Defining cardiotoxicity of doxorubicin and trastuzumab.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23097-e23097
Author(s):  
Abir Khan ◽  
Omid Amidi ◽  
Kenneth R. Hess ◽  
Michael S. Ewer ◽  
Wamique Yusuf ◽  
...  

e23097 Background: Doxorubicin and trastuzumab have been described to cause clinical heart failure and asymptomatic declines in left ventricular ejection fraction (LVEF). Initial studies of doxorubicin in the 1970’s defined cardiotoxicity by the clinical syndrome of heart failure without imaging for LVEF determination. Trials with adjuvant trastuzumab used various LVEF cut-offs that were arbitrarily determined. This study aims to compare the predictive value of commonly used definitions of cardiotoxicity associated with chemotherapy for the development of clinical heart failure. Methods: A retrospective chart review was performed on an IRB approved cohort of 638 patients with breast cancer who received doxorubicin, trastuzumab, or both and who had baseline and follow up echocardiograms, collecting LVEF values for each echocardiogram. Clinical heart failure was determined by formal cardiology evaluations denoting clinical heart failure in patients. Four different definitions of cardiotoxicity were compared; American Society of Echocardiography (ASE), Cardiac Review and Evaluation Committee (CREC), Alexander et al, and Schwartz et al (Table). Results: Only 8 patients (1.25%) developed clinical heart failure. The sensitivity, specificity, positive predictive value, and negative predictive value of each definition of cardiotoxicity are listed in the table. Conclusions: Overall there is a low threshold for detection of clinical heart failure in breast cancer therapy. While the ASE definition has the highest combination of sensitivity, specificity, and positive predictive value, it has a sensitivity of only 62.5%. Thus, cardiologists and oncologists should collaborate to develop a definition of cardiotoxicity better correlated to clinical outcomes. [Table: see text]

2021 ◽  
Author(s):  
Nicolò Matteo Luca Battisti ◽  
Maria Sol Andres ◽  
Karla A Lee ◽  
Tharshini Ramalingam ◽  
Tamsin Nash ◽  
...  

Abstract PurposeTrastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates (left ventricular ejection fraction [LVEF] decline, congestive heart failure [CHF], cardiac death or trastuzumab discontinuation) and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice.MethodsPatients receiving curative trastuzumab between 2011-2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher’s exact test, chi-squared and logistic regression were used.Results931 patients were included in the analysis. Median age was 54 years (range 24-83) and Charlson comorbidity index 0 (0-6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1-18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%).Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline≥10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III-IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed.Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high; p=0.002). ConclusionsCardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C.K Mondo ◽  
Z.I Attia ◽  
E.D Benavente ◽  
P Friedman ◽  
P Noseworthy ◽  
...  

Abstract Background Left ventricular systolic dysfunction (LVSD) is associated with increased morbidity and mortality. Although there are effective treatments for patients with LVSD to prevent mortality, heart failure and to improve symptoms, many patients remain undetected and untreated. We have recently derived a deep learning algorithm to detect LVSD using the electrocardiogram (ECG) which could have an important screening role, particularly in limited resources settings. We evaluated the accuracy of this algorithm for the first time in Africa in a sample of subjects attending a cardiology clinic. Methods We conducted a retrospective study in a general cardiac clinic in Uganda. Consecutive patients ≥18 years who had a digital ECG and echocardiogram done within two days of each other were included. We excluded patients with pacemakers or missing information regarding left ventricular ejection fraction (LVEF). Routine 10-second, twelve-lead surface rest ECG were performed using an Edan PC ECG Model SE-1515, Hamburg, Germany. The probability of LVSD was estimated with the Mayo Clinic artificial intelligence (AI) ECG algorithm. LVEF was calculated by the MMode (Teichholz method) using a Philips Ultrasound system, HD7XE, Bothel, Washington, USA. LVSD was defined as a LVEF≤35%. We assessed the overall diagnostic performance of the algorithm to identify LVSD in this population with the area under the receiver operating curve (AUC), and estimated sensitivity, specificity and accuracy using a pre-specified cut-off based on the probability for LVSD generated by the algorithm. We conducted secondary analyses using different LVEF cutoff values. Results We included 634 subjects, 32% (200) of whom had hypertension and 12% (77) clinical heart failure. Mean age was 57±18.8 years, 58% were women and the overall prevalence of LVSD was 4%. The AI-ECG had an AUC of 0.866 (see figure below), sensitivity 73.08%, specificity 91.10%, negative predictive value 98.75%, positive predictive value 26.03% and an accuracy of 90.96% using the original threshold. Using the optimal cutoff based on the AUCs, the sensitivity was 80.77% and specificity was 81.05% with a negative predictive value of 98.99%. The ROC for the detection of LVEF of 40% or below was 0.821. Conclusion The Mayo AI-ECG algorithm demonstrated good accuracy, sensitivity and specificity to detect LVSD in patients seen in a clinical setting in Uganda. This tool may facilitate the identification of people at a high risk for LVSD in settings with low resources. ROC Funding Acknowledgement Type of funding source: None


