Previous Mediastinal Irradiation Research Articles

Outcomes of Transcatheter Aortic Valve Replacement in Patients With Previous Mediastinal Radiation in the United States: A Propensity Score–Matched Analysis

Outcomes of Transcatheter Aortic Valve Replacement in Patients With Previous Mediastinal Radiation in the United States: A Propensity Score–Matched Analysis

Outcomes of Coronary Artery Bypass Grafting in Patients With Previous Mediastinal Radiation

Studies have shown that patients with radiation therapy-associated coronary artery disease tend to have worse outcomes with percutaneous revascularization. Previous irradiation has been linked with future internal mammary artery graft disease. Studies investigating the outcomes of coronary artery bypass surgery (CABG) among patients with previous radiation are limited. The Nationwide Readmission Database for the years 2016 to 2019 was queried for hospitalizations with CABG and history of mediastinal radiation. Complex samples multivariable logistic and linear regression models were used to determine the association between the history of mediastinal radiation and in-hospital mortality, 90 days all-cause unplanned readmission rates, and acute coronary syndrome readmission rates. A total of 533,702 hospitalizations (2,070 in the irradiation history group and 531,632 in the control group) were included in this analysis. Patients with radiation therapy history were less likely to have traditional coronary artery disease risk factors and more likely to have associated valvular disease. Patients with a history of irradiation had similar in-hospital mortality and 90-day readmission risk at the expense of higher hospitalizations costs (β coefficient: $2,764; p=0.005). They had a higher likelihood of readmission with acute coronary syndrome within 90 days (adjusted odds ratio 1.67, p=0.02). In a conclusion, a history of mediastinal irradiation is not associated with increased rates of short-term mortality or increased all-cause readmission risk after CABG. However, it may be associated with increased acute coronary syndrome readmission rates.

Mitral Valve Repair vs Replacement in Patients with Previous Mediastinal Irradiation

Long-term outcomes of mitral valve surgery after mediastinal radiation therapy (MRT) are not well characterized. We analyzed long-term survival in patients who underwent mitral valve repair or replacement after MRT. From 2001 to 2018, 148 patients underwent mitral valve surgery at our institution after MRT for cancer. The association between surgery group and survival was assessed using Cox proportional hazards modeling, with propensity score adjustment to control for clinical and operative differences between groups. Mitral valve was repaired in 48 (32.4%) and replaced in 100 (67.6%) patients. The groups (repair vs replacement) were similar in age (62.0 vs 57.1 years, p=0.10), gender (female n=38, 79.2% vs n=65, 65%, p=0.08), chronic lung disease (n=12, 25.0% vs n=37, 37.0%, p=0.19), congestive heart failure (n=13, 27.1% vs n=38, 38.4%, p=0.20), but differed in atrial fibrillation (n=17, 35.4% vs n=13, 13.0%, p=0.002), first cardiovascular surgery (n=34, 70.8% vs n=47, 47.0%, p=0.006), and time since MRT (median 12, 7-27 years, vs 30, 19-37 years, p < 0.001). Long term survival was no different between groups in the unadjusted (p=0.835) and propensity-adjusted (p=0.645) analysis, and inferior to the expected survival of an age- and sex-matched population. Mediastinal irradiation negatively impacts survival in patients who undergo mitral valve surgery. The traditional advantage of mitral valve repair over replacement on long-term survival was not seen in patients with radiation associated mitral valve disease.

