Villarraga, Hector R.

Background: The National Comprehensive Cancer Network and American Society of Clinical Oncology recommend consideration of the use of echocardiography 6 to 12 months after completion of anthracycline-based chemotherapy in at-risk populations. Assessment of BNP (B-type natriuretic peptide) has also been suggested by the American College of Cardiology/American Heart Association/Heart Failure Society of America for the identification of Stage A (at risk) heart failure patients. The real-world frequency of the use of these tests in patients after receipt of anthracycline therapy, however, has not been studied previously. Methods and Results: In this retrospective study, using administrative claims data from the OptumLabs Data Warehouse, we identified 31 447 breast cancer and lymphoma patients (age ≥18 years) who were treated with an anthracycline in the United States between January 1, 2008 and January 31, 2018. Continuous medical and pharmacy coverage was required for at least 6 months before the initial anthracycline dose and 12 months after the final dose. Only 36.1% of patients had any type of cardiac surveillance (echocardiography, BNP, or cardiac imaging) in the year following completion of anthracycline therapy (29.7% echocardiography). Surveillance rate increased from 37.5% in 2008 to 42.7% in 2018 (25.6% in 2008 to 40.5% echocardiography in 2018). Lymphoma patients had a lower likelihood of any surveillance compared with patients with breast cancer (odds ratio, 0.79 [95% CI, 0.74–0.85]; P <0.001). Patients with preexisting diagnoses of coronary artery disease and arrhythmia had the highest likelihood of cardiac surveillance (odds ratio, 1.54 [95% CI, 1.39–1.69] and odds ratio, 1.42 [95% CI, 1.3–1.53]; P <0.001 for both), although no single comorbidity was associated with a >50% rate of surveillance. Conclusions: The majority of survivors of breast cancer and lymphoma who have received anthracycline-based chemotherapy do not undergo cardiac surveillance after treatment, including those with a history of cardiovascular comorbidities, such as heart failure.

Abstract Background: Aortic stenosis (AS) causes left ventricular (LV) pressure overload, leading to adverse LV remodeling and dysfunction. Identifying early subclinical markers of LV dysfunction in patients with significant AS is critical as this could provide support for earlier intervention, which may result in improved long-term outcomes. We therefore examined the impact of severe AS and its consequent increase in LV afterload on myocardial deformation and rotational mechanics by 2-dimensional (2D) and 3-dimensional (3D) speckle-tracking echocardiography. Methods: We prospectively measured various strain parameters in 168 patients (42% female, mean age 72±12 years) with severe AS and LV ejection fraction (EF) ≥50%, and compared them to normal values found in literature. 2D and 3D images were analyzed for global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist. We further assessed the degree of concordance between 2D and 3D strain, and examined their association with measures of LV preload and afterload. Results: Patients with severe AS exhibited significantly lower GLS and GRS but higher GCS, apical rotation, and twist by 2D and 3D echocardiography compared with published normal values (P=0.003 for 3D twist,P<0.001 for all others). Agreement between 2D- and 3D-GLS by concordance correlation coefficient was 0.49 (95% confidence interval: 0.39-0.57). GLS was correlated with valvulo-arterial impedance, a measure of LV afterload (r=0.34, p<0.001 and r=0.23, p=0.003, respectively). Conclusion: Patients with severe AS demonstrated lower-than-normal GLS and GRS but appear to compensate with higher-than-normal GCS, apical rotation, and twist in order to maintain a preserved LVEF. GLS showed a modest correlation with valvulo-arterial impedance.

