Herrmann, Joerg

e23081 Background: Anthracycline-induced cardiotoxicity (AIC) is a well-known phenomenon, but the true incidence is poorly defined, and definitions of AIC in the literature are variable. We performed a systematic review and meta-analysis to elucidate AIC definitions and the incidence of clinical heart failure (HF) and subclinical AIC reported in adult breast cancer and lymphoma patients after anthracycline (AC) therapy. Methods: 3,428 abstract and titles were identified via PubMed search. Inclusion criteria for full text review included minimum of 100 adult patients receiving ACs; median/mean follow up of at least 12 months; and specified evaluation of left ventricular ejection fraction. Outcomes were divided into clinical HF and subclinical AIC. Meta-analysis was performed with MedCalc software with random effects model. Results: 366 full text articles were reviewed. 24 studies, including a total of 11,065 patients, reported clinical HF findings; 21 studies, including a total of 8,098 patients, reported subclinical AIC findings. Meta-analysis showed an overall incidence of clinical HF of 3.1% (range 0 to 29%, CI 1.9 to 4.6%, I2= 93.9%); an incidence of 2.0% (CI 0.9 to 3.6%, I2 = 91.6%) in breast cancer patients receiving AC; and 4.8% in lymphoma patients receiving AC (CI 2.1 to 8.6%, I2 = 93.6%). Subclinical AIC was seen in 13.8% overall patients (range 2 to 45%, CI 10.4 to 17.7%, I2= 95.3%); 10.3% of breast cancer patients (CI 7.0 to 14.3%, I2= 95.0%); and 19.8% of lymphoma patients (CI 12.3 to 28.6%, I2= 94.4%). Incidence of HF correlated with increasing age (r = 0.51, p = 0.06) and cumulative dose (r = 0.51 , p = 0.19). There was notable heterogeneity of AIC definitions between studies (Table). Conclusions: Cardiotoxicity is not uncommon among patients who receive AC, particularly at doses given for the treatment of lymphoma. However, there was considerable heterogeneity in HF incidences. More uniform criteria and precise estimates are needed to inform clinical practice and trials. [Table: see text]

3033 Background: QTc interval prolongation can lead to life-threatening complications such as torsade de pointes (TdP), ventricular tachycardia (VT), and sudden cardiac death (SCD). It can occur with various tyrosine kinase inhibitors (TKIs) but comparative analyses on the incidence and complication rates are scarce. We thus conducted a comprehensive analysis of TKI use and QTc prolongation in clinical practice. Methods: We retrospectively reviewed the electronic medical records of all cancer patients who were treated with TKI between 01/2005 and 12/2018 at our institution. QTc prolongation was defined as a QTc ≥ 450 ms or 460 ms among male or female patients, respectively. For each type of TKIs, we determined the administration rate and incidence of QTc interval prolongation. We also studied the frequency of QTc prolongation ≥ 500 ms, rate of increase of the QTc interval by ≥ 60 ms, and the development of complications (VT, TdP and SCD). Results: In the present study, we analyzed the data of 685 cancer patients (431 male and 254 female), including 299 patients with RCC, 188 with chronic leukemia, 55 with acute leukemia, 65 with thyroid cancer, 48 with lung cancer and 39 with GIST. These patients received 902 TKI administrations and QTc prolongation was reported in 1/3 of these (289 administrations). The highest frequency was seen with imatinib, nilotinib and dasatinib (30, 40 and 50%). Among cases of QTc prolongation, a QTc interval ≥ 500 ms was documented in 53 (18.3%) and QTc progression ≥ 60 ms in 72 (25%). Complications were found in 14 cases (5%) including VT in 9, TdP in 2 and SCD in 3 administrations. Conclusions: The current findings suggest that TKI therapy leads to QTc prolongation in 1/3 of patients on average and most commonly with the Bcr-Abl TKIs, imatinib, nilotinib and dasatinib. While SCD is rare (1%) it can still evolve and in 5% of all QTc prolongations with TKIs are potentially life-threatening. These data support recommendations for serial ECGs in cancer patients undergoing TKI therapy. [Table: see text]

