Asymptomatic Cardiac Dysfunction Research Articles

Abstract PO4-12-07: INSTITUTIONAL EXPERIENCE IN PATIENTS WITH EARLY BREAST CANCER WHO RECEIVED CARDIOTOXIC THERAPY IN CARDIONCOLOGY UNIT

Abstract Introduction: Early breast cancer (eBC) is the most frequent malignancy diagnosed in women worldwide; fortunately, survival is increasing related to early diagnosis and the incorporation of new drugs. In this scenario, preventing long-term toxicities become essential. Cardiac adverse events related to anthracyclines or trastuzumab such as reduction in left ventricular (LV) systolic function and clinical heart failure (HF), are well known and are the leading cause of morbidity in breast cancer survivors. Cardioprotective strategies and early diagnoses of asymptomatic cardiac dysfunction are essential to optimized management and prevention of overt cardiovascular (CV) disease. We made a specific cardiac assessment within an Oncocardiology multidisciplinary Unit in patients receiving anticancer therapies. We present the experience in patients with eBC treated with anthracyclines, trastuzumab or both in the past five years. Materials and Methods: We conducted an institutional, interventional, prospective study in patients who received anthracyclines, trastuzumab or both according to the standard of care (SoC) in eBC. Basal CV risk stratification included lipid profile, glycated haemoglobin, high-sensitive troponin T (hs-TnT) and N-terminal ProB-type natriuretic peptide (NT-ProBNP) was done. Image assessment was done by echocardiogram (echo), including myocardial deformation assessed by speckle tracking (STRAIN). Follow-up was done according to anthracycline or trastuzumab therapy with echo and cardiac biomarkers during the systemic therapy and at the end of anticancer treatment, 1, 2 and 5 years after. Patients with uncontrolled CV risks factors according to local protocol, asymptomatic cardiac dysfunction defined as decreased strain (>15% compared with baseline) or increased cardiac biomarkers (Hs-TnT >14 at baseline or x3 basal value during the follow-up; NT-ProBNP > 300 in patients with < 50y; > 600 in patients between 50-75-y or >900 in patients > 75 years or older) or patients who develop heart failure during the treatment or follow-up were referred to cardiologist. Results: between 2018 and 2022, 1125 patients were diagnosed with eBC in our institution, and 435 patients received systemic treatment with anthracyclines, trastuzumab or both. During the study period, 165 of these patients were referred to the cardio-oncologist. 60% received treatment with anthracyclines, 36% with trastuzumab and 4.1% with both. The median age was 58(±23.2), 60% had previous CV risk factors. The main reason to refer patients to the cardio-oncologist was asymptomatic cardiac dysfunction and uncontrolled CV risk factors. (Table 1). 60% of patients initiated angiotensin-converting-enzyme inhibitors or Beta-blockers, and only two patients stopped anticancer therapy due to severe cardiac dysfunction. The period of high risk of developing cardiotoxicity was the first year after the end of treatment. Conclusion: multidisciplinary evaluation within a cardio-oncology unit is useful to optimize CV risk factors and to detect asymptomatic cardiac dysfunction in patients receiving cardiotoxic drugs. Table 1. Main reasons to refer patients to cardiologist. Citation Format: Tamara Martos, Laia Carla Belarte-Tornero, Mireia Ble, Eva Gimeno, Laura Sanhauja, Felicidad Martines-Medina, Maria Martinez-García, Maria Castro-Henriques, Joan Albanell, Sonia Servitja. INSTITUTIONAL EXPERIENCE IN PATIENTS WITH EARLY BREAST CANCER WHO RECEIVED CARDIOTOXIC THERAPY IN CARDIONCOLOGY UNIT [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-07.

Cardiac CARE study: How the ESC Cardio-Oncology guidelines fo 2022 affect the study population

