Decrease In Global Longitudinal Strain Research Articles

Cardiac effects of direct anti-viral treatment in type II diabetic patients with hepatitis C infection.

The link between diabetes mellitus and chronic hepatitis C infection remains well established. It is estimated that up to one third of chronic hepatitis C patients have type II diabetes mellitus. Hepatitis C virus infection is one of the main global health burdens. Sofosbuvir and Daclatasvir are used as effective antiviral inhibitors of hepatitis C virus. The cardiovascular effects of those drugs are not well studied. We used electrocardiography and echocardiography with global longitudinal strain assessment by speckle tracking to detect their effect on cardiac function. One hundred diabetic patients with hepatitis C infection were included in the study. Abdominal ultrasound and laboratory work up were carried out for all participants. Left ventricular systolic and diastolic function were assessed by 2D-echocardiography and global longitudinal strain, before and 3months after treatment. Results showed significant decrease in global longitudinal strain 3months after therapy (-21 ± 4 vs. -18 ± 7; P < 0.001) but other echocardiographic findings showed no significant changes. Sofosbuvir and Daclatasvir were associated with early left ventricular systolic dysfunction as assessed by global longitudinal strain in diabetic patients. More deterioration in left ventricular systolic function was detected among those with Child-Pough class B. Further long-term follow-up may be required.

Global longitudinal strain as a predictor of mortality in patients with cardiogenic shock

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Aarhus University Dagmar Marshalls Fond. Background The assessment of left ventricular (LV) function through transthoracic echocardiography (TTE) is essential for guiding diagnosis and treatment in cases of cardiogenic shock (CS). Myocardial global longitudinal strain (GLS) provides an objective and reproducible measure of systolic function, independently predicting outcomes in acute heart failure, regardless of left ventricular ejection fraction (LVEF). However, whether assessment of GLS can predict mortality in patients with CS remains unknown. Purpose In this study, we aimed to evaluate the prognostic significance of GLS in patients with CS. Methods Data from cardiac intensive care unit (CICU) patients admitted between 2007 and 2018 with CS who received vasoactive agents and/or mechanical circulatory support were analysed. GLS (as absolute values) and biplane LVEF were measured via TTE performed within 24 hours of CICU admission. Patients with CS were categorised based on the GLS quartile: mild (GLS &amp;gt;9.7%), moderate (7.0% &amp;lt; GLS &amp;lt;9.6%), severe (5.0% &amp;lt; GLS &amp;lt; 6.9%), and very severe (GLS ≤ 4.9%). CICU and in-hospital mortality were compared across GLS categories, and the relationship between GLS and mortality was assessed using multivariable logistic regression. Results The study included 626 patients with a median age of 68.6 years, a median LVEF of 31% (IQR 24 to 40%), and a median GLS of 7.0% (IQR 5.0 to 9.7%). In-hospital mortality was 29.1%. As GLS deteriorated, there was an increasing need for vasopressors (P&amp;lt;0.001). Patients with progressively lower GLS exhibited significantly higher CICU and in-hospital mortality across the GLS quartiles (Figure A; P&amp;lt;0.001). Patients in the severe (adjusted OR 2.67; p&amp;lt;0.001) and very severe category (adjusted OR 3.54; P&amp;lt;0.001) had significantly increased risk of in-hospital death compared with mild category. In multivariable analysis, every 1% decrease in GLS corresponded to a 14% higher risk of in-hospital mortality (P&amp;lt;0.001). Finally, GLS outperformed LVEF for discrimination of in-hospital mortality (P=0.002), and when both measurements were included in the same multivariable model, only GLS remained significant. When patients were divided according to whether they had GLS and/or LVEF below the median value, patients with low GLS had higher mortality irrespective of the LVEF (Figure B). Conclusion In patients with CS, GLS assessment surpasses LVEF in its prognostic value and improves risk stratification. Routine evaluation of GLS should be considered for patients with CS.Figure AFigure B

Abstract PO1-10-04: Racial and Ethnic Disparities in Anthracycline and HER2-targeted Cardiotoxicity in Patients With Breast Cancer Using Global Longitudinal Strain Imaging Techniques

