitral valves, the left CAVC PMs are more acutely angled in relation to the annular plane (p<0.001). In addition, the antero-lateral PM is laterally and inferiorly rotated in CAVC, while the postero-medial PM is more superiorly and laterally rotated, relative to normal mitral valves(p<0.001). Lower native CAVC atrioventricular valve annular height and annular height-to-width ratio (AHWR) prior to repair are both associated with moderate or greater left atrioventricular valve (LAVV) regurgitation after repair (p<0.01).
Conclusions
It is feasible to model and quantify 3D CAVC structure using 3DE images. We demonstrate significant variation in CAVC structure across the cohort and differences in annular, leaflet and PM structure compared to the mitral valve. These tools may be used in future studies to catalyze future research intended to identify structural associations of valve dysfunction and to optimize repair in this vulnerable and complex population.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 07 May 2022; epub ahead of print
Nam HH, Herz C, Lasso A, Cianciulli A, ... Glatz AC, Jolley MA
J Am Soc Echocardiogr: 07 May 2022; epub ahead of print | PMID: 35537615
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Abstract

Atrioventricular coupling in infants and children assessed by three-dimensional echocardiography.

Linden K, Otte F, Winkler C, Laser KT, ... Breuer J, Herberg U
Background
Parameters of the interaction of the left atrium (LA) and left ventricle (LV), the atrioventricular coupling (AV coupling), are used in diagnosis and follow up of diastolic dysfunction in adults. Pediatric parameters of AV coupling have not been evaluated so far. The aim of this multicenter study was to investigate parameters of AV coupling in a large cohort of healthy infants and children by noninvasive real-time three-dimensional echocardiography (3DE). We hypothesize that the contribution of the different LA volumes to LV stroke volume differs over a range of different heart rates.
Methods
3DE data sets of 332 subjects (0 days-18.5 years) were analyzed prospectively. Volume-time curves of the LA and LV were generated. Conduit volume was calculated and percentiles were established by the LMS-method of Cole and Green. Contribution of active, passive and conduit volume to LV filling was measured and related to heart rate by linear regression. LV and LA peak filling and peak emptying rates (PFR, PER) and time to PFR and PER normalized to the R-R interval (PFRt(%), PERt(%)) were measured and correlated to each other.
Results
Conduit volume increased with body surface area. Contribution of LA active emptying to LV filling tended to increase with decreasing heart rates while contribution of passive emptying decreased. Conduit volume contributed most to LV filling (median 57.58 %, IQR 12.85%) with a tendency to increase with decreasing heart rates. Close diastolic AV coupling was demonstrated by virtually identical LV-PFRt(%) and LA-PERt(%) during diastole. LV-PERt(%) occurred earlier than LA-PFRt(%) showing less coupling during systole. LV-PFRt(%) and LA-PERt(%) were strongly correlated to heart rate (r = 0.76 and 0.73). Lower heart rates resulted in a prolongation of diastole after LV-PFR.
Conclusions
Assessment of conduit volume and AV coupling by 3DE is feasible in infants and children. The references of this study can serve as a basis to further investigate the role of parameters of AV coupling in pediatric patients with heart diseases concerning diastolic and LA function.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 07 May 2022; epub ahead of print
Linden K, Otte F, Winkler C, Laser KT, ... Breuer J, Herberg U
J Am Soc Echocardiogr: 07 May 2022; epub ahead of print | PMID: 35537616
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Abstract

Incremental Prognostic Value of Left Ventricular Global Longitudinal Strain in Patients with Preserved Ejection Fraction Undergoing Transcatheter Aortic Valve Implantation.

Lee SH, Oh JK, Lee SA, Kang DY, ... Choi JH, Kim DH
Background
Evaluation of left ventricular global longitudinal strain (LVGLS) has allowed better characterization than LVEF of subtle differences in LV performance. We aimed to determine whether LVGLS has a prognostic value in patients with severe aortic stenosis (AS) and a preserved LV ejection fraction (LVEF) undergoing transcatheter aortic valve implantation (TAVI).
Methods
Among 412 consecutive patients who underwent TAVI, 344 patients (mean age, 78.9±5.0 years; 161 men) with a preserved LVEF (≥50%) at baseline were analyzed. Patients with low LVEF (<50%) were used as comparison group in the survival analysis. The primary and secondary endpoints were all-cause death and a composite of cardiovascular death and heart failure hospitalization, respectively.
Results
The mean LVGLS and LVEF values were -17.1±2.7% and 63±5%, respectively. Impaired LVGLS was defined as >-16%, which was the first LVGLS quartile (cutoff value, -16%). The estimated actuarial 5-year survival rate was 81.7±4.2% in the normal LVGLS group and 66.8±7.5% in the impaired LVGLS group (p=0.005). In the multivariable analysis, an impaired LVGLS was an independent predictor of all-cause death (adjusted hazard ratio [HR], 2.26; 95% confidence interval [CI], 1.11-4.60) and the composite outcome (adjusted HR, 3.03; 95% CI, 1.45-6.33). Moreover, the impaired LVGLS group had a poor prognosis similar to the impaired LVEF group (≤50%). The addition of the absolute value of LVGLS to the clinical parameters and LVEF led to significant improvement in the prediction of all-cause mortality.
Conclusion
In patients with severe AS and a preserved LVEF undergoing TAVI, subclinical LV dysfunction defined by an impaired LVGLS is independently associated with poor clinical outcomes. The LVGLS measurement provides an incremental prognostic value above the established clinical and echocardiographic parameters.
Clinical trial registration
http://www.
Clinicaltrials
gov (unique identifier: NCT03298178).

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 30 Apr 2022; epub ahead of print
Lee SH, Oh JK, Lee SA, Kang DY, ... Choi JH, Kim DH
J Am Soc Echocardiogr: 30 Apr 2022; epub ahead of print | PMID: 35504527
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Abstract

Relation Between Early Diastolic Mid-Ventricular Flow and Elastic Forces Indicating Aneurysm Formation in Hypertrophic Cardiomyopathy.

Strachinaru M, Huurman R, Bowen DJ, Schinkel AF, Hirsch A, Michels M
Background
The early diastolic paradoxical mid-ventricular flow (EDF) is suggestive of apical aneurysm (AA) formation in hypertrophic cardiomyopathy (HCM). We aimed to determine whether EDF may be a useful screening tool in patients, following the time progression of HCM to the aneurysmal stage.
Methods
121 HCM patients with dominant hypertrophy in the mid and apical segments, based on echocardiography and/or cardiovascular magnetic resonance (CMR), were selected from our HCM database comprising 1332 patients. They were further stratified according to the presence of AA. All imaging studies in a period of 16 years (2005-2021) were considered for time progression. Mid-ventricular Doppler (PW, CW, color and color M-mode) were analyzed.
Results
35 patients (29% of the study group and 2.6% of all HCM patients) had AA. EDF had a sensitivity of 92% and specificity of 98.6% for the detection of AA in the study group. In 108 patients follow-up echocardiography was performed (median 5 [3-9] studies). Sixteen patients (15%), with 10 [7-12] years follow-up, displayed progressive time changes in LV apical morphology and/or mid-LV flow. Ten patients (9%) progressed to an AA, during 7 [4-11] years follow-up. Patients progressing to AA were younger (p=0.009), with more severe LV hypertrophy (p=0.01) and more often a significant mid-LV systolic gradient (≥ 30mmHg, p<0.001). A wall thickness over 20mm had 70% sensitivity and 69% specificity in detecting evolution towards AA. With significant systolic gradient, sensitivity was 80% and specificity 62%. Furthermore, patients with AA had higher incidence of ventricular tachycardia (Log-rank p=0.03).
Conclusion
EDF reliably detects AA presence and should prompt for extra imaging studies. In HCM with mid and apical dominant involvement there is a progressive trend towards aneurysm formation, especially in patients with wall thickness over 20mm and significant mid-LV systolic gradient (≥30mmHg), which can be monitored through serial Doppler studies.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 27 Apr 2022; epub ahead of print
Strachinaru M, Huurman R, Bowen DJ, Schinkel AF, Hirsch A, Michels M
J Am Soc Echocardiogr: 27 Apr 2022; epub ahead of print | PMID: 35489541
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Abstract

Cardiac Imaging for Diagnosis and Management of Infective Endocarditis.

