scholarly journals Left ventricular segmental strain and the prediction of cancer therapy-related cardiac dysfunction

Author(s):  
Biniyam G Demissei ◽  
Yong Fan ◽  
Yiwen Qian ◽  
Henry G Cheng ◽  
Amanda M Smith ◽  
...  

Abstract Aims We aimed to determine the early changes and predictive value of left ventricular (LV) segmental strain measures in women with breast cancer receiving doxorubicin. Methods and results In a cohort of 237 women with breast cancer receiving doxorubicin with or without trastuzumab, 1151 echocardiograms were prospectively acquired over a median (Q1–Q3) of 7 (2–24) months. LV ejection fraction (LVEF) and 36 segmental strain measures were core lab quantified. A supervised machine learning (ML) model was then developed using random forest regression to identify segmental strain measures predictive of nadir LVEF post-doxorubicin completion. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥10% absolute LVEF decline pre-treatment to a value <50%. Median (Q1–Q3) baseline age was 48 (41–57) years. Thirty-five women developed CTRCD, and eight of these developed symptomatic heart failure. From pre-treatment to doxorubicin completion, longitudinal strain worsened across the basal and mid-LV segments but not in the apical segments; circumferential strain worsened primarily in the septum; radial strain worsened uniformly and transverse strain remained unchanged across all LV segments. In the ML model, anterolateral and inferoseptal circumferential strain were the most predictive features; longitudinal and transverse strain in the basal inferoseptal, anterior, basal anterolateral, and apical lateral segments were also top predictive features. The addition of predictive segmental strain measures to a model including age, cancer therapy regimen, hypertension, and LVEF increased the area under the curve (AUC) from 0.70 (95% confidence interval (CI) 0.60–0.80) to 0.87 (95% CI 0.81–0.92), ΔAUC = 0.18 (95% CI 0.08–0.27) for the prediction of CTRCD. Conclusion Our findings suggest that segmental strain measures can enhance cardiotoxicity risk prediction in women with breast cancer receiving doxorubicin.

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
A Mecinaj ◽  
G Gulati ◽  
SL Heck ◽  
E Holte ◽  
MW Fagerland ◽  
...  

Abstract Background Recent advances in the treatment algorithms of early breast cancer have markedly improved overall survival. However, anthracycline- and trastuzumab-associated cardiotoxicity may lead to dose-reduction or halt in potentially life-saving adjuvant cancer therapy. Early initiated neurohormonal blockade may prevent or attenuate the cardiotoxicity-induced reduction in cardiac function, but prior studies have been inconclusive. The angiotensin receptor-neprilysin inhibitor sacubitril/valsartan has been shown to be superior to traditional treatment in heart failure with reduced ejection fraction, but its cardioprotective effects in the cardio-oncology setting remains to be tested. Objective To assess if sacubitril/valsartan given concomitantly with early breast cancer treatment regimens including anthracyclines, with or without trastuzumab, may prevent cardiac dysfunction. Methods PRADA II is a randomized, placebo-controlled, double blind, multi-center, investigator-initiated clinical trial. Breast cancer patients from four university hospitals in Norway, scheduled to receive (neo-)adjuvant chemotherapy with epirubicin independently of additional trastuzumab/pertuzumab treatment, will be randomized 1:1 to sacubitril/valsartan or placebo. The target dose is 97/103 mg b.i.d. The patients will be examined with cardiovascular magnetic resonance (CMR), echocardiography, circulating cardiovascular biomarkers and functional testing at baseline, at end of anthracycline treatment and following 18 months after enrolment. The primary outcome measure of the PRADA II trial is the change in left ventricular ejection fraction (LVEF) by CMR from baseline to 18 months. Secondary outcomes include change in LV function by global longitudinal strain by CMR and echocardiography and change in circulating cardiac troponin concentrations. Results The study is ongoing. Results will be published when the study is completed. Conclusion PRADA II is the first randomized, placebo-controlled study of sacubitril/valsartan in a cardioprotective setting during (neo-)adjuvant breast cancer therapy. It may provide new insight in prevention of cardiotoxicity in patients receiving adjuvant or neo-adjuvant therapy containing anthracyclines. Furthermore, it may enable identification of patients at higher risk of developing cardiotoxicity and identification of those most likely to respond to cardioprotective therapy. Trial registration The trial is registered in the ClinicalTrials.gov registry (identifier NCT03760588). Registered 30 November 2018.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12531-e12531
Author(s):  
Vasiliki Michalaki ◽  
George Koutroulis ◽  
Ioannis Kontis ◽  
Nikolaos Dafnios ◽  
Dina Tiniakos ◽  
...  

