Multiple-gated Acquisition Scan Research Articles

Does cardiac imaging surveillance strategy influence outcomes in patients with early breast cancer?

Many patients with breast cancer receive therapies with the potential to cause cardiotoxicity. Echocardiography and multiple-gated acquisition (MUGA) scans are the most used modalities to assess cardiac function during treatment in high-risk patients; however, the optimal imaging strategy and the impact on outcome are unknown. Consecutive patients with stage 0-3 breast cancer undergoing pre-treatment echocardiography or MUGA were identified from a tertiary care cancer center from 2010-2019. Demographics, medical history, imaging data and clinical events were collected from hospital charts and administrative databases. The primary outcome is a composite of all-cause death or heart failure event. Clinical and imaging predictors of outcome were evaluated on univariable and multivariable analyses. 1028 patients underwent pre-treatment MUGA and 1032 underwent echocardiography. The groups were well matched for most clinical characteristics except patients undergoing MUGA were younger, had more stage 3 breast cancer and more HER2 over-expressing and triple negative cases. Routine follow-up cardiac imaging scan was obtained in 39.3% of patients with MUGA and 38.0% with echocardiography. During a median follow-up of 2448 (1489, 3160) days, there were 194 deaths, including 7 cardiovascular deaths, and 28 heart failure events with no difference in events between the MUGA and echocardiography groups. There were no imaging predictors of the primary composite outcome or cardiac events. Patients without follow-up imaging had similar adjusted risk for the composite outcome compared to those with imaging follow-up, hazard ratio 0.8 (95% confidence interval 0.5,1.3), p=0.457. The selection of pretreatment echocardiography or MUGA did not influence the risk of death or heart failure in patients with early breast cancer. Many patients did not have any follow-up cardiac imaging and did not suffer worse outcomes. Cardiovascular deaths and heart failure event rates were low and the value of long-term cardiac imaging surveillance should be further evaluated.

Cardiac function of long-responders to dual anti-HER2 antibodies amongst patients with HER2 positive advanced breast cancer.

1043 Background: Dual anti-HER2 antibodies pertuzumab (P) and trastuzumab (T) in combination with taxane (D), followed by PT maintenance, is the standard first line treatment for HER2 positive advanced breast cancer (HER2+ ABC). Treatment associated cardiotoxicity necessitates regular cardiac function surveillance, which is a burden particularly for treatment long-responders. Data for cardiac safety of prolonged P+T exposure is scarce. We investigate the real-world impact on cardiac function in long-responders to treatment with dual anti-HER2 antibodies. Methods: We identified consecutive patients with HER2+ ABC who received the CLEOPATRA regimen (PT-D) between Jan 2014 and Dec 2020 from an institutional cancer registry. All patients had pre-treatment multiple-gated acquisition (MUGA) scan or echocardiogram, and subsequently at 3-monthly intervals until end of treatment to monitor left ventricular ejection fraction (LVEF). Patients on treatment for ≥36 months were considered long-responders. The Wilcoxon signed-rank test was used to assess any significant difference in LVEF at various landmark time-points in comparison to their pretreatment baseline. Results: 101 women with HER2+ ABC were eligible for analysis. Median age at treatment was 62 (IQR, 56.0-69.0). The median duration of treatment was 17.3 months (IQR, 9.0-31.3). 22.8% of patients were long-responders, who received a median of 67 cycles of treatment (IQR, 58-88). Compared to baseline, median LVEF was significantly decreased at 6m (median, 66% vs 69%, p=0.02), however there were no significant differences for any of the subsequent time-points up to 84 m. All of the larger LVEF drop (≥10% from baseline) occurred by the first 24 months, representing 4.7% of the overall measurements. Risk factors present for patients experienced treatment suspension (n=3) included previous exposures to anthracycline and left sided radiotherapy. Conclusions: In patients with HER2+ ABC who were long-responders to first-line PT-D, prolonged exposure to dual anti-HER2 antibodies was not associated with significant cardiotoxicity. It is safe to de-escalate the cardiac surveillance for this population. [Table: see text]

Abstract PS10-58: Cost effectiveness of routine cardiac imaging during adjuvant trastuzumab in HER2-positive breast cancer