Biomarkers' ability to predict cardiac toxicity in oncological patients undergoing to antineoplastic treatment: 5-year follow-up

Abstract Background It is known that anticancer treatment can cause adverse cardiovascular (CV) events, influencing patients' survival and quality of life regardless of their cancer prognosis; today there are no defined protocols for the early identification of cardiotoxicity (CTX). Purpose To evaluate the ability of biomarkers, cardiac TnI and NT-proBNP, to predict CTX induced by antineoplastic therapy. Methods We have enrolled women with non-metastatic breast cancer who had to start a treatment with Anthracycline (ANT), in the patients (pts) with HER2+ cancer, Trastuzumab (TRZ) could also be introduced. The presence of a known heart disease, a previous mediastinal irradiation and a previous treatment with ANT, were the main exclusion criteria. All pts underwent complete cardiological evaluation (ECG, Echo) before the beginning of the therapy (T0), after each ANT cycle and every 3 months up to 1 year of follow-up after the end of therapy with ANT. During each visit, a venous sampling was performed for the determination of biomarkers. We collected the data of the routine cardiological visits carried out by the pts in the following 5 years. Results 179pts finished the follow-up,7pts (21%) were hypertensive, 9pts (5%) diabetic, 32pts (18%) dyslipidemics. 53pts (30%) (“TnI+ group”) showed a significant increase in TnI (&amp;gt;0.04ng/mL) or less than this cut-off but persistently &amp;gt;0.015ng/mL in at least 2 measurements; comparing the LVEF of the two groups detected at 1 year follow-up it was observed a significant difference: 60±6.5% in the “TnI+ group” and 63±4.1% in the “TnI− group” (p=0.005); a tendency to significance was observed from the comparison between LVEF measured at baseline compared to that of 1-year follow-up in the “TnI+ group” (62±4.2% vs 60±6.5%, p=0.06); furthermore 7 patients of the “TnI+ group” developed LV systolic dysfunction (according to the definition of the CREC) early in the first year of follow-up (vs 1 pts of the “TnI− group”, p=0.001), with recovery after the introduction of specific cardiology therapy. 76/179 pts (43%) showed NT-proBNP values ≥125 ng/L in at least two consecutive determinations (“NT-proBNP+ group”), in this group 25% of the pts had more than 3 CV risk factors, compared to 11% in the “NT-proBNP− group” (p=0.011), 3/8 pts that showed LV systolic dysfunction were included in the “NT-proBNP+ group”. Conclusion(s) In a homogeneous group of patients with a low CV risk profile, anticancer treatment with low doses of ANT and with TRZ can induce significant changes in plasma TnI levels that can be correlated with early alterations in LV systolic function, but not with major CV events after 5 years. Significant increases in NT-proBNP have also been reported, but there has been no significant correlation with the progressive development of LV dysfunction and HF. The combination of individual clinical risk factors and biomarkers, especially TnI, in a predictive model could allow early identification of CTX. Funding Acknowledgement Type of funding source: None

The possible role of genetic testing in the early identification of patients at increased risk of developing anthracycline-induced cardiotoxicity

