scholarly journals Role of myocardial deformation analysis in the early detection of subclinical Left Ventricular dysfunction in breast cancer under anthracyclines and trastuzumab

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
R Benmalek ◽  
I Krikez ◽  
A Maaroufi ◽  
A Abouriche ◽  
H Bendahou ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction : Cardio-oncology field has notably raised interest this past decade, it considerably improved cancer patients’ quality of care by monitoring and preventing complications of cardiotoxic treatment like anthracyclines and trastuzumab. Transthoracic echocardiography (TEE) plays a major role in the baseline assessment and follow-up of cardio-oncology patients. While left ventricular ejection fraction (LVEF) still has its place in cardiac monitoring, new modalities like myocardial deformation imaging with speckle tracking strain analysis, show great potential for early detection of subclinical LV dysfunction. Purpose : The aim of this study was to evaluate the role of Global Longitudinal Strain (GLS) in the early detection of cardiotoxicity and its correlation to LVEF. Methods : We conducted a longitudinal prospective study including all the breast cancer patients treated with anthracyclines and/or trastuzumab  followed in the Casablanca cardio-oncology unit from January 2017 to December 2019. All patients underwent baseline TEE, and were followed-up every 3 months after that, with GLS assessment whenever it was possible. We evaluated the frequency of GLS drop and its correlation to LVEF reduction. Results : Out of a total of 793 patients, 677 had available LV GLS assessment. Among them, 83 (12,3%) decreased their GLS during follow-up, 67% of which had no concomitant drop in LVEF. In these patients, impaired LV GLS values were noted at 1 month after chemotherapy and at 3, 6, and 12 months compared with baseline (-22,3 ± 1.8% at baseline, -18.1 ± 2.3% at 1 month, -17.7 ± 2.1% at 3 months, -17.1 ± 2.2% at 6 months, and -16.9 ± 2.1% at 12 months (p < 0,0001). LV GLS at 3 months was strongly correlated to cardiotoxicity (LVEF < 50%) at 12 months (p < 0,0001). A cut-off LV GLS value of -17,7% was then retained to identify LVEF alteration at the end of follow-up. Moreover, lower GLS values were observed in patients under Doxorubicin with a mean cumulative dose >180 mg/m2 (p = 0,0019), while LVEF remained normal. Finally, our study found that GLS at 1 month and 3 months had a prognostic value, since the lower GLS was, the poorest the patient’s clinical outcome was, with further development of symptomatic heart failure (p = 0,0038). Conclusion : Our study demonstrates that myocardial deformation analysis enables detection of early and progressive subclinical cardiac dysfunction, and GLS at 3 month was positively correlated to LVEF drop at 12 months. Thus, routine GLS should be used in patients undergoing cardiotoxic chemotherapy in order to early detect cardiotoxicity and prevent irreversible cardiac dysfunction by early initiating cardio-protective treatment.

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.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
R Karmous ◽  
E Bennour ◽  
I Kammoun ◽  
A Sghaier ◽  
W Chaieb ◽  
...  

Abstract Background Cardio-oncology has arisen as one of the most rapidly expanding fields of cardiovascular medicine. The accumulated evidence on the possibilities of early diagnosis of cardiotoxicity provided by imaging techniques as well as on the benefits of preventive and therapeutic interventions is also increasing. Objective This study reported our echocardiography lab's initial experience of a cardio-oncology follow-up program. Methods We prospectively studied the outcomes of 107 patients diagnosed with breast cancer who attended our follow-up program between 2017 and 2020. An echocardiographic monitoring were realised according to the chemotherapy protocol. Cancer therapy-related cardiac dysfunction (CTRCD) is defined, according to the european society of cardiology (ESC) guidelines of 2016, as a drop of left ventricular ejection fraction (LVEF) by >10 percentage points from baseline to a value <50%. A new entity named subclinical systolic dysfunction, is defined by a drop of global longitudinal strain (GLS) by >15% from baseline, however, LVEF remains >50%. The diagnosis should be confirmed by a second echocardiogram after 2–3 weeks. Results We enrolled 107 patients diagnosed with breast cancer and receiving anthracycline and/or trastuzumab. 27 patients were excluded for many reasons: 17 patients were lost to follow-up, 10 patients had an inadequate echo-imaging (8 had a follow-up without measurement of GLS and 2 patients were poorly echogenic). Only eighty patients were finally retained. The average age of our patients was 49.9±10.8 years. The mean left ventricular ejection fraction (LVEF) was at 64±4.4%. The incidence of CTRCD was 6%. the mean delay of diagnosis from the onset of chemotherapy was 174 days. It was reversible in 60% of cases after the initiation of a cardioprotective treatment which allowed the anti-cancer treatment pursuit. The incidence of subclinical cardiac dysfunction was 25%. The mean delay between the initiation of anti-cancer treatment and the diagnosis was 314.5 days. A cardioprotective treatment with Bblockers and angiotensin-converting enzyme (ACE) inhibitors was prescribed and all these patients recovered a normal GLS with a mean delay of three months and pursuied their chemotherapy. Conclusion We showed that timely cardiovascular evaluation, intervention and close monitoring in the context of a structured service allowed the majority of patients (99%) to pursue their anti-cancer treatment and to avoid the evolution to CTRCD in patients diagnosed with subclinical cardiac dysfunction. FUNDunding Acknowledgement Type of funding sources: None. Treated subclinical cardiac dysfunction