Abstract Introduction The new 2022 ESC Guidelines in Cardio-Oncology focused on cancer therapy-related cardiac dysfunction (CT-RCD), with the formal introduction of biomarkers in the classification and risk stratification of CTR-CD in addition to structural imaging . We here, investigated how these changes affect the classification of patients in the Cardiac CARE study and the value of high sensitivity troponin I (hSTrop-I). Methods The Cardiac CARE study prospectively recruited 191 patients who underwent anthracycline therapy for breast cancer or non-Hodgkin’s lymphoma. All patients underwent regular hSTrop-I levels throughout their anthracycline therapy as well as a baseline and 6-month cardiac magnetic resonance scans including assessment of left ventricular ejection fraction and global longitudinal strain. A post-hoc analysis assessed the association between hSTrop-I and the development of cardiac dysfunction (defined as a reduction in left ventricular ejection fraction <50% or a reduction in GLS by >15%) using logistic regression with data corrected for age and gender. In addition, receiver operator curves (ROC) were drawn and area under the curve (AUC) analysis was performed to assess the value of hSTrop-I as an addition to the classification model. Finally, to compare our data with the new guidelines, a confusion matrix was performed. Results 11 patients were diagnosed as having cardiotoxicity in the Cardiac CARE study but using the 2022 ESC guidelines in Cardio-Oncology, 53 patients were re-classified into the ‘asymptomatic mild cardiotoxicity’ group (95% CI of 0.5162 and 0.6823; kappa value 0.157). Using a logistic regression model, a difference in hSTrop-I measured at the first cycle of anthracycline therapy had an odds ratio of 1.37 (95% CI 0.37-5.10) which when corrected for age dropped to 1.18 (95% CI of 0.28-5.01) and with combined age and sex correction, fell further, to 0.83 (95% CI of 0.12 and 5.56). A ROC analysis looking at the performance of hSTrop-I at predicting cardiac dysfunction demonstrated an area under the curve of 0.605 and when corrected for age and sex, was 0.640. Conclusion The addition of cardiac biomarkers to the new classification, significantly reclassified 53 of 191 (27.7%) of patients who were previously normal, to having asymptomatic mild cancer therapy-related cardiac dysfunction, mostly due to the inclusion of hSTrop I. HSTrop-I prior to anthracycline treatment was not a robust predictor of the development of anthracycline-induced cardiotoxicity in our cohort of patients. Of note, the Cardiac CARE patients are a low-risk group of patients and follow-up data is limited to 6 months.

Abstract 15129: Applying Magnetocardiography to Identify Asymptomatic Ischemic Heart Failure at an Early Stage

Introduction: Asymptomatic cardiac dysfunction (ACD) has management implications, and been shown to have special cardiac electrical signal features, magnetocardiography (MCG) can be used in a range of cardiovascular diseases by tracing subtle changes of the cardiac electromagnetic activity. Hypothesis: MCG could be used to identify ACD in patients with heart failure (HF) risk factors. Methods: This study was a subcohort of a prospective MCG study (NCT05392712), in which patients hospitalized with ischemic heart disease (IHD) were all underwent MCG examination. Patients with asymptomatic HF, according to the American Heart Association Heart Failure Guideline, were divided into “at risk for HF” (stage A) or “pre-HF” (stage B, namely ACD). Supervised machine-learning were undertaken to select specific MCG features and establish MCG recognition model for pre-HF (MCG-HF model), which was further tested in an independent test set. In the end, we compared the performance of MCG-HF model with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the optimized Atherosclerosis Risk in Communities (ARIC) HF risk score for identifying pre-HF. Results: A total of 420 inpatients with IHD, of which 111 were in stage A and 309 in stage B, were included in this study. In an independent test set (n= 126), the MCG-HF model for identifying patients at stage B demonstrated 95.7% sensitivity and 66.7% specificity (area under the receiver-operating characteristic curve [AUC]: 0.904; 95% confidence interval [CI]: 0.800 to 0.957). The AUC for optimized ARIC model and NT-proBNP model were 0.631 (95% CI:0.572 to 0.690) and 0.761 (95% CI:0.716 to 0.807), respectively. Conventional methods for pre-HF recognition showed inferior discriminative ability. Conclusions: The MCG based on machine learning shows valuable performance in identifying ACD, the cardiac magnetic signal detection technology provides a rapid and optimized screening tool in patients at risk for HF.

Association between insulin resistance and cardiac remodeling in HER2-positive breast cancer patients: a real-world study

BackgroundInsulin resistance is an overlapping risk factor for both heart and breast cancer, while its interaction with cardiotoxicity in breast cancer (BC) patients is not clear. This study investigated the impact of insulin resistance on cardiac remodeling in patients with human epidermal growth factor receptor 2 (HER2)-positive BC during and after trastuzumab therapy in real-world clinical practice.MethodsHER2-positive BC patients who received trastuzumab treatment between December 2012 and December 2017 were reviewed and 441 patients with baseline metabolic indices and serial echocardiographic measurements (baseline, 6, 12, and 18 months) after trastuzumab therapy initiation were included. Repeated measurement analysis of variance was used to evaluate temporal trends in multiparameter echocardiography. Linear mixed model was applied to further evaluate the role of insulin resistance in forementioned changes. Correlation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and triglyceride-glucose index (TyG) levels to changes in echocardiography parameters was explored.ResultsOf 441 patients (mean age 54 ± 10 [SD] years), 61.8% received anthracycline-based chemotherapy, 33.5% received left-sided radiotherapy, 46% received endocrine therapy. No symptomatic cardiac dysfunction was observed over the therapy course. A total of 19 (4.3%) participants experienced asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), and the peak onset time was 12 months after the initiation of trastuzumab. Albeit relatively low CTRCD incidence, cardiac geometry remodeling, especially left atrial (LA) dilation over therapy was notable and was more severe in high HOMA-IR and TyG level groups (P < 0.01). Noteworthy, a partial reversibility of cardiac remodeling was observed with treatment cessation. Additionally, HOMA-IR level positively correlated to changes in LA diameter from baseline to 12 months (r = 0.178, P = 0.003). No significant association (all P > 0.10) was detected between HOMA-IR or TyG level and dynamic left ventricular parameter evaluation. Multivariate linear regression analysis demonstrated that higher HOMA-IR level was an independent determinant for LA enlargement in BC patients during anti-HER2 targeted therapy course after adjusting for confounding risk factors (P = 0.006).ConclusionInsulin resistance was associated with left atrial adverse remodeling (LAAR) in HER2-positive BC patients that received standard trastuzumab therapy, indicating that insulin resistance could be a supplementation to baseline cardiovascular risk stratification proforma for HER2-targeted antitumor therapies.

