Jose Banchs

Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.

Cardiac dysfunction resulting from exposure to cancer therapeutics was first recognized in the 1960s, with the widespread introduction of anthracyclines into the oncologic therapeutic armamentarium. Heart failure (HF) associated with anthracyclines was then recognized as an important side effect. As a result, physicians learned to limit their doses to avoid cardiac dysfunction. Several strategies have been used over the past decades to detect it. Two of them evolved over time to be very useful: endomyocardial biopsies and monitoring of left ven- tricular (LV) ejection fraction (LVEF) by cardiac imaging. Examination of endomyocardial biopsies proved to be the most sensitive and spe- cific parameter for the identification of anthracycline-induced LV dysfunction and became the gold standard in the 1970s. However, the interest in endomyocardial biopsy has diminished over time because of the reduction in the cumulative dosages used to treat ma- lignancies, the invasive nature of the procedure, and the remarkable progress made in noninvasive cardiac imaging. The noninvasive evaluation of LVEF has gained importance, and notwithstanding the limitations of the techniques used for its calculation, has emerged as the most widely used strategy for monitoring the changes in cardiac function, both during and after the administration of potentially car- diotoxic cancer treatment.

Assessment of Echocardiography and Biomarkers for the Extended Prediction of Cardiotoxicity in Patients treated with Anthracyclines, Taxanes and Trastuzumab

Background—Because cancer patients survive longer, the impact of cardiotoxicity associated with the use of cancer treatments escalates. The present study investigates whether early alterations of myocardial strain and blood biomarkers predict incident cardiotoxicity in patients with breast cancer during treatment with anthracyclines, taxanes, and trastuzumab. Methods and Results—Eighty-one women with newly diagnosed human epidermal growth factor receptor 2–positive breast cancer, treated with anthracyclines followed by taxanes and trastuzumab were enrolled to be evaluated every 3 months during their cancer therapy (total of 15 months) using echocardiograms and blood samples. Left ventricular ejection fraction, peak systolic longitudinal, radial, and circumferential myocardial strain were calculated. Ultrasensitive troponin I, N-terminal pro–B-type natriuretic peptide, and the interleukin family member (ST2) were also measured. Left ventricular ejection fraction decreased (64 ± 5% to 59 ± 6%; P<0.0001) over 15 months. Twenty-six patients (32%, [22%–43%]) developed cardiotoxicity as defined by the Cardiac Review and Evaluation Committee Reviewing Trastuzumab; of these patients, 5 (6%, [2%–14%]) had symptoms of heart failure. Peak systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines treatment predicted the subsequent development of cardiotoxicity; no significant associations were observed for left ventricular ejection fraction, N-terminal pro–B-type natriuretic peptide, and ST2. Longitudinal strain was <19% in all patients who later developed heart failure. Conclusions—In patients with breast cancer treated with anthracyclines, taxanes, and trastuzumab, systolic longitudinal myocardial strain and ultrasensitive troponin I measured at the completion of anthracyclines therapy are useful in the prediction of subsequent cardiotoxicity and may help guide treatment to avoid cardiac side-effects.

Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging

### A. Definition, classification, and mechanisms of toxicity Cardiac dysfunction resulting from exposure to cancer therapeutics was first recognized in the 1960s, with the widespread introduction of anthracyclines into the oncological therapeutic armamentarium.1 Heart failure (HF) associated with anthracyclines was then recognized as an important side effect. As a result, physicians learned to limit their doses to avoid cardiac dysfunction.2 Several strategies have been used over the past decades to detect it. Two of them evolved over time to be very useful: endomyocardial biopsies and monitoring of left ventricular (LV) ejection fraction (LVEF) by cardiac imaging. Examination of endomyocardial biopsies proved to be the most sensitive and specific parameter for the identification of anthracycline-induced LV dysfunction and became the gold standard in the 1970s. However, the interest in endomyocardial biopsy has diminished over time because of the reduction in the cumulative dosages used to treat malignancies, the invasive nature of the procedure, and the remarkable progress made in non-invasive cardiac imaging. The non-invasive evaluation of LVEF has gained importance, and notwithstanding the limitations of the techniques used for its calculation, has emerged as the most widely used strategy for monitoring the changes in cardiac function, both during and after the administration of potentially cardiotoxic cancer treatment.3–5 The timing of LV dysfunction can vary among agents. In the case of anthracyclines, the damage occurs immediately after the exposure;6 for others, the time frame between drug administration and detectable cardiac dysfunction appears to be more variable. Nevertheless, the heart has significant cardiac reserve, and the expression of damage in the form of alterations in systolic or diastolic parameters may not be overt until a substantial amount of cardiac reserve has been exhausted. Thus, cardiac damage may not become apparent until years or even decades after receiving the cardiotoxic treatment. This is particularly applicable to …