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12529-e12529
Author(s):  
Priyanka Parajuli ◽  
Manjari Rani Regmi ◽  
Ruby Maini ◽  
Odalys Estefania Lara Garcia ◽  
Nitin Tandan ◽  
...  

e12529 Background: Breast cancer is the most common cancer diagnosed in women. Cardiovascular diseases (CVD), alternatively, is the leading cause of mortality in women worldwide. Adjuvant endocrine therapy including AI and SERM is offered to almost 75% of patients with estrogen receptor–positive (ER+) disease and potentially raises concerns for negative effects in cardiovascular health. Our study aims to evaluate cardiac events including acute coronary syndrome (ACS) and heart failure requiring hospitalization (HF) in post-menopausal patients treated with AI and SERM. Methods: An institutional database of 478 patients with histologically confirmed hormone receptor positive breast cancer diagnosed between 01/01/2014 to 12/31/2017 was reviewed after IRB approval. Development of ACS and heart failure requiring hospitalization upon initiating AI or SERM was considered an adverse cardiac event. Statistical analysis was performed with SAS v9.4. software. Chi Square (or Fisher’s Exact test) was used to test associations between various medication and cardiac events. Student’s T-test (or non-parametric equivalent when violations occurred) was used to assess if there was a difference in delta between those on and those not on medication categories. All significance was assumed at the p < 0.05 level. Results: Of 478 patients who met the inclusion criteria, 336 (70%) patients were postmenopausal. Of the 336 patients, 55% (n = 185) and 22% (n = 77) were offered therapy with AI and SERM, respectively. 6.49 % (n = 12) developed cardiac event with AI compared to 7.10 % (n = 13) who were not on AI therapy, (p = 0.814). Similarly, 6.49 % (n = 5) developed cardiac event with SERM compared to 6.87 % (n = 20) who were not on SERM therapy, (p = 0.9064). Moreover, an interesting finding in patients treated with SERM therapy compared to those not on SERM therapy was the delta of left ventricular ejection fraction (LVEF). Median LVEF of 3.5% (0 to 21%) was noted in patients treated with SERM compared to a median LVEF of 5% (0 to 55%) in patients who were not treated with SERM, p = 0.048. Conclusions: Our findings revealed AI and SERM therapy did not increase adverse cardiac events in our patient cohort. Cardiac safety of the patients is less likely to be compromised with AI and SERM therapy and therefore, should be initiated early in the course of treatment for better patient outcome. Furthermore, since SERM therapy can possibly have an effect in the LVEF of patients, a frequent evaluation LVEF is warranted to prevent any unwarranted complications.


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 8 (6) ◽  
pp. 85
Author(s):  
Cristina Lopez ◽  
Jose Luis Holgado ◽  
Raquel Cortes ◽  
Inma Sauri ◽  
Antonio Fernandez ◽  
...  