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11520-e11520
Author(s):  
K. Fedenko ◽  
P. Cortazar ◽  
P. Keegan ◽  
R. Pazdur

e11520 Background: Trastuzumab can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure (CHF), and decreased left ventricular ejection fraction (LVEF). Methods: Data was reviewed from 9837 patients in four randomized trials (NCCTG 9831, NSABP B-31, HERA, and BCIRG-06) that supported trastuzumab HER2 overexpressing adjuvant breast cancer approval. Results: Trastuzumab can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death. Herceptin can also cause asymptomatic decline in LVEF. There is a 4−6 fold increase in the incidence of symptomatic myocardial dysfunction among patients receiving trastuzumab as a single agent or in combination therapy compared with those not receiving trastuzumab. The highest absolute incidence occurs when trastuzumab is administered with an anthracycline. Clinical trials NCCTG 9831, NSABP B-31, and BCIRG-06 included arms with doxorubicin- cyclophosphamide (AC) followed by a taxane plus trastuzumab. Among 32 patients receiving adjuvant chemotherapy from studies NCCTG 9831 and NSABP B-31 who developed CHF, one patient died of cardiomyopathy and all other patients were receiving cardiac medication at last follow-up. Approximately half of the patients recovered to a normal LVEF (defined as ≥ 50%) on continuing medical management at the time of last follow-up. In BCIRG-06 the incidence of CHF was six (6) fold higher in the AC followed by docetaxel plus trastuzumab arm as compared to AC followed by docetaxel. There was a lower incidence of CHF in the non-anthracycline TCH (docetaxel, carboplatin and trastuzumab) arm in BCIRG-06 comparable to trastuzumab monotherapy. Conclusions: Cardiotoxicity manifesting as sub-clinical and clinical cardiac failure is a known side effect of trastuzumab. In an era where trastuzumab is given earlier in the treatment of breast cancer (adjuvant setting), the safety of continuation or resumption of trastuzumab in patients with trastuzumab-induced left ventricular cardiac dysfunction has not been studied. No significant financial relationships to disclose.


2021 ◽  
Author(s):  
Koichi Egashira ◽  
Daisuke Sueta ◽  
Mai Tomiguchi ◽  
Kaori Hidaka ◽  
Lisa Goto-Yamaguchi ◽  
...  

Abstract Background Anthracycline therapies cause myocardial damage and the onset of heart failure, depending on their doses. We investigated prognostic factors for cancer therapeutics-related cardiac dysfunction (CTRCD) in patients receiving modern anthracycline therapies. Methods Of 472 breast cancer patients with complete data treated with anthracycline, 8 were diagnosed with CTRCD. Results Multivariate regression analyses revealed that the anthracycline cumulative dose, concomitant use of molecular targeted drugs and a prechemotherapy left ventricular ejection fraction < 50% were independent and significant predictors of the onset of CTRCD. Conclusions Even in the modern era, the anthracycline cumulative dose is an independent risk factor for the onset of CTRCD.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Steen ◽  
M Montenbruck ◽  
P Wuelfing ◽  
S Esch ◽  
A K Schwarz ◽  
...  

