Artificial intelligence based left ventricular ejection fraction and global longitudinal strain in cardiac amyloidosis.

BACKGROUND: Assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) plays a key role in the diagnosis of cardiac amyloidosis (CA). However, manual measurements are time consuming and prone to variability. We aimed to assess whether fully automated artificial intelligence (AI) calculation of LVEF and GLS provide similar estimates and can identify abnormalities in agreement with conventional manual methods, in patients with pre-clinical and clinical CA. METHODS: We identified 51 patients (age 80 ± 10 years, 53% male) with confirmed CA according to guidelines, who underwent echocardiography before and/or at the time of CA diagnosis (median (IQR) time between observations 3.87 (1.93, 5.44 years). LVEF and GLS were quantified from the apical 2- and 4-chamber views using both manual and fully automated methods (EchoGo Core 2.0, Ultromics). Inter-technique agreement was assessed using linear regression and Bland-Altman analyses and two-way ANOVA. The diagnostic accuracy and time for detecting abnormalities (defined as LVEF ≤ 50% and GLS ≥ -15.1%, respectively) using AI was assessed by comparisons to manual measurements as a reference. RESULTS: There were no significant differences in manual and automated LVEF and GLS values in either pre-CA (p = .791 and p = .105, respectively) or at diagnosis (p = .463 and p = .722). The two methods showed strong correlation on both the pre-CA (r = .78 and r = .83) and CA echoes (r = .74 and r = .80) for LVEF and GLS, respectively. The sensitivity and specificity of AI-derived indices for detecting abnormal LVEF were 83% and 86%, respectively, in the pre-CA echo and 70% and 79% at CA diagnosis. The sensitivity and specificity of AI-derived indices for detecting abnormal GLS was 82% and 86% in the pre-CA echo and 100% and 67% at the time of CA diagnosis. There was no significant difference in the relationship between LVEF (p = .99) and GLS (p = .19) and time to abnormality between the two methods. CONCLUSION: Fully automated AI-calculated LVEF and GLS are comparable to manual measurements in patients pre-CA and at the time of CA diagnosis. The widespread implementation of automated LVEF and GLS may allow for more rapid assessment in different disease states with comparable accuracy and reproducibility to manual methods.

Right Ventricular Thrombus on Echocardiography.

Right ventricular thrombi (RVTs) have been almost exclusively studied in patients with pulmonary embolism (PE). The implications of an isolated RVT, a finding typically encountered on transthoracic echocardiography (TTE), are lacking. In this study, we sought to identify the echocardiographic and clinical features associated with the presence of RVTs. Between 1998 and 2023, 138 patients with RVT documented on TTE were retrospectively identified. Demographic data, presence of intracardiac devices, hypercoagulable conditions, history of deep vein thrombosis (DVT), PE, and/or left ventricular thrombus were abstracted from electronic chart review. Measurements of right and left ventricular size, and function were performed on TTE. Of the total population of patients with RVT, <1/2 had intracardiac devices, 29% had a documented hypercoagulable state (e.g., cancer or a clotting disorder). Most patients had dilated (77%) and dysfunctional (72%) right ventricles. Approximately 50% of RVTs were discovered in nonstandard imaging planes, suggesting that the presence of RVT is likely underestimated in clinical practice. Of those evaluated for PE, 80% had PE. Of those evaluated for DVT, 53% had DVT. In conclusion, further investigations are warranted to better guide when to investigate the right ventricle for RVTs on TTE and the impact of RVTs on patient outcomes.

Defining echocardiographic predictors of outcome in cardiac amyloidosis by subtype.