Longitudinal Changes in Multiple Biomarkers Are Associated with Cardiotoxicity in Breast Cancer Patients Treated with Doxorubicin, Taxanes, and Trastuzumab

BACKGROUND Biomarkers may play an important role in identifying patients at risk for cancer therapy cardiotoxicity. Our objectives were to define the patterns of change in biomarkers with cancer therapy and their associations with cardiotoxicity. METHODS In a multicenter cohort of 78 breast cancer patients undergoing doxorubicin and trastuzumab therapy, 8 biomarkers were evaluated at baseline and every 3 months over a maximum follow-up of 15 months. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included high-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor-1 (sFlt-1), and galectin 3 (gal-3). We determined if biomarker increases were associated with cardiotoxicity at the same visit and the subsequent visit over the entire course of therapy. Cardiotoxicity was defined by the Cardiac Review and Evaluation Criteria; alternative definitions were also considered. RESULTS Across the entire cohort, all biomarkers except NT-proBNP and gal-3 demonstrated increases by 3 months; these increases persisted for GDF-15, PlGF, and hs-cTnI at 15 months. Increases in MPO, PlGF, and GDF-15 were associated with cardiotoxicity at the same visit [MPO hazard ratio 1.38 (95% CI 1.10-1.71), P = 0.02; PlGF 3.78 (1.30-11.0), P = 0.047; GDF-15 1.71 (1.15-2.55), P = 0.01] and the subsequent visit. MPO was robust to alternative outcome definitions. CONCLUSIONS Increases in MPO are associated with cardiotoxicity over the entire course of doxorubicin and trastuzumab therapy. Assessment with PlGF and GDF-15 may also be of value. These findings motivate validation studies in additional cohorts.

Cardiac Monitoring During Adjuvant Trastuzumab-Based Chemotherapy Among Older Patients With Breast Cancer

PURPOSE Patients treated with adjuvant trastuzumab require adequate cardiac monitoring. We describe the patterns of cardiac monitoring and evaluate factors associated with adequate monitoring in a large population-based study of older patients with breast cancer. PATIENTS AND METHODS Patients age 66 years or older with full Medicare coverage, diagnosed with stage I to III breast cancer between 2005 and 2009, and treated with adjuvant trastuzumab-based chemotherapy were identified in the SEER-Medicare and the Texas Cancer Registry-Medicare databases. The adequacy of cardiac monitoring was determined. Chemotherapy, trastuzumab use, cardiac monitoring, and comorbidities were identified by using International Classification of Diseases, 9th revision and Healthcare Common Procedure Coding System codes. Prescribing physician characteristics were also evaluated. Analyses included descriptive statistics and multilevel logistic regression models. RESULTS In all, 2,203 patients were identified; median age was 72 years. Adequate monitoring was identified in only 36.0% of the patients (n = 793). In the multivariable model, factors associated with optimal cardiac monitoring included a more recent year of diagnosis (hazard ratio [HR], 1.83; 95% CI, 1.32 to 2.54), anthracycline use (HR, 1.39; 95% CI, 1.14 to 1.71), female prescribing physician (HR, 1.37; 95% CI, 1.10 to 1.70), and physician graduating after 1990 (HR, 1.66; 95% CI, 1.29 to 2.12). The presence of cardiac comorbidities was not a determinant for cardiac monitoring. Of the variance in the adequacy of cardiac monitoring, 15.3% was attributable to physician factors and 5.2% to measured patient factors. CONCLUSION A large proportion of patients had suboptimal cardiac monitoring. Physician characteristics had more influence than measured patient-level factors in the adequacy of cardiac monitoring. Because trastuzumab-related cardiotoxicity is reversible, efforts to improve the adequacy of cardiac monitoring are needed, particularly in vulnerable populations.