Background Patients with symptomatic severe aortic stenosis and a history of chest radiation therapy represent a complex and challenging cohort. It is unknown how transcatheter aortic valve replacement ( TAVR ) compares with surgical aortic valve replacement in this group of patients, which was the objective of this study. Methods and Results We retrospectively reviewed all patients with severe aortic stenosis who underwent either TAVR or surgical aortic valve replacement at our institution with a history of mediastinal radiation (n=55 per group). End points were echocardiographic and clinical outcomes in‐hospital, at 30 days, and at 1 year. Inverse propensity weighting analysis was used to account for intergroup baseline differences. TAVR patients had a higher STS score than surgical aortic valve replacement patients (5.1% [3.2, 7.7] versus 1.6% [0.8, 2.6], P <0.001) and more often ( P <0.01 for all) a history of atrial fibrillation (45.5% versus 12.7%), chronic lung disease (47.3% versus 7.3%), peripheral arterial disease (38.2% versus 7.3%), heart failure (58.2% versus 18.2%), and pacemaker therapy (23.6% versus 1.8%). Postoperative atrial fibrillation was less frequent (1.8% versus 27.3%; P <0.001) and hospital stay was shorter in TAVR patients (4.0 [2.0, 5.0] versus 6.0 [5.0, 8.0] days; P <0.001). The ratio of observed‐to‐expected 30‐day mortality was lower after TAVR as was 30‐day mortality in inverse propensity weighting–adjusted Kaplan–Meier analyses. Conclusions In patients with severe aortic stenosis and a history of chest radiation therapy, TAVR performs better than predicted along with less adjusted 30‐day all‐cause mortality, postoperative atrial fibrillation, and shorter hospitalization compared with surgical aortic valve replacement. These data support further studies on the preferred role of TAVR in this unique patient population.

Background Trastuzumab is life‐extending therapy for breast cancer patients overexpressing the human epidermal growth factor receptor 2 ( HER 2+), but has known cardiotoxic risk. We sought to determine if trastuzumab can be administered to patients with reduced baseline cardiac function at no higher cardiotoxicity risk than in those with normal cardiac function at baseline. Methods and Results We performed a retrospective study of women treated with trastuzumab for human epidermal growth factor receptor 2 breast cancer at Mayo Clinic Rochester between January 1, 2000 and August 31, 2015 with pre‐ and on‐therapy echocardiograms available for review. A left ventricular ejection fraction (LVEF) <53% was considered abnormal, and a ≥10% decline in LVEF as evidence of cardiotoxicity based on the criteria of the American Society of Echocardiography. A total of 428 women were identified; 408 had a normal cardiac function ( LVEF 63.4±5%) and 20 had an impaired cardiac function ( LVEF 45.4±7%) before trastuzumab. Seven women (35%) with reduced LVEF at baseline had a ≥10% reduction in LVEF , compared with 179 (43.9%) of those with normal LVEF before trastuzumab initiation ( P = NS ). Symptomatic heart failure developed more often in patients with reduced versus normal baseline LVEF (25% versus 4.2%, P <0.05). After adjusting for patient age and breast cancer disease stage, survival rates over 5 years from time of diagnosis were found to be lower for patients with reduced baseline LVEF compared with patients with normal baseline LVEF ( P <0.001); the adjusted proportion of patients surviving at 5 years for those with low LVEF at baseline was 79% and for those with normal LVEF was 93%. Conclusions Women undergoing trastuzumab therapy for breast cancer with impaired baseline cardiac function experience no higher risk of LVEF decline, but more frequently develop symptomatic heart failure. While trastuzumab could be considered, these patients should be co‐managed by a cardiologist.

e12522 Background: Trastuzumab is widely used in management of HER2+ breast cancer patients. A known adverse effect of trastuzumab use is cardiac dysfunction, which can often be reversed with cessation of therapy. Our objectives were to 1) assess if trastuzumab can be safely administered to breast cancer patients with reduced cardiac function and 2) identify patient characteristics that predict susceptibility to trastuzumab-induced cardiac dysfunction. Methods: A retrospective analysis was performed on female patients seen at Mayo Clinic for HER2+ breast cancer and treated with trastuzumab for localized or metastatic disease between January 1, 2000 and August 31, 2015. Eligibility criteria included documentation of and results from at least one echocardiogram prior to and at least one after trastuzumab initiation. Left ventricular (LV) ejection fraction (EF) of 53% or more was considered normal. Any LVEF reduction of 10% or more was considered significant. Among patients with normal EF, age strata of < 45, 45-60, and > 60 at time of trastuzumab initiation were used to assess risk factors for clinically diagnosed cardiac dysfunction (defined as EF < 53 or abnormal strain and physical symptoms of heart failure (HF)). Results: We identified 335 women (mean age 53.3, with 25.3% age < 45, 44.5% age 45-60, and 30.1% age > 60) who had normal LVEF (median EF 64, range: 53-75) and 23 women (mean age 53.4, with 30.4% age < 45, 43.5% age 45-60, and 26.1% age > 60) who had low LVEF at baseline (median EF 52, range: 25-52). Approximately a third (34.3%) of women with normal LVEF prior to initiation of therapy had at least one subsequent echocardiogram showing a drop of 10% or a low LVEF ( < 53). Approximately a quarter (26%) of women with low LVEF at baseline had a 10% drop in LVEF. HF incidence increased with age. Predictive factors for trastuzumab-induced cardiac dysfunction were obesity and history of coronary artery disease (CAD) across all age strata, and chest irradiation (IR) for those aged 45-60 only. Conclusions: Our results suggest that trastuzumab can be administered in women with reduced cardiac function at no greater risk than in those with preserved cardiac function. Some women with no obesity, history of CAD, or history of chest IR may not need echocardiograms during trastuzumab therapy.