BACKGROUND: Current echocardiographic risk factors for prognosis in cardiac amyloidosis (CA) do not distinguish between the two main subtypes: transthyretin cardiomyopathy (TTR) and immunoglobulin light chain cardiomyopathy (AL), each of which require distinct diagnostic and therapeutic approaches. Additionally, only traditional parameters have been studied with little data on advanced techniques. Accordingly, we sought to determine whether differences exist in 2D transthoracic echocardiography (2DE) predictors of survival between the CA subtypes using a comprehensive approach. METHODS: 220 patients (72±12 years) with confirmed CA (AL=89, TTR=131) who underwent 2DE at the time of CA diagnosis were enrolled. Left ventricular (LV) dimensions, indexed mass (LVMi), global longitudinal strain (LVGLS), apical-sparing ratio (LVASR), diastology, right ventricular (RV) size and function indices including tricuspid annular systolic excursion (TAPSE), RV free-wall (RVFWS) and global (RVGLS) strain, indexed left (LA) and right atrial volumes (LAVi and RAVi), LA strain (reservoir and booster) and RV systolic pressure (RVSP) were measured. A propensity-score weighted stepwise variable selection Cox proportional hazards model derived from NYHA class and renal impairment status at diagnosis was used to determine the associations between 2DE parameters and mortality specific to CA subtype over a median follow-up of 36-months. RESULTS: After adjusting for age, atrial fibrillation and treatment, parameters associated with survival were RVFWS (p=0.003, HR 1.15, 95% CI[1.053,1.245]) and RVSP (p=0.03, HR 1.03, 95% CI[1.004,1.063]) in AL and LVASR (p=0.007, HR 6.68, 95% CI[1.75,25.492]) and RAVi (p=0.049, HR 1.03, 95% CI[1.000,1.052]) in TTR. CONCLUSIONS: Echocardiographic prognosticators for survival are specific to cardiac amyloid subtype. These results potentially provide information critical for clinical decision-making and follow-up in these patients.

How Often Does Apical Sparing of Longitudinal Strain Indicate the Presence of Cardiac Amyloidosis?

Echocardiographic diagnosis of cardiac amyloidosis (CA) is frequently suggested by the presence of a left ventricular (LV) apical sparing pattern (ASP) on longitudinal strain (LS) assessment, the so-called "cherry on top" pattern, defined by strain magnitude preserved exclusively at the apex. However, it is unclear how frequently this strain pattern truly represents CA. This study aimed to evaluate the predictive value of ASP in the diagnosis of CA. We retrospectively identified consecutive adult patients who had the following studies performed within an 18-month period: (1) transthoracic echocardiogram and (2) either (a) cardiac magnetic resonance imaging, (b) Technetium-Pyrophosphate (PYP) imaging, or (c) endomyocardial biopsy. LS was retrospectively measured in the apical 4-, 3-, and 2-chamber views in patients who had adequate noncontrast images (n = 466). An apical sparing ratio (ASR) was calculated as (average apical strain)/[(average basal strain) + (average midventricular strain)]. Patients with ASR ≥1 were evaluated for the presence/absence of CA, using established criteria. Basic LV parameters were also measured. A total of 33 patients (7.1%) had ASP. Nine of these patients (27%) had "confirmed" CA, 2 (6.1%) "highly probable" CA, 1 (3.0%) "possible" CA, and 21 (64%) no evidence of CA. When comparing patients with and without confirmed CA, there were no significant differences in ASR, average global LS, ejection fraction, or LV mass. Patients with confirmed CA were older (76 ± 9 vs 59 ± 18 years, p = 0.01) and had thicker posterior wall (15 ± 3 vs 11 ± 3 mm, p = 0.004) with a trend toward thicker septal wall (15 ± 2 vs 12 ± 4 mm, p = 0.05). In conclusion, the presence of ASP on LS represents confirmed or highly probable CA in only 1/3 of patients and is more likely to indicate true CA in older patients with increased LV wall thickness. Although a larger, prospective study is needed to confirm these findings, 1/3 should be considered as a large diagnostic yield that justifies further testing, given the poor outcomes associated with CA diagnosis.

Variations in indexation of left atrial volume across different races.