Abstract Background In the last years prognosis of cancer patients (pts) has been improved, but the develop of cardiotoxicity (CTX) in pts with low CV risk treated with cumulative doses of Anthracycline (ANT) considered safe, led to investigate the possible role of the genetic profile in the onset of CTX. Purpose To study the role of some single nucleotide polymorphisms (SNPs) as predictive genetic markers of individual susceptibility to CTX induced by anticancer treatment. Methods We have enrolled women with non-metastatic breast cancer who had to start a therapy with ANT. The presence of a known heart disease, a previous mediastinal irradiation and a previous treatment with ANT, were the main exclusion criteria. All pts underwent complete cardiological evaluation (ECG, echo) before the beginning of the therapy (T0), after each ANT cycle and every 3 months up to 1 year of follow-up after the end of treatment. During each visit, we performed the determination of troponin I (TnI) and NT-proBNP. The genetic profile of each pts was also investigated, analyzing 6 SNPs belonging to 3 different genes (two for each genes) coding for enzymes or enzyme systems involved in the metabolism of ANT. DNA extraction from blood samples was performed using the QIAamp DNA Mini kit (QIAGEN). The DNA extracted was genotyped (by performing TaqMan SNP Genotyping assays) identifying 3 possible variants for each SNPs: homozygosity for the protective and “at risk” variant and heterozygosity. Results 179 pts finished the follow-up and from the analysis of the trend of biomarkers we found that 53 pts (30%) showed a significant increase in TnI (&amp;gt;0.04ng/mL) or less than this cut-off but persistently &amp;gt;0.015ng/mL in at least 2 measurements (“TnI+ group”), in the remaining 126 pts the TnI remained non-measurable (“TnI− group”); 76 pts (43%) showed NT-proBNP values ≥125 ng/L in at least two consecutive determinations (“NT-proBNP + group”),in the remaining 57% of pts this increase was not detected (“NT-proBNP - group”). Comparing “TnI+ group” to “TnI− group” we observed that only the genotyping of the SNPs rs1149222 (G/T) belonging to the ABCB4 gene is distributed differently in the two groups, in particular the homozygosity for the “at risk” variant (G/G) was present in 13% of the pts of the “TnI+ group” vs 5% in the “TnI− group” (p 0.06). The results of the comparison of “NT-proBNP+ group” vs “NT-proBNP− group”, showed that the genotyping of the SNPs rs6759892 (G/T) belonging to the UGT1A6 gene was distributed differently, the homozygosity for the “at risk” variant (G/G) was present in 28% of the “NT-proBNP+ group” vs 17% in the “NT-proBNP− group” (p 0.07). Conclusion Together with the baseline clinical evaluation, genetic markers could contribute to the early identification of pts at high risk of developing CTX especially following treatment with ANT and they could support future therapeutic decisions and the planning of taylored strategies for the prevention of the CTX development. Funding Acknowledgement Type of funding source: None

Positive family history of cardiovascular disease and long-term outcomes after coronary artery bypass grafting: a genetic paradox?

Parental cardiovascular disease (CVD) is a known risk factor for premature CVD. It is unknown whether a positive family history (PFH) affects outcomes after coronary artery bypass grafting (CABG). Data come from a retrospective longitudinal study of CABG patients consecutively recruited from 2001 to 2018 (n = 5389). From this study, 2535 patients with premature CVD undergoing CABG under the age of 60 years and information on parental CVD were identified. The Framingham offspring study criteria were used to identify PFH of CVD. Multivariable Cox proportional hazards regression models were used to assess the effect of PFH on overall and major adverse cardiovascular and cerebrovascular event-free survival. A total of 273 deaths and 428 major adverse cardiovascular and cerebrovascular events occurred during follow-up. PFH of CVD was found in 54.2% of patients (n = 1375). Within these patients, 66.1% had a father who experienced a premature cardiovascular event (n = 909), 27.8% a mother (n = 382) and 6.1% both a mother and a father (n = 84). In the majority of cases, the patient's parent had experienced a cardiac event (85.9%, n = 1181) and 14.1% of patients with PFH reported parental stroke (n = 194). Following CABG, PFH was associated with improved overall [adjusted hazards ratio (HR) 0.67, 95% confidence interval (CI) 0.50-0.90; P = 0.008] and major adverse cardiovascular and cerebrovascular event-free survival (adjusted HR 0.73, 95% CI 0.68-0.89; P = 0.01). Among the covariates adjusted for age, diabetes, renal insufficiency, peripheral arterial disease, ejection fraction, previous cerebrovascular events and previous mediastinal radiation were all associated with poorer outcomes. Although it is well established that a PFH increases the risk of requiring CABG at younger ages, this study shows that, paradoxically, PFH is also protective regarding long-term outcomes. UN4232 297/4.3 (retrospective study).

P6427Positive family history of cardiovascular disease and long-term outcomes after coronary artery bypass grafting in younger patients: a genetic paradox?

