Reduction In Global Longitudinal Strain Research Articles

Comprehensive Assessment of Cardiac Function in Breast Cancer Patients: Integrating Multiparametric Speckle Tracking Imaging and Conventional Echocardiography Parameters.

Purpose The purpose of this study is to comprehensively evaluate the role of different echocardiography parameters in breast cancer patients undergoing chemotherapy. While echocardiography examination with calculation of ejection fraction (EF), is pivotal for patient monitoring, its operator dependence and insensitivity to subtle changes in left ventricular (LV) contractility present challenges. Global longitudinal strain (GLS), derived from speckle tracking, is more sensitive and stable than EF. Our research aimed to delineate supplementary echocardiography measurements beneficial for the cardiological monitoring of breast cancer patients. Methods Patients were followed up with echocardiography at baseline, during, and after the chemotherapy. Conventional echocardiography and multiple speckle tracking imaging parameters including myocardial work index, atrial strain, twist, and automatic EF were investigated. Results A total of 25 patients were recruited. A subset (15/25) exhibited pronounced GLS reduction, associated with decreased EF and altered cardiac mechanics. Patients with unchanged GLS were often hypertensive and on specific medications, in particular angiotensin-converting enzyme inhibitors (ACE inhibitors)/angiotensin II receptor blockers (ARBs), potentially indicating protective effects. Despite stability in other parameters, GLS and EF sensitivity highlight their importance. A strong correlation between manual and automated EF measurement methods was also observed. Conclusion Despite the small sample size, across diverse echocardiography parameters, GLS and EF are primarily affected by chemotherapy. Hypertensive individuals exhibited lower susceptibility to chemotherapy-induced damage, likely attributed to the cardioprotective properties of ACE inhibitors and angiotensin II receptor blockers. A strong correlation between automatic and Simpson-based EF was found.

Subclinical Left Ventricular Dysfunction Prevention in Breast Cancer Patients after FAC Chemotherapy: A Carvedilol Trial

Objective: To assess the cardioprotective effects of Carvedilol in preventing subclinical left ventricular dysfunction (SLVD) in breast cancer patients after completing FAC chemotherapy.Methods: This prospective study employed a quasi-experimental clinical trial conducted from September 2018 to May 2019. Breast cancer patients receiving FAC chemotherapy were divided into two groups: intervention (IG) and control (CG). The IG received Carvedilol 6.25 mg b.i.d., which was increased every three weeks until reaching a tolerated dose. The study evaluated changes in left ventricular global longitudinal strain (GLS) and the incidence of SLVD (GLS reduction ≥15% and GLS >-18%) 24 weeks after initiating the FAC regimen.Result: Of the 81 women enrolled in the study, 31 were in the IG. No significant changes in GLS were observed during or after completing FAC chemotherapy in the IG, whereas the CG showed contradictory results. At the end of the follow-up period, the delta GLS reduction was lower in the IG (0.7; 95% CI -0.60, 3.60) compared to the CG (3.00; 95% CI -2.16, 4.19), with a p-value of 0.035. Similarly, the percentage reduction in GLS was 3.6% in the IG and 14.29% in the CG, resulting in a p-value of 0.05. The incidence rate of SLVD (GLS reduction ≥15% and GLS > -18%) was lower in the IG (41.9% and 25.8%) than in the CG (58% and 48%).Conclusion: Carvedilol may have a cardioprotective effect in preventing the incidence of SLVD, as evaluated by GLS reduction and changes, in women with breast cancer after completing a full cycle of the FAC regimen.

Trastuzumab in patients with breast cancer and pre-existing left ventricular systolic dysfunction