Background: Left atrial volume (LAV) has prognostic value. Guidelines propose indexation to body surface area (BSA), however studies demonstrate this can overcorrect for body size. Limited studies investigate indexation across different ethnicities. We sought to evaluate the effect of ethnicity on indexation. Methods: Using data from the World Alliance of Societies of Echocardiography (WASE) cohort, healthy subjects were classified by race as White, Black, Asian, or Other. Biplane LAV was indexed to traditional isometric measurements (BSA, height, weight, ideal body weight (IBW) and IBW derived BSA (IBSA)), as well as previously-derived allometric height exponents (2.7 and 1.72). Additionally, an allometric height exponent for our cohort was derived (linear regression of the logarithmic transformation of LAV = a(height)b) as 1.87. All indices were then assessed using Spearman correlation, with a good index retaining correlation of LAV/index to raw LAV (r∼1), while avoiding overcorrection by the index (r∼0). Results: There were 1366 subjects (White: 524, Black: 149, Asian: 523, Other: 170; median age 44 years, 653 females (47.8%)). In the entire group, BSA, IBSA, height1.87 and height1.72 performed well with retaining correlation to raw LAV (r > 0.9 for all), and minimising overcorrection to body size (r < 0.1 for all). On race-specific analysis, BSA overcorrected for body size in the White population (r = 0.128). Height1.72 minimised overcorrection for body size in all populations (r ≤ 0.1 for all races). Conclusion: Despite a cohort with normal BMI, there was still disparity in LAV indexation with BSA across races. Allometric height indexation, particularly using height1.72, is a possible solution, although further validation studies in BMI extremes are required.

Preservation of Circumferential and Radial Left Ventricular Function as a Mitigating Mechanism for Impaired Longitudinal Strain in Early Cardiac Amyloidosis.

BACKGROUND: In patients with cardiac amyloidosis (CA), left ventricular ejection fraction (LVEF) is frequently preserved, despite commonly reduced global longitudinal strain (GLS). We hypothesized that nonlongitudinal contraction may initially serve as a mitigating mechanism to maintain cardiac output and studied the relationship between global circumferential (GCS) and radial (GRS) strain with LVEF and extracellular volume (ECV), a marker of amyloid burden. METHODS: Patients with CA who underwent cardiac magnetic resonance (CMR; n = 140, 70.7 ± 11.5 years, 66% male) or echocardiography (n = 67, 71 ± 13 years, 66% male) and normal controls (CMR, n = 20; echocardiography, n = 45) were retrospectively identified, and GCS, GLS, and GRS were quantified using feature-tracking CMR or speckle-tracking echocardiography and compared between CA patients with preserved and reduced LVEF (CAHFpEF, CAHFrEF) and controls. The prevalence of impaired strain (magnitudes <2.5th percentile of the controls) was compared between CAHFpEF and CAHFrEF and between ECV quartiles. RESULTS: While echocardiography-derived GLS was impaired in both CAHFpEF (-13.4% ± 3.1%, P < .003) and CAHFrEF (-9.1% ± 3.2%, P < .003), compared with controls (-20.8% ± 2.4%), GCS was more impaired in CAHFrEF compared with both controls (-15.6% ± 5.0% vs -32.3% ± 3.3%, P < .003) and CAHFpEF (-30.4% ± 5.7%, P < .003) and did not differ between CAHFpEF and controls (P = .24). The prevalence of abnormal CMR-derived GCS (P < .0001) and GRS (P < .0001) but not GLS (P = .054) varied significantly across ECV quartiles. CONCLUSIONS: Among CA patients with preserved LVEF, preserved GCS and GRS, despite near-universally impaired GLS, may be explained by an initial predominantly subendocardial involvement, where mostly longitudinal fibers are located. If confirmed in future studies, these findings may facilitate identification of patients with early stages of CA, when treatments may be most effective.

Non-invasive diagnosis of transthyretin cardiac amyloidosis utilizing typical late gadolinium enhancement pattern on cardiac magnetic resonance and light chains.

AIMS: While cardiac magnetic resonance (CMR) is often obtained early in the evaluation of suspected cardiac amyloidosis (CA), it currently cannot be utilized to differentiate immunoglobulin (AL) and transthyretin (ATTR) CA. We aimed to determine whether a novel CMR and light-chain biomarker-based algorithm could accurately diagnose ATTR-CA. METHODS AND RESULTS: Patients with confirmed AL or ATTR-CA with typical late gadolinium enhancement (LGE) and Look-Locker pattern for CA on CMR were retrospectively identified at three academic medical centres. Comprehensive light-chain analysis including free light chains, serum, and urine electrophoresis/immunofixation was performed. The diagnostic accuracy of the typical CMR pattern for CA in combination with negative light chains for the diagnosis of ATTR-CA was determined both in the entire cohort and in the subset of patients with invasive tissue biopsy as the gold standard. A total of 147 patients (age 70 ± 11, 76% male, 51% black) were identified: 89 ATTR-CA and 58 AL-CA. Light-chain biomarkers were abnormal in 81 (55%) patients. Within the entire cohort, the sensitivity and specificity of a typical LGE and Look-Locker CMR pattern and negative light chains for ATTR-CA was 73 and 98%, respectively. Within the subset with biopsy-confirmed subtype, the CMR and light-chain algorithm were 69% sensitive and 98% specific. CONCLUSION: The combination of a typical LGE and Look-Locker pattern on CMR with negative light chains is highly specific for ATTR-CA. The successful non-invasive diagnosis of ATTR-CA using CMR has the potential to reduce diagnostic and therapeutic delays and healthcare costs for many patients.