Abstract Background Parental cardiovascular disease (CVD) is a known risk factor for premature CVD in both men and women. It is unknown whether a positive family history (PFH) of premature CVD also affects long-term outcomes after coronary artery bypass grafting (CABG). Purpose We estimated the prevalence of PFH of premature CVD in a large population of CABG patients younger than 60 years of age. We evaluated whether PFH is an independent predictor of survival and freedom from major adverse cardiac and cerebrovascular events (MACCEs) following CABG. Methods Data come from a prospective longitudinal study of first, non-emergent, CABG patients consecutively recruited at the Innsbruck Medical University between August 2001 and February 2018 (n=5389). Patients were followed up for a median of 8 years. From this study, 2553 patients with premature CAD undergoing CABG under the age of 60 years were identified. Self-reported PFH data was available for 99.3% of patients; n=2535 patients were eligible for these analyses. In line with the Framingham offspring study, a premature PFH of CVD was defined when a patient's father and/or mother experienced their first CV event at &lt;55 (father) and &lt;65 (mother) years of age, respectively. Adjusted multivariable Cox proportional hazards regression was used to assess the effect of PFH on overall and MACCE-free survival. Results Premature PFH was found in 54.2% of patients (n=1375). Within these patients, 66.1% had a father who experienced a premature CV event (n=909), 27.8% a mother (n=382) and 6.1% both a mother and a father (n=84). In the majority of cases the patient's parent had experienced a premature cardiac event (85.9%, n=1181), 14.1% of patients with PFH reported their parent(s) had a premature stroke (n=194). Patients with a PFH had lower rates of smoking, diabetes and renal disease but were more likely to be hypertensive. Following CABG, PFH was associated with improved long-term survival (adjusted HR, 0.66; 95% CI, 0.50–0.91; p=0.011) and MACCE-free survival (adjusted HR, 0.73; 95% CI, 0.68–0.89; p=0.01). Among the covariates adjusted for, age, diabetes, renal insufficiency, peripheral arterial disease, impaired left ventricular function, previous cerebrovascular events and previous mediastinal radiation were associated with poorer outcomes. In contrast, multiple arterial grafting by bilateral internal thoracic arteries improved both survival (adjusted HR, 0.52; 95% CI, 0.36–0.74; p&lt;0.001), and MACCE-free survival (adjusted HR, 0.41; 95% CI, 0.31–0.54; p&lt;0.001). Conclusion In this cohort of high-risk patients undergoing CABG under 60 years of age, PFH was highly prevalent. Whilst it is evident that a PFH increases the risk of requiring CABG at younger ages, this study shows that PFH is also, paradoxically, protective regarding long-term outcomes; PFH is associated with both improved overall and MACCE-free survival following CABG.

1769 Esophageal Candidiasis as an Unusual Cause of Upper Esophageal Stricture

INTRODUCTION: The location of an esophageal stricture often provides clues for its etiology. Upper esophageal strictures are most commonly associated with previous mediastinal radiation, caustic ingestion, or bullous dermatologic disorders. They are rarely attributed to infectious etiology. We present a case of an upper esophageal stricture that we believe is secondary to candida infection. CASE DESCRIPTION/METHODS: A 52-year-old female with past medical history significant for diabetes mellitus type 2 and invasive ductal carcinoma of right breast status post mastectomy and chemotherapy, now in remission and only on hormonal therapy, had presented to our gastroenterology clinic complaining of dysphagia with associated unintentional weight loss. Dysphagia had been present for several months prior and was progressive, with near inability to tolerate solids, and not associated with regurgitation or acid reflux symptoms. She had also reported a 15-pound weight loss during this time. Initial esophagogastroduodenoscopy revealed an upper esophageal stricture approximately 15cm from the incisors, preventing initial passage of standard upper endoscope. Neonatal scope was used which both traversed and dilated to 9mm. Past the stenosis, friable and desquamative- appearing mucosa was found. Upper esophageal biopsies were consistent with Candida esophagitis. Gastric cardia biopsy incidentally noted Helicobacter pylori. Patient was subsequently treated with oral fluconazole, triple therapy, and proton-pump inhibitor. Repeat follow-up esophagogastroduodenoscopy again demonstrated the initial upper esophageal stenosis, which could now be traversed with a standard upper endoscope. A Savary dilator was used to dilate the stricture to 39 Fr. Repeat esophageal and stomach biopsies were negative for Candida and H. Pylori, respectively. Subsequently, the patient reported improved symptoms without any dysphagia to solids or liquids. DISCUSSION: Candidal esophagitis is fairly common, however it is not typically known to cause upper esophageal strictures. This case highlights the need for physicians to maintain a broader differential and consider candida as a risk factor for developing stenotic lesions, even in immunocompetent patients and especially in the absence of other more well-known etiologies. Correct identification of etiology is necessary for appropriate treatment and preventing recurrence.

