Related Cardiac Dysfunction Research Articles

P656 Cardiac dysfunction in breast cancer patients treated with anthracyclines: a single-center experience

Abstract Introduction Cardiac dysfunction is a well-documented side effect of cancer treatment, with significant morbidity and mortality. Cardio-oncology units play a vital role in the early identification and management of cancer therapy related cardiovascular side effects and provide a multidisciplinary care for cancer patients. Purpose To describe the incidence of cancer treatment related cardiac dysfunction (CTRCD) in a population of breast cancer patients (pts) under chemotherapy in a single center cardio-oncology unit, and to assess its predictors. Methods We retrospectively evaluated 83 women on anthracycline therapy for breast cancer, with or without anti-HER2 therapy, followed-up between January 2017 and July 2018. CTRCD was defined as more than 10% absolute reduction of LV ejection function (LVEF) to below 50%. Pts with >15% relative percentage reduction from baseline Global longitudinal strain (GLS) or with elevation of high-sensitivity Troponin I (hsTI) levels were considered to be at high risk for developing CTRCD and started cardioprotective treatment with an ACE inhibitor/ARB and a beta-blocker, as did pts with confirmed CRTCD. Also, in pts under antihypertensive drug therapy, switching drugs to cardioprotective ones was performed in the index consultation. Follow-up was organized in our cardio-oncology consultation at 0, 3, 6 and 12 months (or more frequently in selected high-risk cases). Interruption of chemotherapy was a joint decision of the oncology and cardiology teams. Results A total of 83 women with a mean age of 49 years (26-76) were included. 4 pts (4.8%) developed CTRCD. 28 pts (33.7%) were considered to be at high risk due to GLS reduction during follow-up and 17 pts (20.5%) were at high risk due to hsTI elevation. From all the baseline characteristics, only basal BNP correlated with CTRCD (p = 0.033). Other characteristics such as age, presence of cardiovascular risk factors and the previously proposed Cardiotoxicity Risk Score (CRS) did not. There was a high percentage of pts (51.8%; n = 43) under cardioprotective drugs. 37% of the pts initiated cardioprotective drugs following cardio-oncology consultation. Chemotherapy was discontinued in only 2 pts (2.4%). Conclusion CTRCD is difficult to predict by baseline clinical characteristics. Monitoring and management of CTRCD by a multidisciplinary cardio-oncology team resulted in a high rate of cardioprotective drugs use and low rate of permanent discontinuation of chemotherapy. Further studies are needed to further analyze the relationship between these two variables.

The Role of Echocardiography in Cardio-oncology Patients: Contemporary Indications and Future Directions

This review discusses the latest advances, guideline recommendations, and limitations of the use of echocardiography in evaluation of cancer therapeutics–related cardiac dysfunction (CTRCD) and highlights advances in cardio-oncology that have the potential to augment the echocardiographic assessment of CTRCD. Cardio-oncology is a rapidly evolving field aimed at improving the quality of life of cancer patients by preventing and treating the adverse cardiovascular complications of cancer therapy. Cardiac imaging tools, in particular transthoracic echocardiography, play a pivotal role in the early detection and monitoring of CTRCD. Recent studies have indicated the potential benefit of a number of echocardiographic parameters in addition to left ventricular ejection fraction in the evaluation of CTRCD. We anticipate that echocardiography will continue to play a central role in the field of cardio-oncology over the coming years. The utility and predictive value of echocardiographic indices will continue to improve with advances in imaging technology and development of novel biomarkers to supplement imaging parameters. Ensuring equitable and easy access to cardio-oncology services, especially in remote and disadvantaged communities, remains an area of ongoing investigation and will undoubtedly be assisted with new innovations in image acquisition, transmission, and analysis. Lastly, machine learning is likely to revolutionise the evaluation of CTRCD in light of the rapid progress of artificial intelligence–driven automation for the analysis and interpretation of echocardiograms.