BackgroundTrastuzumab is one of the most effective treatments in HER-2 positive breast cancer patients. However, it is associated with development of cardiomyopathy/heart failure (HF) which is often a limiting side effect and associated with overall adverse outcomes. As a result, patients with pre-existing LV systolic dysfunction (LVSD) are often excluded from receiving anti-HER-2 therapy, which may lead to less effective cancer treatment and worse prognosis.ObjectivesThe current study aims to evaluate the safety of trastuzumab in patients with HER-2 positive breast cancer and pre-existing LVSD.MethodsIn this retrospective cohort study, 36 consecutive patients at a single center in Iran with HER-2 positive breast cancer with asymptomatic mild LVSD with LVEF 40–53% without heart failure symptoms and those who were closely followed in the Cardio-Oncology clinic before initiating the treatment and then every two cycles of trastuzumab were included. As per the program standard protocol they received a beta-blocker (carvedilol) and ACE-I (Lisinopril), up to the maximum tolerated dose, if there were no contraindications. Patients underwent routine echocardiography with global longitudinal strain (GLS) assessment every 3 months per guideline recommendations and were followed up 6 months after the end of treatment. Primary composite outcomes included myocardial infarction (MI), cardiac arrhythmia, heart failure(HF) symptoms and cardiovascular death. Secondary outcome was ≥ 10% reduction in LVEF or ≥ 15% reduction in GLS compared to baseline. If the LVEF decreased below 40%, the treatment was temporarily interrupted for one or two cycles, and spironolactone was added to the patient’s treatment. If the LVEF improved ≥ 40%, trastuzumab was rechallenged. Data analysis was performed using IBM SPSS Statistics 24.0. Software. Patients’ characteristics were reported using descriptive statistics, and its association with drop in LVEF or GLS was assessed using Pearson chi-square or Mann-Whitney U test. A p-value of less than 0.05 was considered significant.ResultsThirty-six patients were included in the study. Primary composite outcome was noted in 1(2.8%) patient. LVEF reduction of ≥ 10% occurred in 6(16.7%) of the patients, and a GLS reduction of more than 15% was detected in 4 (11.1%) of the patients. There was a significant association between a ≥ 10% reduction in LVEF and baseline systolic blood pressure (P-value: 0.04). LVEF reduction below 40% was observed in 3 (8.3%) patients, where trastuzumab was interrupted. All of these three patients had obesity (Median BMI 34.11, IQR 9.12) and uncontrolled HTN, and one of them had symptoms of heart failure (NYHA class II), for whom the trastuzumab treatment was discontinued. Among two patients, after the temporary interruption of trastuzumab, and addition of spironolactone, LVEF improved to above 40%, and the treatment was restarted with close cardiac monitoring; therefore, they could complete the entire one-year treatment period.ConclusionsTreatment with trastuzumab seems to be safe in patients with pre-existing LVSD (LVEF = 40–53%). Such high-risk patients should be strictly monitored and cardiovascular risk factors, such as HTN should be regulated.

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<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 <-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<0,001) and demonstrated a direct linear relationship with E/A, IVRT, early diastolic deceleration time (p<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 <-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 (<-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.

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.

Cardiac manifestations of Fabry disease in G3Stg/GlaKO and GlaKO mouse models-Translation to Fabry disease patients.

Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by mutations in the GLA gene encoding alpha-galactosidase A (α-Gal). Loss of α-Gal activity leads to progressive lysosomal accumulation of α-Gal substrate, predominately globotriaosylceramide (Gb3) and its deacylated derivative globotriaosylsphingosine (lyso-Gb3). FD manifestations include early onset neuropathic pain, gastrointestinal symptoms, and later onset life-threatening renal, cardiovascular and cerebrovascular disorders. Current treatments can preserve kidney function but are not very effective in preventing progression of cardiovascular pathology which remains the most common cause of premature death in FD patients. There is a significant need for a translational model that could be used for testing cardiac efficacy of new drugs. Two mouse models of FD have been developed. The α-Gal A-knockout (GlaKO) model is characterized by progressive tissue accumulation of Gb3 and lyso-Gb3 but does not develop any Fabry pathology besides mild peripheral neuropathy. Reports of minor cardiac function abnormalities in GlaKO model are inconsistent between different studies. Recently, G3Stg/GlaKO was generated by crossbreeding GlaKO with transgenic mice expressing human Gb3 synthase. G3Stg/GlaKO demonstrate higher tissue substrate accumulation and develop cellular and tissue pathologies. Functional renal pathology analogous to that found in early stages of FD has also been described in this model. The objective of this study is to characterize cardiac phenotype in GlaKO and G3Stg/GlaKO mice using echocardiography. Longitudinal assessments of cardiac wall thickness, mass and function were performed in GlaKO and wild-type (WT) littermate controls from 5-13 months of age. G3Stg/GlaKO and WT mice were assessed between 27-28 weeks of age due to their shortened lifespan. Several cardiomyopathy characteristics of early Fabry pathology were found in GlaKO mice, including mild cardiomegaly [up-to-25% increase in left ventricular (LV mass)] with no significant LV wall thickening. The LV internal diameter was significantly wider (up-to-24% increase at 9-months), when compared to the age-matched WT. In addition, there were significant increases in the end-systolic, end-diastolic volumes and stroke volume, suggesting volume overload. Significant reduction in Global longitudinal strain (GLS) measuring local myofiber contractility of the LV was also detected at 13-months. Similar GLS reduction was also reported in FD patients. Parameters such as ejection fraction, fractional shortening and cardiac output were either only slightly affected or were not different from controls. On the other hand, some of the cardiac findings in G3Stg/GlaKO mice were inconsistent with Fabry cardiomyopathy seen in FD patients. This could be potentially an artifact of the Gb3 synthase overexpression under a strong ubiquitous promoter. In conclusion, GlaKO mouse model presents mild cardiomegaly, mild cardiac dysfunction, but significant cardiac volume overload and functional changes in GLS that can be used as translational biomarkers to determine cardiac efficacy of novel treatment modalities. The level of tissue Gb3 accumulation in G3Stg/GlaKO mouse more closely recapitulates the level of substrate accumulation in FD patients and may provide better translatability of the efficacy of new therapeutics in clearing pathological substrates from cardiac tissues. But interpretation of the effect of treatment on cardiac structure and function in this model should be approached with caution.