Age-, Sex-, and Race-Based Normal Values for Left Ventricular Circumferential Strain from the World Alliance Societies of Echocardiography Study.

BACKGROUND: Left ventricular (LV) circumferential strain has received less attention than longitudinal deformation, which has recently become part of routine clinical practice. Among other reasons, this is because of the lack of established normal values. Accordingly, the aim of this study was to establish normative values for LV circumferential strain and determine sex-, age-, and race-related differences in a large cohort of healthy adults. METHODS: Complete two-dimensional transthoracic echocardiograms were obtained in 1,572 healthy subjects (51% men), enrolled in the World Alliance Societies of Echocardiography Normal Values Study. Subjects were divided into three age groups (<35, 35-55, and >55 years) and stratified by sex and by race. Vendor-independent semiautomated speckle-tracking software was used to determine LV regional circumferential strain and global circumferential strain (GCS) values. Limits of normal for each measurement were defined as 95% of the corresponding sex and age group falling between the 2.5th and 97.5th percentiles. Intergroup differences were analyzed using unpaired t tests. RESULTS: Circumferential strain showed a gradient, with lower magnitude at the mitral valve level, increasing progressively toward the apex. Compared with men, women had statistically higher magnitudes of regional and global strain. Older age was associated with a stepwise increase in GCS despite an unaffected ejection fraction, a decrease in LV volume, and relatively stable global longitudinal strain in men, with a small gradual decrease in women. Asian subjects demonstrated significantly higher GCS magnitudes than whites of both sexes and blacks among women only. In contrast, no significant differences in GCS were found between white and black subjects of either sex. Importantly, despite statistical significance of these differences across sex, age, and race, circumferential strain values were similar in all groups, with variations of the order of magnitude of 1% to 2%. Notably, no differences in GCS were found among brands of imaging equipment. CONCLUSION: This study established normal values of LV regional circumferential strain and GCS and identified sex-, age-, and race-related differences when present.

Normal Values of Three-Dimensional Right Ventricular Size and Function Measurements: Results of the World Alliance Societies of Echocardiography Study.

BACKGROUND: Normal values for three-dimensional (3D) right ventricular (RV) size and function are not well established, as they originate from small studies that involved predominantly white North American and European populations, did not use RV-focused views, and relied on older 3D RV analysis software. The World Alliance Societies of Echocardiography study was designed to generate reference ranges for normal subjects around the world. The aim of this study was to assess the worldwide capability of 3D imaging of the right ventricle and report size and function measurements, including their dependency on age, sex, and ethnicity. METHODS: Healthy subjects free of cardiac, pulmonary, and renal disease were prospectively enrolled at 19 centers in 15 countries, representing six continents. Three-dimensional wide-angle RV data sets were obtained and analyzed using dedicated RV software (TomTec) to measure end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume, and ejection fraction (EF). Results were categorized by sex, age (18-40, 41-65, and >65 years) and ethnicity. RESULTS: Of the 2,007 subjects with attempted 3D RV acquisitions, 1,051 had adequate image quality for confident measurements. Upper and lower limits for body surface area-indexed EDV, ESV, and EF were 48 and 95 mL/m2, 19 and 43 mL/m2, and 44% and 58%, respectively, for men and 42 and 81 mL/m2, 16 and 36 mL/m2, and 46% and 61%, respectively, for women. Men had significantly larger EDVs, ESVs, and stroke volumes (even after body surface area indexing) and lower EFs than women (P < .05). EDV and ESV did not show any meaningful differences among age groups. Three-dimensional RV volumes were smallest in Asians. CONCLUSIONS: Reliability of 3D RV acquisition is low worldwide, underscoring the importance of future improvements in imaging techniques. Sex and race must be taken into consideration in the assessment of both RV volumes and EF.