Abstract Purpose: Studies of global longitudinal strain (GLS) as a predictor of cancer treatment-related cardiac dysfunction (CTRCD) have been limited in racial/ethnic minority populations who are more likely to have risk factors associated with CTRCD. Our aim was to assess the utilization of GLS and development of CTRCD in a racially and ethnically diverse population of patients at an academic center in New York City. Methods: Patients were included if they had a breast cancer diagnosis and began treatment with anthracycline or HER2-directed therapies at Columbia University Irving Medical Center (CUIMC) from February 1, 2020-July 31, 2022. All patients and variables were identified via the electronic health record. Cardiovascular comorbidities including obesity, hypertension, diabetes, hyperlipidemia, coronary artery disease, congestive heart failure, and other cardiac disease, were recorded. Receipt of transthoracic echocardiogram(s) (TTE) with/without GLS were recorded, along with GLS and left ventricular ejection fraction (LVEF) values. CTRCD was defined as LVEF decrease of ≥10% to a LVEF value &amp;lt; 53% or GLS decrease of ≥ 15% from baseline or GLS &amp;lt; -18%. Analyses included descriptive statistics and univariable and multivariable logistic regression models to evaluate predictors of CTRCD by either LVEF or GLS definition. Results: We identified 270 eligible patients. Mean age was 51.8 years (standard deviation 13.0), 85 (31.5%) identified as White, 47 (17.4%) as Black/African, and 16 (5.9%) as Asian; 135 (50.0%) identified as Non-Hispanic/Latino, and 79 (29.2%) as Hispanic/Latino. Approximately half of the patient cohort, n=137 (50.7%) had a TTE with GLS during the study period. Of the TTEs done at CUIMC (n=658), 270 (41%) were ordered with GLS assessment, of which 184 (68%) reported a GLS value and 86 (32%) were not assessable due to image quality. Forty-three (16%) patients developed CTRCD: 20 (7%) by GLS criteria, 13 (5%) by LVEF criteria, and 10 (4%) by both GLS and LVEF criteria. In univariable analyses, race (OR 5.78, 95%CI 1.62-20.4 Asian compared to White), treatment with HER2 therapy without anthracycline versus anthracycline (OR 2.78, 95%CI 1.34-6.23), and prescription for cardiac medication prior to systemic therapy (OR 2.27, 95%CI 1.08-4.63) were predictors of CTRCD by any definition. In multivariable analysis, race (OR 7.86, 95%CI 1.71-38.50 Asian compared to White), and receipt of HER2 therapy without anthracycline compared to anthracycline (OR 5.13, 95%CI 1.42-25.00) were predictors of CTRCD. In multivariable analysis of CTRCD by GLS criteria only, race (OR 78.47, 95%CI 1.47-53.96 Asian compared to White), and treatment (OR 11.23, 95%CI 1.85-219 HER2 therapy compared to anthracycline; OR 58.7, 95%CI 1.05-60.59 HER2 therapy and anthracycline compared to anthracycline). Conclusions: In this retrospective analysis of a racially and ethnically diverse patient population, more than a third of Asian patients developed CTRCD, although the study is limited by small sample sizes. Asian race and receipt of anti-HER2 therapy were independent risk factors for CTRCD. Asian race was especially a predictor of CTRCD by GLS definition. Detection bias may explain the differences in CTRCD by drug class, as patients complete serial TTEs while receiving HER2-directed therapy, while patients who receive an anthracycline without HER2-directed therapy typically only receive a baseline TTE. Future research to better characterize racial differences in CTRCD incidence and develop interventions to reduce this disparity is an area warranting further investigation. Demographic and Tumor Related Factors Associated with CTRCD (n=270) Univariable and multivariable analysis of CTRCD by LVEF or GLS definition. Multivariable analysis was adjusted for all variables listed. Citation Format: Amanda Wang, Jayant Raikhelkar, Rohit Raghunathan, Julia McGuinness, Neil Vasan, Meghna Trivedi, Kevin Kalinsky, Katherine Crew, Melissa Beauchemin, Jason Wright, Dawn Hershman, Melissa Accordino. Racial and Ethnic Disparities in Anthracycline and HER2-targeted Cardiotoxicity in Patients With Breast Cancer Using Global Longitudinal Strain Imaging Techniques [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-10-04.

Myocardial dysfunction in patients with rheumatoid arthritis in the speckle-tracking echocardiography and its relationship with the clinical characteristics of the disease

patients with RA have an approximately 50% increased risk of cardiovascular events and cardiovascular death. Cardiovascular diseases lead to a decrease in life expectancy, and the determination of the mechanisms of myocardial damage in patients with RA is of great importance for the development of methods for the early prevention of heart failure. The aim of our study was to study myocardial dysfunction using speckle tracking echocardiography (STE) in patients with RA and to find out possible correlations with the course of the disease and risk factors for cardiovascular diseases. Materials and methods. 29 RA patients were examined (5 in remission, 17.2%). Rheumatoid factor (RF), the level of antibodies to cyclic citrullinated peptides (a-CRP), quantitative C-reactive protein (CRP) was determined in the blood of all patients, and echocardiography and speckle-tracking echocardiography were performed to determine indicators of longitudinal deformation of the left ventricle. Disease activity was determined using the DAS28 index (CRP) and other functional and laboratory indicators. The results. The study of STE indicators is much better than "classical" echocardiography, revealing latent preclinical heart lesions. We established a significant decrease in Global Longitudinal Strain in the basal anterior and basal antero-septal segments (-17.24±3.01% and 15.94±9.37%, respectively) and preservation of local strain in the apical and middle segments (respectively -26.95+4.95% and -21.69+3.05%). In general, 41.2% of patients with RA had lesions of the basal segments. When analyzing the correlation between disease activity and deformation in STE, an inverse relationship between the DAS28 index and apical deformation (API Strain) was established (r=-0.50, р=0.06). The highest correlations were found between STE and functional status of disease: HAQ-DI score (r=-0.51, p=0.05) and VAS activity (r=-0.64, p=0.01). Conclusions. Functional activity according to the HAQ-DI score and VAS had a significantly greater relationship with preclinical manifestations of heart damage (detected by STE) than standard cardio-vascular risk factors. It is necessary to continue the search for other important factors that can lead to the formation of heart lesions and are related to both the activity of the disease and the functional status of patients. It is expedient to conduct comparative studies of STE in RA and coronary artery disease to clarify the differences in the processes of formation of myocardial damage.