P687Is sacubitril/valsartan useful in patients with cancer and heart failure? Data from HF-COH Spanish multicenter registry

Abstract Current guidelines recommend sacubitril/valsartan (S/V) for patients (p.) with heart failure and reduced left ventricular ejection fraction (LVEF) but there is lack of evidence of its efficacy and safety in p. with cancer and heart failure. Our aim was to analyze the potential benefit of S/V in specific cardio-oncology clinics. Methods We performed a retrospective multicenter registry (HF-COH) in six Spanish hospitals with cardio-oncology clinics including all p. treated with S/V. Clinical and echocardiographic data, NYHA functional class, type of neoplasms and anti-tumoral treatment were described. Median follow-up was 7.2 [7.9] months. Results Sixty-one p. were included (median age was 64 [21] years old; 64%women, 43% hypertensive, 54% dyslipidemics and 28% diabetics). Most of p. (97%) had cancer therapy related cardiac dysfunction (CTRD) with a median time from anti-cancer therapy to CTRD of 40 [132] months. Breast (46%) and hematological (38%) cancers were the most frequent neoplasms, 31% of p. had metastatic disease and 71% had been treated with anthracyclines. In 5% S/V was initiated at CTRCD diagnosis while in 95% S/V was started to improve clinical status in p. already treated with ACE inhibitors or ARBs. 87% were on beta-blocker therapy and 74% on mineralocorticoid receptor antagonists.Maximal S/V titration dose was achieved in 8.2% of p. (24/26mg: 43%; 49/51mg: 33%) S/V was discontinued in 4 p. (reasons: 2 hypotension; 1: renal failure; 1: pruritus) Baseline NT-proBNP levels, functional class, and LVEF improved at the end of follow-up in p. who continued with S/V (all p values ≤0.01). No statistical differences were found in creatinine clearance or potassium serum levels. Table Patient parameters before and after S/V Before S/V After S/V P value LVEF (%) 33 [7] 39.5 [15] <0.001 Creatinine (mg/dl) 0.9 [0.4] 0.9 [0.5] 0.15 Creatinine clearance (ml/min) 73 [30] 75 [37] 0.22 Potassium serum levels (mg/dl) 4.5 [0.5] 4.5 [0.6] 0.42 Systolic arterial pressure (mmHg) 116 [23] 112 [27] 0.025 Diastolic arterial pressure (mmHg) 70 [13] 68 [10] 0.498 NT-proBNP (pg/ml) 1831 [3132] 842 [1919] 0.007 NYHA 2.2±0.6 1.6±0.62 <0.001 Values are median [interquartile range] or mean ± standard derivation; S/V: sacubitril-valsartan; LVEF: left ventricle ejection fraction. Conclusions Our experience suggests that S/V is well tolerated and improves functional class and left ventricular function parameters in patients with CTRCD.

Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy

ObjectivesThis study determined the effects of doxorubicin and/or trastuzumab on diastolic function and the relationship between diastolic function and systolic dysfunction. BackgroundDoxorubicin and trastuzumab can result in left ventricular ejection fraction (LVEF) declines. However, the effects of these therapies on diastolic function remain incompletely defined. MethodsIn a rigorously phenotyped, longitudinal cohort study of 362 breast cancer participants treated with doxorubicin, doxorubicin followed by trastuzumab, or trastuzumab alone, changes in diastolic function were evaluated using linear models estimated via generalized estimating equations. Associations between baseline and changes in diastolic function with LVEF and longitudinal strain were also determined using generalized estimating equations. The Kaplan-Meier estimator derived the proportion of participants who experienced incident diastolic dysfunction. Cox proportional hazards models estimated the associations between participant characteristics and diastolic dysfunction risk, and between diastolic function and cancer therapy−related cardiac dysfunction risk, defined by an LVEF decline of ≥10% to <50%. ResultsOver a median of 2.1 years (interquartile range [IQR]: 1.3 to 4.2 years), participants treated with doxorubicin or doxorubicin followed by trastuzumab demonstrated a persistent worsening in diastolic function, with reductions in the E/A ratio, lateral and septal e′ velocities, and increases in E/e′ (p < 0.01). These changes were not observed with trastuzumab alone. Incident abnormal diastolic function grade occurred in 60% at 1 year, 70% by 2 years, and 80% by 3 years. Abnormal diastolic function grade was associated with a subsequent decrease in LVEF (−2.1%; 95% confidence intervals [CI]: −3.1 to −1.2; p < 0.001) and worsening in longitudinal strain (0.6%; 95% CI: 0.1 to 1.1; p = 0.013) over time. Changes in E/e′ ratio were modestly associated with worsening longitudinal strain (0.1%; 95% CI: 0.0 to 0.2; p = 0.022). ConclusionsA modest, persistent worsening of diastolic function is observed with contemporary breast cancer therapy. Abnormal and worsening diastolic dysfunction is associated with a small risk of subsequent systolic dysfunction. (Cardiotoxicity of Cancer Therapy [CCT]; NCT01173341)