Abstract Background: Guidelines recommend patients treated with trastuzumab (TRA) undergo a multiple gated-acquisition (MUGA) scan or echocardiogram (ECHO) at baseline and every 3 months thereafter. In this retrospective study, we evaluated the incidence of clinically significant cardiotoxicity and analyzed cost effectiveness of routine cardiac imaging during adjuvant TRA. Methods: HER2-positive breast cancer patients treated with adjuvant TRA between 2015 and 2019 were investigated. Information regarding comorbidities, clinical diagnosis of cardiotoxicity, and alterations in therapy were collected. ECHO and MUGA scans were reviewed to monitor trends in ejection fractions (EF). Data was analyzed via the FREQ procedure. We defined clinically significant cardiotoxicity as holding or discontinuing TRA regimen. Results: We found 108 patients. Median age was 57 years (interquartile range (IQR) of 47-68 years); 86% Caucasian and 12% African American. 3% had preexisting heart failure, 43% hypertension, 14% diabetes, 4% coronary artery diseases, 32% hyperlipidemia, 2% chronic kidney disease, 6% stroke, and 38% were smokers. No patients received anthracycline containing regimens. 30 patients (27.7%) had EF drop >10% from baseline. Six patients (5.5%) were identified with clinically significant cardiotoxicity; 4 (3.7%) had EF < 50% and 3 of those 4 were symptomatic (2.7% of total). Median time from initiation to decline in EF > 10% was 6 months (IQR of 4.5-7.5 months). Conclusions: Current practice for TRA cardiotoxicity monitoring consists of cardiac imaging every 3 months. The average cost for a MUGA scan and ECHO is approximately $3700 and $2500, respectively. We determined that clinically significant cardiotoxicity, occurred in 5.5% of the patients approximately 6 months into treatment. With TRA causing reversible cardiotoxicity and 2.7% of the patients being symptomatic, cardiac imaging every 3 months appears excessive, especially in patients without comorbidities. Baseline cardiac imaging with repeat assessment in 6 months appears sufficient in non-anthracycline containing regimen. This strategy allows cost savings of approximately $6000 per patient. Characteristics of patients with clinical cardiotoxicityClinically Significant Cardiotoxicity (N=6)StageChemotherapy RegimenHeart Failure SymptomsEF drop below 50%Initiation to Drop in EF >10% (months)Discontinuation to Recovery in EF (months)1IIBTCHPNoNo3.21.12IATCHPYesYes6.12.83IIATCHNoNo9.31.34IBTCHYesYes6.54.85IIATHYesYes6.12.66IIATCHPNoYes6.31.2 Citation Format: Vineeth Tatineni, Daniel Redle, Daljeet Singh, Arifa Abid, Sameer Mahesh. Cost effectiveness of routine cardiac imaging during adjuvant trastuzumab in HER2-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-58.

Cardioprotective Approaches to the Management of Patients with Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Do We Need Increased Surveillance in Elderly Women on Trastuzumab?

Cardiotoxic effects in patients with breast cancer may present as asymptomatic left ventricular (LV) dysfunction or symptomatic LV decline, which can progress to overt heart failure (HF). Trastuzumab is a monoclonal antibody against human epidermal growth factor receptor (HER)2 and is a recommended targeted treatment for patients with overexpression of this receptor. However, the use of trastuzumab is associated with cardiotoxicity, manifested as LV dysfunction or HF. This review addresses the key issues related to individualised cardioprotection and surveillance, especially in elderly patients with HER2-positive breast cancer, based on the current cardio-oncology literature. Cardiac imaging techniques (e.g., echocardiography or multiple-gated acquisition scan) and biomarkers (e.g., cardiac troponins) that play a crucial role in the detection and monitoring of cardiotoxicity related to systemic therapies for breast cancer are briefly described. This review presents cardioprotective approaches, including interruption or termination of trastuzumab therapy, and treatment with an angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, or beta-blocker, which have been recommended for the reduction of cardiac adverse effects. Since the data relevant to cardiotoxicity of trastuzumab among real-world older women with breast cancer and cardiovascular diseases are still limited, this article focusses on improvements to the cardiac safety of trastuzumab-based regimens. In particular, this review emphasises the importance of intense surveillance in the elderly female population.

Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial

HER2-targeted treatments have improved outcomes in patients with HER2-positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings; however, some patients remain at risk of relapse or death for many years after treatment of early-stage disease. Therefore, new strategies are needed. We did a phase 3 trial to assess a neoadjuvant regimen for HER2-positive breast cancer that replaces traditional systemic chemotherapy with targeted treatment. We did a randomised, open-label phase 3 KRISTINE trial in 68 Translational Research In Oncology centres (hospitals and specialty cancer centres in Asia, Europe, USA, and Canada). Eligible participants were aged 18 years or older with centrally confirmed HER2-positive stage II-III operable breast cancer (>2 cm tumour size), an Eastern Cooperative Oncology Group performance status of 0-1, and a baseline left ventricular ejection fraction of at least 55% (by echocardiogram or multiple-gated acquisition scan). We randomly assigned participants (1:1) to receive either trastuzumab emtansine plus pertuzumab or docetaxel, carboplatin, and trastuzumab plus pertuzumab. We did the randomisation via an interactive response system under a permuted block randomisation scheme (block size of four), stratified by hormone receptor status, stage at diagnosis, and geographical location. Patients received six cycles (every 3 weeks) of neoadjuvant trastuzumab emtansine plus pertuzumab (trastuzumab emtansine 3·6 mg/kg; pertuzumab 840 mg loading dose, 420 mg maintenance doses) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (docetaxel 75 mg/m2; carboplatin area under the concentration-time curve 6 mg/mL × min; trastuzumab 8 mg/kg loading dose, 6 mg/kg maintenance doses) plus pertuzumab [same dosing as in the other group]). All treatments were administered intravenously. The primary objective was to compare the number of patients who achieved a pathological complete response (ypT0/is, ypN0), between groups in the intention-to-treat population (two-sided assessment), based on local evaluation of tumour samples taken at breast cancer surgery done between 14 days and 6 weeks after completion of neoadjuvant therapy. Safety was analysed in patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02131064, and follow-up of the adjuvant phase is ongoing. Between June 25, 2014, and June 15, 2015, we randomly assigned 444 patients to neoadjuvant treatment with trastuzumab emtansine plus pertuzumab (n=223) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (n=221). A pathological complete response was achieved by 99 (44·4%) of 223 patients in the trastuzumab emtansine plus pertuzumab group and 123 (55·7%) of 221 patients in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group (absolute difference -11·3 percentage points, 95% CI -20·5 to -2·0; p=0·016). During neoadjuvant treatment, compared with patients receiving docetaxel, carboplatin, and trastuzumab plus pertuzumab, fewer patients receiving trastuzumab emtansine plus pertuzumab had a grade 3-4 adverse event (29 [13%] of 223 vs 141 [64%] of 219) or a serious adverse event (11 [5%] of 223 vs 63 [29%] of 219). The most common grade 3-4 adverse events in the trastuzumab emtansine plus pertuzumab group were decreased platelet count (three [1%] of 223 patients vs 11 [5%] of 219 with docetaxel, carboplatin, and trastuzumab plus pertuzumab), fatigue (three [1%] vs seven [3%]), alanine aminotransferase increase (three [1%] vs four [2%]), and hypokalaemia (three [1%] vs five [2%]). The most common grade 3-4 adverse events in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group were neutropenia (55 [25%] of 219 vs one [<1%] of 223 with trastuzumab emtansine plus pertuzumab), diarrhoea (33 [15%] vs 2 [<1%]), and febrile neutropenia (33 [15%] vs 0). No deaths were reported during neoadjuvant treatment. Traditional neoadjuvant systemic chemotherapy plus dual HER2-targeted blockade (docetaxel, carboplatin, and trastuzumab plus pertuzumab) resulted in significantly more patients achieving a pathological complete response than HER2-targeted chemotherapy plus HER2-targeted blockade (trastuzumab emtansine plus pertuzumab); however, numerically more grade 3-4 and serious adverse events occurred in the chemotherapy plus trastuzumab and pertuzumab group. Further efforts to improve the efficacy of chemotherapy without imparting more toxicity are warranted. F Hoffmann-La Roche and Genentech.