Abstract Background: Sarcoidosis is a systemic granulomatous disease that may affect the myocardium. This study evaluated the diagnostic and prognostic value of 2-dimensional speckle tracking echocardiography in cardiac sarcoidosis (CS). Methods: Eighty-three patients with extracardiac, biopsy-proven sarcoidosis and definite/probable diagnosis of cardiac involvement diagnosed from January 2005 through December 2016 were included. Strain parameters in early stages of CS, in a subgroup of 23 CS patients with left ventricular ejection fraction (LVEF) within normal limits (LVEF>52% for men: >54% for women, mean value: 57.3%±3.8%) and no wall motion abnormalities was compared with 97 controls (1:4) without cardiac disease. LV and right ventricular (RV) global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain and strain rate (SR) analyses were performed with TomTec software and correlated with cardiac outcomes (including heart failure and arrhythmias). This study was approved by the Mayo Clinic Institutional Review Board, and all patients gave informed written consent to participate. Results: Mean age of CS patients was 53.6±10.8 years, and 34.9% were women. Mean LVEF was 43.2%±12.4%; LV GLS, -12.4%±3.7%; LV GCS, -17.1%±6.5%; LV GRS, 29.3%±12.8%; and RV wall GLS, 14.6%±6.3%. In the 23 patients with early stage CS with normal LVEF and RV systolic function, strain parameters were significantly reduced when compared with controls (respectively: LV GLS, -15.9%±2.5% vs -18.2%±2.7% [ P =.001]; RV GLS, -16.9%±4.5% vs -24.1%±4.0% [ P <.001]). A LV GLS value of -16.3% provided 82.2% sensitivity and 81.2% specificity for the diagnosis of CS (AUC 0.91), while a RV value of -19.9% provided 88.1% sensitivity and 86.7% specificity (AUC 0.93). Hospital admission and heart failure significantly correlated to impaired LV GLS (> -14%). Conclusion: Reduced strain values in the LV GLS and RV GLS can be used in the diagnostic algorithm in patients with suspicion of cardiac sarcoidosis. These values also correlate with adverse cardiovascular events.

Abstract Background: Aortic stenosis (AS) causes left ventricular (LV) pressure overload, leading to adverse LV remodeling and dysfunction. We examined the impact of severe AS and its consequent increase in LV afterload on myocardial deformation and rotational mechanics by 2-dimensional (2D) and 3-dimensional (3D) speckle-tracking echocardiography. Methods: We prospectively measured various strain parameters in 168 patients (42% female, mean age 72±12 years) with severe AS and LV ejection fraction (EF) ≥50%, and compared them to normal values found in literature. 2D and 3D images were analyzed for global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist. We further assessed the degree of concordance between 2D and 3D strain, and examined their association with measures of LV preload and afterload. Results: Patients with severe AS exhibited significantly lower GLS and GRS but higher GCS, apical rotation, and twist by 2D and 3D echocardiography compared with published normal values (P=0.003 for 3D twist,P<0.001 for all others). There was modest agreement between 2D and 3D GLS measurements (concordance correlation coefficient 0.49, 95% confidence interval 0.39-0.57). GLS was modestly correlated with valvulo-arterial impedance, a measure of LV afterload (r=0.34, p<0.001 for 2D and r=0.23, p=0.003 for 3D). Conclusion: Patients with severe AS demonstrate lower-than-normal GLS and GRS as a result of increased afterload but appear to compensate with higher-than-normal GCS, apical rotation, and twist in order to maintain a preserved LVEF. Our study provides, to our knowledge, the most comprehensive analysis to date of myocardial deformation and rotational mechanics by 2D and 3D speckle-tracking echocardiography in patients with severe AS and preserved LVEF.