An international survey of healthcare providers\u2019 knowledge of cardiac complications of cancer treatments

BackgroundCardio-oncology is a young sub-specialty that addresses the needs of cancer patients at risk of, or who have experienced cancer therapy related cardiac dysfunction (CTRCD). This study assessed clinicians’ understanding of cardio-oncology, opinions towards current practice, and approach to diagnosing and managing CTRCD.MethodsA 45-question survey was administered online via Survey Monkey and WeChat to health care providers (HCPs) comprising of cardiologists, oncologists, and others from September 2017 to March 2018. Implementation of the survey followed a modified Dillman’s Total Design Method.ResultsIn total, 160 responses were collected from 22 countries; majority were from cardiologists (53.8%) and oncologists (32.5%). The remaining 13.7% identified themselves as “others,” including general internists, cardio-oncologists, pediatric oncologists, radiation oncologists, cardiac rehabilitation therapists, nurse practitioners, research students, and pharmacists. In the setting of metastatic cancer, there was a difference in risk tolerance for cardiotoxicity between subspecialties. In this case, more cardiologists (36.7%) accepted a 5–10% risk of cardiotoxicity compared to oncologists (20.0%). Majority of cardiologists felt that cardiotoxicity should be monitored, even in asymptomatic cancer patients (55.8%). Only 12% of oncologists selected this response. In contrast, 50.0% of oncologists reported that cardiologists should be involved only when patients develop cardiotoxicity. In comparison, 6.5% of cardiologists selected this response. Majority of cardiologists stated that cardio-oncology clinics would significantly improve cancer patients’ prognosis (88.3%); only 45.8% of oncologists shared this opinion. Of all respondents, 66.9% stated they were familiar with a variety of international guidelines for managing cardiotoxicity. Of all oncologists, 65.3% indicated that they referred to these guidelines for clinical decision making.ConclusionsDespite the growth of cardio-oncology clinics, there are significant knowledge gaps regarding prevention and treatment strategies for CTRCD among health care providers. Knowledge translation from guidelines and collaboration between cardiologists and oncologists are needed to improve cardiovascular outcomes of cancer patients.

Assessment of Prognostic Value of Left Ventricular Global Longitudinal Strain for Early Prediction of Chemotherapy-Induced Cardiotoxicity

Echocardiographic left ventricular global longitudinal strain (GLS) detects early subclinical ventricular dysfunction and can be used in patients receiving potentially cardiotoxic chemotherapy. A meta-analysis of the prognostic value of GLS for cancer therapy-related cardiac dysfunction (CTRCD) has not been performed, to our knowledge. To explore the prognostic value of GLS for the prediction of CTRCD. Systematic search of the MEDLINE, Embase, Scopus, and the Cochrane Library databases from database inception to June 1, 2018. Cohort studies assessing the prognostic or discriminatory performance of GLS before or during chemotherapy for subsequent CTRCD. Random-effects meta-analysis and hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the prognostic and discriminatory performance of different GLS indices. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity. The primary outcome was CTRCD, defined as a clinically significant change in left ventricular ejection fraction with or without new-onset heart failure symptoms. Analysis included 21 studies comprising 1782 patients with cancer, including breast cancer, hematologic malignancies, or sarcomas, treated with anthracyclines with or without trastuzumab. The incidence of CTRCD ranged from 9.3% to 43.8% over a mean follow-up of 4.2 to 23.0 months (pooled incidence, 21.0%). For active treatment absolute GLS (9 studies), the high-risk cutoff values ranged from -21.0% to -13.8%, with worse GLS associated with a higher CTRCD risk (odds ratio, 12.27; 95% CI, 7.73-19.47; area under the HSROC, 0.86; 95% CI, 0.83-0.89). For relative changes vs a baseline value (9 studies), cutoff values ranged from 2.3% to 15.9%, with a greater decrease linked to a 16-fold higher risk of CTRCD (odds ratio, 15.82; 95% CI, 5.84-42.85; area under the HSROC, 0.86; 95% CI, 0.83-0.89). Both indices showed significant publication bias. Meta-regression identified differences in sample size and CTRCD definition but not GLS cutoff value as significant sources of interstudy heterogeneity. In this meta-analysis, measurement of GLS after initiation of potentially cardiotoxic chemotherapy with anthracyclines with or without trastuzumab had good prognostic performance for subsequent CTRCD. However, risk of bias in the original studies, publication bias, and limited data on the incremental value of GLS and its optimal cutoff values highlight the need for larger prospective multicenter studies.