Cardiotoxicity of trastuzumab in patients with HER2-positive gastric cancer

Trastuzumab-induced cardiotoxicity (TIC) is the primary adverse event that limits the use of trastuzumab in HER2-positive breast cancer patients. However, the incidence and risk factors of TIC in HER2-positive gastric cancer are not known. Therefore, we evaluated the incidence and predictive factors of TIC in gastric cancer patients treated with trastuzumab in clinical practice. We reviewed cardiac dysfunction in HER2-positive gastric cancer patients between December 2005 and April 2015 in a prospectively-collected database that included prospective clinical trials at Yonsei Cancer Center, Republic of Korea. TIC was defined as an absolute decline in left ventricular ejection fraction (LVEF) of at least 10 percentage points from the baseline to a value less than 55%, as identified by a multiple-gated acquisition scan or an echocardiogram. Among the 115 patients, 70 patients (60.9%) received trastuzumab combined with chemotherapy, and 45 patients (39.1%) received chemotherapy alone as a first-line therapy. Symptomatic heart failure was not observed in either group, but a significant asymptomatic drop in LVEF was noted in five (7.1%) of the trastuzumab combined-group patients and in one (2.2%) chemotherapy-only group patient [hazard ratio (HR), 3.47; 95% confidence interval (CI), 0.40–29.8; P=0.257]. TIC was observed more frequently in elderly patients than in younger patients (HR, per age in year, 1.16; 95% CI, 1.02–1.31; P=0.019). Similar to prior observations in breast cancer, TIC in gastric cancer patients is not frequent or reversible. However, the asymptomatic drop in LVEF should be monitored continually in HER2-positive gastric cancer patients treated with trastuzumab, especially in elderly patients.

Comparison of two care schedules for monitoring of cardiotoxicity in patients receiving trastuzumab-based therapy for early-stage breast cancer: study protocol for a randomized controlled non-inferiority trial

Background: Cardiotoxicity is a toxic side effect of trastuzumab-based therapy. Current guidelines for cardiac monitoring (every 3 months) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving trastuzumab-based therapy have been dictated by the increased risk of cardiotoxicity observed in clinical trials. However, the majority of these patients are at a low risk of cardiac complications and may not require such frequent monitoring. Objective: This randomized controlled clinical trial will be performed to demonstrate that cardiac monitoring (echocardiography (ECHO)/multiple gated acquisition scan (MUGA) every 4 months is not inferior to every 3 months in the detection of cardiac dysfunction (decrease in left ventricular ejection fraction (LVEF)) in patients receiving trastuzumab-based therapy for early-stage HER2-positive breast cancer. Study period: From June 2016 to December 2018. Study location: The Ottawa Hospital Cancer Centre. Principal investigator: Dr. Olexiy Aseyev and Dr. Susan Dent at Department of Medicine, Division of Medical Oncology, The Ottawa Hospital, University of Ottawa, Canada. Study design: A prospective, single-center, randomized controlled non-inferiority clinical trial. Study population: A total of 200 patients with early-stage HER2-positive breast cancer (n = 100 in each group) receiving trastuzumab-based therapy will be enrolled. Inclusion criteria: Patients with histologically confirmed early-stage HER2-positive breast cancer receiving trastuzumab-based therapy, who are over 18 years of age, have a normal baseline LVEF (> 53%) and are able to provide verbal consent will be included in this study. Exclusion criteria: Patients will be excluded if they have any contraindication to transthoracic echocardiography or MUGA. Randomization: Eligible and consented patients will be randomized using a permuted block design to receive cardiac evaluation (by either transthoracic echocardiography or MUGA) every 3 months, or every 4 months while on treatment, 100 patients for each type of cardiac evaluation. Primary outcome measure: The rate of changes in LVEF diagnosed by ECHO or MUGA throughout trastuzumab-based therapy in both groups. Secondary outcome measures: Rates of trastuzumab delay/discontinuation, referral to cardiology, rate of cardiac events. Human specimen collection: Not involved. Ethical approval: This study was approved by the Ottawa Health Science Network Research Ethics Board. Trial registration: ClinicalTrials.gov identifier: NCT02696707 on February 18, 2016. Study status: This study is currently recruiting participants. Study enrolment is expected to be completed by July 2018 and analysis of primary outcome measure will be completed by October 2018 and the study will be completed by December 2018. Discussion: This study will present data on the cardiac safety of less frequent cardiac monitoring in patients with early-stage HER2-positive breast cancer. Future trials will explore cardiac monitoring strategies using composite data including baseline cardiac risk factors, baseline cardiac imaging and cardiac biomarkers. Health care economics will be explored.

Accuracy of left ventricular ejection fraction by contemporary multiple gated acquisition scanning in patients with cancer: comparison with cardiovascular magnetic resonance