Silbiger JJ, Rashed E, Chen H, Wiesenfeld E, Robinson SE, Cagliostro M
Imaging is central to the care of patients with infective endocarditis. While transthoracic and transesophageal echocardiography are the principle imaging techniques, additional modalities including positron emission tomography and cardiac computed tomography, and to a lesser extent intracardiac echocardiography, play an increasing role. This review discusses the role of cardiac imaging in establishing the diagnosis of endocarditis, in predicting its embolic risk and in making decisions regarding the need for and timing of surgery.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 26 Apr 2022; epub ahead of print
Silbiger JJ, Rashed E, Chen H, Wiesenfeld E, Robinson SE, Cagliostro M
J Am Soc Echocardiogr: 26 Apr 2022; epub ahead of print | PMID: 35487472
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Abstract

Color Doppler splay in mitral regurgitation: hemodynamic correlates and outcome in a clinical cohort.

Verbeke J, Kamoen V, Calle S, De Buyzere M, Timmermans F
Background
Recently, an artifactual horizontal extension of the color Doppler signal was described in patients with mitral regurgitation (MR), called color Doppler splay (CDS). This side-lobe artifact was shown to be associated with concealed and significant MR. In the current study, we assessed the prognostic significance of CDS and its hemodynamic correlates.
Methods
Consecutive patients with primary and secondary MR underwent comprehensive transthoracic echocardiography. Machine settings were fixed for all patients. MR severity was assessed using an integrated approach, as advocated by current international guidelines. The presence of CDS, CDS width and duration were assessed. The outcome measures included the incidence of major adverse cardiac events (composite of cardiovascular mortality, hospitalization for decompensated heart failure, mitral valve surgery or percutaneous mitral intervention).
Results
127 out of 469 (27%) patients with MR demonstrated CDS. The presence of CDS was associated with worse MR, and CDS width correlated with effective regurgitant orifice area, regurgitant volume and vena contracta width. Mitral annular or leaflet calcification was inversely associated with the presence of CDS. Patients with CDS experienced worse event-free survival. For CDS width, a cutoff >29 mm was identified as optimal regarding outcome prediction in our cohort and termed \'severe CDS\'. In multivariate Cox regression, the presence of severe CDS was associated with adverse outcome, independent of MR etiology or severity and other clinical and echocardiographic predictors of outcome, and provided incremental prognostic value on top of these parameters.
Conclusions
In patients with MR, the presence of CDS is associated with more severe MR and worse outcome. Severe CDS provides incremental prognostic value on top of traditional MR metrics and should alert the echocardiographer that MR severity may be underestimated.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 23 Apr 2022; epub ahead of print
Verbeke J, Kamoen V, Calle S, De Buyzere M, Timmermans F
J Am Soc Echocardiogr: 23 Apr 2022; epub ahead of print | PMID: 35472569
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Abstract

Adverse Prognostic Impact of Even Mild or Moderate Tricuspid Regurgitation: Insights from The National Echocardiography Database of Australia.

Offen S, Playford D, Strange G, Stewart S, Celermajer DS
Background
The prevalence and prognostic impact of tricuspid regurgitation (TR) remains incompletely characterized.
Methods
The distribution of TR severity was analyzed in 439,558 adults (mean age 62.1 ±17.8 years, 51.5% men) being investigated for heart disease, from 2000-2019, by 25 centers contributing to the National Echocardiography Database of Australia. Survival status and cause of death were ascertained, in all adults, from the National Death Index of Australia. The relationship between TR severity and mortality was examined.
Results
Of those studied, 311,604 (70.9%) had no/trivial TR; 94,172 (21.4%) mild TR; 26,056 (5.9%) moderate TR; and 7,726 (1.8%) severe TR. During a median 4.1 years (interquartile range 2.2-7.0 years) follow up, 109,004 died (49% from cardiovascular causes). Moderate or greater TR was associated with older age and female sex (p<0.001). Individuals with moderate and severe TR had a 2.0- to 3.2-fold increased risk of all-cause long-term mortality after adjustment for age and sex, compared to those with no/trivial TR (p<0.001 for both comparisons). Even those with mild TR had a significantly increased risk for mortality (HR 1.29, 95% CI 1.27-1.31). In fully adjusted models, including for RV systolic pressure, atrial fibrillation and significant left-heart disease, there remained a 1.24 to 2.65-fold increased risk of mortality with mild (HR 1.24, 95% CI 1.23-1.26), moderate (HR 1.72, 95% CI 1.68-1.75) or severe TR (HR 2.65, 95% CI 2.57-2.73), compared to those with no/trivial TR (p<0.001 for all).
Conclusions
TR is a common condition in adults referred for echocardiography. Moreover, even in the presence of other cardiac disease, increasing grades of TR are independently associated with increasing risks of CV and all-cause mortality. Furthermore, we show that even mild TR is independently associated with a significant increase in mortality.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 11 Apr 2022; epub ahead of print
Offen S, Playford D, Strange G, Stewart S, Celermajer DS
J Am Soc Echocardiogr: 11 Apr 2022; epub ahead of print | PMID: 35421545
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Abstract

Prevalence of Right Atrial Impairment and Association with Outcomes in Cardiac Amyloidosis.

Singulane CC, Slivnick JA, Addetia K, Asch F, ... Mor-Avi V, Lang RM
Background
Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy in which abnormally folded proteins deposit within the myocardium and the atrial walls. While left atrial dysfunction has been previously reported, the impact of CA on right atrial (RA) structure and function is unknown.
Methods
We retrospectively studied 118 patients (67 immunoglobulin light chain [AL-CA], 51 transthyretin [ATTR-CA]; age 70±12, 57% male) who underwent transthoracic echocardiogram (TTE) in sinus rhythm. RA reservoir, conduit, and booster strain were quantified using speckle tracking and compared between CA and 50 healthy age, sex-, and race-matched controls using chi-squared or Mann-Whitney test. The relationship between RA parameters and mortality was assessed using Cox regression.
Results
RA volume was significantly larger in CA compared to controls: 29[22 - 37] vs 21[15 - 25] mL/m2, p<0.001. RA reservoir (21[14 - 35] vs 37[34 - 43]%, p<0.001), conduit 11[18 - 6] vs 14[11 - 17]%, p<0.001) and booster (10[17 - 5] vs 23[20 - 27]%, p<0.001) strains were all significantly more impaired in the CA group compared with controls. Compared with AL-CA, ATTR-CA patients had significantly larger RA volume (34[26 - 44] vs 28[20 - 35] mL/m2, p=0.005) and significantly more impaired RA reservoir (17[10 - 30] vs 27[17 - 37]%, p=0.007), conduit (8[13 - 6] vs 13[20 - 8]%, p=0.031), and booster (7[14 - 4] vs 11[18 - 6]%, p=0.030) strain. Among CA patients, RA reservoir (HR 0.97 per %, p=0.006) and RA conduit (HR 1.05 per %, p=0.004) were significantly associated with mortality, while RA volume (p=0.362) and RA booster strain (p=0.180) were not.
Discussion
In CA, abnormalities in RA size and strain are highly prevalent and associated with worse prognosis, suggesting the presence of intrinsic RA atriopathy. RA strain appears to be a potentially useful marker in the diagnosis, subtype differentiation and risk stratification of CA.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 07 Apr 2022; epub ahead of print
Singulane CC, Slivnick JA, Addetia K, Asch F, ... Mor-Avi V, Lang RM
J Am Soc Echocardiogr: 07 Apr 2022; epub ahead of print | PMID: 35398489
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Abstract

Longitudinal arrhythmic risk assessment based on ejection fraction in patients with recent-onset non-ischemic dilated cardiomyopathy.