Biomarkers and subclinical left ventricular dysfunction in patients with type 2 diabetes without clinical manifestations of cardiovascular diseases

Aim. To study the relationship between the structural and functional left ventricular (LV) parameters and N-terminal pro-brain natriuretic peptide (NT-proBNP) and inflammatory markers in patients with type 2 diabetes (T2D) without clinical manifestations of cardiovascular diseases, as well as to evaluate the possibility of their use for early diagnosis of subclinical LV dysfunction.Material and methods. Data from 120 patients of both sexes aged 45-75 years (57,11±7,9 years) were analyzed. They were divided into three following groups: 1st — with T2D (n=47), 2nd — with prediabetes (n=20), 3rd — control (n=53). All participants underwent transthoracic echocardiography with assessment of the linear and volumetric heart dimensions, systolic and diastolic LV function. Speckle tracking echocardiography was analyzed with calculation of LV global longitudinal strain (GLS). The blood levels of NT-proBNP and inflammatory markers were determined (high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-6).Results. According to echocardiography, patients with carbohydrate metabolism disorders revealed significantly higher LV mass values, LV posterior wall thickness, and relative wall thickness in comparison with the control group. Transmitral flow parameters, as well as tissue Doppler sonography, in the T2D and prediabetes groups were significantly different from those in the control group. GLS in the groups of patients with carbohydrate metabolism disorders was lower than in the control group (p=0,001). The level of NT-proBNP was significantly higher in the T2D and prediabetes groups compared to the control group, while in all three groups it did not exceed normal values (p&lt;0,001). A higher level of NT-proBNP was associated with hypertension — odds ratio (OR) 3,64 [1,02-13,04] (p=0,005), a decrease in LV ejection fraction — OR 1,25 [1,06-1 ,47] (p=0,007), concentric hypertrophy — OR 4,84 [1,43-16,41] (p=0,011) and decreased GLS — OR 1,85 [1,62-2,06] (p=0,005), an increase in the ratio of early and late diastolic transmitral flow (E/A) — OR 0,01 [0,008-0,416] (p=0,024) and isovolumic relaxation time (IVRT) — OR 1,08 [1,03-1,14] (p=0,03). The sensitivity and specificity of NT-proBNP as a test for predicting GLS reduction &lt;-18% were 86 and 27%, respectively. The hsCRP level, within the reference values, was significantly higher in the T2D and prediabetes groups compared to the control group (p&lt;0,001) and demonstrated a direct linear relationship with E/A, IVRT, early diastolic deceleration time (p&lt;0,05). A higher level of hsCRP was significantly associated with diastolic dysfunction — OR 1,16 [1,02-1,32] (p=0,023), as well as with a GLS decrease &lt;-18% — OR 1,58 [1,12-4,65] (p=0,03).Conclusion. In patients with T2D without clinical manifestations of cardiovascular disease, the presence of concentric LV myocardial hypertrophy, LV diastolic dysfunction and decreased GLS (&lt;-18%) is associated with higher blood levels of NT-proBNP and hsCRP. However, in all cases, the levels of biomarkers do not exceed the reference values, which does not allow their use in the early diagnosis of subclinical LV dysfunction in T2D.

Early signs of myocardial systolic dysfunction in patients with type 2 diabetes are strongly associated with myocardial microvascular dysfunction independent of myocardial fibrosis: a prospective cohort study

BackgroundPatients with diabetes demonstrate early left ventricular systolic dysfunction. Notably reduced global longitudinal strain (GLS) is related to poor outcomes, the underlying pathophysiology is however still not clearly understood. We hypothesized that pathophysiologic changes with microvascular dysfunction and interstitial fibrosis contribute to reduced strain.Methods211 patients with type 2 diabetes and 25 control subjects underwent comprehensive cardiovascular phenotyping by magnetic resonance imaging. Myocardial blood flow (MBF), perfusion reserve (MPR), extracellular volume (ECV), and 3D feature tracking GLS and global circumferential (GCS) and radial strain (GRS) were quantified.ResultsPatients (median age 57 [IQR 50, 67] years, 70% males) had a median diabetes duration of 12 [IQR 6, 18] years. Compared to control subjects GLS, GCS, and GRS were reduced in the total diabetes cohort, and GLS was also reduced in the sub-group of patients without diabetic complications compared to control subjects (controls − 13.9 ± 2.0%, total cohort − 11.6 ± 3.0%; subgroup − 12.3 ± 2.6%, all p < 0.05). Reduced GLS, but not GCS or GRS, was associated with classic diabetes complications of albuminuria (UACR ≥ 30 mg/g) [β (95% CI) 1.09 (0.22–1.96)] and autonomic neuropathy [β (95% CI) 1.43 (0.54–2.31)] but GLS was not associated with retinopathy or peripheral neuropathy. Independently of ECV, a 10% increase in MBF at stress and MPR was associated with higher GLS [multivariable regression adjusted for age, sex, hypertension, smoking, and ECV: MBF stress (β (95% CI) − 0.2 (− 0.3 to − 0.08), MPR (β (95% CI) − 0.5 (− 0.8 to − 0.3), p < 0.001 for both]. A 10% increase in ECV was associated with a decrease in GLS in univariable [β (95% CI) 0.6 (0.2 to 1.1)] and multivariable regression, but this was abolished when adjusted for MPR [multivariable regression adjusted for age, sex, hypertension, smoking, and MPR (β (95% CI) 0.1 (− 0.3 to 0.6)]. On the receiver operating characteristics curve, GLS showed a moderate ability to discriminate a significantly lowered stress MBF (AUC 0.72) and MPR (AUC 0.73).ConclusionsMyocardial microvascular dysfunction was independent of ECV, a biomarker of myocardial fibrosis, associated with GLS. Further, 3D GLS could be a potential screening tool for myocardial microvascular dysfunction. Future directions should focus on confirming these results in longitudinal and/or interventional studies.