Artificial Intelligence is creating a paradigm shift in health care, with phenotyping patients through clustering techniques being one of the areas of interest. Objective: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), by using available data from Electronic Health Records (EHR). Subjects and methods: 2854 subjects over 25 years old with a diagnosis of HF and LVEF, measured by echocardiography, were selected to develop an algorithm to predict patients with reduced EF using supervised analysis. The performance of the developed algorithm was tested in heart failure patients from Primary Care. To select the most influentual variables, the LASSO algorithm setting was used, and to tackle the issue of one class exceeding the other one by a large amount, we used the Synthetic Minority Oversampling Technique (SMOTE). Finally, Random Forest (RF) and XGBoost models were constructed. Results: The full XGBoost model obtained the maximum accuracy, a high negative predictive value, and the highest positive predictive value. Gender, age, unstable angina, atrial fibrillation and acute myocardial infarct are the variables that most influence EF value. Applied in the EHR dataset, with a total of 25,594 patients with an ICD-code of HF and no regular follow-up in cardiology clinics, 6170 (21.1%) were identified as pertaining to the reduced EF group. Conclusion: The obtained algorithm was able to identify a number of HF patients with reduced ejection fraction, who could benefit from a protocol with a strong possibility of success. Furthermore, the methodology can be used for studies using data extracted from the Electronic Health Records.


Author(s):  
Jayanti Venkata Balasubramaniyan ◽  
Ashutosh Prasad Tripathi ◽  
J. S. Satyanarayana Murthy

Background: Mitral annular plane systolic excursion (MAPSE) has been proposed as a parameter for assessing left ventricular function. The assessment of LVF has major diagnostic and prognostic implications in patients with cardiovascular diseases. LVF is measured by Left Ventricular Ejection Fraction, however the accuracy of LVEF estimation by two dimensional echocardiography is limited especially in patients with poor image quality. Mitral annular plane systolic excursion (MAPSE) measurement predicts left ventricular function even in conditions with suboptimal echo window. Objective: To assess the correlation of MAPSE derived LVEF with LVEF measured by Modified Simpson’s method. Methods: This is a cross sectional study which included 279 patients admitted at our tertiary care hospital from December 2019 to March 2020 and the patients were divided in two groups. Group A – Patients with LVEF>= 50% and Group B – Patients with LVEF<50%. All patients underwent 2D echocardiographic examination using Modified Simpsons’ method and MAPSE measurement. The VIVID E9, VIVID T8, VIVID E95 and PHILIPS echocardiography machine was used for the non-invasive measurements. MAPSE was recorded at medial and lateral mitral annuli in the apical four-chamber approach. Results: On analysis, a cut off value for average MAPSE-S (medial mitral annuli) was 8.5 was obtained, denoting preserved LV function with sensitivity of 81.7%, specificity of 84.9%, positive predictive value of 91.6% and negative predictive value of 84.9%. The AUC for MAPSE-S was 0.822. Similarly, the cut off value of average MAPSE-L (lateral mitral annuli) was 7.5 denoting impaired LV functions with an AUC of 0.826, sensitivity of 82.8%, specificity of 72.0%, positive predictive value of 85.6% and negative predictive value of 72.0%. The AUC of 82.6% was observed for MAPSE-L. Conclusion: MAPSE reflects longitudinal myocardial shortening. MAPSE is a rapid and sensitive echocardiographic parameter for assessing normal LV function and global LV systolic dysfunction.


2015 ◽  
Vol 37 (1) ◽  
pp. 53-57 ◽  
Author(s):  
Y Urun ◽  
G Utkan ◽  
B Yalcin ◽  
H Akbulut ◽  
H Onur ◽  
...  

Aim: Identification of patient with increased risk of cardiotoxicity would allow not only prevention and early diagnosis of chemotherapy related cardiotoxicity but also administration of optimal dose and duration of chemotherapy. Materials and methods: Fiftytwo women with HER2+ breast cancer treated with trastuzumab were included in this study. Patients were prospectively followed with routine cardiac evaluation. Before and after administration of trastuzumab blood samples for NT-proBNP were also taken. Results: The median age was 48.5 year (range: 26–74). Hypertension and obesity were two most common co-morbidities. The median duration application of trastuzumab was 52 weeks. During median 14.5 (3–33) months follow-up cardiac adverse events occurred in 5 (9.6%) patients and 2 out of 5 was grade III–IV heart failure. Both patients had preserved left ventricular ejection fraction and no symptom of heart failure before trastuzumab but older than 65 years old and had diabetes mellitus and obesity. High level of NT-proBNP (> 300 ng/ml) was observed in both patients and heart failure recovery was not observed. There was statistically significant difference regarding body mass index (p = 0.004) and diabetes mellitus (p = 0.002) between patients with and without cardiotoxicity. Conclusion: Although, cardiac biomarkers still cannot replace routine cardiac monitoring, natriuretic peptides may provide additional tool for detection of patients with high risk of cardiotoxicity and early detection of cardiotoxicity.