De Angelis G, Merlo M, Barbati G, Bertolo S, ... Adamo L, Sinagra G
Background
Practice guidelines suggest implantable cardioverter defibrillators (ICD) in patients with left ventricular ejection fraction (LVEF) ≤35% despite 3-6 months of guideline-directed medical therapy (GDMT). It remains unclear whether this strategy is appropriate for patients with dilated cardiomyopathy (DCM), who can experience reverse ventricular remodeling for up to 24 months after initiation of GDMT. We sought to assess the longitudinal dynamic relationship between LVEF ≤35% and arrhythmic risk in patients with recent onset non-ischemic DCM under GDMT.
Methods
We retrospectively analyzed patients with recent onset DCM (≤6 months) and recent initiation of GDMT (≤3 months), consecutively enrolled in a longitudinal registry. We assessed risk of major ventricular arrhythmic events or sudden cardiac death (MVAs/SCD) in relationship to LVEF ≤35% at enrollment, 6-months and 24-months post initiation of GDMT.
Results
544 patients met inclusion criteria. LVEF ≤35% identified patients with increased risk of MVAs/SCD starting from 24-months after initiation of GDMT (hazard ratio 2.126, 95% confidence interval 1.065-4.245, p=0.03). However, LVEF ≤35% at presentation or at 6 months post enrollment did not have prognostic significance. 67% of 131 patients with LVEF ≤35% at 6 months after initiation of GDMT improved their LVEF to >35% by 24 months. This late LVEF improvement correlated with a lower arrhythmic risk (p=0.012) and was preceded by a reduction of LV dimensions in the first 6 months of GDMT.
Conclusions
In patients with DCM, our findings suggest risk stratification for major ventricular arrhythmic events or sudden cardiac death based on LVEF ≤35% is effective after 2 years of GDMT, but not after 6 months. In selected DCM patients, it would be appropriate to wait 24 months before primary prevention ICD implantation.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 31 Mar 2022; epub ahead of print
De Angelis G, Merlo M, Barbati G, Bertolo S, ... Adamo L, Sinagra G
J Am Soc Echocardiogr: 31 Mar 2022; epub ahead of print | PMID: 35367610
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Abstract

Association of Post-procedural Left Atrial Volume and Reservoir Function with Outcomes in Patients with Atrial Fibrillation Undergoing Catheter Ablation.

Wen S, Pislaru SV, Lin G, Scott CG, ... Kane GC, Pislaru C
Background
The value of left atrial (LA) volume and reservoir function (ResF) after ablation for atrial fibrillation (AF) for predicting overall outcomes needs further investigations particularly in large cohorts. Our aim was to test the hypothesis that abnormal LA volume and ResF post-ablation are associated with adverse outcomes.
Methods
Patients who underwent primary AF ablation between 2007-2016 and had available measurements of LA volume index [maximum (LAVImax) and minimum (LAVImin)] and LA ResF [emptying fraction (LAEF) and expansion index (LAEI)] at 3-month echocardiographic examination post-ablation were included in this analysis. Primary endpoint was the composite of cardiac hospitalization for heart failure or acute ischemic events, stroke/TIA, and all-cause death; secondary endpoints were cardiac hospitalization and all-cause death.
Results
A total of 792 patients were studied (age 60±10 years). Over a median of 7.5 [IQR 3.0-9.7] years follow-up, 96 patients experienced adverse events. After adjustment for several parameters including age, comorbidities, and left ventricular structure and function, increased LA volumes and impaired ResF were each independently associated with primary endpoint (LAVImax >34 ml/m2: adjusted-HR 2.37 [95% CI, 1.49-3.76], P=0.0003; LAVImin ≥20.5 ml/m2: adjusted-HR 3.21 [1.97-5.24], P<0.0001; LAEF <40%: adjusted-HR 2.00 [1.29-3.10], P=0.002; LAEI <66%: adjusted-HR 1.91 [1.22-2.98], P=0.005) as well as with secondary endpoints of cardiac hospitalization (P<0.05 for adjusted-HR for all LA parameters) and all-cause death (P<0.05 for adjusted-HR for LAVImin, LAEF and LAEI). ResF measures were incremental to LAVImax (all P<0.05), but not to LAVImin. In patients with normal LA (LAVImax ≤34 ml/m2; n=403), those with higher LAVImin (≥17 ml/m2) were at 4-times higher risk of primary endpoint events (age-adjusted HR 4.32 [1.90-9.81], P=0.0005). All these findings were independent of atrial tachyarrhythmia (ATa) recurrence.
Conclusions
Enlarged LA and impaired ResF at 3-month post-ablation for AF are strongly associated with long-term outcomes, independent of LV function or cardiac rhythm at follow-up. LAVImin showed the strongest associations and even identified a high-risk subgroup among patients with non-dilated LA.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 25 Mar 2022; epub ahead of print
Wen S, Pislaru SV, Lin G, Scott CG, ... Kane GC, Pislaru C
J Am Soc Echocardiogr: 25 Mar 2022; epub ahead of print | PMID: 35346805
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Abstract

The Impact of Maternal Hyperoxygenation on Myocardial Deformation and Loading Conditions in Fetuses With and Without Left-Heart Hypoplasia.

Cox KL, Morris SA, Tacy T, Long J, ... Zhang Rdcs J, Maskatia SA
Background
Maternal hyperoxygenation (MHO) is used in a variety of clinical applications, but its impact on fetal cardiovascular physiology is poorly understood. Our aims were: to describe the effects of MHO on myocardial deformation parameters and on ultrasound-based metrics of preload and afterload, and to assess the differential effect of MHO on fetuses with left heart hypoplasia (LHH). We hypothesized that the effects of MHO would be modulated by loading conditions, and that fetuses with LHH would be more sensitive to changes in preload and afterload induced by MHO.
Methods
We performed a post-hoc analysis of 36 fetal echocardiograms performed as part of a pilot study of MHO in LHH (n=9) and control (n=9) fetuses. Oxygen was administered via 8L face mask for 10 minutes. RV and LV longitudinal strain and strain rate, estimated aortic and pulmonary cardiac output, pulmonary vein velocity time integral (VTI) and pulsatility indices (PI) of the middle cerebral artery (MCA), pulmonary arteries (PA) and umbilical artery (UA) were measured at 3 time points: baseline, during MHO, and 10 minutes after removal of MHO.
Results
MHO induced decreases in LV strain and strain rate and increases in RV strain and strain rate. PA PI decreased and pulmonary vein VTI increased suggesting decreased pulmonary vascular resistance and increased pulmonary venous return. Most findings did not return to baseline after removal of MHO. We found no significant effect of MHO on MCA or UA PI. LHH cases demonstrated similar effects of MHO to control cases, with larger changes in pulmonary vein VTI and LV strain rate.
Conclusion
The effects of MHO on LV and RV mechanics suggest that changes in deformation indices may be explained by increases in LV preload and decreases in RV afterload. The time period for recovery of fetal hemodynamics from MHO is ill-defined.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 25 Mar 2022; epub ahead of print
Cox KL, Morris SA, Tacy T, Long J, ... Zhang Rdcs J, Maskatia SA
J Am Soc Echocardiogr: 25 Mar 2022; epub ahead of print | PMID: 35346806
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Abstract

Automated Global Longitudinal Strain Exhibits a Robust Association with Death in Asymptomatic Chronic Aortic Regurgitation.

Yang LT, Takeuchi M, Scott CG, Thapa P, ... Enriquez-Sarano M, Michelena HI
Background
Whether automated left ventricular global longitudinal strain (LVGLS) is associated with outcomes in asymptomatic aortic regurgitation (AR) is unknown.
Objective
To explore the impact of automated LVGLS on survival and compare it with conventional LV parameters in chronic asymptomatic AR.
Methods
LVGLS (presented as absolute value) was measured using fully-automated two-dimensional strain software in consecutive patients with isolated chronic ≥moderate-severe AR between 2004 and 2020; incremental value of LVGLS was assessed. Limited correction of endocardial border tracking was performed if needed.
Results
Of 550 asymptomatic patients (age 60±17 years; 86% men), average LVGLS was 17±3% (1st and 2nd tertile, 15.8% and 18.5%). In 16% cases, tracking border was partially corrected; average time for analysis was 25±5 seconds. At a median (interquartile range) of 4.8(1.5-9.9) years, 87 patients had died (19 died after aortic-valve surgery [AVS]). Separate multivariable models adjusted for age, sex, Charlson index, AR severity and time-dependent AVS demonstrated that LVEF(hazard ratio[HR] per 10%: 0.9), LV end-systolic volume index(LVESVi; HR per 5ml/m2: 1.08) and LVGLS(HR per unit: 0.87) were independently associated with death(all p≤0.018); however, LVGLS remained statistically significant (HR: 0.86-0.9; P≤0.007) as compared head-to-head to LVEF, LVESVi and LV end-systolic dimension index(LVESDi). The association of LVGLS and mortality was consistent across all subgroups (P for interaction all≥0.08). Spline curves showed that continuous risk of death rose at LVGLS <15%. Those with LVGLS <15% had 2.6-fold risk of death [95% CI 1.54-4.23] while those with LVGLS <15% plus LVESVi≥45ml/m2 had 3.96-fold risk[95% CI 1.94-8.03].
Conclusion
In this large cohort of asymptomatic patients with ≥moderate-severe AR, automated LVGLS was feasible, efficient, and independently associated with death on head-to-head comparison with conventional LVEF, LVESDi, and LVESVi. The automated-LVGLS threshold of <15% alone or combined with LVESVi≥45ml/m2, was significantly associated with increased mortality risk and may be considered in early surgery decision-making.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 24 Mar 2022; epub ahead of print
Yang LT, Takeuchi M, Scott CG, Thapa P, ... Enriquez-Sarano M, Michelena HI
J Am Soc Echocardiogr: 24 Mar 2022; epub ahead of print | PMID: 35341954
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Abstract

Understanding Complex Interactions in Pediatric Diastolic Function Assessment.