Left ventricular remodeling in twin pregnancy, noninvasively assessed using hemodynamic forces and pressure-volume relation analysis: prospective, cohort study.

This study was designed to prospectively investigate the pattern of intraventricular hemodynamic forces (HDFs) associated with left ventricular (LV) function and remodeling in women with uncomplicated twin pregnancy. Transthoracic echocardiography was performed on 35 women (aged 35.9 ± 4.7-yr old) during gestation (T1, <14 wk; T2, 14-27 wk; T3, >28 wk) and 6-7 mo after delivery (T0). LV HDFs were computed from echocardiography long-axis data sets using a novel technique based on endocardial boundary tracking, both in apex-base (A-B) and latero-septal (L-S) directions. HDF distribution was evaluated by L-S over A-B HDF ratio (L-S:A-B HDF ratio). At T1, L-S:A-B HDF ratio was higher than in T0 (P < 0.05) indicating HDF misalignment. At T2, a slight impairment of cardiac function was then recorded with a reduction of global longitudinal strain (GLS) and left ventricular end-systolic elastance (Ees) at pressure-volume relationship analysis versus T1 (both P < 0.05). Finally, at T3, when HDF misalignment and LV contractility reduction (GLS and Ees) were all restored, a rightward shift of the end-diastolic pressure-volume relationship (EDPVR) with an increase of ventricular capacitance was documented. In twin pregnancy, HDF misalignment in the first trimester precedes the slight temporary decrease in left ventricular systolic function in the second trimester; at the third trimester, a rightward shift of the EDPVR was associated with a realignment of HDF and normalization of ventricular contractility indexes. These coordinated changes that occur in the maternal heart during twin pregnancy suggest the role of HDFs in cardiac remodeling.NEW & NOTEWORTHY These changes indicate that 1) the misalignment of hemodynamic forces (HDFs) precedes a mild reduction in systolic function in twin pregnancy and 2) the positive left ventricular (LV) response to hemodynamic stress is mainly due to an improved diastolic function with enhanced LV cavity compliance.

Biomarkers and Strain Echocardiography for the Detection of Subclinical Cardiotoxicity in Breast Cancer Patients Receiving Anthracyclines.

The optimal surveillance and management strategies for breast cancer patients receiving anthracycline therapy are limited by our incomplete understanding of the role of biomarkers heralding the onset of cardiotoxicity. The purpose of this study was to determine whether there is a temporal correlation between cardiac biomarkers and subclinical left ventricular dysfunction in breast cancer patients receiving anthracycline chemotherapy. Thirty-one females between 46 and 55 years old with breast cancer treated with anthracycline chemotherapy were prospectively enrolled. Cardiac biomarkers were correlated with echocardiography with speckle tracking at baseline, post-anthracycline therapy, and 6 months post-anthracycline chemotherapy. Subclinical cardiotoxicity was defined as ≥ 10% reduction in global longitudinal strain (GLS). There was a relative reduction in left ventricular ejection fraction (LVEF) ≥ 10% in 5/30 (17%) and 7/27 (26%) patients post-anthracycline therapy and 6 months post-anthracycline therapy, respectively. Subclinical cardiotoxicity was noted in 8/30 (27%) and 10/26 (38%) patients post-anthracycline and 6 months post-anthracycline therapy, respectively. Baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) was the strongest predictor of LVEF (ρ = -0.45; p = 0.019), with post-therapy NT-proBNP values illustrating similar predictive value (ρ = -0.40; p = 0.038). Interim changes in suppression of tumorigenicity 2 (ST2) and galectin-3 correlated with a 6-month change in LVEF (ρ = -0.48; p = 0.012 and ρ = -0.45; p = 0.018, for ST2 and galectin-3, respectively). Changes in galectin-3 from baseline to mid-therapy paralleled changes in GLS. NT-proBNP, ST2, and galectin-3 correlate with reduced LVEF among breast cancer patients receiving anthracycline therapy. Additional trials focusing on a cardiac biomarker approach may provide guidance in the early diagnosis and management of anthracycline-induced cardiotoxicity.

Preventing broken hearts in women with breast cancer: a concise review on chemotherapy-mediated cardiotoxicity.