BackgroundMultiple gated acquisition scanning (MUGA) is a common imaging modality for baseline and serial assessment of left ventricular ejection fraction (LVEF) for cardiotoxicity risk assessment prior to, surveillance during, and surveillance after administration of potentially cardiotoxic cancer treatment. The objective of this study was to compare the accuracy of left ventricular ejection fractions (LVEF) obtained by contemporary clinical multiple gated acquisition scans (MUGA) with reference LVEFs from cardiovascular magnetic resonance (CMR) in consecutive patients with cancer.MethodsIn a cross-sectional study, we compared MUGA clinical and CMR reference LVEFs in 75 patients with cancer who had both studies within 30 days. Misclassification was assessed using the two most common thresholds of LVEF used in cardiotoxicity clinical studies and practice: 50 and 55%.ResultsCompared to CMR reference LVEFs, MUGA clinical LVEFs were only lower by a mean of 1.5% (48.5% vs. 50.0%, p = 0.17). However, the limits of agreement between MUGA clinical and CMR reference LVEFs were wide at −19.4 to 16.5%. At LVEF thresholds of 50 and 55%, there was misclassification of 35 and 20% of cancer patients, respectively.ConclusionsMUGA clinical LVEFs are only modestly accurate when compared with CMR reference LVEFs. These data have significant implications on clinical research and patient care of a population with, or at risk for, cardiotoxicity.

MUGA image artefacts caused by metallic injection ports in breast reconstruction tissue expanders: a report of two breast cancer patients

Expander-based breast reconstruction is a popular form of post-mastectomy reconstruction and involves the temporary subcutaneous implantation of breast tissue expanders that require periodic, incremental inflation with sterile saline by injection until the desired amount of tissue is developed. One type of tissue expander injection port system currently on the market is made of titanium and rare-earth magnets that enhance injection accuracy. These highly dense metallic materials, however, can cause attenuation artefacts on multiple gated acquisition cardiac studies. In this report, we present the cases of two breast cancer patients with artefacts on multiple gated acquisition scans, characteristic of these tissue breast expanders.

RADIONUCLIDE METHODS IN THE DETECTION AND FORECAST OF ANTHRACYCLINE-INDUCED CARDIOTOXICITY IN BREAST CANCER PATIENTS

Purpose: To compare the possibility of using multiple-gated acquisition scan (MUGA) and 99mTc-MIBI GATE SPECT for evaluation and forecast of anthracycline–induced cardiotoxicity in breast cancer patients. material and methods. The study included 67 women (mean age – 44 ± 4.9 years) with breast cancer without significant pathology of the cardiovascular system. For the treatment of these patients used doxorubicin in dose of 50 mg/m 2 per course in combination with various drugs. All patients were studied by MUGA (n=33) or GATE SPECT (n=34) before starting chemotherapy, at 1 hour after the first administration of doxorubicin and after the 4th course. results. After administration of doxorubicin at a dose of 50 mg/m 2 was found that 11 patients according MUGA and 14 patients according GATE SPECT had a significant (10 % or more) reduction in left ventricular ejection fraction (LVEF). Significant inhibition of systolic function in this patient group remained after the 4th course treatment. In the individual analysis of the MUGA and GATE SPECT results, registered after the administration of doxorubicin at a dose of 200 mg/m2, was revealed that the criterion of LVEF reduction (10 % or more) in response to the first dose of doxorubicin can predict the development of chronic cardiotoxicity. Conclusion. The MUGA and GATE SPECT can be applied with equal effectiveness for evaluation of acute and chronic anthracycline–induced cardiotoxicity in breast cancer patients. The decrease in LVEF (10 % or more) in response to the first dose of doxorubicin can predict the development of chronic cardiotoxicity.

Acute effects of chemoradiation on cardiac function in oesophageal cancer: a MUGA scan and echo-based study

ObjectiveTo study the acute effects of concurrent chemoradiation on global and regional cardiac contractility and correlate with radiation dose.Methods16 patients of locally advanced oesophageal squamous cell carcinoma were serially followed...

Single-Photon Emission Computed Tomography and &lt;sup&gt;99m&lt;/sup&gt;Tc-Methoxy-Isobutyl-Isonitrile in the Detection and Forecast of Cardiotoxicity of Chemotherapeutic Agents

To compare the possibility of using multiple-gated acquisition (MUGA) scan and Tc-99m MIBI gated SPECT for evaluation and forecast of anthracycline–induced cardiotoxicity. For the treatment of these patients we used doxorubicin in combination with various drugs. All patients were examined by MUGA or Gated SPECT before starting chemotherapy, at 1 hour after the first administration of doxorubicin and after the 4th course. The MUGA and Gated SPECT can be applied with equal efficiency for evaluation of acute and chronicanthracycline–induced cardiotoxicity in patients with malignant tumors. The decrease in LVEF (10% or more) in response to the first dose of doxorubicin can predict the development of chronic cardiotoxicity.