Nguyen MB, Dragulescu A, Chaturvedi R, Fan CS, ... Friedberg MK, Mertens LL
Background
Diagnosing left ventricular diastolic dysfunction (DD) non-invasively in children is difficult as no validated pediatric diagnostic algorithm is available. The aim of this study is to explore the use of machine learning (ML) to develop a model that uses echocardiographic measurements that explains patterns in invasively measured markers of DD in children.
Methods
We enrolled children at-risk for developing DD including patients with Kawasaki disease, heart transplant, aortic stenosis, and coarctation of the aorta when undergoing clinical left heart catheterization. We obtained simultaneous invasive pressure measurements with high-fidelity catheter (time constant of isovolumic relaxation [Tau], LV end diastolic pressure [LVEDP], -dP/dt max) and echocardiographic DD measurements. Spearman correlations were performed for each echo feature with invasive markers to understand pairwise relationships. Separate random forest (RF) models were implemented to assess all echocardiographic features, key demographic data, and clinical diagnosis in predicting invasive markers. A backward stepwise regression model was simultaneously implemented as a comparative conventional reference model. The relative importance of all parameters was ranked in terms of accuracy reduction. Model approximation was then performed using a regression tree with the top ranked features of each RF model to improve model interpretability. Regression coefficients of the linear models were presented.
Results
Fifty-nine children were included. Spearman correlations were generally low. The RF models\' performance measures were non-inferior to the linear model. However, the linear model\'s regression coefficients were unintuitive. The highest-ranked important features for the RF models were propagation velocity (Vp) for Tau; E/Vp ratio for LVEDP; and systolic global longitudinal strain rate for -dP/dt max.
Conclusions
Estimating individual components of DD can potentially improve the noninvasive assessment of pediatric DD. Although pairwise correlations measured were weak and linear regression coefficients unintuitive, approximated ML models aided in understanding how echocardiographic and invasive parameters of DD are related. This ML approach could help in further development of pediatric-specific diagnostic algorithms.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 24 Mar 2022; epub ahead of print
Nguyen MB, Dragulescu A, Chaturvedi R, Fan CS, ... Friedberg MK, Mertens LL
J Am Soc Echocardiogr: 24 Mar 2022; epub ahead of print | PMID: 35341955
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Abstract

Left Ventricular Global Longitudinal Strain in Patients with Moderate Aortic Stenosis.

Stassen J, Pio SM, Ewe SH, Singh GK, ... Delgado V, Bax JJ
Moderate aortic stenosis (AS) is associated with an increased risk for adverse events. Although reduced left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe AS, its prognostic value in patients with moderate AS is unknown. The aim of this study was to investigate the prognostic implications of LV GLS in patients with moderate AS.
Methods
LV GLS was evaluated using speckle-tracking echocardiography in patients with moderate AS (aortic valve area 1.0-1.5 cm2) and reported as absolute (i.e., positive) values. Patients were divided into three groups: LV ejection fraction (LVEF) < 50% (group 1), LVEF ≥ 50% but LV GLS < 16% (group 2), and LVEF ≥ 50% and LV GLS ≥ 16% (group 3). The LV GLS value of 16% was based on spline curve analysis. The primary end point was all-cause mortality.
Results
A total of 760 patients (mean age, 71 ± 12 years; 61% men) were analyzed. During a median follow-up period of 50 months (interquartile range, 26-94 months), 257 patients (34%) died. Patients with LVEF < 50% and LVEF ≥ 50% but LV GLS < 16% showed significantly higher mortality rates at 1-, 3-, and 5-year follow-up (82%, 71%, and 58%; and 92%, 77%, and 58%, respectively) compared with those with LVEF ≥ 50% and LV GLS ≥ 16% (96%, 91%, and 85%, respectively; P < .001). Long-term outcomes were not different between patients with LVEF < 50% and those with LVEF ≥ 50% but LV GLS < 16% (P = .592). LV GLS discriminated higher risk patients even among those with LVEF ≥ 60% (P < .001) or those who were asymptomatic (P < .001). On multivariable analysis, LVEF < 50% (hazard ratio, 2.384; 95% CI, 1.614-3.522; P < .001) and LVEF ≥ 50% but LV GLS < 16% (hazard ratio, 2.467; 95% CI, 1.802-3.378; P < .001) were independently associated with all-cause mortality.
Conclusions
In patients with moderate AS, reduced LV GLS is associated with an increased risk for all-cause mortality, even if LVEF is still preserved.

Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 15 Mar 2022; epub ahead of print
Stassen J, Pio SM, Ewe SH, Singh GK, ... Delgado V, Bax JJ
J Am Soc Echocardiogr: 15 Mar 2022; epub ahead of print | PMID: 35301093
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Abstract

The Diagnostic Role of Echocardiographic Strain Analysis in Patients Presenting with Chest Pain and Elevated Troponin: A Multicenter Study.

Schauer J, Caris E, Soriano B, Ait-Ali L, ... Ferguson M, Buddhe S
Background
Myocarditis presenting as acute chest pain with elevated troponins without significant cardiac compromise is rare in previously healthy children, often referred to as myopericarditis. Diagnosis is challenging as conventional echocardiographic measures of systolic function can be normal. This study aimed to demonstrate the diagnostic utility of strain imaging in this scenario.
Methods
This is a multi-center retrospective study including patients presenting with chest pain and elevated troponin from 10 institutions who underwent cardiac MRI (CMR) and transthoracic echocardiogram (echo) within 30 days of each other (group 1). Findings were compared to 19 controls (group 2). Clinical data, conventional echo and CMR data were collected. Echo-derived strain was measured at the core lab. Group 1 was divided into subgroups as CMR myocarditis positive (group 1a) or negative (group 1b) based on established criteria.
Results
Group 1 included 108 subjects (88 in group 1a, 20 in group 1b). While all groups had normal mean fractional shortening (FS) and mean left ventricular ejection fraction (LVEF), group 1 had significantly lower EF (56.8+/-7.0) compared to group 2 ( 62.3+/- 4.9, P<0.005) and FS (31.2+/- 4.9) compared to group 2 (34.1+/-3.5, p<0.05). Additionally, peak global longitudinal strain (GLS%) was markedly abnormal in group 1 (-13.9+/-3.4 ) compared to group 2 (-19.8+/-2.1 , P<0.001). In subgroup analysis, GLS% was markedly abnormal in group 1a (-13.2 ± 3.0%) compared to group 1b (-17.3 ± 2.6% and p<0.001). Fifty-four subjects had follow up echocardiograms (46 in group 1a, 8 in group 1b) with mean follow-up time of 10 months (SD=11 months). At follow up, while EF and FS returned to normal in all patients, abnormalities in strain persisted in group 1, with 22% of them still having abnormal GLS. Moreover, mean GLS was more abnormal in group 1a (-16.1 +/- 2.6) compared to group 1b (-17.4+/- 1.2, p<0.05).
Conclusions
Our study demonstrates that echo GLS% is significantly worse in subjects with myopericarditis presenting with chest pain and elevated troponins compared to controls even when conventional measures of systolic function are largely normal and that these abnormalities persisted overtime.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 14 Mar 2022; epub ahead of print
Schauer J, Caris E, Soriano B, Ait-Ali L, ... Ferguson M, Buddhe S
J Am Soc Echocardiogr: 14 Mar 2022; epub ahead of print | PMID: 35301094
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Abstract

Comparison of mitral regurgitant volume assessment between proximal flow convergence and volumetric methods in patients with significant primary mitral regurgitation: an echocardiographic and CMR study.