Longitudinal strain analysis allows the identification of subclinical deterioration of right ventricular function in patients with cancer therapy-related left ventricular dysfunction

Background: This study was designed to assess right ventricular systolic function in cancer patients. Methods and Results: 68 consecutive patients receiving potentially cardiotoxic agents were followed for 6 months in a single-center, observational, cohort-study. Left ventricle and free-wall right ventricular longitudinal strain were analyzed prior and after 6 months of treatment, using a vendor-independent software, together with left ventricle ejection fraction, tricuspid annulus plane systolic excursion and right ventricular fractional area change. Cancer therapy-related cardiac dysfunction was defined as a left ventricle ejection fraction drop of >10% to <53%. Both left ventricle ejection fraction (59±7% vs. 55±8%, p<0.0001) and left ventricle longitudinal strain (−19.7±2.5% vs. −17.1±2.6%, p<0.0001) were reduced at follow up, along with free-wall right ventricular longitudinal strain (−24.9±4.5% vs. −21.6±4.9%, p<0.0001). Cancer therapy-related cardiac dysfunction was detected in 20 patients (29%). In 15 out of these 20 patients (75%), a concomitant relative reduction in free-wall right ventricular longitudinal strain magnitude by 17±7% was detected. Moreover, there was a significant correlation between left ventricle and free-wall right ventricular longitudinal strain at follow-up examinations (r=0.323, p<0.0001). A relative drop of right ventricular longitudinal strain >17% had a sensitivity of 55% and a specificity of 70% (AUC=0.75, 0.7-0.8, 95% CI) to identify patients with cancer treatment related cardiac dysfunction. Neither tricuspid annulus plane systolic excursion (24±5 vs. 23±4 mm, p=0.07), nor right ventricular fractional area change (45±8% vs. 44±7%, p=0.6) showed any significant change between examinations.Conclusions: Longitudinal strain analysis allows the identification of subclinical right ventricular dysfunction appearing in the course of cancer treatment when conventional indices of right ventricular dysfunction function are unaffected.

Effect of obesity, dyslipidemia, and diabetes on trastuzumab-related cardiotoxicity in breast cancer.