Longitudinal assessment of cardiac parameters through MRI in breast cancer patients treated with anti-HER2 therapy

BackgroundWe evaluated the early changes in left ventricular (LV) volumetric, functional, and tissue characteristics in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with trastuzumab and/or pertuzumab at cardiac magnetic resonance imaging (MRI).MethodsHER2-positive breast cancer patients undergoing planned anti-HER2 therapy and nonanthracycline-based chemotherapy were enrolled and subdivided into dual anti-HER2 (trastuzumab plus pertuzumab) group and trastuzumab group. Cardiac MRI was performed before treatment and three months after starting, covering ventricular volumes, cardiac function, systolic myocardial strain, myocardial oedema, and T1 and T2 relaxation times. Cardiac dysfunction was primarily defined as a > 10% reduction in LV ejection fraction (LVEF) to < 55% and/or a > 15% global longitudinal strain (GLS) change at the follow-up MRI examination.ResultsTwenty-four HER2-positive patients were evaluated (16 in the dual anti-HER2 group, 8 in the trastuzumab group). Six patients developed cardiac dysfunction at follow-up, five of them in the dual anti-HER2 group. One patient developed symptomatic heart failure, and five patients developed asymptomatic cardiac dysfunction. Patients displayed significantly decreased systolic function and increased T1 and T2 relaxation time at follow-up (p ≤ 0.031). Systolic dysfunction remained significant in the dual anti-HER2 group. The decrease in GLS in the trastuzumab group was not significant (p = 0.169). T1 and T2 relaxation times tended to increase, but this was not significant at subgroup analysis.ConclusionsCardiac MRI scans showed frequent signs of subclinical cardiotoxicity after short-term anti-HER2 therapy and nonanthracycline-based chemotherapy; the effect was slightly stronger in patients treated with dual therapy.Key points• A frequent subclinical cardiotoxicity was detected by cardiac magnetic resonance imaging after short-term anti-human epidermal growth factor receptor 2 (HER2) therapy.• The change in myocardial strain was more marked in patients treated with dual (trastuzumab plus pertuzumab) than with trastuzumab only anti-HER2 therapy.• Cardiotoxicity surveillance through MRI is an interesting option particularly in patients treated with dual anti-HER2 therapy.

Echocardiographic Findings in Asymptomatic Mediastinal Lymphoma Survivors Years after Treatment Termination.

Patients treated due to mediastinal lymphomas are at risk of cardiovascular complications, as they receive chemotherapy, usually containing anthracyclines, often combined with thoracic radiotherapy. The aim of this prospective study was to assess early asymptomatic cardiac dysfunction using resting and dobutamine stress echocardiography (DSE) at least 3 years after the end of mediastinal lymphoma treatment. Two groups of patients were compared: those treated with chemoradiotherapy and those exclusively treated with chemotherapy. Left ventricular contractile reserve (LVCR) during DSE was assessed using changes in LV ejection fraction (LVEF), LV global longitudinal strain (LV GLS), and a novel parameter-Force, which is the ratio of the systolic blood pressure to the LV end-systolic volume. The study included 60 patients examined at a median of 89 months after the end of treatment. Resting echocardiography showed normal LVEF of 58.9 ± 9.6%, borderline LV GLS of -17.7 ± 3%, decreased mean stroke volume (SV) of 51.4 ± 17 mL, and indexed SV of 27.3 ± 8 mL/m2, and the right ventricular free wall longitudinal strain (LS) was impaired in some patients but not in all. There were no significant differences between the groups, with the exception of arterial hypertension, which was more common in the chemotherapy group (32% vs. 62.5%, p = 0.04). In resting echocardiography, only LV posterior wall LS differed significantly and was impaired in patients treated with chemotherapy (-19.1 ± 3.1% vs. -16.5 ± 5.1%, p = 0.04). DSE, performed in 21 patients after a median of 166 months from the end of cancer treatment, detected new contractility disorders in 1 patient (4.8%) and decreased LVCR in the majority of patients when determined using changes in LVEF or LV GLS, and in all patients when assessed with changes in Force. Conclusions: Most asymptomatic mediastinal lymphoma survivors showed preserved ventricular function on resting echocardiography. However, all of them showed impaired LV contractile reserve on DSE, as assessed with a simple parameter-Force. This may indicate subtle LV dysfunction and confirms the need for long-term monitoring of patients with potentially cardiotoxic cancer treatment.