Altes A, Levy F, Iacuzio L, Dumortier H, ... Tribouilloy C, Maréchaux S
Background
Discrepancies have been observed between transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR) severity grading in primary mitral regurgitation (MR).
Objectives
We sought to compare mitral regurgitant volume (RVol) determined by the TTE proximal flow convergence (proximal isovelocity surface area [PISA]) method and by volumetric methods (TTE and CMR), and to study the relationship between left ventricle (LV) size and RVol obtained by either the PISA or volumetric methods.
Methods
Two centers prospectively recruited 188 patients with at least moderate-to-severe primary MR due to prolapse in sinus rhythm who underwent TTE and CMR examinations. RVol was estimated by either PISA (PISA-RVol) or volumetric methods (total LV stroke volume - systolic aortic forward outflow volume) using either CMR (CMR-RVol) or TTE (TTE-RVol).
Results
PISA-RVol was weakly correlated with CMR-RVol and TTE-RVol (r=0.29 and 0.30, respectively, P<0.001 for both). On multivariable analysis, smaller CMR-LVEDV and absence of mitral annular disjunction independently correlated with increased magnitude of RVol difference between PISA and volumetric methods. While PISA-RVol and LVEDV were unrelated, CMR-RVol and TTE-RVol moderately correlated with LVEDV (r=0.66 and 0.68, respectively, P<0.001 for both). In contrast, LVEDV and regurgitant fraction (RF = RVol/LVEDV), assessed with either TTE or CMR, were poorly correlated (r=0.17, P=0.02 and r=0.12, P=0.10, respectively).
Conclusions
Mitral regurgitant volume values estimated by PISA and volumetric methods are not directly comparable. The expected proportional relationship between volumetric RVol and LV size, which was not observed with PISA-RVol, suggests PISA-RVol would be inaccurate. Given that RVol assessed with volumetric methods depends on LV size, determination of a unique RVol threshold for severe MR is challenging. In contrast to RVol, calculating RF by volumetric methods allows to quantify MR severity independently from LV size.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 10 Mar 2022; epub ahead of print
Altes A, Levy F, Iacuzio L, Dumortier H, ... Tribouilloy C, Maréchaux S
J Am Soc Echocardiogr: 10 Mar 2022; epub ahead of print | PMID: 35288306
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Abstract

Accuracy of Fetal Echocardiography in Defining Anatomical Details: A Single Institutional Experience Over a 12-year Period.

Haberer K, He R, McBrien A, Eckersley L, ... Adatia I, Hornberger Fase LK
Background
Fetal echocardiography (FE) has evolved over four decades, now permitting the prenatal diagnoses of most major congenital heart disease (CHD). To identify areas for targeted improvement, we explored the diagnostic accuracy of FE in defining major fetal CHD.
Methods
All fetuses with major fetal CHD (11 subtypes) were identified in our institution between 2007-2018 (n=827). We compared FE reports to postnatal imaging and surgical or autopsy reports and categorized findings into: 1, no errors, and 2, minor errors without impact on care, considered \"accurate\" and 3, errors with minor impact on surgical approach, and 4, errors with major impact on neonatal care/outcomes, considered \"inaccurate\". We further examined the contribution of era, gestational age at first FE, serial FE, maternal weight and reviewer level of training.
Results
Of 589 fetuses with autopsy or postnatal confirmation, an accurate diagnosis was made in 530(90%). Highest rates of accuracy were observed in univentricular hearts (97.6%, 87.4-99.6%CI), tetralogy of Fallot (97.2%, 90.0-99.2%CI) and transposition of the great arteries (96.1%, 89.2-98.6%CI), whereas, lowest were observed in double outlet right ventricle (81.1%, 70.4-88.6% CI), truncus arteriosus (72.7%, 51.8-86.8% CI) and heterotaxy (71.1%, 56.6-82,2% CI). Greater accuracy was associated with later diagnostic era (2012-2018, p=0.026), first fetal echo at <25 weeks (p =0.028), and formal fetal cardiology training in the reviewer (p=0.001). Maternal pre-pregnancy weight did not impact accuracy.
Conclusion
The diagnostic accuracy of FE for major CHD is high particularly in the hands of fetal cardiology trained practitioners. There are lesion specific as well as general, modifiable and non-modifiable factors that impact diagnostic accuracy.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 10 Mar 2022; epub ahead of print
Haberer K, He R, McBrien A, Eckersley L, ... Adatia I, Hornberger Fase LK
J Am Soc Echocardiogr: 10 Mar 2022; epub ahead of print | PMID: 35288307
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Abstract

Impaired Right Atrial Reserve Function in Heart Failure with Preserved Ejection Fraction.

Kagami K, Harada T, Yoshida K, Amanai S, ... Adachi T, Obokata M
Background
Patients with heart failure (HF) with preserved ejection fraction (HFpEF) have multiple cardiac reserve limitations during exercise. However, no data are available regarding RA reserve capacity in HFpEF. We sought to determine the association of right atrial (RA) reserve impairments with right ventricular (RV) function and exercise capacity in HFpEF and to explore its diagnostic value.
Methods
Patients with HFpEF (n=89) and control subjects without HF (n=108) underwent bicycle exercise echocardiography. RA reservoir, conduit, and booster pump strain at rest and during exercise were measured using speckle tracking echocardiography. In a subset, simultaneous expired gas analysis was performed to measure peak oxygen consumption (VO2).
Results
At rest, RA reservoir strain was lower in HFpEF patients than controls (27.0±17.1 vs. 38.6±17.1 %, p<0.0001) while RA conduit and booster pump strain were similar between groups. During peak exercise, patients with HFpEF displayed marked reserve limitations in RA reservoir and booster pump function compared to controls and the differences remained significant even after adjusting for confounding factors. During peak exercise, RA reservoir and booster pump strain were correlated with RV systolic function. Lower RA booster pump strain during exercise was also weakly associated with lower cardiac output (r=0.34, p<0.0001) and reduced peak VO2 (r=0.47, p<0.0001). RA reservoir strain during exercise had incremental diagnostic value to differentiate HFpEF from controls over the established HFpEF diagnostic algorithms and left-sided strain parameters.
Conclusions
Limitations in RA reservoir and booster pump function during exercise are present in HFpEF and the severity is associated with RV systolic reserve, poor cardiac output, and depressed exercise capacity. Exercise RA strain assessment may help the diagnosis of HFpEF.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 09 Mar 2022; epub ahead of print
Kagami K, Harada T, Yoshida K, Amanai S, ... Adachi T, Obokata M
J Am Soc Echocardiogr: 09 Mar 2022; epub ahead of print | PMID: 35283241
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Abstract

Global longitudinal strain analysis of the singe right ventricle: leveling the playing field.

Wilkinson JC, Colquitt JL, Doan TT, Liu AM, ... Pignatelli RH, Loar RW
Background
All available echocardiographic methods to assess single, systemic right ventricle (sRV) systolic function have limitations. Subjective grading is prone to bias and varies among readers. Quantitative methods that require significant manual input, such as fractional area change (FAC), are often not reproducible. The aim of this study is to determine whether global longitudinal strain (GLS) is more reproducible than FAC and subjective grading in sRV patients among individual readers and across different levels of experience.
Methods
Clinically indicated echocardiograms for 40 patients with functional systemic right ventricles were assessed by 5 readers with varying reading experience: one sonographer, one cardiology fellow, and three attending cardiologists at different career stages. All readers were blinded to patient data and other reader responses. Each reader reviewed the same images for subjective grade (scale 1-8, normal to severely depressed), RV end-diastolic and end-systolic area measurements, and longitudinal strain analysis. A repeat analysis was performed under identical conditions after at least 2 weeks on all 40 patients. Inter- and intra-reader reproducibility was assessed with intraclass correlation coefficient (ICC). Correlations between responses were assessed with Spearman\'s correlation coefficient.
Results
The subjective method had fair to good reproducibility (ICC 0.7, interquartile range (IQR) 0.60,0.72) while the FAC method was poor (ICC 0.46, IQR 0.39,0.51) between readers. Reproducibility for GLS was excellent (ICC 0.88, IQR 0.88,0.89). Intra-reader reproducibility was excellent by subjective grading (ICC 0.85, IQR 0.73,0.88), poor by FAC (ICC = 0.63, IQR 0.35,0.66) and excellent by GLS (ICC 0.93, IQR 0.88,0.96). Attending-level readers were more consistent with their subjective grading, while all readers were excellent with GLS.
Conclusion
GLS is more reproducible than conventional methods at assessing sRV systolic function between readers with different levels of experience. For most readers it was more consistent than their own subjective grade of RV function. Laboratories staffed by multiple readers are likely to be more consistent in grading systemic RV systolic function using GLS.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 07 Mar 2022; epub ahead of print
Wilkinson JC, Colquitt JL, Doan TT, Liu AM, ... Pignatelli RH, Loar RW
J Am Soc Echocardiogr: 07 Mar 2022; epub ahead of print | PMID: 35271990
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Abstract

Impact of Fetal Echocardiogram Comprehensiveness on Diagnostic Accuracy.