Developing Insights Regarding Tricuspid Valve Regurgitation: Morphology, Assessment of Severity, and the Need for a Novel Grading Scheme.

Current understanding that progressive tricuspid regurgitation (TR) is associated with worse outcomes has highlighted the clinical need for a more accurate assessment of TR morphology and severity. This need has been further emphasized owing to the development of a myriad of percutaneous right-sided interventions, which may offer successful treatment of TR in selected patients. Understanding the etiology and quantification of the severity of TR has important implications in the selection of novel therapeutic strategies, i.e., medical vs. percutaneous vs. surgical approaches. Newer grading schemas that better reflect the TR lesion severity have been recently proposed and may facilitate monitoring of the evolution of TR following percutaneous and/or surgical treatment. In this review, we summarize contemporary concepts regarding tricuspid valve morphology, TR etiology, and associated mechanisms and echocardiographic approaches to grade TR severity.

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

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 years; 57% men) who underwent transthoracic echocardiogram in sinus rhythm. Right atrial reservoir, conduit, and booster strain were quantified using speckle-tracking and compared between patients with CA and 50 healthy age-, sex-, and race-matched controls using the chi-squared or Mann-Whitney test. The relationship between RA parameters and mortality was assessed using Cox regression. RESULTS: Right atrial volume was significantly larger in cases with CA compared with in controls: 29 (22-37) vs 21 (15-25) mL/m2, P < .001. Right atrial reservoir (21% [14%-35%] vs 37% [34%-43%], P < .001), conduit 11% [18%-6%] vs 14% [11%-17%], P < .001), and booster (10% [17%-5%] vs 23% [20%-27%], P < .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 = .005) and significantly more impaired RA reservoir (17% [10%-30%] vs 27% [17%-37%], P = .007), conduit (8% [13%-6%] vs 13% [20%-8%], P = .031), and booster (7% [14%-4%] vs 11% [18%-6%], P = .030) strain. Among CA patients, RA reservoir (hazard ratio = 0.97 per %, P = .006) and RA conduit (hazard ratio = 1.05 per %, P = .004) were significantly associated with mortality, while RA volume (P = .362) and RA booster strain (P = .180) were not. CONCLUSIONS: In CA, abnormalities in RA size and strain are highly prevalent and associated with worse prognosis, suggesting the presence of intrinsic RA atriopathy. Right atrial strain appears to be a potentially useful marker in the diagnosis, subtype differentiation, and risk stratification of CA.

Utility of transillumination and transparency renderings in 3D transthoracic imaging.

Transillumination (TI) is a new 3D rendering tool that uses a freely movable virtual light source to enhance depth, contours, and image detail. The TI model was recently modified to allow the operator adjust the degree of transparency of both cardiac and extra-cardiac structures. While the addition of transparency was shown to significantly improve quality in 3D transesophageal imaging, this has not yet been shown for transthoracic (TTE) imaging. We prospectively studied 35 patients who underwent clinically indicated TTE with standard 3D acquisition, as well as TI with and without transparency. Six experienced echocardiographers were shown images of all three display types in random order. Each image was scored independently using a Likert Scale while assessing each of the following aspects: ability to identify anatomy or pathology, depth perception, degree of anatomic detail, and border delineation. All experts perceived an incremental value of the transparency mode, compared to TI without transparency and standard 3D rendering, in terms of ability to identify anatomy or pathology (4.15 ± 0.97 vs. 3.88 ± 0.99 vs. 2.52 ± 1.41, p < 0.01), depth perception (4.33 ± 0.78 vs. 3.88 ± 0.82 vs. 2.29 ± 1.07, p < 0.01), degree of anatomic detail (4.08 ± 1.0 vs. 3.89 ± 0.79 vs. 2.31 ± 1.08, p < 0.01), and border delineation (4.44 ± 0.80 vs. 3.90 ± 0.78 vs. 2.42 ± 1.13, p < 0.01). Compared to standard 3D and TI renderings of TTE images, the addition of transparency significantly improves both image quality and diagnostic confidence.

Human versus Artificial Intelligence-Based Echocardiographic Analysis as a Predictor of Outcomes: An Analysis from the World Alliance Societies of Echocardiography COVID Study.