Unique Considerations for Females Undergoing Esophagectomy.

To improve understanding of sex differences in clinicopathologic characteristics, treatment and outcomes between male and female patients undergoing esophagectomy for esophageal cancer. Esophageal cancer is a male predominant disease, and sex has not been considered in previous studies as an important factor in diagnosis or management. Sex differences in demographics, clinicopathologic characteristics, and postoperative outcomes remain largely undefined. Retrospective review of 1958 patients (21% female) with esophageal cancer who underwent esophagectomy at a single institution between 1995 and 2017. Most patients had adenocarcinoma (83%); however, the rate of squamous cell carcinoma was significantly higher in females (35% vs 11%, respectively; P < .0001). Females had a lower rate of smoking (62 vs 73%) and heavy alcohol use (12 vs 19%) but a higher rate of previous mediastinal radiation (8.4 vs 1.8%) (P < 0.001). Postoperative mortality and overall survival (OS) were similar between sexes. However, subanalysis of patients with locoregional disease (clinical stage II/III) demonstrated that females received neoadjuvant therapy less frequently than males and had worse OS (median OS 2.56 yrs vs 2.08; P = 0.034). This difference remained significant on adjusted analysis (HR 1.24, 95% CI 1.06-1.46). Female patients had higher incidence of squamous cell carcinoma despite lower prevalence of behavioral risk factors. Among patients with locoregional disease, undertreatment in females may reflect treatment bias and history of previous mediastinal radiation. Esophageal cancer in females should be considered a unique entity as compared with the presentation and treatment of males.

Management and prognosis of esophageal carcinosarcoma

Management and prognosis of esophageal carcinosarcoma

Esophageal cancer after mediastinal irradiation for malignancies: A case-control study

Esophageal cancer after mediastinal irradiation for malignancies: A case-control study

Risk assessment methods for cardiac surgery and intervention.

Surgical risk models estimate operative outcomes while controlling for heterogeneity in 'case mix' within and between institutions. In cardiac surgery, risk models are used for patient counselling, surgical decision-making, clinical research, quality assurance and improvement, and financial reimbursement. Importantly, risk models are only as good as the databases from which they are derived; physicians and investigators should, therefore, be aware of shortcomings of clinical and administrative databases used for modelling risk estimates. The most frequently modelled outcome in cardiac surgery is 30-day mortality. However, results of randomized trials to compare conventional surgery versus transcatheter aortic valve implantation (TAVI) indicate attrition of surgical patients at 2-4 months postoperatively, suggesting that 3-month survival or mortality might be an appropriate procedural end point worth modelling. Risk models are increasingly used to identify patients who might be better-suited for TAVI. However, the appropriateness of available statistical models in this application is controversial, particularly given the tendency of risk models to misestimate operative mortality in high-risk patient subsets. Incorporation of new risk factors (such as previous mediastinal radiation, liver failure, and frailty) in future surgical or interventional risk-prediction tools might enhance model performance, and thereby optimize patient selection for TAVI.