Behera SK, Ding VY, Chung S, Tacy TA
Background
Fetal echocardiography is a major diagnostic imaging modality for prenatal detection of critical congenital heart disease (CHD). Diagnostic accuracy is essential for appropriate planning of delivery and neonatal care. The relationship between study comprehensiveness and diagnostic error is not well understood.
Objectives
We hypothesized that high fetal echocardiogram study comprehensiveness would be associated with low diagnostic error. Diagnostic errors were defined as discordant fetal and postnatal diagnoses, and were further characterized by potential causes, contributors, and clinical significance.
Methods
Fetal echocardiograms performed at Lucile Packard Children\'s Hospital (LPCH) in which fetuses with critical CHD were anticipated to require postnatal surgical or catheter intervention in the first year of life were identified using the fetal cardiology program database. For this cohort, initial fetal echocardiogram images were reviewed and given a fetal echocardiogram comprehensiveness score (FECS). Fetal diagnoses obtained from initial fetal echocardiogram images and reports were compared with postnatal diagnoses confirmed by transthoracic echocardiogram and other imaging studies, and/or surgery to determine diagnostic error. The relationship between FECS and diagnostic error was evaluated using multivariable logistic regression.
Results
Of the 304 initial fetal echocardiograms, diagnostic error (discrepant diagnosis, false negative, or false positive) occurred in 92 cases (30.3%). FECS was not associated with diagnostic error, but low FECS (< 80% complete) was associated with false negatives and procedural/conditional (p<0.001) and technical contributors (p=0.005) compared with high FECS (>80% complete). Cognitive factors made up the largest proportion of contributors to error.
Conclusions
Study comprehensiveness of fetal echocardiograms was not related to diagnostic error. The most common contributor to error were cognitive factors. Echocardiogram laboratories can work to mitigate preventable cognitive error through quality improvement initiatives.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 03 Mar 2022; epub ahead of print
Behera SK, Ding VY, Chung S, Tacy TA
J Am Soc Echocardiogr: 03 Mar 2022; epub ahead of print | PMID: 35257895
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Impact:
Abstract

3D Transthoracic Static and Dynamic Normative Values of the Mitral Valve Apparatus: Results from the Multicenter World Alliance of Societies of Echocardiography Study.

Henry MP, Cotella J, Mor-Avi V, Addetia K, ... Lang RM, Asch FM
Background
Recent advances in mitral valve (MV) percutaneous interventions have escalated the need for a more quantitative and comprehensive assessment of the MV, which can be best achieved by 3D echocardiography. Understanding normal valve size, structure and function is essential for differentiation of healthy from disease states. We aimed to establish normative values for the MV apparatus size and morphology and determine how they vary across age, sex and race groups, using data from the World Alliance of Societies of Echocardiography (WASE) normal values study.
Methods
3D volumetric datasets obtained with transthoracic echocardiography in 748 normal subjects (51% male) were analyzed using commercial MV analysis software (TOMTEC) to determine annular and leaflet dimensions and areas. The subjects were divided into groups by sex (378 men and 370 women) and age: 18-40 years (N=266), 41-65 years (N=249) and >65 years (N=233) to identify sex- and age-related differences. In addition, differences between black, white and Asian populations were studied. Inter- and intra-observer variability was assessed in a subset of 30 subjects and expressed as mean absolute difference between pairs of repeated measurements.
Results
Compared to women, men had larger annular size measurements, larger tenting size parameters, and larger leaflet length and area. Compared to the black and white populations, Asian population showed significantly smaller mitral annular size. While many of the age-, sex, and race differences in MV parameters were statistically significant, they were comparable to or smaller than the corresponding measurement variability. Indexing by body surface area and height did not eliminate these differences consistently, suggesting that parameters may need to be indexed according to their dimensionality.
Conclusion
This analysis of the WASE data provides normative values of the mitral apparatus size and morphology. While sex- and age-related differences were noted, they need to be interpreted with caution in view of the associated measurement variability.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 28 Feb 2022; epub ahead of print
Henry MP, Cotella J, Mor-Avi V, Addetia K, ... Lang RM, Asch FM
J Am Soc Echocardiogr: 28 Feb 2022; epub ahead of print | PMID: 35245668
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Impact:
Abstract

Aortic Root Anatomy Is Related to the Bicuspid Aortic Valve Phenotype.

Milleron O, Masi P, Eliahou L, Paul JF, ... Ou P, Jondeau G
Background
Bicuspid aortic valve (BAV) is associated with an asymmetric (not circular) aortic root, resulting in variability in the aortic root diameter measurements obtained using different techniques. The objective of this study was to describe aortic root asymmetry, including its orientation in the thorax, in relation to the various phenotypes of BAV and its impact on aortic root diameter measurements obtained using transthoracic echocardiography.
Methods
Aortic root asymmetry, orientation of the largest root diameter, and orientation of the valve opening were studied using computed tomographic scans of patients with BAV without significant aortic valve dysfunction referred for evaluation of a thoracic aortic aneurysm. Eighty-five patients with BAV were evaluated; BAV with fusion of the left and the right coronary cusps (L-R BAV), with or without raphe (n = 63), was compared with BAV with fusion of the right coronary and noncoronary cusps (N-R BAV), with or without raphe (n = 22).
Results
Asymmetry of the aortic root and its orientation in the thorax can be predicted from BAV phenotype: orientation of the valve opening differed from orientation of the largest root diameter by nearly 75° in both groups. The angle of the largest root diameter with the reference sagittal plane was 64.3° in the L-R BAV group versus 143.1° in the N-R BAV group (P < .0001). Therefore, using the parasternal long-axis view on transthoracic echocardiography, in N-R BAV, the ultrasound beam is roughly parallel to the valve opening orientation and almost orthogonal to the maximum diameter of the root. On the contrary, in L-R BAV, the ultrasound beam is roughly perpendicular to the valve opening orientation and almost parallel to the maximum diameter of the root. Consequently, the parasternal long-axis view on transthoracic echocardiography significantly underestimates maximal aortic root diameter in N-R BAV and modestly underestimates root diameter in L-R BAV (-6.1 ± 0.96 vs -2.3 ± 0.47 mm, P = .0008).
Conclusions
Aortic root morphology in patients with BAV can be predicted by BAV phenotype: the largest root diameter is roughly perpendicular to the orientation of the valve opening. Therefore, echocardiographic measurements according to present recommendations (parasternal long-axis view) underestimate maximal diameter in patients with N-R BAV.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 27 Feb 2022; 35:278-286
Milleron O, Masi P, Eliahou L, Paul JF, ... Ou P, Jondeau G
J Am Soc Echocardiogr: 27 Feb 2022; 35:278-286 | PMID: 34861352
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Impact:
Abstract

Global Myocardial Work Combined with Treadmill Exercise Stress to Detect Significant Coronary Artery Disease.