BACKGROUND: Transthoracic echocardiography is the leading cardiac imaging modality for patients admitted with COVID-19, a condition of high short-term mortality. The aim of this study was to test the hypothesis that artificial intelligence (AI)-based analysis of echocardiographic images could predict mortality more accurately than conventional analysis by a human expert. METHODS: Patients admitted to 13 hospitals for acute COVID-19 who underwent transthoracic echocardiography were included. Left ventricular ejection fraction (LVEF) and left ventricular longitudinal strain (LVLS) were obtained manually by multiple expert readers and by automated AI software. The ability of the manual and AI analyses to predict all-cause mortality was compared. RESULTS: In total, 870 patients were enrolled. The mortality rate was 27.4% after a mean follow-up period of 230 ± 115 days. AI analysis had lower variability than manual analysis for both LVEF (P = .003) and LVLS (P = .005). AI-derived LVEF and LVLS were predictors of mortality in univariable and multivariable regression analysis (odds ratio, 0.974 [95% CI, 0.956-0.991; P = .003] for LVEF; odds ratio, 1.060 [95% CI, 1.019-1.105; P = .004] for LVLS), but LVEF and LVLS obtained by manual analysis were not. Direct comparison of the predictive value of AI versus manual measurements of LVEF and LVLS showed that AI was significantly better (P = .005 and P = .003, respectively). In addition, AI-derived LVEF and LVLS had more significant and stronger correlations to other objective biomarkers of acute disease than manual reads. CONCLUSIONS: AI-based analysis of LVEF and LVLS had similar feasibility as manual analysis, minimized variability, and consequently increased the statistical power to predict mortality. AI-based, but not manual, analyses were a significant predictor of in-hospital and follow-up mortality.

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

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.

Sex-, Age-, and Race-Related Normal Values of Right Ventricular Diastolic Function Parameters: Data from the World Alliance Societies of Echocardiography Study.

BACKGROUND: Although the assessment of right ventricular (RV) diastolic function is feasible, it has garnered far less momentum for use compared with its left ventricular counterpart. The scarcity of data defining normative RV diastolic function and the fact that implications of RV diastolic dysfunction in different disease states on outcomes are less well known both hinder integration into routine clinical assessment. The aim of this study was to establish normal values of RV diastolic parameters stratified by sex, age, and race using data from the World Alliance Societies of Echocardiography study. METHODS: A subset of 888 normal subjects from the World Alliance Societies of Echocardiography database were analyzed, including measurements of tricuspid valve (TV) inflow E- and A-wave velocities, E-wave deceleration time, and TV annular tissue Doppler e' and a' velocities. Additionally, right atrial (RA) maximal volume and RA peak reservoir strain were measured. Patients were grouped by age (<40, 41-65, and >65 years) and stratified by sex and race. Differences were analyzed using unpaired t tests. RESULTS: Compared with men, women had significantly higher TV e' and E-wave and A-wave velocities, though differences were modest. Increasing age was associated with stepwise lower TV E wave, e' velocity, and TV E/A ratio and higher a' velocity and E/e' ratio. RA peak reservoir strain was also lower, and RA end-systolic volume trended toward being smaller for older age groups. Asian subjects demonstrated significantly higher a' velocities, lower E wave, the smallest RA end-systolic volumes, and the lowest RA peak strain values compared with white subjects of both sexes. CONCLUSIONS: This study provides normal values for parameters used in the assessment of RV diastolic function stratified by race, sex, and age. The results demonstrate significant differences in RV diastolic parameters between age groups, which manifest in both individual parameters and composite ratios of TV inflow and annular velocities. Although limited sex- and race-related differences were also noted, age appears to have the most significant impact on RV diastolic parameters. These findings may aid in refining current normative values.

Normal Values of Left Atrial Size and Function and the Impact of Age: Results of the World Alliance Societies of Echocardiography Study.