Abstract Background: Sarcoidosis is a systemic granulomatous disease that may affect the myocardium. This study evaluated the diagnostic and prognostic value of 2-dimensional speckle tracking echocardiography in cardiac sarcoidosis (CS). Methods: Eighty-three patients with extracardiac, biopsy-proven sarcoidosis and definite/probable diagnosis of cardiac involvement diagnosed from January 2005 through December 2016 were included. Strain parameters in early stages of CS, in a subgroup of 23 CS patients with left ventricular ejection fraction (LVEF) within normal limits (LVEF>52% for men: >54% for women, mean value: 57.3%±3.8%) and no wall motion abnormalities was compared with 97 controls (1:4) without cardiac disease. LV and right ventricular (RV) global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain and strain rate (SR) analyses were performed with TomTec software and correlated with cardiac outcomes (including heart failure and arrhythmias). This study was approved by the Mayo Clinic Institutional Review Board, and all patients gave informed written consent to participate. Results: Mean age of CS patients was 53.6±10.8 years, and 34.9% were women. Mean LVEF was 43.2%±12.4%; LV GLS, -12.4%±3.7%; LV GCS, -17.1%±6.5%; LV GRS, 29.3%±12.8%; and RV wall GLS, 14.6%±6.3%. In the 23 patients with early stage CS with normal LVEF and RV systolic function, strain parameters were significantly reduced when compared with controls (respectively: LV GLS, -15.9%±2.5% vs -18.2%±2.7% [P=.001]; RV GLS, -16.9%±4.5% vs -24.1%±4.0% [P<.001]). A LV GLS value of -16.3% provided 82.2% sensitivity and 81.2% specificity for the diagnosis of CS (AUC 0.91), while a RV value of -19.9% provided 88.1% sensitivity and 86.7% specificity (AUC 0.93). Hospital admission and heart failure significantly correlated to impaired LV GLS (> -14%). Conclusion: Reduced strain values in the LV GLS and RV GLS can be used in the diagnostic algorithm in patients with suspicion of cardiac sarcoidosis. These values also correlate with adverse cardiovascular events.

Abstract Background Anthracyclines are one of the most effective chemotherapeutic agents but can lead to a decline in cardiac function. Two-dimensional (2D) speckle tracking echocardiography derived strain can predict cancer therapeutics-related cardiac dysfunction (CTRCD). However, little is known about the role of three-dimensional (3D) strain imaging in this setting. Purpose To evaluate different methods of Left Ventricular Ejection Fraction (LVEF) and strain, and to identify the best strain parameter for the prediction of CTRCD in this group of patients during treatment with anthracycline based chemotherapy. Methods Patients with Hodgkin's or non-Hodgkin's lymphoma receiving anthracycline based chemotherapy were enrolled. 2D-and 3D echocardiography was performed at 3 time points: baseline, at the completion of chemotherapy and at 1 year. 2D- and 3D LVEF (2D Modified Quinones, M-mode, 2D Biplane, 3D Philips, 3D GE and 3D TomTec), peak systolic left and right ventricular longitudinal, radial and circumferential strain and strain rate were measured. CTRCD was defined as a decrease in LVEF >10% to an absolute value of <53%. Lin's Concordance Correlation Coefficient (CCC) was calculated to compare LVEF methods. ANOVA, uni and multivariate analysis was performed. Results A total of 130 patients (79 males, mean age 57±16 years) were enrolled; 104 non-Hodgkin.3D Philips and GE (CCC 0.88 [0.84, 0.92]), 3D Philips and biplane (CCC 0.84 [0.79, 0.89]), 3D Philips and Modified Quinones (CCC 0.86 [0.82, 091]) as well as 3D Philips and M-mode (CCC 0.77 [0.70, 0.85]) showed strong correlation for LVEF. 15 patients (12%) developed CTRCD. Mean cumulative anthracycline dose was 263±65 mg/m2. 2D and 3D global longitudinal and circumferential peak systolic strain, 2D global longitudinal systolic and early diastolic strain rate, 2D global early diastolic strain rate, 2D right ventricular longitudinal peak systolic strain and systolic strain rate, 2D global radial peak systolic strain and systolic strain rate measured at the completion of chemotherapy were independent predictors of the development of CTRCD at 1 year post-chemotherapy. The strongest predictors of CTRCD were 3D global longitudinal and circumferential strain either individually (area under the curve, 0.90 and 0.95 respectively) or combined (area under the curve, 0.95) at the completion of chemotherapy; a cutoff value of <-18% in 3D global longitudinal strain had a sensitivity of 82% and specificity of 99%, while for 3D global circumferential peak systolic strain of <-24% had a sensitivity of 82% and specificity of 95%. Conclusions To our knowledge this is the first prospective trial that shows that 3D EF correlates well with other EF methods and 3D strain predicts cardiac toxicity in this group of patients with a very good sensitivity and specificity. Acknowledgement/Funding Department of Cardiovascular Medicine-Mayo Clinic Rochester MN