Changes in left ventricular systolic and diastolic function after chemotherapy for breast cancer with doxorubicin

Introduction. Detection of the cardiotoxic effect during chemotherapy (CT) for malignant neoplasms is one of the most important tasks of a practicing physician. Purpose: to study changes in left ventricular systolic and diastolic function using echocardiography (EchoCG) during chemotherapy with doxorubicin in patients with primary breast cancer (BC) and to identify potential markers of early cardiotoxicity (CT).Material and Methods. The study included 100 patients with a confirmed diagnosis of breast cancer who were treated at the health care institution “Grodno University Clinic” (Grodno, Belarus).Results. In the study sample, a number of EchoCG parameters were measured before and after chemotherapy in 100 patients with breast cancer. Depending on the choice of the threshold level of relative reduction in global longitudinal strain (GLS) in %, different median values were recorded in the subgroups with and without CT (before and after chemotherapy). Data are presented on the difference in the relative dynamics of EchoCG indicators in % between the subgroups with CT and without CT, which shows how large the differences between the subgroups are in % after the end of chemotherapy. Against the background of the absence of statistically significant differences, trends towards an increase or decrease in indicators were recorded, which can characterize them as potential CT markers.Conclusion. We hypothesize that indexed end-systolic volume, indexed end-diastolic volume, early diastolic peak velocity of lateral mitral annulus motion may be considered as potential CT markers in the subclinical stage along with GLS; if it is impossible to measure a relative decrease in GLS, these indicators collectively may indicate the development of a CT effect at the subclinical stage. When diagnosing a relative decrease in the GLS index by less than 15 %, but by more than 10 %, we propose to consider the indexed end-systolic volume index as a marker of the early CT effect if its increase after the end of chemotherapy is recorded by 10 % or more, respectively.

Diastolic function is more sensitive than GLS in identifing cardiotoxicity. The SAFE trial results

Abstract Echocardiographic measures of diastolic dysfunction are associated with an increased risk of incident heart failure. Previous studies have shown that changes in diastolic function occur with anthracycline cancer therapy. However, they did not incorporate the newest classification of diastolic function nor evaluated the association with subsequent declines in systolic function. Design The SAFE trial is a four-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study. Recruitment was conducted between July 2015 and June 2020. Patients with breast cancer were eligible if they had indication to primary or postoperative systemic therapy using an anthracycline-based regimen. Known cardiovascular disease or high-risk features were exclusion criteria. Cardioprotective therapy (bisoprolol(B), ramipril(R), or both drugs, as compared to placebo(P)) was administered for 1 year since chemotherapy initiation or until the end of trastuzumab therapy in the case of HER2-positive patients. Each drug was systematically titrated, up to the target dose of B(5 mg OD), R(5 mg OD), if tolerated. The primary endpoint was defined as any subclinical impairment (worsening ≥10%) of 3D left ventricular ejection fraction and global longitudinal strain (GLS) at the end-of-therapy (EOT) and at 2-year follow-up (EOF). Individual measures indicative of diastolic function (mitral E/A ratio, septal and lateral e’ velocities, indexed LA volume, TR velocity, and E/e’ ratio) were recorded and diastolic function was graded according to the 2016 ASE/EACVI guidelines. Results Out of 262 women (median age 48 years; range, 24-75 years) enrolled and treated, 222 patients completed the pre-planned cardiological assessment at 24 months. Baseline demographic, tumor, and cardiovascular profiles were similar between the study arms. All patients received anthracyclines, 217 also received taxane, and 77 adjuvant trastuzumab. Forty-nine patients were treated with neoadjuvant chemotherapy, 154 with adjuvant endocrine therapy, and 124 had postoperative radiation therapy. At EOT GLS worsened by 10% or greater in 57% of patients in the P arm, 20%, 13%, and 18% in the R, B, and R+B arms, respectively (P&amp;lt; 0.05). At EOF GLS worsened by 10% or greater in 65 % of patients in the P arm, 13%, 9%, and 10% in the R, B, and R+B arms, respectively (P&amp;lt; 0.05). In all patients, diastolic function was normal at baseline. Changes in any diastolic parameter were not significant (Table). AT EOT 9% of the patients with &amp;lt;10% GLS decrease showed diastolic dysfunction (22% in P arm, 8%, 6%, and 4% in the R, B, and R+B arms, respectively, P&amp;lt;0.05). At EOF 78% of patients with ≥10% GLS decrease showed diastolic dysfunction (Figure). Our findings provide evidence that 1. abnormal diastolic function precedes systolic dysfunction, 2 there are significant changes in diastolic function grade over time, 3. cardioprotective therapy may be useful in low-risk breast cancer patients.TableFigure

Left ventricular dysfunction in patients following high-dose chemotherapy and autologous hematopoietic stem cell transplantation

To evaluate the dynamics of LV global longitudinal strain (GLS) and other EchoCG parameters after high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (aHSCT). The risk of LV dysfunction in patients after HDCT followed by aHSCT has not been sufficiently studied. This study included 74 patients with hemoblastosis aged 20 to 65 years who had undergone HDCT followed by aHSCT. All patients had a history of antitumor treatment. EchoCG with assessment of LV GLS and measurements of troponin T and N-terminal pro-brain natriuretic peptide (NT-proBNP) were performed for all patients before and after the treatment. A decrease in GLS by 15 % or more from the baseline was detected in 6 (8.1 %) patients. The decrease in GLS was associated with increased NT-proBNP &gt;125 pg / ml at baseline (odds ratio, 8.667; 95 % confidence interval, 1.419-52.942; p=0.022). The decrease in LV GLS in patients after aHSCT was associated with increased NT-proBNP before the intervention.