Incidence, predictors, and impact on survival of left ventricular systolic dysfunction and recovery in advanced cancer patients

Although left ventricular (LV) dysfunction occurs not uncommonly in the course of cancer therapy, little is known about its natural history and prognostic impact on patients. To investigate the incidence, predictors, and impact on survival of LV systolic dysfunction and recovery during cancer therapy, we conducted a retrospective cohort observational study over 1 year at the University of Texas MD Anderson Cancer Center. We enrolled patients with a decrease in ejection fraction by echocardiography to <50% while undergoing cancer therapy from January 2009 to December 2009. We collected and analyzed their chart data. Of 7,648 patients with echocardiograms in 2009, 366 (4.8%) had ejection fraction <50% and 104 met study criteria. LV systolic dysfunction was associated with cardiotoxic therapy in 53 patients (51%). Recovery occurred in 57 patients (55%) and was independently predicted by younger age, smaller left atrial volume index, and lower B-type natriuretic peptide. At last follow-up, 69 patients (66%) were dead, and 35 (34%) were alive. There was a 20% advantage in 2-year survival among patients with LV systolic recovery compared with those without (95% confidence interval 4% to 41%, p = 0.02). In this retrospective study, LV systolic dysfunction recovery occurred in over half of the patients, appeared independent of cardiotoxic etiology, and associated with a 20% survival benefit at 2 years. Multivariable predictors of recovery are younger age, a small left atrial volume index, and lower B-type natriuretic peptide.

Cardiac 18F-fluorodeoxyglucose uptake on positron emission tomography after thoracic stereotactic body radiation therapy

BACKGROUND AND PURPOSE Previous studies have shown that increased cardiac uptake of (18)F-fluorodeoxyglucose (FDG) on positron emission tomography (PET) may be an indicator of myocardial injury after radiotherapy. We reviewed patients treated with thoracic stereotactic body radiation therapy (SBRT) and established correlations between SBRT dose and observed changes in cardiac FDG-PET uptake. MATERIAL AND METHODS Retrospective analysis identified 39 patients that were treated with SBRT for lung tumors close to the heart. Patients were grouped according to whether or not they had changes in cardiac FDG-PET uptake within the planned SBRT field. RESULTS At a median follow-up interval of 39 months (range, 6-81 months), nine patients (23%) showed increased cardiac FDG uptake associated with the heart V₂₀. Of the 19 patients who received 20 Gy to ≥5 cm(3) of the heart, nine (47%) developed increased FDG uptake (vs. 0% for the 20 patients who received 20 Gy to <5 cm(3)) (P=0.0004), all within the 20-Gy isodose line. Patients with hypercholesterolemia prior to SBRT were also more likely to show increased cardiac FDG uptake (P=0.0190). CONCLUSION Increased FDG uptake in the heart after SBRT was observed when the 20 Gy isodose line exceeded 5 cm(3) of the heart.

Role of a 12-Lead Electrocardiogram in the Diagnosis of Cardiac Tamponade as Diagnosed by Transthoracic Echocardiography in Patients With Malignant Pericardial Effusion

Few studies have looked at the utility of the 12‐lead electrocardiogram (ECG) in diagnosing cardiac tamponade in malignant pericardial effusion (PE). The aim of this study was to determine the sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of 12‐lead ECG in diagnosing cardiac tamponade in PE.

Pericardial disease: A clinical review

ABSTRACT Pericardial disease is infrequently encountered in cardiovascular practice, but can lead to significant morbidity and mortality. Clinical data and practice guidelines are relatively sparse. Early recognition and prompt treatment of pericardial diseases are critical to optimize patient outcomes. In this review we provide a concise summary of acute pericarditis, constrictive pericarditis and pericardial effusion/tamponade.

Preoperative Echocardiographic Parameters of Diastolic Dysfunction Did Not Provide a Predictive Value for Postoperative Atrial Fibrillation in Lung and Esophageal Cancer Surgery

OBJECTIVE To evaluate the predictive value of preoperative transthoracic echocardiography in the development of postoperative atrial fibrillation after non-cardiac thoracic surgery. DESIGN This was a retrospective study. SETTING Academic hospital. PARTICIPANTS A total of 703 adult patients with non-small cell lung cancer. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Retrospective data of 177 non-cardiac thoracic surgical oncologic patients undergoing lung or esophageal cancer surgery with preoperative transthoracic echocardiograms (TTE) (within 30 days before surgery) were analyzed. The Wilcoxon rank sum test was used to evaluate the difference in continuous variables. Fishers exact test or the chi-square test was used to evaluate the association between two categoric variables. Logistic regression models were used for multivariate analysis to include important and significant covariates. Among the demographic and echocardiographic variables measured age, systemic hypertension, e` septal, e` lateral and E/e` ratio were significantly different between patients who would develop postoperative atrial fibrillation (POAF) and those who did not. The logistic regression models only identify age as a predictor factor of POAF. CONCLUSIONS These results were similar to those published elsewhere on POAF incidence and risk factors. The preoperative echocardiographic variables in this study did not provide predictive value for POAF in non-cardiac thoracic surgery.