To study asymptomatic cardiac dysfunction in childhood cancer survivors exposed to Adriamycin

To study asymptomatic cardiac dysfunction in childhood cancer survivors exposed to Adriamycin

May standard basal echocardiogram allow to obtain predictors of asymptomatic cardiac dysfunction in alcoholics?

Long-lasting heavy alcohol intake has been progressively recognized as a leading cause of nonischemic dilated cardiomyopathy, involving 10% of all people who use alcohol. It is of huge importance to identify the earliest markers of this dysfunction and it is known that the newest echocardiographic techniques such as speckle tracking may allow to do it. In this study we investigated if standard basal echocardiogram features allow to obtain predictors of asymptomatic cardiac dysfunction in alcoholics. A population of 80 consecutive asymptomatic alcoholics was enrolled. None presented history, signs or symptoms of cardiovascular disease. All of them underwent a conventional transthoracic monobidimensional and doppler echocardiography. Our cohort did not present echocardiographic findings of increased left ventricular sizes, mass or relative wall thickness. Hence, a significant rate of systolic dysfunction was not found. Furthermore, statistical analysis displayed an inverse relationship between alcohol consumption and systolic pulmonary arterial pressure as well as between alcohol abuse and left atrium enlargement. This may be explained by a potential vasodilator mechanism occurring in the earliest stages of alcohol intake. On the contrary, a positive correlation with the E/A ratio was found, and this might be ascribed to state of high cardiac output determined by alcohol abuse. There were modes sex-related differences. This study has demonstrated that standard echocardiography may allow to predict cardiac dysfunction in asymptomatic alcoholics, and sex-related differences may be identified in this regard. These data need to be confirmed by further studies involving larger population.

Long-term morbidity and mortality in 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies.

Prognosis of hepatoblastoma patients has increased with cisplatin-based chemotherapy and high-quality resection including liver transplant. Consequently current risk-adapted therapeutic strategy aims to reduce long-term side effects in patients with standard risk disease. We report long-term mortality and morbidity data concerning 151 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies (sex-ratio M/F = 1.6, median age at diagnosis = 2.6years [range 0-17.7], median year at diagnosis = 2008 [1994-2017]). Fifty-three patients had loco-regional risk factors VPEFR, 12 were PRETEXT-IV and 30 were metastatic. All received cisplatin and 84 anthracyclines. Twelve had liver transplant. To assess hearing, renal and cardiac functions, audiograms were performed in 116/151 patients (76.8%), glomerular filtration rate in 113/151 (74.8%) and cardiac ultrasound in 65/84 (77.4%) anthracycline-exposed patients. With a median follow-up of 9.4years (range 2.1-25.8), four late relapses, one second malignancy (Acute Myeloid Leukemia AML-M5) and two deaths (one from hepatoblastoma, one from AML) occurred. The 10-years event free survival and overall survival probabilities were 95.5% (95% CI 91.9-99.1) and 98.7% (95% CI 96.8-100), respectively. Sixty-eight non-oncologic health-events included 57 cases of hearing loss (including 25 Brock 3-4), three liver cirrhosis, three pre-operative portal cavernoma, two focal nodular hyperplasia, two grade-1 chronic kidney diseases and one asymptomatic cardiac dysfunction were reported. Ototoxicity was significantly associated with cisplatin cumulative dose (OR = 2.07, 95% CI 1.32-3.24, p = 0.001) and carboplatin exposure (OR = 3.14, 95% CI 1.30-7.58, p = 0.01) in multivariable analysis adjusted for sex and age at diagnosis. With current risk-adapted strategies, hepatoblastoma is a highly curable disease, with very rare relapses, and few late effects except hearing loss which remains a serious condition in these very young patients.

N-Terminal Pro Brain Natriuretic Peptide, sST2, and Galectin-3 Levels in Breast Cancer Survivors.