Abstract 17680: MIBG Myocardial Scintigraphy is Useful for Predicting CTRCD Caused by Trastuzumab

Introduction: Trastuzumab is known to reduce the mortality rate, recurrence rate, and metastasis rate in Human epidermal growth factor receptor type 2 (HER2)-positive breast cancer patients, and it is recommended to administer it for 12 months to all early-stage HER2-positive breast cancer patients. However, trastuzumab administration can lead to Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD). The guidelines suggest that regular echocardiography every 3 months is useful for early detection of CTRCD, but there are no tests available to predict it before its onset.The purpose of this study is to determine whether cardiac sympathetic nerve evaluation using MIBG myocardial scintigraphy before trastuzumab administration can predict the development of CTRCD three months after administration. Methods: MIBG myocardial scintigraphy was performed before trastuzumab administration in 35 HER2-positive breast cancer patients, and cardiac function assessment was conducted using echocardiography before administration, at 1 month, and at 3 months. Simultaneously, NT-proBNP and troponin levels were measured. CTRCD was defined as a decrease in global longitudinal strain (GLS) of 10% or more from before administration at the 3-month follow-up. Results: Anthracycline and trastuzumab regimens were used in 21 patients (60%). CTRCD occurred in 17 patients at the 3-month follow-up. There were no significant differences in age or previous medication between the CTRCD group and the non-CTRCD group, but the early H/M ratio in MIBG myocardial scintigraphy was significantly lower in the CTRCD group (2.77±0.36) compared to the non-CTRCD group (3.10±0.36) (p&lt;0.01). There were no significant differences in the delay H/M ratio or washout rate. None of the echocardiographic parameters, NT-proBNP levels, or troponin levels showed significant differences and did not become predictive factors. Conclusions: MIBG myocardial scintigraphy is useful for predicting CTRCD caused by trastuzumab. Preclinical studies have suggested that HER2 transactivation from β-adrenergic receptors in the myocardium confers cardioprotection. Suppression of HER2 signaling during cardiac sympathetic nerve dysfunction potentially contributes to the development of CTRCD.

Abstract 15906: Cardiovascular Effects of CAR-T Cell Therapy: A Prospective Study

Background: Previous retrospective studies have shown that CAR-T cell therapy may be associated with major adverse cardiovascular events (MACE) especially in context of cytokine release syndrome (CRS) events. Objectives. The aim of this prospective observational study was to define the occurrence of MACE in adults undergoing treatment with CAR-T cell therapy and identify associated risk factors. Methods: Vital signs, blood samples and an echocardiogram were collected prior to, two days, one week, one month, and six months after CAR-T cell infusion, and chart consulted at 12 months. In the event of CRS, an echocardiogram was repeated within 72 hours. MACE were defined as cardiovascular death, symptomatic heart failure, acute coronary syndrome, ischemic stroke, and de novo cardiac arrhythmia. Results: A total of 44 patients were enrolled (58 ±11 years-old, 77 % male). The median follow-up was 487 days (258-622 days). There were 24 episodes of CRS in 23 patients (52%) (13 with grade 1, 10 with grade 2, and one with grade 3) with a median time to CRS of 4 days. Two patients had MACE (HFpEF and atrial fibrillation) within one year, six and seven days after CAR-T cell infusion respectively. There was no change in left ventricular ejection fraction (LVEF), however, a modest decrease in global longitudinal strain (GLS) was noted. Conclusions: There were few cardiac effects associated with contemporary CAR-T cell therapy. A small decline in LV mechanics was detected. As MACE occurred after CRS episodes, aggressive treatment and close follow-up during CRS events are essential.

Incidence of MACE in Patients Treated With CAR-T Cell Therapy: A Prospective Study

BackgroundPrevious retrospective studies have shown that chimeric antigen receptor T (CAR-T) cell therapy may be associated with major adverse cardiovascular events (MACE), especially in the context of cytokine-release syndrome (CRS) events. ObjectivesThe aim of this prospective observational study was to define the occurrence of MACE in adults undergoing treatment with CAR-T cell therapy and identify associated risk factors. MethodsVital signs, blood samples, and an echocardiogram were collected prior to and 2 days, 1 week, 1 month, and 6 months after CAR-T cell infusion, and charts were consulted at 12 months. In the event of CRS, echocardiography was repeated within 72 hours. MACE were defined as cardiovascular death, symptomatic heart failure, acute coronary syndrome, ischemic stroke, and de novo cardiac arrhythmia. ResultsA total of 44 patients were enrolled (mean age 58 ± 11 years, 77% men). The median follow-up duration was 487 days (Q1-Q3: 258-622 days). There were 24 episodes of CRS in 23 patients (52%) (13 grade 1, 10 grade 2, and 1 grade 3), with a median time to CRS of 4 days. Two patients had MACE (heart failure with preserved ejection fraction and atrial fibrillation) within 1 year and 6 and 7 days after CAR-T cell infusion. There was no change in left ventricular ejection fraction, but a modest decrease in global longitudinal strain was noted. ConclusionsThere were few cardiac effects associated with contemporary CAR-T cell therapy. As MACE occurred after CRS episodes, aggressive treatment and close follow-up during CRS events are essential.