Optimizing Adherence to Adjuvant Trastuzumab Therapy: a Prospective Controlled Clinical Trial of Monitoring Cardiotoxicity

ABSTRACT Aim: Cardiotoxicity is the main reason for premature discontinuation of neo/adjuvant trastuzumab therapy. Guidelines currently recommend follow-up of left ventricular ejection fraction (LVEF) measured either by multiple gated acquisition scan (MUGA) or echocardiography (ECHO), without specifying the preferred method and an interruption of treatment if LVEF declines ≥10%. In a prospective study we assessed the separate and combined impact of MUGA, ECHO, and a comprehensive cardio-oncology team approach in detecting cardiotoxicity thus safely minimizing premature therapy discontinuation. Methods: Breast cancer patients undergoing post-anthracycline trastuzumab neo/adjuvant therapy were included. MUGA, ECHO and clinical evaluation of potential cardiotoxicity was performed at baseline, after 4, 8 and 12 months. Therapy discontinuation because of cardiotoxicity was considered not only based on LVEF decline as determined by either method alone, but after thorough assessment of both methods and clinical status by a dedicated cardio-oncology team. Results: From October 2011 to November 2013 a total of 92 patients were included, all female, median age was 53 (35-76) years. We found a significant overall correlation between MUGA-LVEF and ECHO-LVEF (Interclass correlation coefficient 0.87, 95% CI 0.81-0.91, p Conclusions: We found a significant correlation between MUGA-LVEF and ECHO-LVEF. Determination of LVEF decline by MUGA or ECHO may overestimate the incidence of clinically significant trastuzumab-induced left ventricular dysfunction. Findings of our study suggest that therapy discontinuation might be minimized by integrating both methods with a comprehensive cardio-oncology team approach in case of LVEF decline detected by the preferred routinely used method. Disclosure: All authors have declared no conflicts of interest.

Multiple-Gated Acquisition Scan With Normal Left Ventricular Ejection Fraction and LBBB

Multiple-gated blood pool angiography (MUGA) using 99mTc-UltraTag (Mallinckrodt Inc., Maryland Heights, MO) labeled RBCs was performed in a patient with B-cell lymphoma for evaluation of the left ventricular ejection fraction before starting chemotherapy. Quantitative measurements from MUGA demonstrated normal left ventricular ejection fraction. However, cine images revealed delayed contraction of the left ventricle compared with that of the right, and phase contrast images demonstrated offset of the ventricles' phases. Evaluation with ECG showed delayed depolarization of the left ventricle consistent with LBBB. Phase imaging abnormalities detected on MUGA may be overlooked. Specific patterns of phase abnormalities may direct the physicians' attention toward yet unrecognized diagnoses.

Utility Of Routine Left Ventricular Ejection Fraction (LVEF) Measurement Prior To Administration Of Anthracycline-Based Chemotherapy In Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