Clinical trials have demonstrated an increased risk of cardiotoxicity in patients with breast cancer (bca) receiving trastuzumab-based therapy. Diabetes, dyslipidemia, and obesity are known risk factors for cardiovascular disease. Studies have yielded conflicting results about whether those factors increase the risk of cardiotoxicity in patients with bca receiving trastuzumab. In this retrospective cohort study, data were collected for 243 patients with bca positive for her2 (the human epidermal growth factor receptor 2) who were receiving trastuzumab and who were referred to The Ottawa Hospital Cardio-oncology Referral Clinic between 2008 and 2013. The data collected included patient demographics, reason for referral, cardiac function, chemotherapy regimen (including anthracycline use), and 3 comorbidities (diabetes, dyslipidemia, obesity). Rates of symptomatic cancer treatment-related cardiac dysfunction (sctcd) and asymptomatic decline in left ventricular ejection fraction (adlvef) were calculated for patients with and without the comorbidities of interest. Of the 243 identified patients, 104 had either diabetes, dyslipidemia, or obesity. In that population, the most likely reason for referral to the cardio-oncology clinic was adlvef. The combination of 2 or 3 comorbidities significantly increased the incidence of sctcd in our population, reaching a rate of 67% for patients with obesity and dyslipidemia [relative risk (rr): 2.2; p = 0.04], 69% for patients with obesity and diabetes (rr: 2.3; p = 0.02), and 72% for patients with all 3 risk factors (rr: 2.4; p = 0.08). The combination of 2 or 3 comorbidities significantly increases the incidence of symptomatic cancer treatment-related cardiotoxicity. Patients with bca experiencing cancer treatment-related cardiotoxicity who have a history of diabetes, dyslipidemia, and obesity might require more proactive strategies for prevention, detection, and treatment of cardiotoxicity while receiving trastuzumab-based treatment.

P15-T Increased HCN4 expression in hippocampus of SUDEP patients

Background Sudden Unexpected Death in Epilepsy (SUDEP) accounts for approximately 17% of epilepsy related deaths though the pathophysiological mechanisms remain poorly understood. Seizure related cardiac and respiratory dysfunction if often seen as the terminal event with sodium and potassium cardiac channelopathies causing a long QT syndrome. More recently the hyperpolarization-activated cyclic nucleotide–gated (HCN) channels have been shown to be involved in animal models of epilepsy and abnormal genotypes seen in some patients. Here we report the first studies of HCN expression in tissue form human SUDEP patients. Methods Anonymous donor human brain tissue from patients aged 19–31 years and normal controls was obtained from Oxford Brain Bank, UK. Standardised Immunohistochemistry was performed using primary antibodies against HCN1-4 subunits. Cells expressing the HCN were counted using Volocity Software (Perkin Elmer). All results were expressed as a mean (±SEM). Results Immunoreactivity for HCN channels was detected principally in pyramidal neurons of the CA1 area and in the dentate gyrus (DG) of the hippocampus. The only observed difference was a significant increase in HCN4 expression in the DG of SUDEP tissue. (231 ± 41 vs. 111 ± 10, p = 0.044). Discussion HCN4 has been implicated in patients with cardiac dysfunction and one HCN4 gene abnormality linked directly to SUDEP. We are unable to tell whether this upregulation represents a primary cause of the epilepsy of a secondary bystander phenomenon that has led to sudden death but feel that the role of HCN channel regulation in epilepsy and SUDEP has yet to be fully understood.

Cardio-toxicity among patients with sarcoma: A Cardio-Oncology Registry.

e22530 Background: Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracycline (ANT). Cardio-toxicity among patients with breast cancer is well studied but the impact on patients with sarcoma is limited, even though they are exposed to higher ANT doses. The commonly used term for cardio-toxicity is cancer therapeutic related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (EF) reduction of &gt; 10%, to a value below 53%. Our objective was to estimate the prevalence of CTRCD among patients with sarcoma, to evaluate echocardiography parameters associated with its development and whether CTRCD is associated with mortality. Methods: Data were collected as part of the International Cardio-Oncology Registry (ICOR), enrolling all patients who were evaluated in the cardio-oncology clinic at our institution. All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. "Preserved EF" group. Results: Among 43 consecutive patients, 6 (14%) developed CTRCD. Elevated left ventricular end systolic diameter (p = 0.007) and a trend of reduced Global Longitudinal Strain (p = 0.092) were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the "Preserved EF" group. In a multivariate analysis, adjusted to age and EF, CTRCD remained a significant predictor for mortality (p = 0.039). Conclusions: CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors, and is associated with mortality. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.