Author(s):  
Gary L Murray ◽  
Joseph Colombo

Objective: To review our studies of the ease and importance of Parasympathetic and Sympathetic (P&S) measures in managing cardiovascular patients. Background: The autonomic nervous system is responsible for the development or progression of Hypertension (HTN), orthostasis, Coronary Disease (CAD), Congestive Heart Failure (CHF) and arrhythmias. Finally, new technology provides us with rapid, accurate P and S measures critically needed to manage these patients much more successfully. Methods: Using the ANX 3.0 autonomic monitor, P&S activity was recorded in 4 studies: 163 heart failure patients in total, mean follow-up (f/u) 12-24.5 months; 109 orthostasis patients, f/u 2.28 years and 483 patients with risk factors or known HTN, CAD or CHF, f/u 4.92 yrs. All were on guideline-driven therapy. Results: 59% of CHF patients had dangerously high Sympathovagal Balance (SB) or Cardiac Autonomic Neuropathy (CAN) and Ranolazine markedly improved 90% of these, improved left ventricular ejection fraction in 70% of patients on average 11.3 units, and reduced Major Adverse Cardiac Event (MACE) [Acute Coronary Syndromes (ACS), death, acute CHF, Ventricular Tachycardia/Ventricular Fibrillation (VT/VF)] 40%. 66% of orthostatic patients corrected with (r) Alpha Lipoic Acid ([r]ALA); non-responders had the lowest S-tone. In the 483 patient study, SB>2.5 best predicted MACE when compared to nuclear stress and echocardiography (sensitivity 0.59 or 7.03 [CI (Confidence Interval) 4.59-10.78], specificity 0.83, positive predictive value 0.64 and negative predictive value 0.80). Conclusion: Parasympathetic and sympathetic measures significantly improve care of cardiovascular patients.


Cardiology ◽  
2020 ◽  
Vol 145 (6) ◽  
pp. 350-355
Author(s):  
Nili Schamroth Pravda ◽  
Shaul Lev ◽  
Osnat Itzhaki Ben Zadok ◽  
Ran Kornowski ◽  
Zaza Iakobishvili

Introduction: Patients undergoing chemotherapy are extremely vulnerable to cardiotoxicity. Early detection of cardiac dysfunction is of vital importance to optimize the management of these patients. Objective: The aim of this study was to test the effectiveness of non-invasive hemodynamic whole-body bioimpedance (WBI) technology as a modality to detect heart failure in patients undergoing chemotherapy treatment. Methods: This retrospective observational trial included 84 patients treated at the cardio-oncology outpatient clinic of the Rabin Medical Center. Clinical assessments were performed including biomarker testing and measurement of hemodynamic and volume status parameters as measured by WBI. Results: We included 84 patients with a median age of 64.8 years, and 40.5% were males. Clinical heart failure was detected in 43% of the whole group. Patients were divided into two groups according to baseline NT-proBNP levels with a cut-off of 900 pg/mL. Left ventricular ejection fraction did not differ between the groups. Those with NT-proBNP >900 pg/mL had lower levels of stroke index, cardiac index, and Granov-Goor index (GGI; 25.9 vs. 34.0, 2.0 vs. 2.3, 8.3 vs. 11.4, respectively, with p < 0.001 for all comparisons). The optimal cut-off value for the GGI to detect NT-proBNP >900 pg/mL was 8.3. The area under the curve of a GGI cut-off <8.3 to detect NT-proBNP >900 pg/mL was 0.81 (positive predictive value 95% and negative predictive value 72%), with a 51% sensitivity and 98% specificity. Conclusion: GGI, a parameter measured by WBI, can reliably correlate to biomarker evidence of heart failure in patients after chemotherapy. Its use as a screening tool for cardiotoxicity in patients with ongoing anticancer therapy is promising.


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