Tracking Changes in Global Longitudinal Strain in Lung Cancer Patients Receiving Thoracic Radiation

Thoracic radiation improves survival in many lung cancer patients. However, radiation-induced cardiotoxicity is a major source of morbidity and mortality in such patients. Global longitudinal strain (GLS), a novel echocardiography (ECHO) method of assessing left ventricular function, has been shown to predict long-term adverse cardiovascular risk in diverse patient populations. We hypothesized that receipt of thoracic radiation is associated with GLS changes in lung cancer patients. We retrospectively identified patients with lung cancer treated at our institution between 2005-2020 who had ECHOs performed both before and after RT, and in whom GLS was extractable. ECHO Board-Certified cardio-oncologists measured GLS and left ventricular ejection fraction (LVEF) from these ECHOs. A total of 40 patients met inclusion criteria. Median time to ECHO was 78 days prior and 172 days after RT. Two chamber (2C), 3C, 4C, and average GLS were significantly decreased after RT on paired t-test [mean difference (SD) 2.23 (3.29), 2.99 (2.78), 2.25 (3.63), 2.51 (2.66) respectively, all p < 0.001]. Thirteen patients (32.5%) had abnormal GLS (<18%) prior to RT. 5 of those 13 patients (38.5%) had abnormal LVEF (< 50%). 27/40 patients (67.5%) had an abnormal GLS or clinically significant (≥15%) drop in GLS after RT. This difference (32.5% patients pre-RT vs 67.5% post-RT) was statistically significant (p < 0.01). Among patients (n = 27) who had normal LVEF before RT, 1 patient (3.7%) developed abnormal LVEF (<50%) after RT. Backwards logistic regression showed significant interaction between heart volume receiving 5 Gray and change in GLS. This cohort exhibited a significant decrease in 2C, 3C, 4C, and average GLS after RT. ∼1/3 of patients had abnormal GLS at baseline (suggesting a high-risk group for cardiac complications) and 67.5% of patients had clinically significant decrease in GLS after RT. Among the patients with normal GLS before RT, although 51.9% of patients demonstrated a clinically significant drop in GLS after RT, only 3.7% of patients developed abnormal LVEF, suggesting that this is a late occurrence. GLS changes may serve as a valuable tool for early identification of patients who are at high risk for future cardiac complications after receiving thoracic radiation.

Changes of biventricular contractile function depending on the types of left ventricular involvement in patients 1 year after COVID-19 pneumonia

Aim. To study the changes of biventricular contractile function depending on the types of left ventricular involvement according to the speckle tracking echocardiography (STE).Material and methods. Of the 380 patients from the Prospective Registry of People Survived COVID-19 Pneumonia, the study included 85 patients, which can be followed-up — 3 months (visit 1) and 12 months (visit 2) after COVID-19 pneumonia (men — 68,2%; mean age — 50,6±10,9 years).At visit 2, patients with diffuse left ventricle (LV) involvement according to STE (visual involvement of ≥4 segments of the same LV level) comprised group I (n=27), patients with regional LV involvement (≥3 segments corresponding to anterior, circumflex or right coronary arteries) — group II (n=39), patients without visual LV involvement — group III (n=19).Results. The groups were comparable in main clinical, functional and echocardiographic (conventional) parameters 3 and 12 months after COVID-19 pneumonia, with the exception of sex and body mass index. STE in group I showed a significant decrease in global longitudinal strain (GLS) (-18,0±2,0% at visit 1 and -16,9±1,4% at visit 2, p=0,025) and LS of all LV levels; in group II — an increase in right ventricular free wall strain (RV FWS) (-22,8±3,2% and -24,0±2,6%, respectively, p=0,006); in group III — an increase in GLS (-19,3±2,3% and -21,2±1,9%, p=0,005), LS of basal and medium LV levels, RV FWS (-23,3±2,9% and -25,0±3,0%, p=0,033). In group I, a significant increase in affected LV segments was revealed (7,0 [5,0;9,0] and 9,0 [7,0;10,0], p=0,010), while in group III there was a decrease in their number (5,0 [3,0;6,0] and 10,0 [1,0;2,0], p&lt;0,001). According to logistic regression, LV basal LS at visit 1 (odds ratio 0,420; 95% confidence interval 0,273-0,644; p&lt;0,001) had an independent association with diffuse LV involvement at visit 2. When it decreases, &lt;15,8% sensitivity and the specificity of this model in predicting diffuse LV involvement was 74,1% and 74,1%, respectively (AUC=0,807; p&lt;0,001).Conclusion. Patients with diffuse LV involvement according to STE are characterized by suppression of global biventricular contractile function during 1-year follow-up.

Association between epicardial adipose tissue and cardiac dysfunction in subjects with severe obesity.