Cardiac MRI: a Promising Diagnostic Tool to Detect Cancer Therapeutics–Related Cardiac Dysfunction

Recent advances in oncological research have led to a major improvement of mortality amongst cancer patients. However, survivors are at an increased risk to develop cancer therapeutics–related cardiac dysfunction (CTRCD). The management of CTRCD may pose a challenge due to its heterogeneous clinical presentation. This warrants the need for a multi-modality diagnostic tool to objectively acquire prognostic information for timely commencement of cardio-protective treatment. Cardiac magnetic resonance (CMR) imaging offers considerable potential due to its non-invasive, reproducible protocol. Moreover, biomarkers such as T1 and T2 mapping allow discrimination between oedematous and fibrotic myocardium, providing an invaluable diagnostic algorithm to track the temporal evolution of CTRCD. In this review, we appraise current evidence for the role of CMR in the management of CTRCD, placing emphasis on ventricular function, strain, late gadolinium enhancement and parametric mapping. We recommend a central role for CMR in the interdisciplinary management of CTRCD.

ASSOCIATION OF BODY FAT MASS WITH LEFT VENTRICULAR MYOCARDIAL SYSTOLIC LONGITUDINAL DYSFUNCTION IN TYPE 2 DIABETES MELLITUS

Left ventricular (LV) longitudinal myocardial systolic dysfunction (LVSD) recently may be considered the first marker of a preclinical form of type 2 diabetes mellitus (T2DM)-related cardiac dysfunction. On the other hand, overweight has been postulated to contribute to the development of LVSD in

BASELINE ECHOCARDIOGRAPHIC PARAMETERS TO PREDICT CARDIOTOXICITY IN BREAST CANCER PATIENTS RECEIVING CHEMOTHERAPY

Breast cancer is often treated with anthracyclines and HER2 inhibitors, which are well-known cardiotoxic agents. Cancer therapeutics related cardiac dysfunction (CTRCD) has been defined by most guidelines using arbitrary left ventricular ejection fraction (LVEF) cut-off points or decreases. Our

Abstract P4-16-12: Does initial cardiac imaging impact clinical outcomes in patients with breast cancer?

Abstract Background: Echocardiography (echo) and multigated acquisition (MUGA) scans are the most commonly used modalities to assess cardiac function during breast cancer (BC) treatment. However, a case series of 176 patients with cancer suggests enhanced cardiac care with echo surveillance. We hypothesized that patients with early BC imaged by echo have improved cardiac outcomes compared to those imaged by MUGA. Methods: Consecutive patients with stage I to III breast cancer undergoing pre-treatment echo or MUGA were retrospectively screened from January 2010 to December 2014. Patients participating in clinical trials with mandated imaging and/or cardiac reviews were excluded. Demographics, medical history and clinical events were collected via chart review and electronic health records. All patients had a minimum 1 year of follow-up. The primary outcome was a composite of death, cardiac hospitalization or cardiac emergency room visit. Results: 598 patients were identified as having a baseline echo and 636 had had baseline MUGA. Mean follow-up was 4.5±1.4 years. Patients undergoing MUGA were younger, had more advanced stage of disease and received more anthracycline and trastuzumab (table1). Patients imaged by MUGA had lower cardiac function at baseline compared to echo, LVEF 64% vs. LVEF 65% respectively, P &amp;lt;0.001. Cancer therapy related cardiac dysfunction was similar between groups, 10% vs. 11%, p=0.81. Patients in the echo group were more likely to be seen by cardiology, 7% vs. 3%, p&amp;lt;0.0001, and to be initiated on beta blocker, 4% vs. 1%, p=0.006, or angiotensin converting enzyme inhibitor, 3% vs. 1%, p=0.002.However, there was no difference between groups for the primary outcome, 10% event rate in each group, even after adjustment for age, BC stage, chemotherapy and cardiac medications, hazard ratio 1.04 (CI 0.72-1.49), p=0.842. Conclusion: For patients with early stage BC, the choice of cardiac imaging modality at baseline does not impact adverse cardiac events. However, patients undergoing echo were more likely to be evaluated and managed by cardiology. Table 1.Baseline Characteristics Echo (N=598)MUGA (N=636)Age mean54±1053±10*BMI mean29±629±7Cardiovascular HistoryDiabetes66(11%)56(9%)Hypertension154(26%)155(24%)Dyslipidemia83(14%)75(12%)CAD9(2%)6(1%)CHF7(1%)4(1%)Beta Blocker22(4%)28(4%)ACE-Inhibitor51(9%)64(10%)Angiotensin Receptor Blocker69(12%)44(7%)*Cancer HistoryStage*Stage I65(11%)56(9%)Stage II377(63%)361(57%)Stage III155(26%)219(34%)Receptor StatusTriple negative64(11%)76(12%)HER2 negative, hormone positive342(58%)387(61%)HER2 positive192(32%)173(27%)Cancer TherapyChemotherapy (any)528(88%)594(93%)*Anthracycline310(52%)394(62%)*Trastuzumab170(28%)148(23%)*Anthracycline &amp; trastuzumab6(1%)19(3%)*Hormone therapy459(77%)487(77%)Radiation (any)487(81%)527(83%)Radiation left side237(49%)259(49%)Surgery597(100%)633(100%)* p&amp;lt;0.05 for comparison between echo and MUGA groups Citation Format: Parent S, Xu L, Becher H, Mackey J, King K, Pituskin E, Paterson I. Does initial cardiac imaging impact clinical outcomes in patients with breast cancer? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-16-12.