Lin J, Wu W, Gao L, He J, ... Liu M, Wang H
Background
Myocardial work (MW) derived from the left ventricular pressure-strain loop is a novel and noninvasive method for assessing left ventricular function that accounts for loading conditions. We aimed to explore whether global MW combined with treadmill exercise stress could detect significant coronary artery disease (CAD) in patients with angina pectoris.
Methods
Eighty-five patients with angina pectoris and no prior CAD history were included. All patients underwent treadmill exercise stress echocardiography and coronary angiography. Global MW was constructed from speckle-tracking echocardiography indexed to the brachial systolic blood pressure. The association between MW parameters and the presence of significant CAD was assessed with logistic regression. The discriminative power of MW parameters to detect CAD was assessed with receiver operative characteristic curve, net reclassification improvement, and integrated discrimination improvement analysis.
Results
Twenty-five patients had a positive exercise echocardiogram, while significant coronary artery stenosis (≥70% in one or more major epicardial vessels or ≥50% in the left main coronary artery) was observed in 41 patients. The global wasted work (GWW) and global work efficiency (GWE) were significantly higher or lower, respectively, in patients with significant CAD compared with those of nonsignificant CAD at the peak exercise and during recovery periods (P < .05 for all). Multivariate logistic regression analysis demonstrated that peak GWE and recovery GWW could predict significant CAD. Peak GWE had the highest area under the receiver operating characteristic curve (AUC) among all global MW parameters (AUC = 0.836). Furthermore, a model comprising peak GWE and recovery GWW performed better for the identification of significant CAD than peak GWE alone (AUC = 0.856).
Conclusions
Peak GWE could detect significant CAD. The new model, incorporating peak GWE and recovery GWW, not only identified but also provided additional value for estimating the probability of significant CAD. Global MW parameters combined with exercise stress perform as an accurate noninvasive screening before the invasive diagnostic technique.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 27 Feb 2022; 35:247-257
Lin J, Wu W, Gao L, He J, ... Liu M, Wang H
J Am Soc Echocardiogr: 27 Feb 2022; 35:247-257 | PMID: 34710569
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Abstract

Echocardiographic Killip Classification.

Milwidsky A, Greidinger D, Frydman S, Hochstadt A, ... Mizrachi M, Topilsky Y
Background
Although routine echocardiographic parameters such as ejection fraction are used to risk-stratify for death in patients referred for echocardiography, they have limited predictive value. The authors speculated that noninvasive hemodynamic echocardiographic data, assessing left ventricular filling pressure and output, stratified on the basis of the clinical Killip score, might have additive prognostic value on top of routine echocardiographic parameters. The authors created an echocardiographic correlate of this classification, using diastolic grade and stroke volume index (SVI) as indicators of pulmonary congestion and systemic perfusion, respectively, and evaluated the prognostic value of this correlate.
Methods
A retrospective study of consecutive patients (hospitalized or not) referred for echocardiography for a range of cardiac diagnoses in a tertiary medical center. A total of 556 patients in sinus rhythm who were evaluated by two sonographers, and reviewed by a single cardiologist, were included. Normal filling pressure and normal SVI (>35 mL/m2) defined echocardiographic Killip (eKillip) class 1. Patients with pseudonormal or restrictive diastolic patterns and normal SVI were ascribed to eKillip class 2 or 3, respectively. A pseudonormal or restrictive diastolic pattern and a subnormal SVI defined eKillip class 4.
Results
eKillip class 1 was present in 382 patients (68%); 115 (20%), 26 (5%), and 42 (7%) patients were in eKillip classes 2 to 4, respectively. Median follow-up time was 1,056 days (interquartile range, 729-1,390 days). A total of 105 deaths occurred. Univariate Cox regression analysis showed that eKillip class was associated with all-cause mortality; hazard ratios (HR) -2.73 (95% CI, 1.67-4.48), 3.19 (95% CI, 1.42-7.17), and 4.79 (95% CI, 2.58-8.89) for each eKillip class above 1 (P < .001). In a multivariate analysis adjusted for the Charlson comorbidity index, eKillip class remained independently associated with all-cause mortality (P = .04).
Conclusions
eKillip class was associated with all-cause mortality among all patients undergoing echocardiography at a tertiary hospital.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 27 Feb 2022; 35:287-294
Milwidsky A, Greidinger D, Frydman S, Hochstadt A, ... Mizrachi M, Topilsky Y
J Am Soc Echocardiogr: 27 Feb 2022; 35:287-294 | PMID: 34767929
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Abstract

Prenatal Diagnosis of Vascular Ring: Evaluation of Fetal Diagnosis and Postnatal Outcomes.

Aly S, Papneja K, Mawad W, Seed M, Jaeggi E, Yoo SJ
Background
The impact of fetal echocardiography on the diagnosis and outcomes of vascular ring has not been well examined. We hypothesized that prenatal detection of vascular ring has improved over time and that prenatal diagnosis of vascular ring is associated with earlier intervention and favorable outcomes.
Methods
This is a single-center, retrospective study of the evolution and outcomes of prenatal diagnosis of vascular ring from 2000 to 2020. We compared clinical presentation, timing of surgical intervention, and outcomes between the prenatally and postnatally diagnosed cases during the same study period.
Results
A total of 170 patients were included: 50 with prenatal and 120 with postnatal diagnosis of vascular ring. Prenatal diagnoses included 42 patients (84%) with right aortic arch (RAA), aberrant left subclavian artery (ALSCA), and a left-sided ductus arteriosus and eight (16%) patients with double aortic arch (DAA). The postnatal cohort consisted mainly of 90 patients (75%) with DAA and 22 (18%) with RAA-ALSCA. None of the postnatally diagnosed cases had undergone a fetal echocardiogram. Numbers (percentage) of prenatally diagnosed cases of vascular ring compared with the postnatal cases improved from 4/31 (13%), to 10/29 (34%), to 14/25 (56%), and to 22/35 (69%), respectively, during 2000-2005, 2005-10, 2010-15, and 2015-20 (P = .032). Vascular ring was an isolated abnormality in 84% and 85% of the prenatal and postnatal cohorts, respectively. Compared with the prenatal cohort, postnatally diagnosed patients with an isolated vascular ring were more frequently symptomatic (66% vs 48%, P < .03) and underwent cross-sectional imaging (69% vs 44%, P = .009) and surgery more frequently (79% vs 48%, P = .003). Surgery was performed at a later patient age (18 [2-147] months vs 4.8 [0.5-42] months, P = .01) and was more often associated with residual symptoms (27/81 [33%] vs 1/20 [5%], P = .01) in the postnatal cohort than in the prenatal cohort.
Conclusions
The diagnosis of vascular ring by fetal echocardiography has improved over time. A significantly higher incidence of RAA-ALSCA in the prenatal compared with the postnatal cohort suggests that patients with this form of vascular ring often do not present to medical attention with significant symptoms postnatally. Prenatal diagnosis of vascular ring was associated with a lower incidence of symptoms, less frequent use of cross-sectional imaging, earlier age at surgical intervention, and lower likelihood of residual symptoms.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 27 Feb 2022; 35:312-321
Aly S, Papneja K, Mawad W, Seed M, Jaeggi E, Yoo SJ
J Am Soc Echocardiogr: 27 Feb 2022; 35:312-321 | PMID: 34600045
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Abstract

Normal Values of Aortic Root Size According to Age, Sex, and Race: Results of the World Alliance of Societies of Echocardiography Study.

Patel HN, Miyoshi T, Addetia K, Citro R, ... Lang RM, WASE Investigators
Background
Accurate measurements of the aortic annulus and root are important for guiding therapeutic decisions regarding the need for aortic surgery. Current echocardiographic guidelines for identification of aortic root dilatation are limited because current normative values were derived predominantly from white individuals in narrow age ranges, and based partially on M-mode measurements. Using data from the World Alliance Societies of Echocardiography study, the authors sought to establish normal ranges of aortic dimensions across sexes, races, and a wide range of ages.
Methods
Adult individuals free of heart, lung, and kidney disease were prospectively enrolled from 15 countries, with even distributions among sexes and age groups: young (18-40 years), middle aged (41-65 years) and old (>65 years). Transthoracic two-dimensional echocardiograms of 1,585 subjects (mean age, 47 ± 17 years; 50.4% men; mean body surface area [BSA], 1.77 ± 0.22 m2) were analyzed in a core laboratory following American Society of Echocardiography guidelines. Measurements, indexed separately by BSA and by height, included the aortic annulus, sinuses of Valsalva, and sinotubular junction. Differences among age, sex, and racial groups were evaluated using unpaired two-tailed Student\'s t tests.
Results
All aortic root dimensions were larger in men compared with women. After indexing to BSA, all measured dimensions were significantly larger in women, whereas men continued to show larger dimensions after indexing to height. Of note, the upper limits of normal for all aortic dimensions were lower across all age groups, compared with the guidelines. Aortic dimensions were larger in older age groups in both sexes, a trend that persisted regardless of BSA or height adjustment. Last, differences in aortic dimensions were also observed according to race: Asians had the smallest nonindexed aortic dimensions at all levels.
Conclusions
There are significant differences in aortic dimensions according to sex, age, and race. Thus, current guideline-recommended normal ranges may need to be adjusted to account for these differences.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 27 Feb 2022; 35:267-274
Patel HN, Miyoshi T, Addetia K, Citro R, ... Lang RM, WASE Investigators
J Am Soc Echocardiogr: 27 Feb 2022; 35:267-274 | PMID: 34619294
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Abstract

Ventricular Changes in Patients with Acute COVID-19 Infection: Follow-up of the World Alliance Societies of Echocardiography (WASE-COVID) Study.