Epicardial adipose tissue (EAT) plays a role in obesity-related heart failure with preserved ejection fraction. However, the association of EAT thickness with the development of cardiac dysfunction in subjects with severe obesity without known cardiovascular disease is unclear. Determine the association between EAT thickness and cardiac dysfunction and describe the potential value of EAT as an early marker of cardiac dysfunction. Subjects with BMI ≥35 kg/m2 aged 35 to 65 years, who were referred for bariatric surgery, without suspicion of or known cardiac disease, were enrolled. Conventional transthoracic echocardiography and strain analyses were performed. A total of 186 subjects were divided into tertiles based on EAT thickness, of whom 62 were in EAT-1 (EAT <3.8 mm), 63 in EAT-2 (EAT 3.8-5.4 mm), and 61 in EAT-3 (EAT >5.4 mm). Parameters of systolic and diastolic function were comparable between tertiles. Patients in EAT-3 had the lowest global longitudinal strain (GLS) and left atrial contractile strain (LASct). Linear regression showed that a one-unit increase in EAT thickness (mm) was independently associated with a decrease in GLS (%) (β-coefficient - 0.404, p = 0.002), and a decrease in LASct (%) (β-coefficient - 0.544, p = 0.027). Furthermore, EAT-3 independently predicted cardiac dysfunction as defined by a GLS < 18% (OR 2.8, p = 0.013) and LASct<14% (OR 2.5, p = 0.045). Increased EAT thickness in subjects with obesity without known cardiac disease was independently associated with subclinical cardiac dysfunction. Our findings suggest that EAT might play a role in the early stages of cardiac dysfunction in obesity before this may progress to overt clinical disease. This article is protected by copyright. All rights reserved.

Abnormal Global Longitudinal Strain During Anthracycline Treatment Predicts Future Cardiotoxicity in Children.

Global longitudinal strain (GLS) is a sensitive predictor of cardiotoxicity in adults with cancer. However, the significance of abnormal GLS during childhood cancer treatment is less well-understood. The objective was to evaluate the use of GLS for predicting later cardiac dysfunction in pediatric cancer survivors exposed to high-dose anthracyclines. This was a retrospective study of pediatric patients exposed to a doxorubicin isotoxic equivalent dose of ≥ 225mg/m2. Transthoracic echocardiograms (TTE) were obtained prior to chemotherapy (T1), during anthracycline therapy (T2), and following completion of therapy (T3). Cardiotoxicity was defined as meeting at least one of the following criteria after anthracycline therapy: a decrease in left ventricle ejection fraction (LVEF) by 10% from baseline to a value < 55%, fractional shortening < 28%, or a decrease in GLS by ≥ 15% from baseline. Nineteen of 57 (33%) patients met criteria for cardiotoxicity at T3. Cardiotoxicity was associated with a lower LVEF at T2 (p = 0.0003) and a decrease in GLS by ≥ 15% at T2 compared to baseline (p = < 0.0001). ROC analysis revealed that the best predictor of cardiotoxicity at T3 was the percent change in GLS at T2 compared to baseline (AUC 0.87). A subgroup analysis revealed that a decrease in GLS by ≥ 15% from baseline at 0-6months from completion of anthracycline therapy was associated with cardiotoxicity > 1-year post-treatment (p = 0.017). A decline in GLS during chemotherapy was the best predictor of cardiotoxicity post-treatment. GLS serves as an important marker of cardiac function in pediatric patients undergoing treatment with anthracyclines.

Study of usefulness of speckle-tracking echocardiography in detecting left ventricular dysfunction among adult cancer patients undergoing chemotherapy

Objective: Cancer treatment-related cardiac dysfunction (CTRCD) is a significant concern for patients undergoing chemotherapy. The aim of the present study was to study the accuracy and value of longitudinal strain in prediction of left ventricular dysfunction (LVD) in cancer patients undergoing cancer therapy. Methods: This was a prospective observational study conducted among 183 adult patients undergoing chemotherapy between 2018 and 2020. Patients with congenital or acquired valvular disease, prior myocardial infarction, coronary revascularization, or cardiac surgery were excluded. The patients were evaluated using a detailed history, clinical examination and echocardiography at baseline, 1 month, 3 months, and 6 months after chemotherapy. Speckle-tracking strain analysis was used to evaluate left ventricular (LV) global longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS). LVD was defined as &amp;qt;15% decrease in GLS, GCS, or GRS from baseline to 6 months. Accuracy of longitudinal strain in prediction of LVD was studied using ROC analysis. Results: Of the 183 patients, 59% were male, and 54.1% were between 46-60 years of age. Breast cancer was the most common malignancy (10.9%). The most common chemotherapy regimen was doxorubicin + paclitaxel (9.9%). At baseline, the mean GLS, GCS, and GRS were -18.6 (1.03)%, -20.4 (1.11)%, and 39.9 (6.09)%, respectively. At the 6-month follow-up, 27 (14.8%) patients had LVD. The incidence of LVD was higher (51.48%) in patients who received doxorubicin-containing regimens compared to non-doxorubicin-containing regimens (P &amp;lt;0.0001). GLS has good accuracy in prediction of LVD at 6 months of follow-up (88.37%). Conclusions: The incidence of LV dysfunction was higher (51.48%) in patients who received doxorubicin-containing regimens. GLS is different in LVD vs non LVD and the accuracy of GLS is more in prediction of LVD development during 6-month follow-up (88.37%).

Paradoxical increase in global longitudinal strain by handgrip exercise despite left ventricular diastolic dysfunction.