Usefulness of Global Longitudinal Strain for Early Identification of Subclinical Left Ventricular Dysfunction in Patients With Active Cancer

Cardiotoxicity from cancer therapy has become a leading cause of morbidity and mortality in cancer survivors. The most commonly used definition is cancer therapeutic related cardiac dysfunction defined as a left ventricular ejection fraction (LVEF) reduction of >10%, to a value below 50%. However, according to the recent American and European Society of Echocardiography, global longitudinal strain (GLS) is the optimal parameter for early detection of subclinical left ventricular dysfunction. The objective of this study was to evaluate the frequency of GLS reduction in patients with active cancer and its correlation to other echocardiographic parameters. Data were collected as part of the International Cardio-Oncology Registry. All patients performed at least 2 echocardiograms including GLS. We evaluated the frequency of GLS reduction (≥10% relative reduction), its correlation to LVEF reduction and whether there are other predicting echocardiographic parameters. In 64 consecutive patients, 12 (19%) had ≥10% GLS relative reduction, of which 75% had no concomitant ejection fraction reduction. There were no significant differences in the baseline cardiac risk factors (hypertension, diabetes, hyperlipidemia, or smoking). Treatment with Doxorubicin, Pertuzumab, or Ifosfamide was significantly more frequent in patients GLS reduction. No other echocardiographic parameters, including diastolic function or systolic pulmonary artery pressure were significant predictors for GLS reduction. In conclusion, our study demonstrates that GLS reduction is frequent in active cancer patients, precedes LVEF reduction and cannot be anticipated by other echocardiographic parameters. Using GLS routinely during therapy may lead to an early diagnosis of cardiotoxicity.

Evolution of echocardiography in subclinical detection of cancer therapy-related cardiac dysfunction.

Cancer therapies have resulted in increased survivorship in oncological patients. However, the benefits have been marred by the development of premature cardiovascular disease. The current definition outlines measurement of ejection fraction as a mean to diagnose cancer therapeutic-related cardiac dysfunction (CTRCD); however, up to 58% of the patients do not regain their cardiac function after the CTRCD diagnosis, despite therapeutic interventions. Therefore, there has been a growing interest in the markers for early myocardial changes (ie, changes with normal left ventricular ejection fraction [LVEF]) that may predict the development of subsequent left ventricular ejection fraction reduction or progression to heart failure. This review will highlight the use of diastolic parameters, tissue Doppler imaging (TDI), and speckle tracking echocardiogram (STE) as emerging technologies which can potentially detect cardiac dysfunction thereby stratifying patients for cardioprotective therapies. The goal of this manuscript was to highlight the concepts and discuss the current controversies surrounding these echocardiographic imaging modalities.