Cancer and cardiovascular disease are the leading causes of death for Canadian women. One in eight Canadian women will receive the life-changing diagnosis of breast cancer (BC) in their lifetime, with 1 in 34 dying from the disease. Although doxorubicin (DOX) and trastuzumab (TRZ) have significantly improved survival in women diagnosed with human epidermal growth factor receptor 2 (HER2)-positive BC, approximately one in four women who receive this treatment are at risk of developing chemotherapy-induced cardiotoxicity. Cardiotoxicity is defined as a decline in left ventricular ejection fraction (LVEF) of>10% to an absolute value of<53%. Current guidelines recommend the serial monitoring of LVEF in this patient population using non-invasive cardiac imaging modalities including transthoracic echocardiography or multi-gated acquisition scan; however, this will only allow for the detection of established cardiotoxicity. Recent studies have demonstrated that a reduction in global longitudinal strain by speckle tracking echocardiography can identify pre-clinical systolic dysfunction prior to a decline in overall LVEF. Implementation of early detection techniques would allow for the prompt initiation of cardioprotective strategies. In addition to the early detection of chemotherapy-mediated cardiotoxicity, the prophylactic use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, statins, exercise, and nutraceutical therapies have been studied in the setting of cardio-oncology.

Atrial Strain Assessment for the Early Detection of Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer Women (The STRANO STUDY: Atrial Strain in Cardio-Oncology).

Left ventricular global longitudinal strain (GLS) has an important role in the diagnosis of cancer therapy-related cardiac dysfunction (CTRCD). Little is known about the role of atrial function in diagnosing CTRCD. The aim of our study was to assess the impact of anti-cancer drugs on atrial function measured by speckle-tracking echocardiography in breast cancer women. A prospective multicenter study was conducted enrolling 169 breast cancer women treated with anthracyclines. A cardiological evaluation including an electrocardiogram and echocardiogram with an analysis of GLS, left atrial (LA) strain, and LA stiffness (LASi) was performed at baseline (T0), 3 (T1), and 6 months (T2) after starting chemotherapy. The patients were divided into two groups: patients with asymptomatic mild cardiotoxicity at T1 (with a relative reduction in GLS > 15%; Group 1) and those without (Group 2). We did not find a significant change in left ventricular ejection fraction (LVEF) at T1 and T2; we found a significant change in GLS (p-value < 0.0001) in the peak atrial longitudinal strain (PALS) and in LASi (p-value < 0.0001). Impairment of atrial function was greater in Group 1 compared to Group 2. A PALS variation > 20.8% identified patients who were most likely to develop asymptomatic mild cardiotoxicity [AUC 0.62; CI (0.51-0.73) p = 0.06, sensitivity 45%, specificity 69.5%]. Conclusions: PALS and LASi significantly change during chemotherapy in association with GLS. Atrial strain is an additional parameter that could be measured together with GLS to detect cardiotoxicity early.

Multi-dimensional evaluation in patients with aortic stenosis who are candidates for cardiac surgery

Abstract Introduction In patients with severe aortic stenosis (AS), the presence of left ventricular systolic dysfunction is one of the main predictors of adverse events after valve replacement surgery (SAVR). However, more and more patients are being referred for surgery early on and have preserved systolic function at the time of surgery. Within this category, global longitudinal strain (GLS) has been proposed as a marker of ventricular remodeling after cardiac surgery. Objectives Our study aims to identify the variation of GLS in patients undergoing SAVR and any differences compared to classes of diastolic dysfunction. Materials and methods From June 2020 to October 2022, we analyzed 100 patients with AS with an indication for cardiac surgery treatment admitted to the cardiac surgery department of our AOU. All patients underwent an echocardiogram immediately before surgery and in the early postoperative period (mean 7 days); 52 of them were enrolled for follow-up and repeated an echocardiogram at least 3 months after surgery. In all cases, the GLS of the left ventricle was calculated and patients were divided into four classes by the degree of diastolic dysfunction (0-III) according to the most recent international guidelines; moreover, patients were divided into 2 groups: group A for grades 0-1 of diastolic dysfunction and Group B for grades 2-3. The data were analyzed with SPSS 28 software. Analysis of variance was performed with a t-test and ANOVA test. Results In the final analysis, 100 patients with AS were included, with a mean age of 70.8±8.27, of whom 43 were women (43%) and 57 were men (57%). In 20 patients (20%) ischaemic heart disease with an indication for coronary revascularization was also present. The mean preoperative ejection fraction was 58.98±9.5%. The mean GLS values before surgery were 15.13±4.56% with a reduction immediately post-cardiac surgery of 12.26±3.67%, p&amp;lt;0.0001. GLS values were comparable within the various classes of diastolic dysfunction at preoperative examination (p=0.579) and immediately postoperative (p=0.286). At follow-up, analysis was repeated for 52 patients: an improvement in mean GLS was found: 16.09±3.64%, p&amp;lt;0.0001. The mean GLS in the two groups at follow-up was statistically different: 17.38±3.35% in group A vs 13.44±3.63% in group B, p&amp;lt;0.0001. Conclusions In our case series, patients with severe aortic stenosis undergoing SAVR show a significant early reduction in GLS regardless of the degree of diastolic dysfunction, while after at least 3 months of follow-up, they show a great recovery, significantly better in patients with Grades 0 or 1 diastolic dysfunction.GLS at the 3 times