NT-proBNP, soluble ST2 (sST2), and galectin-3 are biomarkers of cardiac dysfunction that have been proposed as identifiers of patients experiencing asymptomatic cardiac dysfunction after anthracycline-based chemotherapy. This study aimed to compare the proportion of breast cancer (BC) survivors with elevated serum levels of these three putative biomarkers by prior receipt of anthracycline (yes vs. no). Five-hundred-eighty survivors of BC who had received anthracycline-based chemotherapy were matched by age and time between diagnosis and serum storage to 580 who had not. Cardiac biomarker levels were analyzed using immunoassays. Analyses were carried out using linear and logistic regression models. Anthracycline recipients had higher values of NT-proBNP than non-recipients (mean 116.0 ng/L vs. 97.0 ng/L, respectively; p < 0.001). Values for ST2 and galectin-3 did not significantly differ by receipt of anthracycline. After further adjustment for age at breast cancer diagnosis, ethnicity, and receipt of trastuzumab, associations between receipt of anthracycline and higher NT-proBNP persisted (p < 0.001), showing that NT-proBNP may be a biomarker of cardiovascular toxicity after receipt of anthracycline-based chemotherapy. Further research to assess the clinical utility of NT-proBNP testing after receipt of anthracycline is recommended. sST2 and galectin-3 do not appear to differentiate between anthracycline recipients and non-recipients amongst breast cancer survivors.

Anthracycline-induced cardiotoxicity: A case report and review of literature

BACKGROUNDDoxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment. The use of anthracycline is limited by dose-dependent cardiotoxicity, which may manifest initially as asymptomatic cardiac dysfunction with subsequent progression to congestive heart failure. Despite baseline assessment and periodic monitoring of cardiac function for patients receiving anthracycline agents, there are unmet needs in prediction and prevention of anthracycline-induced cardiotoxicity (AIC).CASE SUMMARYA 35-year-old African American female was found to have a 9-cm high-grade osteosarcoma of right femur and normal baseline cardiac function with left ventricular ejection fraction of approximately 60%-70% determined by transthoracic and dobutamine stress echocardiogram. She underwent perioperative doxorubicin and cisplatin chemotherapy with 3 cycles before surgery and 3 cycles after surgery, and received a total of 450 mg/m2 doxorubicin at the end of her treatment course. She was evaluated regularly during chemotherapy without any cardiac or respiratory symptoms. Approximately two months after her last chemotherapy, the patient presented to the emergency department with dyspnea for one week and was intubated for acute hypoxic respiratory failure. Echocardiogram showed an ejection fraction of 5%-10% with severe biventricular failure. Despite attempts to optimize cardiac function, the patient’s hemodynamic status continued to decline, and resuscitation was not successful on the seventh day of hospitalization. The autopsy showed no evidence of osteosarcoma, and the likely cause of death was cardiac failure with the evidence of pulmonary congestion, liver congestion, and multiple body cavity effusions.CONCLUSIONWe present a case of 35-year-old African American female developing cardiogenic shock shortly after receiving a cumulative dose of 450 mg/m2 doxorubicin over 9 mo. Cardiac monitoring and management of patients receiving anthracycline chemotherapy have been an area of intense research since introduction of these agents in clinical practice. We have reviewed literature and recent advances in the prediction and prevention of AIC. Although risk factors currently identified can help stratify patients who need closer monitoring, there are limitations to our current understanding and further research is needed in this field.

Peripheral endothelial dysfunction is a novel risk factor for systolic dysfunction and heart failure progression.

ACC/AHA guidelines recognize the progressive nature of heart failure (HF). Patients with risk factors (Stage A) are at risk for developing asymptomatic cardiac dysfunction (Stage B), which may then lead to symptomatic HF (Stage C). As such, therapies targeting abnormalities in stages A and B may protect against development of symptomatic HF. peripheral endothelial dysfunction (PED) is an independent predictor of adverse outcomes in patients with stage C HF. The aim of the current study was to evaluate whether PED might be associated with Stage B HF, where therapeutic interventions to prevent progression might be more efficacious. We performed a retrospective cross-sectional analysis of patients who were referred for routine cardiovascular evaluation that included an assessment of peripheral endothelial function with reactive hyperemia-peripheral arterial tonometry. Individuals in this study underwent routine clinically indicated echocardiography within 2months of testing for PED. Patients with clinical HF were excluded. The study included 355 patients (mean age 51.5±14.6years, 231 (65.1%) female). There was a significant association between PED and Stage B HF (Odds Ratio (OR) 6.38; P<0.0001) that persisted after stratifying by sex. In multivariate analyses PED was significantly associated with Stage B HF (OR 5.33; P=0.0038), and was also associated with progression to overt stage C HF (OR 4.63; P=0.033). Peripheral endothelial dysfunction is risk factor for Stage B HF, even in low risk individuals. Further study is warranted to better understand the mechanistic basis of PED in HF to reduce the risk of symptomatic progression.