Abstract Background Cardiotoxicity during cancer treatment has become an acknowledged problem of chemotherapy medications and radiation therapy. Limitations of biomarkers and imaging tests such as echocardiography left ventricular ejection fraction (LVEF) hinder early detection of cardiotoxicity and proactive cardioprotective therapy. Once the heart is unable to compensate for subclinical dysfunction, systemic damage and remodeling occurs increasing the potential for heart failure. Fast-SENC segmental intramyocardial strain (fSENC) is a unique cardiac magnetic resonance imaging (CMR) test that regionally detects subclinical intramyocardial dysfunction in 1 heartbeat. This study evaluates the ability of fSENC to detect subclinical cardiotoxicity and manage cardioprotective therapy in cancer patients. Methods This single center, prospective Prefect Study was used to evaluate cardiotoxicity and the impact of cardioprotective therapy in Breast Cancer and Lymphoma patients (NCT03543228). fSENC was acquired with a 1.5T MRI and processed with the MyoStrain software to quantify intramyocardial strain. Segmental strain was measured in three short axis scans (basal, midventricular & apical) with 16LV/6RV longitudinal segments & three long axis scans (2-, 3-, 4-chamber) with 21LV/5RV circumferential segments. fSENC CMR was performed before chemotherapy, during and after anthracycline/taxan therapy, at 1 year follow-up, and as needed in between designated follow-up periods. Cardioprotective therapy was offered to patients meeting the definition of cardiotoxicity by the ESC Guidelines on Cardiotoxicity and/or ESMO Clinical Practice Guidelines or those observing a substantial decline in cardiac function. Comparisons were made with paired t-Test with a 95% confidence interval. Results Two hundred eight (208) CMRs were performed in fifty-two (52) patients (44 female). Patients had an average (± stdev) age of 53 (15) yrs, BMI of 26 (5) kg/m2; 77% had breast cancer, 23% had Lymphoma. fSENC CMRs required 11 (2) min total exam time. Figure 1 shows bar graphs of the % of normal LV myocardium (e.g. % LV MyoStrain Segments <−17%) at baseline and sequential follow-ups for patients without cardiotoxicity and with cardiotoxicity requiring cardioprotective therapy. Patients observing cardiotoxicity had a statistically significant decline in cardiac function measured by segmental fSENC (p=0.0002) which resolved after cardioprotective therapy. Figure 1 Conclusion Segmental fSENC intramyocardial strain detects subclinical cardiotoxicity during chemotherapy and impact of cardioprotective therapy. The ability to serve as a surrogate safety endpoint for chemotherapy or other pharmacological agents, and aid management of cardiotoxicity by serving as a surrogate efficacy endpoint for cardioprotection agents, dosage, and patient compliance may help physicians detect subclinical cardiac dysfunction, and proactively manage cancer patients to avoid early or late heart failure.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Vincenzo Riverso ◽  
Antonio Curcio ◽  
Alessia Tempestini ◽  
Emilia De Luca ◽  
Sabrina La Bella ◽  
...  

Abstract Aims Complications of acute myocardial infarction (MI) can be life-threatening leading to sudden cardiac death. While guidelines recommend prompt revascularization and prolonged intensive care hospitalization, predictors of major adverse cardiovascular outcomes are yet poorly understood. The role of implantable cardioverter-defibrillators, even in cases of non-sustained arrhythmias is still debated. To date, it is unknown how to follow-up patients with mild cardiac dysfunction after MI. Implantable cardiac monitors (ICMs) can be helpful for stratifying patients in the early discharge period, and remote monitoring might speed up arrhythmia recognition and treatment. We investigated the role of remote monitoring of ICMs to detect arrhythmic events in post-MI patients without overt cardiac dysfunction. Methods and results We enrolled 13 patients (9 males; 69.8 years) after either ST-segment (N = 7) or non-ST-segment elevation (N = 6) MI with a left ventricular ejection fraction (LVEF) &gt;35%, admitted to our coronary care unit for urgent revascularization between September 2019 and September 2021. Twelve patients underwent percutaneous myocardial revascularization, whereas one was treated with medical therapy only. All patients received an ICM during hospitalization according to echo and EKG parameters. We considered LVEF ≤ 40% as sole risk factor or LVEF between 40% and 50% in addition to either PQ length prolongation, or QRS widening, or pathologic heart rate variability, or non-sustained ventricular tachycardia/paroxysmal advanced second degree atrioventricular block. Patients with multiple revascularization procedures and several hospital admissions were excluded. Implanted ICM were frequently monitored both remotely and in-office when required. During follow-up, brady- and tachy-arrhythmias were recorded in four patients (30.8%). The remote monitoring of the ICM documented new-onset atrial fibrillation, high-degree atrioventricular block, severe bradycardia, and sustained ventricular tachycardia. Three patients required hospitalization and upgrade of the implanted device with pacemakers and cardioverter/defibrillator. For arrhythmic risk stratification, patients were divided into two subgroups; group A included patients with LVEF 40% associated with heart rate &gt; 60 b.p.m., PQ length &gt;160 ms and QRS width &gt;86 ms (N = 4); group B included patients with EF 41%/50%, PQ length &lt;159 and QRS width &lt;85 ms (N = 10). First group experienced more advanced rhythm disorders than group B (P &lt; 0.05). Device implantation was significantly higher in group A (P &lt; 0.05%). Conclusions OFF-label implementation of ICMs coupled with remote device monitoring may be effective for early detection of serious adverse cardiac rhythm alterations in patients after MI and LVEF higher than 35%. Further monitoring is ongoing for assessing the occurrence of multiple arrhythmias or their increased occurrence.