The potentially protective effect of dapagliflozin on the development of cardiotoxicity in cancer patients

Abstract Introduction The clinical trial "DECLARE-TIMI 58" (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), demonstrated that dapagliflozin, a Sodium glucose cotransporter 2 inhibitor, reduces the composite end point of cardiovascular death/hospitalization for heart failure in a broad population of patients with type 2 diabetes mellitus.Chemotherapy is known for its potetial adverse effects on myocardium.We hypothesized that early initiation of treatment with dapagliflozin could prevent cardiotoxicity . Purpose We aimed to study if dapagliflozin could exert cardioprotective effects in anthracycline,carfilzomib and trastuzumab-induced cardiotoxicity through the analysis of ejection fraction, global longitudinal strain (GLS) of both left and right ventricle. Methods 32 diabetic patients who were diagnosed with cancer at our medical center were randomized (16 dapagliflozin;16 placebo). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). Our patients, receiving potentially cardiotoxic treatment: 52% were treated with only trastuzumab, 34% were treated with only anthracycline and 14% with carfilzomib. The primary endpoint was the development of cardiotoxicity after treatment with chemotherapy. Cardiotoxicity was defined as a decrease of LVEF by 5% or more to less than 55% in the presence of symptoms of heart failure or an asymptomatic decrease in LVEF by 10% or more to less than 55%. Results In the first trimester of observation compared to baseline, patients treated with dapagliflozin did not show a deterioration of LV GLS [(GLS = −20,2±3,1% vs −19,8±3,1%, p=0,551] .Similarly in the placebo group [(GLS= −23,02±3,6% vs −22,6±3,5%, p=0,572). No significant changes were found in LVEF after treatment with dapagliflozin (57,9±5,6% vs 57,6±6,1%, p=0,733) or the placebo (60,1±5,6% vs 57,8±6,6%, p=0,166).There was a trend in GLS reduction of left ventricle in 2 patients receiving carfilzomib treatment in the placebo group (p=0.058) Conclusions At the best of our knowledge, our study is the first to investigate the early prophylactic use of dapagiflozin in the development of non-ischemic cardiomyopathy in patients receiving anthracycline or trastuzumab,carflilzomib therapies. During the first trimester of observation there was no benefit by dapagliflozin administration but 2 of our patients in the placebo group demonstrated reduction in GLS of left ventricle.

Mitochondrial function and oxidative stress in isolated peripheral blood mononuclear cells and trastuzumab-induced cardiotoxicity: a prospective longitudinal study

Abstract Introduction Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is believed to cause cardiotoxicity through mitochondrial dysfunction and oxidative stress. Although peripheral blood mononuclear cells (PBMCs) could represent systemic oxidative stress, they are also involved in trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity. The usefulness of isolated PBMCs in the assessment of trastuzumab-induced cardiotoxicity remains uncertain. Purpose We aimed to determine the temporal changes of mitochondrial function and oxidative stress in isolated PBMCs, and cardiac function in breast cancer patients receiving sequential doxorubin and trastuzumab treatment. Methods Fourteen HER-2 positive breast cancer patients with apparently normal cardiac function at baseline were recruited from September 1, 2020 to August 31, 2022. After breast surgery, all patients received doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) every 3 weeks for 4 cycles, followed by trastuzumab (8 mg/kg loading then 6 mg/kg) every 3 weeks for 18 cycles. Adjuvant paclitaxel (175 mg/m²) every 3 weeks for 4 cycles was an additional treatment in patients with positive lymph node(s). Echocardiography and blood samples were collected at baseline, cycle 4 of doxorubicin chemotherapy, every 3 months during trastuzumab treatment and &amp;gt;1 month after treatment. Seahorse extracellular flux analyzer was used to determine mitochondrial oxygen consumption, and MitoSox/MitoTracker staining to determine oxidative stress in isolated PBMCs. Results Of 14 patients (mean age of 50.4 ±8.8 years), 2 had hypertension and 4 had hyperlipidemia. The serum troponin I levels were significantly increased during doxorubicin treatment, then gradually decreased afterward, while the serum NT-proBNP levels remained statistically unchanged (Figure 1A and B). The numerical reduction of ejection fraction was remarked during the treatment, however there was no clinical cardiac dysfunction (Figure 1C). Subclinical cardiac dysfunction, defined as a &amp;gt;15% relative reduction in global longitudinal strain (GLS), was observed in 9 of 14 patients during trastuzumab treatment (Figure 1D). Mitochondrial oxidative stress in isolated PBMCs, although unchanged during doxorubicin treatment, was gradually increased during trastuzumab treatment (Figure 2A and B). Mitochondrial proton leak was also increased, while oxygen consumption and ATP production remained unchanged (Figure 2C and D). After treatment completion, cardiac function, as well as mitochondrial oxidative stress, tended to improve. Interestingly, there was a strong positive correlation between mitochondrial oxidative stress at baseline and maximum GLS reduction during treatment (r=0.811, p=0.001). Conclusions Mitochondrial oxidative stress in isolated PBMCs could be a potential marker for the evaluation and prediction of trastuzumab-induced cardiotoxicity. Further studies are warranted.Figure 1Figure 2