N-terminal pro-brain natriuretic peptide levels after receipt of anthracycline for breast cancer.

e24103 Background: Many of the 200,000 patients diagnosed with breast cancer (BC) annually in the United States receive anthracycline-based therapy, increasing their risk of future congestive heart failure. N-terminal brain natriuretic peptide (NT-proBNP) has been used as a biomarker of asymptomatic cardiac dysfunction in the general population and is of interest to identify patients who might benefit from echocardiography during survivorship. This study aimed to assess how age, baseline comorbidities, and time since BC diagnosis impact NT-proBNP levels after anthracycline-based chemotherapy. Methods: This retrospective study, using samples collected in our ongoing prospective Mayo Clinic Breast Disease Registry, included 20 survivors of non-metastatic BC patients per year for each of the first 5 years after anthracycline-based chemotherapy (n=100 total). NT-pro-BNP levels were assessed using a Roche immunoassay. Cardiac risk factors were obtained by chart review. Multivariable linear regression models assessed associations between NT-proBNP values and these independent variables: baseline cardiac risk factors (including hypertension, hyperlipidemia, obesity, diabetes mellitus, and smoking), tumor ER status (surrogate for possible endocrine therapy), time between diagnosis and serum collection, T and N status, use of trastuzumab, and age. Results: The mean age at the time of BC diagnosis was 52.2 (SD 9.8). 13% of tumors were human epidermal growth factor receptor (HER2)-positive and 71% were estrogen receptor (ER) positive. NT-proBNP was elevated in 34%. Mean NT-BNP level was higher (p=0.047) for those in years 4-5 (158 pg/mL) compared to those in years 1-3 (106 pg/mL) (See Table.) Models revealed years from diagnosis to serum draw (p=0.026), older age (p=0.006), more cardiac risk factors (p=0.064), and N2-3 (p=0.001) were associated with elevated NT-pro-BNP level. Use of trastuzumab, ER status, and tumor size were not associated with NT-proBNP. Conclusions: NT-proBNP is elevated in 1/3 of survivors who received anthracycline therapy for BC. As expected, cardiac risk factors and advancing age are associated with higher NT-proBNP. NT-proBNP values &gt;300 were only found in patients who were 4-5 years after diagnosis. Additional research will be needed to further define the diagnostic and prognostic merit of NT-proBNP in survivors after receipt of anthracycline therapy. [Table: see text]

Prevalence and determinants of the precursor stages of heart failure: results from the population-based STAAB cohort study.

Prevention of heart failure relies on the early identification and control of risk factors. We aimed to identify the frequency and characteristics of individuals at risk of heart failure in the general population. We report cross-sectional data from the prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of residents of Würzburg, Germany. Sampling was stratified 1:1 for sex and 10:27:27:27:10 for age groups of 30-39/40-49/50-59/60-69/70-79 years. Heart failure precursor stages were defined according to American College of Cardiology/American Heart Association: stage A (risk factors for heart failure), stage B (asymptomatic cardiac dysfunction). The main results were internally validated in the second half of the participants. The derivation sample comprised 2473 participants (51% women) with a distribution of 10%/28%/25%/27%/10% in respective age groups. Stages A and B were prevalent in 42% and 17% of subjects, respectively. Of stage B subjects, 31% had no risk factor qualifying for stage A (group 'B-not-A'). Compared to individuals in stage B with A criteria, B-not-A were younger, more often women, and had left ventricular dilation as the predominant B qualifying criterion (all P < 0.001). These results were confirmed in the validation sample (n = 2492). We identified a hitherto undescribed group of asymptomatic individuals with cardiac dysfunction predisposing to heart failure, who lacked established heart failure risk factors and therefore would have been missed by conventional primary prevention. Further studies need to replicate this finding in independent cohorts and characterise their genetic and -omic profile and the inception of clinically overt heart failure in subjects of group B-not-A.

Subclinical cardiac dysfunction in cancer patients: a case report

Abstract Cardiotoxicity is a relatively new clinical entity which, in the case of heart failure, is a marker of poor prognosis in cancer survivors who have received more frequent treatments with anthracyclines or trastuzumab. In these patients, detecting a cardiac dysfunction in the subclinical stage can reveal early myocardial involvement and avoid further damage to the heart. Technological advances in imaging, such as the global longitudinal strain, and the increase in troponin I enable the detection of this condition. This case report involves a 17-year-old female patient who was diagnosed with osteosarcoma in her left leg and received anthracyclines. In the cardiovascular evaluation, she was asymptomatic, and showed normal left ventricular function (60 %), decreased strain rate (-15 %) and elevated troponin I levels (115 ng/mL). Asymptomatic cardiac dysfunction was diagnosed and carvedilol 6.25 mg/day was prescribed. After 3 months of treatment, the strain rate (-20 %) and troponin I (19 ng/mL) levels returned to normal. This is an example of the usefulness of new cardiooncology units that allow cancer patients to be evaluated, diagnosed and treated early in order to avoid cardiotoxicity and the resulting mortality.