e12531 Background: Although epirubicin has improved outcome in breast cancer (BC) patients, its application is limited by its cardiotoxicity . Assessment of left ventricular (LV) ejection fraction (EF) is performed to demonstrate cardiac dysfunction. Changes in cardiac function induced by this therapy, however, are difficult to quantitate by conventional echocacardiography. Tissue Doppler myocardial imaging (TDI) derived wall motion velocity, and strain rate (SR) have been shown to sensitively quantify abnormalities in cardiac function. The aim of this study was to determine if sensitive indices of LV dysfunction, would be useful for addressing the early detection of cardiotoxic side effects of epirubicin. Methods: BC patients (N = 45 median age 60.2years) without cardiovascular risk factors were prospectively included. All patients received epirubicin. Twenty patients received further trastuzumab. Conventional and TDI echocardiography were obtained at baseline , every 2cycles of treatment and 3 months after chemotherapy. Segmental peak systolic longitudinal and radial velocity, SR and strain, were measured. Results: at baseline, median LV-EF was > 55 %. There was no overall change in LV dimensions, EF and peak systolic velocity. In contrast, a significant reduction in longitudinal and radial SR and strain was found after 3 cycles (longitudinal strain -10.2% +/- 1.3 % vs baseline 22 +/- 4.1 %, P = .001; radial strain 26.1% +/-4,2% vs baseline 47.3% +/- 9.2 %, P < .001). Changes in radial strain appeared earlier and were more pronounced than longitudinal strain. Conclusions: In this study we confirm the clinical use of TDI parameters for early detection of epirubicin mediated cardiac dysfunction. TDI detected subtle changes of LV function after 3 cycles of therapy. Use of Strain Rate Imaging detects subclinical LV dysfunction and can predict further changes in EF ,therefore can be used to monitor epirubicin-induced cardiotoxicity.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jingyuan Guan ◽  
Wuyun Bao ◽  
Yao Xu ◽  
Wei Yang ◽  
Mengmeng Li ◽  
...  

No study has examined myocardial work in subjects with cancer therapy-related cardiac dysfunction (CTRCD). Myocardial work, as a new ultrasonic indicator, reflects the metabolism and oxygen consumption of the left ventricle. The aim of this study was to test the relative value of new indices of myocardial work and global longitudinal strain (GLS) in detecting changes in myocardial function during the treatment of breast cancer by two-dimensional and three-dimensional echocardiography. We enrolled 79 breast cancer patients undergoing different tumor treatment regimens. Follow-up observation was conducted before and after chemotherapy. The effects of breast cancer chemotherapy and targeted therapy on the development of CTRCD [defined as an absolute reduction in left ventricular ejection fraction (LVEF) of &gt;5% to &lt;53%] were detected by two-dimensional and three-dimensional speckle tracking echocardiography. Our findings further indicate that LVEF, myocardial work index (GWI) and myocardial work efficiency (GWE) showed significant changes after the T6 cycle, and GLS showed significant changes after the T4 cycle (p &lt; 0.05). The three-dimensional strain changes after T6 and T8 had no advantages compared with GLS. Body mass index (BMI), the GLS change rate after the second cycle of chemotherapy (G2v) and the 3D-GCS change rate after the second cycle of chemotherapy (C2v) were independent factors that could predict the occurrence of CTRCD during follow-up, among which BMI was the best predictor (area under the curve, 0.922). In conclusion, the current study determined that GLS was superior to GWI in predicting cardiac function in patients with tumors with little variation in blood pressure. BMI, G2v and C2v can be used to predict the occurrence of CTRCD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hsien-Yuan Chang ◽  
Chun-Hui Lee ◽  
Po-Lan Su ◽  
Sin-Syue Li ◽  
Ming-Yueh Chen ◽  
...  