Prognostic value of 6-minute walking test for early prediction of doxorubicin induced cardiotoxicity

Abstract BACKGROUND/OBJECTIVES The 6-minute walking test (6MWT) is an easily performed, widely available and well-tolerated test for assessing the functional capacity of patients with HF in everyday clinical practice. The measurement properties of the 6MWT, such as reliability and validity, have been studied in patients with chronic heart failure, coronary artery disease, and cancer. However, little is currently known about the 6MWT and cardiotoxicity. The study was aimed at assessing the incidence of cancer therapy-related cardiovascular toxicity, identified the role of 6MWT as early predictor of early onset cardiotoxicity. Methods We performed a prospective study of 85 patients with breast cancer, treated with doxorubicin-based chemotherapy in the Department of Oncology and Hematology. 2D echocardiography and speckle tracking echocardiography were performed before anticancer treatment was started and after the treatment. We defined anthracycline-induced subclinical cardiotoxicity if a decline in global longitudinal strain (GLS) by &amp;gt;15% from baseline was observed and based on that patients were divided into two groups– patients with subclinical cardiotoxicity and patients without subclinical cardiotoxicity. The 6MWT was developed by the American Thoracic Society comprehensive guidelines. The 6MWT was performed in a long straight hospital corridor, over a 30-m distance. Statistical analysis was performed with „IBM SPSS statistics 27.0" program. Statistical significance level p&amp;lt;0.05. Results In the study population statistically significant GLS reduction was detected before and after the anticancer treatment (-21±0.53 vs. -18.1± 1.18, p&amp;lt;0.01). Of 85 women (mean age, 54.5 (9.3) years) subclinical left ventricle dysfunction was identified in 51 (60%). We found a significant negative correlation between baseline 6MWT and cardiotoxicity (r = 0.3 and p = 0.02). The baseline 6MWT results were significantly lower among patients with subclinical cardiotoxicity (494.3 ± 40.5 m vs 629.8 ± 60.1 m, p&amp;lt;0.001). The diagnostic validity of 6 MWT as a cardiotoxicity biomarker was evaluated using the non-parametric ROC curve (Pic. 1). We obtained an optimal cut-off point of 6MWT of ≤540m. (AUC = 0.98; p &amp;lt; 0.001). Conclusions Baseline 6MWT may be used as independed prognostic predictor of subclinical anthracycline-induced cardiotoxicity.ROC curve for 6MWT and cardiotoxicity

Abstract 16194: Relationship Between Change in Global Longitudinal Strain and Sustained Handgrip Induced Afterload as Assessed Using Invasive Left Ventricular Pressure Measurements and Machine Learning Analytics

Introduction: Global longitudinal strain (GLS) is a sensitive, quantitative measure of left ventricular (LV) systolic function and affected by afterload. We sought to compute the impact of LV systolic pressure (LVP) increase on GLS using handgrip stress during invasive LVP measurements. Methods: Patients undergoing left heart catheterization (n=51; mean age 64+/-11 years; 31% women; Table) for standard of care indications underwent echocardiography during handgrip stress with a catheter in the LV cavity. GLS and LVP were measured simultaneously over 15 seconds of continuous handgrip. GLS and LVP relationships were analyzed using linear regression and machine learning methods. Results: Sustained handgrip (HG) stress significantly increased LVP and reduced GLS. There was no significant correlation between resting and peak HG stress LVP and GLS (p= 0.32 &amp; 0.36, respectively). However, change in GLS was significantly correlated with change in LVP (p&lt;0.0001; Figure) with every 10 unit increase in LVP associated with a 0.6 reduction in GLS. The penalized maximum likelihood machine learning method was used to select key factors associated with the within subject slope of % change in GLS over % change in LVP (median slope -0.53; IQR-0.91 to -0.29). LV ejection fraction was identified as an important predictor of the GLS-LVP slope. LV ejection fraction was significantly associated with the slope (p=0.0005; Figure) with a 10 unit increase in LV ejection fraction corresponding to 0.22 increase in the slope. Conclusions: LV afterload is associated with significant decrements in GLS. LV ejection fraction is an important predictor of the GLS-LVP slope. These data provide the foundation to build models that would account for change in LVP during serial measurements of GLS thus allowing reliable comparison of repeated GLS measurements.