BACKGROUND: Left atrial (LA) evaluation includes volumetric and functional parameters with an abundance of diagnostic and prognostic implications. Solid normal reference ranges are compulsory for accurate interpretation in individual patients, but previous studies have yielded mixed conclusions regarding the effects of age, sex, and/or race. The present report from the World Alliance Societies of Echocardiography study focuses on two-dimensional (2D) and three-dimensional (3D) measures of LA structure and function, with subgroup analysis by age, sex, and race. METHODS: Transthoracic 2D and 3D echocardiographic images were obtained in 1,765 healthy individuals (901 men, 864 women) evenly distributed among age subgroups: 18 to 40 years (n = 745), 41 to 65 years (n = 618), and >65 years (n = 402); the racial distribution was 38.4% white, 39.9% Asian, and 9.7% black. Images were analyzed using dedicated LA analysis software to measure LA volumes and phasic function from 3D volume and 2D strain curves. RESULTS: Three-dimensional maximum and minimum LA volumes adjusted for body surface area were nearly identical for men and women, but women demonstrated higher 3D total and passive emptying fractions (EFs). Two-dimensional reservoir strain was similar for both sexes. Age was associated with an incremental rise in LA volumes alongside characteristic shifts in functional indices. Total 2D EF and reservoir and conduit strain varied inversely with age, counteracted by higher booster strain, with a greater magnitude of effect in women. Active 3D EF was significantly higher, while total and passive EFs decreased with age. Interracial differences were noted in LA volumes, without substantial differences in functional indices. CONCLUSION: Although similar normal values for LA volumes and strain can be applied to both sexes, meaningful differences in LA size occur with aging. Indices of function also shift with age, with a compensatory rise in booster function, which may serve to counteract observed lower total and passive EFs. Defining age-associated normal values may help differentiate age-associated "healthy" LA aging from pathologic processes.

PPARα polymorphisms as risk factors for dyslipidemia in a Brazilian population.

BACKGROUND AND AIMS: Peroxisome proliferator-activated receptor α is a nuclear receptor involved in the regulation of several biochemical pathways. Polymorphisms within its gene have been associated with several metabolic traits. We aimed to investigate the association of L162V and Intron 7G>C polymorphisms with serum level markers and common morbidities affecting an older adult/elderly cohort from Cuiaba City, Mato Grosso State, Brazil, as well as to compare the results with a previously studied population from São Paulo City, Brazil. METHODS AND RESULTS: The studied population consisted of 570 subjects from Cuiaba City, Brazil, who were subjected to clinical interviews and blood collection for laboratory examinations and DNA extraction. Dyslipidemia was defined when participants were taking oral hypolipemiants or those with total cholesterol above 200mg/dL, HDL-c below 40 mg/dL, LDL-c above 130 mg/dL and TG above 150 mg/dL. Restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) was used for polymorphism genotyping. Individual polymorphism and haplotype data were available for analyses. In the studied sample, allele frequencies were 0.052 and 0.292 for 162V and Intron 7C, respectively. In brief, 162V allele was associated with dyslipidemia (p=0.025), and after correction for alcohol consumption and waist-to-rip ratio, a tendency of association could still be observed (p=0.050). In addition, Intron 7C allele was associated with dyslipidemia even after correction for the same variables (p=0.029). When compared to our previous study from São Paulo, we found some divergences regarding these results, which may be explained by differences between the two populations. Haplotype association analyses revealed an association between L/C haplotype and dyslipidemia (p=0.021) and between V/C haplotype and lower LDL-c levels when compared to L/G haplotype (p=0.044). CONCLUSION: These results may help to clarify the role of PPARα gene in lipid and lipoprotein metabolism and the evaluation of its polymorphisms and haplotypes as being characterized as genetic risk factors for metabolic disturbances.

Comparison of clinical and echocardiographic features of first and second waves of COVID-19 at a large, tertiary medical center serving a predominantly African American patient population.