AbstractLeft ventricular (LV) global peak systolic longitudinal strain (GLS) is a sensitive measurement for detecting subtle LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving cancer therapy remains unknown. We prospectively enrolled 74 lymphoma patients (57.9 ± 17.0 years old, 57% male). We performed echocardiographic studies after the 3rd and 6th cycles and 1 year after chemotherapy and a cardiopulmonary exercise test upon completion of 3 cycles of anticancer therapy. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥ 15% relative reduction in GLS value from baseline. The primary outcome was a composite of all-cause mortality and heart failure events. Thirty-six patients (49%) had CTRCD (LV GLS: baseline vs. after 3rd cycle of therapy: 20.1 ± 2.6 vs. 17.5 ± 2.3%, p < 0.001). CTRCD was detected after the 3rd cycle of anticancer therapy. CTRCD patients had impaired exercise capacity (minute oxygen consumption/kg, CTRCD vs. CTRCD (-): 13.9 ± 3.1 vs. 17.0 ± 3.9 ml/kg/min, p = 0.02). More primary outcome events occurred in the CTRCD group (hazard ratio 3.21; 95% confidence interval 1.04–9.97; p = 0.03). LV GLS could detect subtle but clinically significant cardiac dysfunction in lymphoma patients in the early stage of anticancer therapy. CTRCD may be associated with not only a reduced exercise capacity but also a worse prognosis.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y.W Liu ◽  
H.Y Chang ◽  
C.H Lee ◽  
W.C Tsai ◽  
P.Y Liu ◽  
...  

Abstract Background and purpose Left ventricular (LV) global peak systolic longitudinal strain (GLS) by speckle-tracking echocardiography is a sensitive modality for the detection of subclinical LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving anti-cancer therapy remains unknown. Methods We prospectively enrolled 74 patients (57.9±17.0 years old, 57% male) with lymphoma who underwent echocardiography prior to chemotherapy, post 3rd and 6th cycle and 1 year after chemotherapy. Cancer therapy-related cardiac dysfunction (CTRCD) is defined as the reduction of absolute GLS value from baseline of ≥15%. All the eligible patients underwent a cardiopulmonary exercise test (CPET) upon completion of 3 cycles of anti-cancer therapy. The primary outcome was defined as a composite of all-cause mortality and heart failure events. Results Among 36 (49%) patients with CTRCD, LV GLS was significantly decreased after the 3rd cycle of chemotherapy (20.1±2.6% vs. 17.5±2.3%, p&lt;0.001). In the multivariable analysis, male sex and anemia (hemoglobin &lt;11 g/dL) were found to be independent risk factors of CTRCD. Objectively, patients with CTRCD had lower minute oxygen consumption/kg (VO2/kg) and lower VO2/kg value at anaerobic threshold in the CPET. The incidence of the primary composite outcome was higher in the CTRCD group than in the non-CTRCD group (hazard ratio 3.21; 95% CI, 1.04–9.97; p=0.03). Conclusion LV GLS is capable of detecting early cardiac dysfunction in lymphoma patients receiving anti-cancer therapy. Patients with CTRCD not only had a reduced exercise capacity but also a higher risk of all-cause mortality and heart failure events. Change of LVEF and GLS after cancer Tx Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Ministry of Science and Technology (MOST), Taiwan


2007 ◽  
Vol 25 (25) ◽  
pp. 3859-3865 ◽  
Author(s):  
Thomas M. Suter ◽  
Marion Procter ◽  
Dirk J. van Veldhuisen ◽  
Michael Muscholl ◽  
Jonas Bergh ◽  
...  

Purpose The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2–positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF ≥ 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Results Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m2 v 257 mg/m2) or epirubicin (480 mg/m2 v 422 mg/m2) and had a lower screening LVEF and a higher body mass index. Conclusion Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Felix Heggemann ◽  
Hanna Buggisch ◽  
Grit Welzel ◽  
Christina Doesch ◽  
Jochen Hansmann ◽  
...  