Anthracycline-based chemotherapy regimens are considered the gold standard for treating patients with DLBCL. Prior to administration of chemotherapy, LVEF is routinely measured, usually by multiple-gated acquisition (MUGA) scans or echocardiography, as a screening tool for detecting asymptomatic left ventricular dysfunction. LVEF screening is recommended by the National Comprehensive Cancer Network clinical practice guidelines, is endorsed by the American Heart Association and the American College of Cardiology, appears on Federal Drug Administration-approved labeling guidelines, and is often required for patients to participate in US cancer cooperative group clinical trails. However, despite these recommendations, evidence supporting the utility of LVEF measurement prior to administration of anthracycline-based chemotherapy in patients with DLBCL is lacking (Conrad, J Oncol Pract 2012).The most common chemotherapy regimen currently administered to DLBCL patients is rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients with stage III or IV DLBCL typically receive 6 to 8 cycles of R-CHOP, with cumulative doses of doxorubicin ranging from 300 - 400 mg/m2. Cumulative doses of doxorubicin greater than 400 mg/m2have been associated with an increased risk of congestive heart failure (CHF) (Von Hoff, Ann Intern Med 1979).We are performing a retrospective analysis of approximately 325 patients with DLBCL who received treatment at Virginia Mason Medical Center from 2001-2011. Our objectives include the following: (1) to determine whether LVEF was measured by echocardiogram or MUGA scan prior to administration of anthracycline-based chemotherapy, (2) to establish whether the chemotherapy treatment regimen was modified based on LVEF values, and (3) to document the incidence of CHF in patients with DLBCL who did receive anthracycline-based chemotherapy.Patients were identified through a search of the Virginia Mason Cancer Registry. Specific data currently being collected through chart review include the following: age at diagnosis; Ann Arbor lymphoma stage; type of chemotherapy given; cumulative doxorubicin dose administered (mg/m2); LVEF measurement and modality used to assess LVEF; and incidence of CHF. We are also recording the number of CHF risk factors that patients possess, including male sex, obesity, hypertension, hyperlipidemia, prior cardiac disease, diabetes mellitus, smoking history, prior chemotherapy, radiation to the chest area, and other cardio-toxic exposures. Statistical analyses will include a Fischer's exact or Chi-squared test to compare study groups and a Wilcoxon rank sum test to compare the number of CHF risk factors. A P value of less than 0.05 will be used to determine if an association is significant.In a preliminary sample of DLBCL patients (n = 50), 28 are men (56%). LVEF was measured in 40 patients (80%) prior to initiation of chemotherapy using echocardiogram (95%) and MUGA scan (5%). LVEF values were normal (55 – 75%) in 36 patients (90%), low (< 55%) in 3 patients (8%), and unknown in 1 patient (2%). Of the 36 patients with normal LVEF values, 30 received CHOP or R-CHOP regimens (83%), 2 received non-anthracycline chemotherapy (5%), 1 was treated by surgical excision alone (3%), 2 received no treatment (6%), and 1 patient's treatment was unknown (3%). Of the 3 patients with initial low screening LVEF values, none had a prior history of CHF and all received R-CHOP (100%). Three patients did have CHF prior to treatment; however, only one received CHOP therapy. Of our initial 50 patients, 31 (62%) are alive and 2 (4%) were lost to follow-up. CHF was listed as a major contributor of death in 3 patients (6%). The median number of CHF risk factors did not differ significantly between patients who did develop CHF post-treatment and those who did not (4 vs. 2, P = 0.133).Our preliminary results suggest that the decision to administer an anthracycline-based chemotherapy regimen was not directly affected by echocardiogram or MUGA scan results. If these findings are reinforced at completion of our chart review, it may challenge the existing policy of routinely screening patients with DLBCL with echocardiograms or MUGA scans prior to initiation of treatment. Disclosures:No relevant conflicts of interest to declare.

Rationale and Design of a Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of B-Type Natriuretic Peptide for the Preservation of Left Ventricular Function After Anterior Myocardial Infarction

BackgroundB-type natriuretic peptide (BNP) is a hormone with pleiotropic cardioprotective properties. Previously in our non–placebo-controlled non-blinded pilot study (BELIEVE) in human ST-segment-elevation anterior acute myocardial infarction (AMI), a 72-hour intravenous (IV) infusion of recombinant human BNP (nesiritide) at a dose of 0.006 μg kg−1 min−1 suppressed plasma aldosterone, reduced cardiac dilatation, and improved left ventricular (LV) ejection fraction (LVEF) at 1 month compared with baseline. Methods and DesignThe BELIEVE II study is a phase II, randomized, double-blind, placebo-controlled, single-center clinical trial to assess the efficacy of 72-hour IV infusion of nesiritide therapy (0.006 μg kg−1 min−1) in humans with first-time ST-segment-elevation anterior AMI and successful reperfusion, in preventing adverse LV remodeling and preserving LV function. A total of 60 patients will be randomized to placebo or nesiritide therapy. The primary efficacy end point is LV end-systolic and end-diastolic dimensions determined by multiple gated acquisition scan between placebo and nesiritide groups at 30 days; secondary end points include 30-day LVEF, diastolic function, infarct size, LV mass, and combined total mortality and heart failure hospitalization. ConclusionsThis will be the first randomized, double-blind, placebo-controlled clinical trial to assess the clinical efficacy of nesiritide in human ST-segment-elevation anterior AMI.

Role of Pre‐operative Multiple Gated Acquisition Scanning in Predicting Long‐Term Outcome in Patients Undergoing Elective Abdominal Aortic Aneurysm Repair