COMPARATIVE ANALYSIS OF LONG-TERM OUTCOMES FOLLOWING THE STIMULATION OF CARDIAC CONDUCTION SYSTEM AND RIGHT VENTRICULAR PACING IN PATIENTS WITH BRADYARRHYTHMIAS

Introduction. Right ventricular myocardial pacing induces asynchronous ventricular contraction, potentially resulting in pacing-induced cardiomyopathy and adverse long-term clinical outcomes. Conduction system pacing is a physiological alternative to right ventricular myocardial pacing. The objective of this study is to analyze the long-term outcomes of the conduction system pacing in comparison with right ventricular myocardial pacing in patients requiring permanent ventricular pacing and who have preserved initial left ventricular ejection fraction (≥ 50%). Materials and methods. 48 patients with indications for permanent ventricular pacing were selected for comparative analysis. Of these, 18 patients had cardiac conduction system pacing and 30 patients had right ventricular myocardial pacing. Permanent pacemaker implantation in both groups of this study was performed from 2012 to 2022. Patients in both groups had to meet the following selection criteria for this study: 1) preserved systolic function of the left ventricle at the time of pacemaker implantation (≥ 50%); 2) total percentage of ventricular pacing from the time of implantation had to be not less than 90%.&#x0D; Results. The observation period was 35.3 ± 37 months in the conduction system pacing group and 46 ± 28.73 months in the right ventricular pacing group. Since the time of pacemaker implantation, pacing-induced cardiomyopathy occurred in 7 (23%) patients in the right ventricular pacing group and in none in the conduction system pacing group. The mean left ventricular ejection fraction at the control visit was significantly lower in the right ventricular pacing group (51.59 ± 8.55 vs. 58.64 ± 4.58%, p =.004). A significant reduction in global longitudinal strain was observed in the right ventricular pacing group compared to the conduction system pacing group (14.22 ± 3.66 vs. 18.49 ± 2.5%, p = &lt;.001). Paced QRS width was significantly greater in the right ventricular pacing group (152.32 ± 18.13 vs. 119.12 ± 8.8 ms, p &lt;.001). Conclusions. Applying new physiological methods of cardiac pacing enables to avoid the negative consequences of an asynchronous pattern of ventricular activation during conventional right ventricular pacing.

Early detection of reduced left ventricular systolic function by 2D speckle tracking echocardiography in patients with primary mitral regurgitation in a Vietnamese cohort.

Background: Mitral regurgitation (MR) is a common heart valve disease, causing many serious complications in several organ systems, especially the cardiovascular system. The 2D speckle tracking echocardiography (STE) is a new technique for detecting potential cardiac dysfunction when only tissue function abnormalities are present. The study aimed to assess left ventricular (LV) systolic function early by STE in patients with primary MR through global LV deformity along the global longitudinal strain (GLS). Methods: An analytical cross-sectional study was performed on 46 patients with moderate to severe primary MR as recommended by the American Society of Echocardiography (ASE) 2017. Results: The prevalence of patients with GLS reduction with ejection fraction (EF) >60%, New York Heart Association (NYHA) I, and left ventricular internal diameter systolic (LVIDs) <40mm was 38.1%, 35.7%, and 39.5%, respectively. 100% of patients with EF<60% and LVIDs ≥40mm had reduced GLS (<16%). The GLS index strongly correlates with the NYHA classification, degree of MR, EF, and echocardiographic parameters. Conclusion: GLS index gives a significant sign in the early detection of cardiac function abnormalities before symptoms or other echocardiographic parameters in patients with MR.

Evaluation of left ventricular systolic function by speckle tracking echocardiography in type 2 diabetic patients

Background: Cardiovascular complications are the leading cause of death in diabetic patients. Speckle tracking echocardiography can early detect left ventricular systolic dysfunction even when normal ejection fraction. The study aims to evaluate left ventricular systolic function by Speckle tracking echocardiography and its correlation with some cardiovascular risk factors in type 2 diabetic patients; Materials and method: Controlled cross-sectional descriptive study in 60 subjects (30 in type 2 diabetic patients and 30 controls) at Hue University of Medicine and Pharmacy Hospital. Data collection: age, sex, time to detect diabetes, body mass index, waist circumference, blood pressure, fasting blood glucose, HbA1c, lipid blood, traditional Doppler echocardiographic parameters, values of left ventricular longitudinal strain in 2-chamber, 3-chamber, 4-chamber view and value of total left ventricular longitudinal strain; Results: Type 2 diabetic patients had 2-chamber longitudinal strain (-17.01 ± 3.26%), 3-chamber longitudinal strain (-16.41 ± 3.69%), 4-chamber longitudinal strain (-18.46 ± 3.23%, global longitudinal strain (-17.31 ± 2.87%), was lower than control group (p &lt; 0.05). The global longitudinal strain was positively correlated with diabetes duration (r = 0.3), heart rate (r = 0.3), systolic blood pressure (r=0.4), diastolic blood pressure (r = 0.4), fasting plasma glucose (r = 0.4), HbA1c (r = 0.4) (p &lt; 0.05); Conclusion: Type 2 diabetic patients have reduced global longitudinal strain. The reduction of global longitudinal strain was correlated with diabetes duration, heart rate, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, and HbA1c. Key words: diabetes, speckle tracking echocardiography, left ventricular ejection fraction, global longitudinal strain, cardiovascular risk factors.