Although global longitudinal strain (GLS) is recognized as a sensitive marker of intrinsic left ventricular (LV) dysfunction, its afterload dependency has also been pointed. We hypothesized that decrease in GLS during handgrip exercise could be more sensitive marker of intrinsic myocardial dysfunction. Handgrip exercise-stress echocardiography was performed in 90 cardiovascular disease patients with preserved LV ejection fraction. LV diastolic function was graded according to the guidelines. Diastolic wall stress (DWS) and ratio of left atrial (LA) volume index to late-diastolic mitral annular velocity (LAVI/a') were measured at rest as LV stiffness. As well, LA strains were measured to assess LA function. GLS was expressed as absolute value and significant changes in GLS by handgrip exercise was defined as changes over prespecified mean absolute test-retest variability (2.65%). While mean value of GLS did not change by the exercise, substantial patients showed significant changes in GLS: decreased (group I, n=28), unchanged (group II, n=34), and increased (group III, n=28). Unexpectedly, patients in group I did not show any clinical and echocardiographic characteristics, while those in group III were characterized by elevated natriuretic peptide levels, blunted heart rate response to handgrip exercise, and advanced LV diastolic dysfunction. Multivariable analyses revealed that DWS, left atrial booster strain, and grade II or more diastolic dysfunction determined the increase in GLS even after adjustment for elevated natriuretic peptides and the changes in heart rate by the exercise. In contrast to our hypothesis, paradoxical increase in GLS by handgrip exercise could be associated with advanced LV diastolic dysfunction in cardiovascular patients with preserved LV ejection fraction. Our findings suggest that HG exercise for heart failure patients does not enhance the afterload straightforward, resulting in variable changes of GLS according to the individual conditions.

Longitudinal assessment of cardiac parameters through MRI in breast cancer patients treated with anti-HER2 therapy

BackgroundWe evaluated the early changes in left ventricular (LV) volumetric, functional, and tissue characteristics in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with trastuzumab and/or pertuzumab at cardiac magnetic resonance imaging (MRI).MethodsHER2-positive breast cancer patients undergoing planned anti-HER2 therapy and nonanthracycline-based chemotherapy were enrolled and subdivided into dual anti-HER2 (trastuzumab plus pertuzumab) group and trastuzumab group. Cardiac MRI was performed before treatment and three months after starting, covering ventricular volumes, cardiac function, systolic myocardial strain, myocardial oedema, and T1 and T2 relaxation times. Cardiac dysfunction was primarily defined as a > 10% reduction in LV ejection fraction (LVEF) to < 55% and/or a > 15% global longitudinal strain (GLS) change at the follow-up MRI examination.ResultsTwenty-four HER2-positive patients were evaluated (16 in the dual anti-HER2 group, 8 in the trastuzumab group). Six patients developed cardiac dysfunction at follow-up, five of them in the dual anti-HER2 group. One patient developed symptomatic heart failure, and five patients developed asymptomatic cardiac dysfunction. Patients displayed significantly decreased systolic function and increased T1 and T2 relaxation time at follow-up (p ≤ 0.031). Systolic dysfunction remained significant in the dual anti-HER2 group. The decrease in GLS in the trastuzumab group was not significant (p = 0.169). T1 and T2 relaxation times tended to increase, but this was not significant at subgroup analysis.ConclusionsCardiac MRI scans showed frequent signs of subclinical cardiotoxicity after short-term anti-HER2 therapy and nonanthracycline-based chemotherapy; the effect was slightly stronger in patients treated with dual therapy.Key points• A frequent subclinical cardiotoxicity was detected by cardiac magnetic resonance imaging after short-term anti-human epidermal growth factor receptor 2 (HER2) therapy.• The change in myocardial strain was more marked in patients treated with dual (trastuzumab plus pertuzumab) than with trastuzumab only anti-HER2 therapy.• Cardiotoxicity surveillance through MRI is an interesting option particularly in patients treated with dual anti-HER2 therapy.

Association of the triglyceride-glucose index with subclinical left ventricular dysfunction in type 2 diabetes mellitus patients: A retrospective cross-sectional study.

The triglyceride-glucose (TyG) index is a simple and reliable indicator of insulin resistance, and is associated with the development and poor outcomes of cardiovascular disease. Subclinical left ventricular dysfunction (SLVD) is frequently detected in approximately one-third of diabetes patients, but it has not been established whether the TyG index correlates with SLVD. We carried out this research to evaluate the relationship between the TyG index and SLVD in type 2 diabetes mellitus patients. This was a cross-sectional and observational study of 183 type 2 diabetes mellitus inpatients at Nanjing Drum Tower Hospital, Nanjing, China. The TyG index and homeostasis model assessment 2 estimates for insulin resistance (HOMA2-IR) were calculated from biochemical measurements, and speckle-tracking echocardiography was carried out. According to global longitudinal strain (GLS) by echocardiography, participants were categorized into the SLVD (GLS <18%) group or the non-SLVD (GLS ≥18%) group. In comparison with non-SLVD participants, SLVD participants had higher insulin resistance, as reflected by elevated TyG and HOMA2-IR indices, as well as a higher body mass index, waist circumference and triglyceride level (P < 0.05 for each). When grouped by TyG index tertiles, an elevated TyG index was correlated with other cardiometabolic risk factors, as well as a decrease in GLS. In the multivariate logistic regression analyses, the TyG index was an independent risk factor for SLVD in type 2 diabetes mellitus patients (odds ratio 2.047, 95% confidence interval 1.07-3.914, P = 0.03), whereas HOMA2-IR was not. The TyG index is independently associated with SLVD in type 2 diabetes mellitus patients and is a more reliable indicator of SLVD than HOMA2-IR.