Abstract Background Despite over a decade of evidence, uptake of GLS into guidelines and practice has been slow. Age, BP, and software have been reported to influence GLS, and have led to uncertainty about defining the normal range (NR). As there have been software changes since the last meta-analysis, we sought to define NR in the current era. Methods Pubmed, Cochrane, and EMBASE were searched using the keywords “Left Ventricle”, “Normal global longitudinal strain”, and “Speckle tracking Echocardiography” and relevant synonyms from 2011. Studies were included if they reported GLS based on speckle tracking techniques, included at least 20 healthy individuals, and had up to date contact details available. Healthy was defined as lack of known disease. Platforms used included General Electric, Philips, Canon and Tomtec. The authors of 8 of the 12 studies (67% response) provided individual patient data. Linear regression was used to determine predictors of GLS. Results There were 2396 pts, mean age 42 years (range 18–92), weight 66±12kg, height 169±9cm, BSA 1.7±0.2m2, and SBP 120±13 mmHg. Normal range for GLS was 21.0±2.6%. In multivariable analysis age (β=-0.02, p<0.01), weight (β=-0.03, p<0.01), SBP (β=-0.01, p<0.01) and platform were associated with GLS. GLS tends to vary with extremes of age and BP (see Figure 1 and Figure 2). GLS vs Age group Conclusion Extremes of age and BP may lead to low GLS, but generally, GLS is <16% is abnormal. Acknowledgement/Funding None

Abstract Background Left ventricular ejection fraction (LVEF), end diastolic, end systolic volumes (EDV, ESV) and global longitudinal strain (GLS) are very important parameters that are frequently reported in cardiology. Normal cardiac geometry was not considered in articles that published normal values. It is important to know normal parameters for population studies. Our hypothesis is to analyze how EF, volumes and GLS may vary by age groups, gender and BMI in a population with normal cardiac geometry. Purpose To define the values in EF, volumes and GLS measurements in a healthy population with normal cardiac geometry stratified by age groups, gender and body mass index (BMI). Methods This is a single center retrospective study conducted from 2008 to 2018. We selected 4557 subjects (2605 females, 1952 males) >18 years with ≤ mild valvular heart disease, who underwent 2D-echocardiography (2DE) at Mayo clinic, Rochester. All selected subjects had normal LV geometry (i.e., LV mass index≤88g/m2 in females and ≤102g/m2 in males and relative wall thickness ≤0.42 measured by 2DE) and without any cardiovascular risk factors or structural or functional abnormality determined by 2DE. Based on age groups, gender and BMI, we assessed the variability in volumes indexed to body surface area, EF and GLS by Mean ± SD and two sample t-test. Results Mean age was 54±15 years (females = 53±15, males = 56±16), body surface area was 1.9 m2±0.2 (females = 1.8±0.2, males = 2.1±0.2), LV GLS −20.7% ±2 SD (females = −21.2±2, males= −20.2±1.9) ranging −16.1 to −27.6 in both genders (Figure); LVEF by Biplane volume method 62.6% ± 4 SD (females = 63±4.3, males=62±4.5). The end diastolic volume 63.6±11.7 cc/m2 (female = 59.9±10.3, males = 68.1±11.8) and end systolic volume 23.9 cc/m2±5.4 (female = 22.3±4.8, males = 25.9±5.5). LV GLS, Biplane EF values were higher in females and EDV and ESV values were higher in males. LV GLS values decreased with age in females (P<0.0001). While EF increased with age in both genders (P<0.0001), EDV and ESV values decreased with age (P<0.0001). When each gender is sub-divided based on their BMI (<25 and ≥25), GLS, EDV and ESV values were higher in population with BMI <25 (P<0.0001). Normal geometry variables Conclusion To our knowledge, this is the biggest single center study to evaluate LV GLS values, LV EF, ED, ES volumes. These results can be used as reference values in a normal population. Acknowledgement/Funding None