To determine whether resting pre-operative left ventricular ejection fraction (LVEF) estimated by multiple gated acquisition scanning (MUGA) predicts long-term survival in patients undergoing elective abdominal aortic aneurysm (AAA) repair. A retrospective study of MUGA scans which were performed to estimate pre-operative resting LVEF in 127 patients [106 (83 %) males, mean age 74 ± 7.6 years] who underwent elective AAA repair over a period of 4 years from March 2007. We compared outcomes and long-term survival between patients who had a pre-operative LVEF ≤ 40 % (Group 1, n = 60) and LVEF > 40 % (Group 2, n = 67). Overall 19 (15 %) patients died during the follow-up period (13 patients in group 1 and 6 patients in group 2). 30-day mortality was 8 %. There was no significant difference between group 1 and 2 in terms of patients' mean age or median length of hospital stay (8 days for both groups, p = 0.61). However, group 2 had more females than group 1(18 vs. 3, p = 0.001). Median survival for patients in group 2 was significantly higher than patients in group 1 (1,258 days vs. 1,000 days, p = 0.03). In a Cox regression model which included age, sex, smoking status and LVEF as covariates, only smoking status and LVEF predicted survival [Hazard ratio (HR) = 1.06, p = 0.04 and HR = 0.93, p = 0.00, respectively]. This study shows that there is a role for pre-operative MUGA scan assessment of resting LVEF in predicting long-term survival post elective AAA repair and that the lower the pre-operative LVEF the poorer the long-term outcome.

Relationship between average leucocyte telomere length and the presence or severity of idiopathic dilated cardiomyopathy in black Africans

A reduced average leucocyte telomere length is associated with ischaemic heart failure. Whether this relationship represents a cause or consequence of heart failure or is attributed to associated risk factors and coronary artery disease is uncertain. We evaluated if average leucocyte telomere length is associated with idiopathic dilated cardiomyopathy (IDC) or its severity. We compared average leucocyte telomere length in 223 patients with heart failure due to IDC and 227 healthy controls of black African ancestry. We also evaluated the relationship between average leucocyte telomere length and left ventricular ejection fraction (LVEF). LVEF was determined using echocardiography and radionuclide multiple-gated acquisition (MUGA) scan in patients with IDC. Relative leucocyte telomere length (T/S) was measured using a quantitative real-time polymerase chain reaction assay. Log T/S was negatively correlated with age in patients with IDC (P = 0.0007) and in controls (P = 0.030), and with alcohol consumption (P = 0.032) and regular smoking (P = 0.021) in patients with IDC. Log T/S did not differ between IDC and control groups either before (P = 0.11) or after (IDC = 0.071 ± 0.187, control = 0.071 ± 0.187, P = 0.99) adjustments for confounders. Log T/S was not associated with echocardiographic (P = 0.47) or MUGA (P = 0.99) LVEF or LV end-diastolic diameter (LVEDD) (P = 0.34) in patients with IDC. With adjustments for age, sex, alcohol consumption, and smoking, log T/S was similarly not associated with echocardiographic (P = 0.60) or MUGA (P = 0.91) LVEF or LVEDD (P = 0.53) in patients with IDC. Average relative leucocyte telomere length is not associated with IDC or its severity in groups of black African ancestry.

Seven-Year Follow-Up Assessment of Cardiac Function in NSABP B-31, a Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Paclitaxel (ACP) With ACP Plus Trastuzumab As Adjuvant Therapy for Patients With Node-Positive, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care. In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified. At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab. The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.

Positive spillover effects of prescribing requirements: increased cardiac testing in patients treated with trastuzumab for HER2+ metastatic breast cancer

Cardiotoxicity is a concern in patients on trastuzumab therapy, and cardiac function assessment is a recommended practice. In 2006, trastuzumab was publically subsidised for human epidermal growth factor receptor-2 early stage breast cancer with a requirement for cardiac testing prior to and during treatment. To investigate the spillover effects of this requirement on testing rates in metastatic patients treated with trastuzumab where no monitoring requirements are applied. We examined cardiac testing (echocardiography or multiple-gated acquisition scan) in 3779 women with metastatic breast cancer receiving trastuzumab between December 2001 and February 2010 and used interrupted time-series analyses to estimate changes in testing rates. The main outcome measures were the proportion of eligible patients, by quarter, receiving a cardiac function test pretreatment and during trastuzumab therapy. Only 21% of women had a cardiac function test pretreatment, and 47% were tested at some point during the first year of trastuzumab therapy. The introduction of mandatory cardiac testing for early breast cancer was associated with an immediate 8% increase (95% confidence interval, 2-14%) in pretreatment cardiac testing and an immediate 7% increase (95% confidence interval, 4-10%) in testing during therapy in metastatic patients. Testing rates during therapy increased steadily from early 2005, coinciding with the release of interim results from several trastuzumab trials reporting cardiac-safety outcomes. The introduction of mandatory cardiac testing for early stage disease spilled over to the metastatic setting. While deviation from guidelines may be warranted in some cases, this study suggests underutilisation of cardiac testing among patients treated with trastuzumab in the metastatic setting.