Stratification of Outcomes After Transcatheter Aortic Valve Replacement According to Surgical Inoperability for Technical Versus Clinical Reasons

The goal of this study was to examine the impact of reasons for surgical inoperability on outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). Patients with severe aortic stenosis may be deemed inoperable due to technical or clinical reasons. The relative impact of each designation on early and late outcomes after TAVR is unclear. Patients were studied from the inoperable arm (cohort B) of the randomized PARTNER (Placement of Aortic Transcatheter Valve) trial and the nonrandomized continued access registry. Patients were classified according to whether they were classified as technically inoperable (TI) or clinically inoperable (CLI). Reasons for TI included porcelain aorta, previous mediastinal radiation, chest wall deformity, and potential for injury to previous bypass graft on sternal re-entry. Reasons for CLI were systemic factors that were deemed to make survival unlikely. Of the 369 patients, 23.0% were considered inoperable for technical reasons alone; the remaining were judged to be CLI. For TI, the most common cause was a porcelain aorta (42%); for CLI, it was multiple comorbidities (48%) and frailty (31%). Quality of life and 2-year mortality were significantly better among TI patients compared with CLI patients (mortality 23.3% vs. 43.8%; p< 0.001). Nonetheless, TAVR led to substantial survival benefits compared with standard therapy in both inoperable cohorts. Patients undergoing TAVR based solely on TI have better survival and quality of life improvements than those who are inoperable due to clinical comorbidities. Both TI and CLI TAVR have significant survival benefit in the context of standard therapy. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

Frequency of Severe Valvular Disease Caused by Mediastinal Radiation Among Patients Undergoing Valve Surgery in a Community‐Based, Regional Academic Medical Center

Our goal was to define the prevalence of radiation-induced valvular heart (RIVD) disease among patients undergoing cardiac valve surgery in a community-based, regional academic medical center. Mediastinal radiation is a treatment modality for various hematologic and solid malignancies; however, long-term cardiac complications, including radiation-induced valvular heart disease, can occur years after the radiation treatments. Mediastinal radiation exposure is an independent risk factor for valvular heart disease often necessitating valve replacement in patients without other risk factors for valve disease. Between January 1, 1998 and September 1, 2007, we retrospectively analyzed our institution's cardiac surgical database over a 10 year period and identified 189 consecutive patients ≤ 50 years of age who underwent valve surgery. Using case-control matching, we assessed the prevalence of mediastinal radiation among these young patients with valve disease necessitating surgery and to their matched controls from all patients admitted to the hospital. Nine individuals (4.8%) were identified as having received previous mediastinal radiation, significantly increased from controls (p<0.0001), and 8 of whom had surgical or pathologic findings consistent with radiation damage. Compared with a matched case-control population, individuals who had severe valve disease and underwent valve replacement had a markedly increased prevalence of prior mediastinal radiation therapy. In conclusion, cardiologists must remain aware of the potential long term valvular complications in patients treated with mediastinal radiation. Increased surveillance for RIVD may be considered in the decades following radiation therapy.

Factors affecting the development of atrial fibrillation and atrial flutter (AF/AFL) following autologous hematopoietic SCT (auto-HSCT)

The use of autologous hematopoietic SCT (auto-HSCT) has expanded to include older patients. Increasing age is a well-appreciated risk factor for the development of atrial fibrillation and/or atrial flutter (AF/AFL) in the general population. As more elderly patients undergo auto-HSCT, the risk of developing AF/AFL post transplant may also increase. However, few data evaluating other risk factors for the development of AF/AFL following auto-HSCT exist. Therefore, we performed a retrospective study to determine the incidence of AF/AFL following auto-HSCT and to determine the risk factors associated with the development of AF/AFL. Patients who developed AF/AFL were compared with a group of patients who received auto-HSCT within the same time period (April 1999 to May 2005) and were within 5 years of age. Of the 516 patients who underwent auto-HSCT at the University of Nebraska Medical Center 44 (8.5%) developed AF/AFL at a median time of 4 days (range, days 1-9) following auto-HSCT. In multivariate analysis, risk factors for developing AF/AFL were older age, odds ratio and 95% CI of 1.14 (1.07-1.21), elevated serum creatinine level, 2.69 (1.00-7.22), history of previous arrhythmia, 9.33 (3.01-28.99), and history of previous mediastinal irradiation, 11.12 (1.33-92.96).