Open Medicine ◽  
2009 ◽  
Vol 4 (3) ◽  
pp. 327-330
Author(s):  
Refik Erdim ◽  
Aydin Celiker ◽  
Gökmen Gemici ◽  
Sena Tokay ◽  
Gözde Ülfer ◽  
...  

AbstractThe aim of the study was to investigate the role of cTnT for the prediction of long term cardiac dysfunction after epirubicin-containing adjuvant chemotherapy for breast cancer. The study group comprised of 45 patients (all female; mean age 48 ±8 years), treated with epirubicin-containing adjuvant chemotherapy for stage 2 and stage 3 breast cancer. Patients received either 4 cycles of cyclophosphamide plus epirubicin (90 mg/m2) (n=23; stage 2 breast cancer) or 6 cycles of cyclophosphamide plus epirubicin (75 mg/m2) plus fluorouracil (n=18; stage 3 breast cancer). Venous blood samples were drawn, before and 72 hours after, every cycle of chemotherapy for the measurement of cTnT. Cardiac assessment was carried out at baseline and 1 year after chemotherapy by clinical evaluation, electrocardiography, radio-nuclide ventriculography (RNV) and transthoracic echocardiography. All patients remained free of clinical heart failure during the study period. In 26 patients (63%), cTnT was elevated after chemotherapy. Mean left ventricular ejection fraction, assessed by RNV at baseline and one year after chemotherapy, were 61±8% and 56±7% (p<0.0001). The sensitivity and specifity of cTnT for the detection of left ventricular systolic dysfunction at one year were 69% and 39% respectively. Echocardiographic examinations at baseline and one year after chemotherapy revealed a significant decrease in E/A ratio from 1.15±0.3 to 0.9±0.2 in cTnT positive patients, suggesting diastolic dysfunction. In conclusion, elevated serum cTnT levels after epirubicin-containing adjuvant chemotherapy for stage 2 and stage 3 breast cancer, predict future cardiac dysfunction with moderate sensitivity and poor specificity.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Esther Una Cidon ◽  
Tamas Hickish ◽  
Pilar Alonso

Trastuzumab, a humanized monoclonal antibody against the extracellular domain of human epidermal growth factor receptor 2 (HER-2) prolongs disease-free survival (DFS) and overall survival (OS) in patients with early-stage breast cancer. Although it is generally well tolerated, it has been associated with cardiotoxicity, mainly a reduction of left-ventricular ejection fraction (LVEF), especially if the patient has received anthracyclines.It is generally known that a drop in LVEF has limited diagnostic ability. Therefore, the identification of serum biomarkers of cardiotoxicity, able to detect damage at an earlier phase, has become ideal. Troponins (conventional and high sensitive), natriuretic peptides, reactive C protein (CRP), myeloperoxidase (MPO), etc are different molecular markers which have been assessed to check their role in the detection of treatment induced cardiotoxicity (CTIC) with controversial results.OBJECTIVEThis systematic review will synthesize available evidence assessing the role of different serum biomarkers in early prediction of cardiotoxicity in breast cancer patients treated with adjuvant trastuzumab.METHODS/DESIGNSystematic review conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Distinct scientific databases such as Google Scholar, Pubmed, EBSCOhost, and PsycINFO were searched to aid in the investigation of the research problem.Randomized clinical trials (RCT) and observational studies of patients with early breast cancer receiving adjuvant trastuzumab were eligible for inclusion. Two investigators have independently evaluated those studies and used standardized data extraction templates to collect data on the study and patients’ characteristics.RESULTS 11 articles were selected, one RCT and ten observational studies. The most studied biomarker was N-terminal-pro-brain natriuretic peptide (NT-proBNP) followed by troponins. Findings showed that NT-proBNP was not predictive of CTIC while conflictive results were seen with troponins.One study showed a predictive role of high sensitive (hs) CRP and another found a relationship with the levels of MPO.CONCLUSIONBiomarkers offer a unique potential to improve the effectiveness and safety of trastuzumab through timely detection of CTIC and prompt initiation of appropriate treatment. Troponins I and T have shown a predictive role in early detection of CTIC but further research would be needed to enable more insight and improve the overall patient outcome.


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.


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