Introduction: Cardiotoxic side effects are of concern in long-term survivors of left-sided breast cancer therapy. 3-dimensional conventional radiotherapy (3DCRT) deposits high doses in defined regions of the heart. Intensity modulated radiotherapy (IMRT) reduces local high-dose exposition at the expense of exposing more heart tissue to lower doses. Cardio-MRI was performed in this study to assess MRI-morphologic and functional alterations after 3DCRT and IMRT/ additional chemotherapy, with IMRT only performed in patients that would have been exposed to unacceptably high heart doses with 3DCRT. Methods: 49 patients with left-sided breast cancer (38 3DCRT and 11 IMRT; 20 patients with additional adjuvant chemotherapy (ACH) (13 3DCRT, 7 IMRT) were included prospectively. Baseline (pre-treatment) and 24 months post-treatment MRI was performed. With MRI, enddiastolic left ventricular mass (LVM), enddiastolic left ventricular volume (LVEDV) and stroke volume (SV) were assessed. LVRI was calculated with the formula LVM/LVEDV. Results: Mean dose for the whole heart was higher in IMRT than in 3DCRT patients (12.9±3.9 vs. 4.5 ±2.4 Gy). Larger regions received a higher radiation dose (>40Gy) in 3DCRT than in IMRT patients (3.3% vs. 1.3% of the whole heart). High local radiation dose > 50 Gy only occurred in the 3DCRT group (0.74% of the heart volume). After 24 months LVRI decreased significantly in patients with ACH (0.80 vs. 0.70, p=0.028). Non-significant decrease of LVRI was observed in the whole cohort (0.85 vs. 0.79), after IMRT (0.74 vs. 0.71), after 3DCRT (0.88 vs. 0.82) and without ACH (0.87 vs. 0.84). Decrease of LVRI in patients with ACH was caused by significant decrease of LVM (102.4 vs. 89.7 g, p=0.028) whereas LVEDV was stable (128.3 vs. 128.1g). In all groups, no significant decrease of SV could be assessed after 24 months. Conclusions: 24 months after therapy, significant decrease of LVRI due to decreased LVM could be found only in patients with additional chemotherapy. Radiotherapy alone did not have a significant impact on LVRI, LVM and SV. Low doses to the whole heart with IMRT did not cause significant decreases in LVRI, LVM and SV. LVM and LVRI are to be assessed in larger cohorts in patients with cancer therapy especially with additional chemotherapy.


2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Johan Kihlberg ◽  
Vikas Gupta ◽  
Henrik Haraldsson ◽  
Andreas Sigfridsson ◽  
Sebastian I. Sarvari ◽  
...  

Abstract Background Several cardiovascular magnetic resonance (CMR) techniques can measure myocardial strain and torsion with high accuracy. The purpose of this study was to compare displacement encoding with stimulated echoes (DENSE), tagging and feature tracking (FT) for measuring circumferential and radial myocardial strain and myocardial torsion in order to assess myocardial function and infarct scar burden both at a global and at a segmental level. Method 116 patients with a high likelihood of coronary artery disease (European SCORE > 15%) underwent CMR examination including cine images, tagging, DENSE and late gadolinium enhancement (LGE) in the short axis direction. In total, 97 patients had signs of myocardial disease and 19 had no abnormalities in terms of left ventricular (LV) wall mass index, LV ejection fraction, wall motion, LGE or a history of myocardial infarction. Thirty-four patients had myocardial infarct scar with a transmural LGE extent (transmurality) that exceeded 50% of the wall thickness in at least one segment. Global circumferential strain (GCS) and global radial strain (GRS) was analyzed using FT of cine loops, deformation of tag lines or DENSE displacement. Results DENSE and tagging both showed high sensitivity (82% and 71%) at a specificity of 80% for the detection of segments with > 50% LGE transmurality, and receiver operating characteristics (ROC) analysis showed significantly higher area under the curve-values (AUC) for DENSE (0.87) than for tagging (0.83, p < 0.001) and FT (0.66, p = 0.003). GCS correlated with global LGE when determined with DENSE (r = 0.41), tagging (r = 0.37) and FT (r = 0.15). GRS had a low but significant negative correlation with LGE; DENSE r = − 0.10, FT r = − 0.07 and tagging r = − 0.16. Torsion from DENSE and tagging had a weak correlation (− 0.20 and − 0.22 respectively) with global LGE. Conclusion Circumferential strain from DENSE detected segments with > 50% scar with a higher AUC than strain determined from tagging and FT at a segmental level. GCS and torsion computed from DENSE and tagging showed similar correlation with global scar size, while when computed from FT, the correlation was lower.


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