As clinicians have gained experience in treating patients with the novel SARS-CoV-2 (COVID-19) virus, mortality rates for patients with acute COVID-19 infection have decreased. The Centers for Disease Control (CDC) has identified the African American population as having increased risk of COVID-19 associated mortality, however little is known about echocardiographic markers associated with increased mortality in this patient population. We aimed to compare the clinical and echocardiographic features of a predominantly African American patient cohort hospitalized with acute COVID-19 infection during the first (March-June 2020) and second (September-December 2020) waves of the COVID-19 pandemic, and to investigate which parameters are most strongly associated with composite all-cause mortality. We performed consecutive transthoracic echocardiograms (TTEs) on 105 patients admitted with acute COVID-19 infection during the first wave and 129 patients admitted during the second wave. TTE parameters including left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LVGLS), right ventricular global longitudinal strain (RVGLS), right ventricular free-wall strain (RVFWS), and right ventricular basal diameter (RVBD) were compared between the two groups. Clinical and demographic characteristics including underlying co-morbidities, biomarkers, in-hospital treatment regimens, and outcomes were collected and analyzed. Univariable and multivariable analyses were performed to determine variables associated with all-cause mortality. There were no significant differences between the two waves in terms of age, gender, BMI, or race. Overall all-cause mortality was 35.2% for the first wave compared to 14.7% for the second wave (p < 0.001). Previous medical conditions were similar between the two waves with the exception of underlying lung disease (41.9% vs. 29.5%, p = 0.047). Echocardiographic parameters were significantly more abnormal in the first wave compared to the second: LVGLS (- 17.1 ± 5.0 vs. - 18.9 ± 4.8, p = 0.02), RVGLS (- 15.7 ± 5.9% vs. - 19.0 ± 5.9%, p < 0.001), RVFWS (- 19.5 ± 6.8% vs. - 23.2 ± 6.9%, p = 0.001), and RVBD (4.5 ± 0.8 vs. 3.9 ± 0.7 cm, p < 0.001). Stepwise multivariable logistic analysis showed mechanical ventilation, RVFWS, and RVGLS to be independently associated with mortality. In a predominantly African American patient population on the south side of Chicago, the clinical and echocardiographic features of patients hospitalized with acute COVID-19 infection demonstrated marked improvement from the first to the second wave of the pandemic, with a significant decrease in all-cause mortality. Possible explanations include implementation of evidence-based therapies, changes in echocardiographic practices, and behavioral changes in our patient population. Mechanical ventilation and right-sided strain-based markers were independently associated with mortality.

Echocardiographic Correlates of In-Hospital Death in Patients with Acute COVID-19 Infection: The World Alliance Societies of Echocardiography (WASE-COVID) Study.

BACKGROUND: The novel severe acute respiratory syndrome coronavirus-2 virus, which has led to the global coronavirus disease-2019 (COVID-19) pandemic is known to adversely affect the cardiovascular system through multiple mechanisms. In this international, multicenter study conducted by the World Alliance Societies of Echocardiography, we aim to determine the clinical and echocardiographic phenotype of acute cardiac disease in COVID-19 patients, to explore phenotypic differences in different geographic regions across the world, and to identify parameters associated with in-hospital mortality. METHODS: We studied 870 patients with acute COVID-19 infection from 13 medical centers in four world regions (Asia, Europe, United States, Latin America) who had undergone transthoracic echocardiograms. Clinical and laboratory data were collected, including patient outcomes. Anonymized echocardiograms were analyzed with automated, machine learning-derived algorithms to calculate left ventricular (LV) volumes, ejection fraction, and LV longitudinal strain (LS). Right-sided echocardiographic parameters that were measured included right ventricular (RV) LS, RV free-wall strain (FWS), and RV basal diameter. Multivariate regression analysis was performed to identify clinical and echocardiographic parameters associated with in-hospital mortality. RESULTS: Significant regional differences were noted in terms of patient comorbidities, severity of illness, clinical biomarkers, and LV and RV echocardiographic metrics. Overall in-hospital mortality was 21.6%. Parameters associated with mortality in a multivariate analysis were age (odds ratio [OR] = 1.12 [1.05, 1.22], P = .003), previous lung disease (OR = 7.32 [1.56, 42.2], P = .015), LVLS (OR = 1.18 [1.05, 1.36], P = .012), lactic dehydrogenase (OR = 6.17 [1.74, 28.7], P = .009), and RVFWS (OR = 1.14 [1.04, 1.26], P = .007). CONCLUSIONS: Left ventricular dysfunction is noted in approximately 20% and RV dysfunction in approximately 30% of patients with acute COVID-19 illness and portend a poor prognosis. Age at presentation, previous lung disease, lactic dehydrogenase, LVLS, and RVFWS were independently associated with in-hospital mortality. Regional differences in cardiac phenotype highlight the significant differences in patient acuity as well as echocardiographic utilization in different parts of the world.