Abstract Background The left ventricle (LV) undergoes different types of remodeling to normalize its wall stress. There has been an increase in the trend in research regarding the process of remodeling but little is known about how LV volumes and global longitudinal strain (GLS) may vary depending upon the type of remodeling. Purpose To define the values of LV volumes and GLS in patients with different types of LV remodeling with normal ejection fraction (EF). Methods Single center retrospective study conducted from 2008 to 2018. We selected 10,356 subjects >18 years (5808 females, 4548 males) with normal EF and who underwent 2D echocardiography (2DE) at Mayo clinic, Rochester. They were categorized into 4 groups (Figure) i.e., group 1 = normal geometry, group 2 = concentric remodeling, group 3 = concentric hypertrophy, group 4 = eccentric hypertrophy based on their LV mass index (102 g/m2 in males, 88 g/m2 in females) and relative wall thickness (0.42) values measured by 2DE (figure). The patterns of LV GLS, end diastolic and end systolic volumes (EDV, ESV) indexed to body surface area were analyzed in these four groups by gender and body mass index (BMI). Mean±SD, One-way Anova, two sample t-test and Tukey- Kramer HSD were applied. Results The mean age of the selected population is 57.9 years ±14.9 (females=57.7±14.7, males=58.2±15.1) and the body surface area of 1.9 m2±0.2 (females=1.8±2 and males=2.1±0.2). The LV GLS values (Figure) of groups 1, 2, 3 and 4 were −20.7, −18.9, −17.5 and −19.9 and their EDV cc/m2 values were 63.6, 58.5, 61.2 and 68.2 respectively. LV GLS and Biplane EF values were higher in females while Biplane EDV and ESV were higher in males. When each gender is sub-divided based on their BMI (<25 and ≥25), the LV GLS, EDV and ESV values were higher in all groups with BMI<25 except in males with concentric remodeling and females with concentric hypertrophy where they were low. Remodeling distribution Conclusion To our knowledge, this is the biggest single center study to evaluate LV GLS and volumes based on type of remodeling by gender and BMI. When compared with normal geometry, LV volumes and GLS values were statistically different among each type of remodeling as well as for gender and BMI. These results can be used as reference values in patient population studies where remodeling is being analyzed in subjects with normal LV EF. Acknowledgement/Funding None

Abstract Background: Sarcoidosis is a systemic granulomatous disease that may affect the myocardium. This study evaluated the diagnostic and prognostic value of 2-dimensional speckle tracking echocardiography in cardiac sarcoidosis (CS). Methods: Eighty-three patients with extracardiac, biopsy-proven sarcoidosis and definite/probable diagnosis of cardiac involvement diagnosed from January 2005 through December 2016 were included. In order to analyze the alteration of strain parameters in early stages of CS, a subgroup of 23 CS patients with left ventricular ejection fraction (LVEF) within normal limits (LVEF>52% for men: >54% for women, mean value: 57.3%±3.8%) and no wall motion abnormalities was compared with 97 controls (1:4) without cardiac disease. LV and right ventricular (RV) global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain and strain rate (SR) analyses were performed with TomTec software and correlated with cardiac outcomes (including heart failure and arrhythmias). This study was approved by the Mayo Clinic Institutional Review Board, and all patients gave informed written consent to participate. Results: Mean age of CS patients was 53.6±10.8 years, and 34.9% were women. Mean LVEF was 43.2%±12.4%; LV GLS, -12.4%±3.7%; LV GCS, -17.1%±6.5%; LV GRS, 29.3%±12.8%; and RV wall GLS, 14.6%±6.3%. In the 23 patients with early stage CS with normal LVEF and RV systolic function, strain parameters were significantly reduced when compared with controls (respectively: LV GLS, -15.9%±2.5% vs -18.2%±2.7% [ P =.001]; RV GLS, -16.9%±4.5% vs -24.1%±4.0% [ P <.001]). A LV GLS value of -16.3% provided 82.2% sensitivity and 81.2% specificity for the diagnosis of CS (AUC 0.91), while a RV value of -19.9% provided 88.1% sensitivity and 86.7% specificity (AUC 0.93). Hospital admission and heart failure significantly correlated to impaired LV GLS (> -14%). Conclusion: Reduced strain values in the LV GLS and RV GLS can be used in the diagnostic algorithm in patients with suspicion of cardiac sarcoidosis. These values also correlate with adverse cardiovascular events.