Reversal of asymptomatic cardiac dysfunction following renal transplantation

Reversal of asymptomatic cardiac dysfunction following renal transplantation

Systematic echo-doppler screening identifies subtle structural and functional cardiac abnormalities in type 2 diabetes mellitus without documented cardio vascular disease: DIACAR a prospective study

Type 2 diabetes mellitus (DM2) is associated with a high prevalence of cardio vascular (CV) disorders including heart failure. The prevalence of asymptomatic cardiac dysfunction in DM2 remains poorly documented in patients without a history of cardio vascular disease. The purpose of DIACAR is to characterize cardiac function by doppler-echocardiography in a population of DM2 without documented CV disease. One hundred and sixteen consecutive outpatients (63 males, 53 females) with DM2 were evaluated prospectively in a single center: 2D (Simpson biplane) & 3D (Heart Model Philips) left ventricular (LV) ejection fraction (EF), LV and left atrial (LA) volumes, 2D global longitudinal strain, diastolic function and LV mass index were measured. All patients with a documented history of CV disease or presenting with symptoms suggestive of any cardiac disorder were excluded. Patients were 57.8 ± 10.9 years old and had a history of DM2 of 12.7 ± 8.7 years. Fifty-two patients (45%) were treated with insulin. Body mass index was 29 ± 4.9 kg/m 2 . Mean values of the echo Doppler parameters were in the normal range ( Table 1 ). 2D Simpson EF and E/e’ were normal in all except one and two patients respectively. However, LV mass index was increased in 8/63 men and 10/53 women and LA volume index was increased in 14/116 patients whereas 2D Simpson LV volumes were all in the normal range. Finally, 2D global longitudinal strain was reduced in 44/105 patients. In a selected population of DM2 without documented CV disease, cardiac function assessed by EF and E/e’ was in the normal range in nearly all patients. By contrast, subtle abnormalities of LV and LA morphology as well as 2D global longitudinal strain were found in a significant proportion of these asymptomatic patients. These results suggest that a systematic screening of DM2 patients by doppler- echocardiography with 2D global longitudinal strain is useful for the early detection of cardiac abnormalities.

P1532Asymptomatic structural heart disease in individuals without apparent cardiovascular risk factors An unnoticed potential precursor stage of heart failure. Results from the STAAB cohort study

Abstract Background and aim Prevention of heart failure (HF) relies on early identification and elimination of cardiovascular risk factors. ACC/AHA guidelines define consecutive asymptomatic precursor stages of HF, i.e. stage A (with risk factors for HF), and stage B (asymptomatic cardiac dysfunction). We aimed to identify frequency and characteristics of individuals at risk for HF, i.e. stage A and B, in the general population. Methods The prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study phenotyped a representative sample of 5000 residents (aged 30–79 y) of a medium sized German town, reporting no previous HF diagnosis. Echocardiography was highly quality-controlled. We applied these definitions: HF stage A: ≥1 risk factor for HF (hypertension, arteriosclerotic disease, diabetes mellitus, obesity, metabolic syndrome), but no structural heart disease (SHD); HF stage B: asymptomatic but SHD [reduced left ventricular (LV) ejection fraction, LV hypertrophy, LV dilation, stenosis or grade 2/3 regurgitation of aortic/mitral valve, grade 2/3 diastolic dysfunction], or prior myocardial infarction; Normal (N): no risk factor and no SHD. We focused on subjects in stage B without apparent cardiovascular risk factors qualifying for A (B-not-A) compared to those with risk factors (BA) and N. The first half of the sample (n=2473) served as derivation set (D), the second half (n=2434) as validation set (V). Results We found 42% (D)/45% (V) of subjects in stage A, and 18% (D)/17% (V) in stage B. Among stage B subjects, 31% (D)/29% (V) were B-not-A. Compared to BA, B-not-A subjects were younger [47 vs. 63 y (D)/50 vs 63 years (V); both p&lt;0.001] and more often female [78% vs 56% (D)/79% vs 62% (V); both p&lt;0.001], had higher LV ejection fraction [59% vs 56% (D)/53% vs 48% (V); both p&lt;0.05], lower E/e' [6.7 vs 9.9 (D)/6.9 vs. 9.3 (V); both p&lt;0.001], higher LV volume [64 vs 59 mL/m2 (D)/54 vs 48 mL/m2 (V); both p≤0.01], lower hemoglobin [13.3 vs 13.9 g/dL (D, p=0.02)/13.4 vs 13.8 g/dL (V, p=0.08); both adjusted for sex], and lower QTc interval [423 vs 433 ms (D)/427 vs 438 ms (V); both p≤0.001). Compared to N, subjects in B-not-A were more often female [78% vs 56% (D)/79% vs 61% (V); both p&lt;0.001], had larger QTc interval [423 vs 418 ms (D)/427 vs 420 ms (V); both p&lt;0.05], and more often anemia [11% vs 5% (D, p=0.02)/9% vs 5% (V, p=0.12)]. Conclusions We confirmed, by extensive internal validation, the presence of a hitherto undescribed group of individuals with relevant myocardial alterations, but lacking respective risk factors. Since algorithms in primary prevention do not include echocardiography, this subgroup might be missed. Further investigations should 1) externally validate our finding, 2) study the prognostic course of subjects in group B-not-A, and 3) elaborate the material differences between B-not-A and N to identify potential further novel risk factors for HF. Acknowledgement/Funding German Ministry of Research and Education within the Comprehensive Heart Failure Centre Würzburg (BMBF 01EO1004 and 01EO1504)