Cardioprotective effect of telmisartan in cancer patients treated with telmisartan.

9153 Background: We showed previously in 31 cancer patients (pts) that early cardiac abnormalities, i.e. strain rate (SR) reduction detected by tissue Doppler imaging (TDI), occurred at epirubicin (EPI) doses of 200 mg/m2 and persisted throughout subsequent EPI doses and even up to 18 months. Renin-angiotensin system activation plays an important role in the pathogenesis of anthracycline-induced cardiotoxicity. Methods: A phase II randomized placebo-controlled study was designed to investigate the possible role of telmisartan (an antagonist of angiotensine II type I receptor) in preventing both early preclinical and late myocardial damage induced by EPI. The correlation with changes of biochemical/inflammatory markers was also assessed. Planned sample size was 100 pts. Inclusion criteria: 18–70 y, histologically confirmed cancer, previously untreated and candidates for an EPI-based regimen; LVEF ≥55%; ECOG PS 0- 2, no history of cardiac disease and previous mediastinal irradiation. Eligible pts were randomized to receive telmisartan 40 mg (1 tablet)/day or placebo, starting 1 week before EPI up to 6 months after the end of EPI administration. TDI as well as inflammatory/oxidative stress markers were assessed at baseline and after 7 days at EPI doses of 100, 200, 300, 400 mg/m2. Results: At January 2010 we enrolled 45 pts (M/F: 11/34, mean±SD age 53±10 years): 25 in Telmisartan and 20 in placebo arm. Forty-two pts completed EPI treatment (22 telmisartan and 20 placebo). A significant reduction of SR peak was observed at 200 mg/m2 of EPI both in the placebo (p<0.001) and the telmisartan arm (p=0.03). Vice versa, at higher cumulative doses (300 and 400 mg/m2 EPI) a significant higher reduction was observed in the placebo arm vs the telmisartan arm (p<0.001for both). Moreover, the diastolic function as assessed by Em/Am was significantly reduced in the placebo arm both at 200 and 300 mg/m2 of EPI (p <0.05 for both) whilst it was not reduced significantly in the telmisartan arm. Proinflammatory cytokines and oxidative stress markers did not change in the telmisartan arm whilst reactive oxygen species and IL-6 increased significantly in the placebo arm at EPI dosages≥ 200 mg/m2. Conclusions: The study is in progress up to pts accrual completion. No significant financial relationships to disclose.

Predictive factors for the severity of congestive heart failure after an epirubicin-based treatment for metastatic breast cancer.

1124 Background: Patients treated with anthracyclines have a well described risk for developing congestive heart failure (CHF). However, little is known about possible predictive factors for the severity of the CHF acquired. Methods: 125 patients who developed CHF class ≥ II according to New York Heart Association (NYHA) guidelines were included in this retrospective study. The patients were recruited consecutively from 1,097 patients with metastatic breast cancer admitted to Herlev Hospital from November 1983 through November 2003 for an epirubicin-based chemotherapy. No patients treated had a history of cardiac disease before start of epirubicin. Statistics: Univariate analysis based on ordinal logistic regression with NYHA class at time of cardiac disease as the outcome. Results: The median time after cessation of epirubicin to onset of CHF was 3 months (range 0.01 to 66.7 months). The median survival was 7.3 months (range 0.01 to +121.1 months), with eights patients (6.4%) still alive. The distribution of patients in the NYHA class II, III, IV and class ≥ II was: 35 patients (28%), 38 patients (30.4%), 39 patients (31.2%), and 13 patients (10.4%), respectively. Following variables were tested in the univariate analysis: cumulative dose of epirubicin mg/m2, age at the time of epirubicin treatment, previous antihormonal treatment or mediastinal irradiation, and comorbidity with disposition to heart disease. Variables there all previously had been demonstrated as a risk factor for developing CHF after an epirubicin treatment. Moreover, the time from the cessation of epirubicin treatment to the onset of cardiotoxicity and the value of serum-lactatdehydrogenase at the onset of the CHF were included. None of these variables became significant, even at a level of 0.20. Conclusions: No predictive factor for the degree of congestive heart failure (NYHA class) was identified in patients with heart failure due to an epirubicin treatment. Even cumulative epirubicin dose mg/m2, age, comorbidity with disposition to heart disease, or previous mediastinal irradiation had an influence of its own. No significant financial relationships to disclose.