Abstract P365: Left Ventricular Hypertrophy In Hypertension-correlation Of Electrocardiography Criteria, Echocardiography And Myocardial Strain Imaging

Background: LVH on ECG has been defined by 37 different criteria with modest degree of differences in accuracy amongst them leading to a lack of consensus. Objectives: Study aims to correlate sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) of selected 17 standard ECG criteria in the diagnosis of LVH, correlation with echocardiography and myocardial global longitudinal strain (GLS). Demographics: Average age of the 104 hypertensive individuals included in the study was 61.86 years with 43.3% women. 73% of subjects had LVH on echocardiography with mean LVMI 115.97g/m2 and mean RWT 0.5. Results: Groningen criteria (24.70%) and Cornell voltage criteria (20.98%) had the best sensitivity for LVH detection. Groningen criteria was defined as QV2+R1+RV5+RV6+SV2+SV4+SV5+SV6 &gt;= 49.5 mm in women and R1+RV5+SII+ SV2+SV6 x QRS duration &gt;= 4500mm msec in men. Sensitivity for other criteria were lesser; Peguero Lo presti(PL) 13.58%, Sokolow Lyon index(SL) 11.11% and Cornell voltage product (CVP) 6.17%. Specificity and Positive predictive value (PPV) with Groningen criteria were 90% and 95.6% and with Cornell voltage criteria 100% and 100% respectively. Best sensitivity results were on combining all 17 ECG LVH criteria (39.5%). Addition of Groningen criteria improved the sensitivity of SL+CV+PL from 28.39% to 38.3%. Combination of the commonly used CV+SL+PL criteria yielded better sensitivity (28.39%) as compared to CV (20.98%) alone. Subjects with mild LVH on echo had an average GLS of -15.46+/-2.4% in 75%, subjects with moderate LVH had an average GLS of -14.23+/-2.8% in 71.4% and subjects with severe LVH had an average GLS of -12.6+/-4.9% in 80%. Conclusion: Irrespective of the voltage criteria used, singular or in combination, sensitivity to diagnose LVH proven on echocardiography is low. Novel Groningen criteria was more sensitive than the previously established standard ECG LVH criteria and had the highest association amongst all in patients with reduction in average GLS. Combination of four criteria SL+CV+PL+Groningen had the best sensitivity (38.3%) which improved only by 1.2% if all 17 criteria were combined.

Chemotherapy-related cardiac dysfunction: the usefulness of myocardial work indices.

The role of left ventricular global longitudinal strain (GLS) in the diagnosis of subclinical cardiac damage induced by anticancer drugs is now consolidated. Considering some strain disadvantages such as the dependence on the haemodynamic loading conditions, the aim of our study was to investigate the usefulness of non-invasive myocardial work indices (MWI) derived from pressure-strain analysis, in the early diagnosis of cardiotoxicity. We enrolled 61 consecutive patients with breast cancer undergoing adjuvant treatment with anthracycline-containing chemotherapy followed by taxane + trastuzumab. Patients underwent a cardiological evaluation with 2D echocardiography including measurement of the left ventricular ejection fraction (LVEF) and other conventional parameters of systolic and diastolic function, GLS and MWI at baseline (T0), 3 months (T1) and 6 months (T2) after starting chemotherapy. At T1 and T2, we did not find a significant reduction in LVEF but we found a significant reduction in GLS and MWI (p value < 0.05). In addition, at T2, 31% of patients developed subclinical cardiac dysfunction defined as a relative decrease ≥ 12% of GLS from baseline. Global work index (GWI), global constructive work (GCW) and global work efficiency (GWE) decreased significantly in both patients with subclinical dysfunction and in those without subclinical dysfunction (p value < 0.05). Patients with subclinical dysfunction at T2 showed lower values of GCW at T0. MWI changed significantly during chemotherapy and appeared to alter precociously compared to GLS. Therefore, a multiparametric approach including left ventricular GLS and MWI measurements should be used in the evaluation of patients undergoing cardiotoxic antineoplastic treatment.