427-P: The Prevalence of Asymptomatic Cardiac Dysfunction Diagnosed by Tissue Doppler Echocardiography in Subjects with Type 2 Diabetes

Background: The sodium-glucose transporter 2 inhibitors have been found to reduce the risk of hospitalization for heart failure (HF). However, in the majority of clinical studies of diabetes, HF is usually defined as administration to hospital with typical symptoms without measurements of cardiac-function using tissue Doppler echocardiography (TDE). Therefore, the incidence of cardiac-dysfunction in diabetic subjects would be underestimated, leading to a delay in the initiation of treatment. Thus, we analyzed the prevalence of asymptomatic cardiac-dysfunction (ACD) diagnosed by TDE in subjects with diabetes. Methods: We recruited inpatients or outpatients with type 2 diabetes at university hospital. Subjects with symptomatic HF, atrial fibrillation, myocardial infarction, valvular disease, and hypertrophic cardiomyopathy were excluded from this study. Finally, 343 diabetic subjects were enrolled. Cardiac-dysfunction was defined as left ventricular ejection fraction &amp;lt;50% (systolic dysfunction) and/or the ratio of early transmitral flow velocity to TDE diastolic mitral annular velocity&amp;gt;15 (diastolic dysfunction). To determine optimum cut-off values for BNP and eGFR associated with ACD, we performed ROC curve analyses. Results: Twenty-four % of subjects had ACD. Seventy-eight % of these subjects had diastolic dysfunction. Age, the proportion of females, pulse wave velocity and BNP were higher, and eGFR was lower in subjects with cardiac-dysfunction than those without cardiac-dysfunction. ROC curve analyses revealed that AUCROC for BNP was 0.66 with a sensitivity of 57% and a specificity of 70% at a cut-off value of 32 mg/gCr, and eGFR was 0.53 with a sensitivity of 74% and a specificity of 70% at a cut-off value of 62 mL/min/1.73m2 (both p&amp;lt;0.001). Conclusions: About a quarter of diabetic subjects had ACD, and the majority of them were diastolic dysfunction. Therefore, TDE would be needed to accurately assess ACD in subjects with diabetes. Disclosure Y. Takata: None. M. Takakado: None. T. Hadate: None. R. Kawamura: None. H. Osawa: None.

Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease.

Although the relationship between protein-bound uremic toxins (PBUTs) and cardiac structure and cardiac mortality in chronic kidney disease (CKD) has been studied in the past, the association between cardiac dysfunction and PBUTs has not yet been studied. We therefore evaluated the association between impaired peak cardiac performance and the serum free and total concentrations of potentially cardiotoxic PBUTs. In a cross-sectional study of 56 male CKD patients (stages 2–5 (pre-dialysis)) who were asymptomatic with no known cardiac diseases or diabetes we measured peak cardiac power (CPOmax), aerobic exercise capacity (VO2max), and echocardiographic parameters of cardiac morphology and evaluated their association with PBUTs. The serum total and free concentrations of indoxyl sulfate (IXS), p-cresyl sulfate (PCS), p-cresyl glucuronide, indole acetic acid, and hippuric acid showed significant negative correlation with CPOmax and VO2max. IXS and PCS were independently associated with CPOmax and VO2max even after controlling for eGFR. No correlation between left ventricular mass index (LVMI) and PBUTs was seen. The present study for the first time has demonstrated the association between subclinical cardiac dysfunction in CKD and serum levels of a panel of PBUTs. Further studies are required to evaluate the mechanism of cardiotoxicity of the individual uremic toxins.