Cardioprotective effect of telmisartan in cancer patients treated with epirubicin

e20671 Background: We previously showed on 31 cancer patients (pts) that early cardiac abnormalities occurred at epirubicin (EPI) doses of 200 mg/m2 and persisted throughout subsequent EPI doses and even up to 18 months. Early contractility impairment, i.e. Strain rate (SR) reduction was detected by tissue doppler imaging (TDI) associated with high levels of inflammatory/oxidative stress markers. Renin-angiotensin system activation has been suggested to play an important role in the pathogenesis of Anthracycline-induced cardiotoxicity. Methods: A phase II placebo-controlled study was designed to investigate the possible role of telmisartan (an antagonist of angiotensine II type I receptor) in preventing both early preclinical and late myocardial damage induced by EPI. The correlation with changes of biochemical/inflammatory markers was also assessed. Planned sample size was 100 pts (50 pts per arm). Inclusion criteria: 18–70 y, histologically confirmed cancer, previously untreated and candidates for an EPI-based regimen; LVEF ≥55%; ECOG PS 0–2, no history of cardiac disease and previous mediastinal irradiation. Eligible pts were randomized to receive telmisartan 40 mg (1 tablet)/day or placebo starting 1 week before EPI until 6 months after the end of EPI administration. TDI as well as inflammatory/oxidative stress markers were assessed at baseline, 24 hours and 7 days at EPI doses of 100, 200, 300, and 400 mg/m2. Results: At December 2008 we enrolled 27 pts (M/F: 7/20, mean±SD age 58±14 years): 14 telmisartan and 13 placebo. 15 pts completed EPI treatment (8 telmisartan and 7 placebo). A significant reduction of SR peak was observed at 200mg/m2 of EPI in the placebo arm. Viceversa no significant TDI changes occurred in the treatment arm. Proinflammatory cytokines did not change in both arms whilst reactive oxygen species increased significantly in the placebo arm. Conclusions: The study is in progress. No significant financial relationships to disclose.

Bilateral coronary ostial disease following mediastinal irradiation: a case report

IntroductionOstial coronary artery disease is rare with a reported incidence of 0.07 to 0.25% in all patients undergoing angiography. It has a strong association with previous mediastinal irradiation, which induces specific histological changes distinct from atherosclerotic lesions. The radiation also affects the myocardium and surrounding structures, which can alter the surgical approach.Case presentationWe present a case of a 62-year-old female who developed bilateral ostial coronary artery stenosis 32 years following therapeutic radiotherapy for Hodgkin’s disease. She underwent successful coronary artery bypass surgery using a combination of arterial and venous conduits. Postoperatively she developed a clinical picture of diastolic impairment not detected pre-operatively. She was managed appropriately and made a successful recovery.ConclusionsThis case highlights the cardiac pathology associated with mediastinal irradiation, which should be suspected during surgical assessment, especially in long-term survivors. It heightens the surgeon’s awareness so a more thorough evaluation of coronary anatomy, ventricular function and potential conduits is made prior to surgery.

Long-term outcome of CABG – patients after previous mediastinal irradiation due to cancer. A retrospective survival-rate-analysis of 125 patients within 14 years

Objectives: The number of patients with mastectomy or Hodkin's/non-Hodkin's- Lymphoma and prior mediastinal irradiation requiring CABG is increasing. Aim of the study was to review the long term outcome of this specific,higher risk population.