Karagodin I, Singulane CC, Descamps T, Woodward GM, ... Asch FM, WASE-COVID Investigators
Background
COVID-19 infection is known to cause a wide array of clinical chronic sequelae, but little is known regarding the long-term cardiac complications. We aim to report echocardiographic follow-up findings and describe the changes in left (LV) and right ventricular (RV) function that occur following acute infection.
Methods
Patients enrolled in the World Alliance Societies of Echocardiography-COVID study with acute COVID-19 infection were asked to return for a follow-up transthoracic echocardiogram. Overall, 198 returned at a mean of 129 days of follow-up, of which 153 had paired baseline and follow-up images that were analyzable, including LV volumes, ejection fraction (LVEF), and longitudinal strain (LVLS). Right-sided echocardiographic parameters included RV global longitudinal strain, RV free wall strain, and RV basal diameter. Paired echocardiographic parameters at baseline and follow-up were compared for the entire cohort and for subgroups based on the baseline LV and RV function.
Results
For the entire cohort, echocardiographic markers of LV and RV function at follow-up were not significantly different from baseline (all P > .05). Patients with hyperdynamic LVEF at baseline (>70%), had a significant reduction of LVEF at follow-up (74.3% ± 3.1% vs 64.4% ± 8.1%, P < .001), while patients with reduced LVEF at baseline (<50%) had a significant increase (42.5% ± 5.9% vs 49.3% ± 13.4%, P = .02), and those with normal LVEF had no change. Patients with normal LVLS (<-18%) at baseline had a significant reduction of LVLS at follow-up (-21.6% ± 2.6% vs -20.3% ± 4.0%, P = .006), while patients with impaired LVLS at baseline had a significant improvement at follow-up (-14.5% ± 2.9% vs -16.7% ± 5.2%, P < .001). Patients with abnormal RV global longitudinal strain (>-20%) at baseline had significant improvement at follow-up (-15.2% ± 3.4% vs -17.4% ± 4.9%, P = .004). Patients with abnormal RV basal diameter (>4.5 cm) at baseline had significant improvement at follow-up (4.9 ± 0.7 cm vs 4.6 ± 0.6 cm, P = .019).
Conclusions
Overall, there were no significant changes over time in the LV and RV function of patients recovering from COVID-19 infection. However, differences were observed according to baseline LV and RV function, which may reflect recovery from the acute myocardial injury occurring in the acutely ill. Left ventricular and RV function tends to improve in those with impaired baseline function, while it tends to decrease in those with hyperdynamic LV or normal RV function.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 27 Feb 2022; 35:295-304
Karagodin I, Singulane CC, Descamps T, Woodward GM, ... Asch FM, WASE-COVID Investigators
J Am Soc Echocardiogr: 27 Feb 2022; 35:295-304 | PMID: 34752928
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Abstract

Resting Left Ventricular Global Longitudinal Strain to Identify Silent Myocardial Ischemia in Asymptomatic Patients with Diabetes Mellitus.

Albenque G, Rusinaru D, Bellaiche M, Di Lena C, ... Tribouilloy C, Bohbot Y
Background
Screening for silent coronary artery disease in asymptomatic patients with diabetes mellitus (DM) is challenging and controversial. In this context, it seems crucial to identify early markers of coronary artery disease.
Methods
The aim of this study was to investigate the incremental value of resting left ventricular (LV) global longitudinal strain (GLS) for the prediction of positive results on stress (exercise or dobutamine) transthoracic echocardiography in 273 consecutive asymptomatic high-risk patients with DM. Positive results on stress transthoracic echocardiography were defined as stress-induced LV wall motion abnormalities (new or worsening preexisting abnormalities).
Results
Compared with patients with negative stress results, those with positive stress results (n = 28 [10%]) more frequently had cardiovascular risk factors, complications of DM, vascular disease, moderate and severe calcification of the aortic valve and mitral annulus, and worse resting LV GLS (-16.7 ± 2.9% vs -19.0 ± 1.9%, P < .001). On multivariable logistic regression analysis, DM duration > 10 years, diabetic retinopathy, LV hypertrophy, and impaired LV GLS (odds ratio, 1.39 [95% CI, 1.14-1.70] per percentage increase; odds ratio, 5.16 [95% CI, 1.96-13.59] for LV GLS worse than -18%) were independently associated with positive results on stress transthoracic echocardiography. The area under the curve to predict positive results was 0.74 for LV GLS with a cutoff of -18.0% (sensitivity 68%, specificity 78%). The area under the curve of the multivariable model to predict test results was improved by the addition of LV GLS (P < .001), with a bias-corrected area under the curve after bootstrapping of 0.842 [95% CI, 0.753-0.893].
Conclusions
The present findings show that resting LV GLS is associated with the presence of silent ischemia and could be useful to better identify asymptomatic patients with DM who might benefit from coronary artery disease screening.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 27 Feb 2022; 35:258-266
Albenque G, Rusinaru D, Bellaiche M, Di Lena C, ... Tribouilloy C, Bohbot Y
J Am Soc Echocardiogr: 27 Feb 2022; 35:258-266 | PMID: 34752929
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Abstract

Acute Echocardiographic Effects of Exogenous Ketone Administration in Healthy Participants.

Selvaraj S, Hu R, Vidula MK, Dugyala S, ... Kelly DP, Bravo PE
Background
Interest in therapeutic applications of exogenous ketones has grown significantly, spanning patients with heart failure to endurance athletes. Exogenous ketones engender significant effects on cardiac function in heart failure and provide an ergogenic benefit in athletes. The aim of this study was to assess the effects of exogenous ketones on cardiac function in healthy participants.
Methods
In a single-arm intervention study, 20 fasting, healthy participants underwent comprehensive echocardiography (two-dimensional, Doppler, and strain) before and 30 min after weight-based oral ketone ester administration. The relationship between changes in log-transformed biomarker levels and change in absolute global longitudinal strain (GLS) was assessed using linear regression.
Results
The mean age was 30 ± 7 years, 50% were women, 45% were nonwhite, and the average body mass index was 24.3 ± 3.1 kg/m2. Ketone ingestion acutely elevated β-hydroxybutyrate levels from a median of 0.13 mmol/L (interquartile range, 0.10-0.37 mmol/L) to 3.23 mmol/L (interquartile range, 2.40-4.97 mmol/L) (P < .001). After ketone ester consumption, systolic blood pressure, heart rate, biventricular function, left ventricular GLS, and left atrial (LA) strain all augmented, while systemic vascular resistance decreased. Displayed as mean change, increases in ejection fraction (3.1%; 95% CI, 2.0%-4.2%; P < .001), GLS (2.0%; 95% CI, 1.4%-2.7%; P < .001), right ventricular S\' (1.1 cm/sec; 95% CI, 0.4-1.8 cm/sec; P = .004), LA reservoir strain (7%; 95% CI, 3%-12%; P = .005), and LA contractile strain (4%; 2%-6%; P = .001) were observed. During robustly achieved ketosis, change in GLS was inversely associated with change in nonesterified fatty acids (P = .019).
Conclusions
In a single-arm study, systolic blood pressure, heart rate, biventricular function, and LV and LA strain acutely augmented after ketone ester ingestion in healthy, fasting participants, similar to several effects observed in the failing heart. These data may provide supporting data for the ergogenic benefits observed in athletes and may become increasingly relevant with exogenous ketone consumption across a variety of cardiovascular and noncardiovascular applications.

Copyright © 2021 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

J Am Soc Echocardiogr: 27 Feb 2022; 35:305-311
Selvaraj S, Hu R, Vidula MK, Dugyala S, ... Kelly DP, Bravo PE
J Am Soc Echocardiogr: 27 Feb 2022; 35:305-311 | PMID: 34798244
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This program is still in alpha version.