Crocin attenuates cigarette smoke-induced lung injury and cardiac dysfunction by anti-oxidative effects: the role of Nrf2 antioxidant system in preventing oxidative stress

BackgroundChronic obstructive pulmonary disease (COPD) has been emerging as a great health problem in world. Cigarette smoke is known to cause oxidative stress and deplete glutathione (GSH) levels. Nuclear erythroid-related factor 2 (Nrf2) is involved in transcriptional regulation of glutamate-cysteine ligase catalytic subunit (GCLc). Antioxidant compounds may be of therapeutic value in monitoring disease progression. Crocin demonstrates antioxidant and anti-inflammatory functions. The aim of this study was to investigate the protective role of crocin against CSE-mediated oxidative stress, inflammatory process, Nrf2 modifications and impairment of cardiac function in rats with COPD.MethodsEighty rats were divided into four groups: Control, Cigarette smoke exposure (CSE), Crocin, Crocin+CS. Each group was divided into the two parts: 1) to evaluate lung inflammatory and oxidative process, 2) to evaluate the effect of Cigarette smoke induced-lung injuries on cardiac electrocardiogram (such as heart rate and QRS complex) and hemodynamic parameters (such as perfusion pressure and left ventricular developed pressure).ResultsCSE rats showed a significant increase in cotinine concentration (17.24 ng/ml), and inflammatory parameters and a decrease in PO2 (75.87 mmHg) and expression of PKC (0.86 fold), PI3K (0.79 fold), MAPK (0.87 fold), Nrf2 (0.8 fold) and GCLc (0.75 fold) genes, antioxidant activity, and finally cardiac abnormalities in electrocardiogram and hemodynamic parameters. Co-treatment whit crocin could restore all these values to normal levels.ConclusionsCS induced-COPD in rat model provides evidence that chronic CS exposure leads to lung injury and mediated cardiac dysfunction. Crocin co-treatment by modulating of Nrf2 pathway protected lung injury caused by COPD and its related cardiac dysfunction. In this study, we showed the importance of Nrf2 activators as a therapeutic target for the development of novel therapy for lung oxidative injuries.

PREGNANCY OUTCOMES IN PATIENTS WITH AND WITHOUT CANCER-TREATMENT-RELATED CARDIAC DYSFUNCTION: A SYSTEMATIC REVIEW AND META-ANALYSIS

The impact of a prior history of cancer treatment related cardiac dysfunction (CTRCD) on cardiac decompensation (CD) during pregnancy in female cancer survivors has not been examined. Our objective was to perform a meta-analysis to quantify the risk of CD during pregnancy in cancer survivors with

Biomarkers in cancer therapy related cardiac dysfunction (CTRCD)

Biomarkers are at the cornerstone of preventive measures and contribute to the screening process. More recently, biomarkers have been used to gauge the biological response to the employed therapies. Since it is ubiquitously used to detect subclinical disease process, biomarkers also have found its place in cancer therapy related cardiac dysfunction (CTRCD). The aim of this review is to comprehensively present up-to-date knowledge of biomarkers in CTRCD and highlight some of the future biomedical technologies that may strengthen the screening process, and/or provide new insight in pathological mechanisms behind CTRCD.

Potential impact of SGLT2 inhibitors on left ventricular diastolic function in patients with diabetes mellitus.

The pathogenesis of diabetes mellitus (DM)-related cardiac dysfunction is thought to be multifactorial, and possibly a key factor for the development of heart failure with preserved ejection fraction (HFpEF) in patients with DM and preserved left ventricular (LV) ejection fraction. Currently, there is no effective treatment for HFpEF, which is presented as LV diastolic dysfunction. Furthermore, it is well known that, in addition to DM, hypertension and overweight/obesity are also important factors associated with HFpEF. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of diabetic medications indicated only for the treatment of type 2 DM, and a recent clinical trial showed that patients with this disease and at high risk for cardiovascular events attained cardiovascular benefits from SGLT2 inhibitor in comparison with placebo efficacy. In addition to reduction of glycated hemoglobin levels in patients with type 2 DM, SGLT2 inhibitors are associated with weight loss and reductions in blood pressure. However, despite such intriguing results, it remains uncertain whether SGLT2 inhibitors are beneficial for LV diastolic function in patients with DM. This review deals with the impact of SGLT2 inhibitors on LV diastolic function in patients with DM and their current potential for prevention of the future development of HFpEF in such patients.