Chemotherapy-related Cardiac Dysfunction Research Articles

Extracellular volume measured by whole body CT scans predicts chronic cardiotoxicity in breast cancer patients treated with neoadjuvant therapies based on anthracyclines: a retrospective study

IntroductionNeoadjuvant chemotherapies for breast cancer (BC) are effective but potentially cardiotoxic, and expose long survivors at risk of chemotherapy-related cardiac dysfunction (CTRCD). Unfortunately, early screening for CTRCD has actual diagnostic limits. Myocardial extracellular volume (mECV) is a radiological marker used in cardiac CT scans and cardiac magnetic resonance for diagnosis and follow-up of CTRCD. It can be measured in whole-body CT (WB-CT) scan, routinely performed in patients at high risk of relapse, to evaluate CTRCD occurrence during oncological follow-up. Methods82 WB-CT scans were examined at baseline (T0) and during oncological follow-up at first year (T1) and fifth year (T5) after the end of neoadjuvant treatment. mECV was measured at 1 minute (PP) and 5 minutes (DP) after contrast injection. 31 echocardiograms were retrieved in T1 to perform a linear correlation between mECV and left ventricular ejection fraction (LVEF). ResultsmECV values in T0 were similar between the two groups both in PP and in DP. Significant results were found for PP values in T1 (37.0% vs 32%, p=0.0005) and in T5 (27.2% vs 31.2%, p=0.025). A cut-off value of 35% in PP proved significant in T1 (OR=12.4, p=0.004), while mECV was inversely correlated with LVEF both in PP (adj-S=-3.54, adj-p=0.002) and in DP (adj-S=-2.51, adj-p=0.0002), suggesting a synergistic action with the age at diagnosis (p<0.0001, respectively). ConclusionsWB-CT scans performed during oncological reassessment in patients at high-risk of recurrence could be used for CTRCD screening in cardiovascular low-risk patients, especially in aging patients with mECV values above 35%.

Beta-Adrenergic Signaling Induces Arrhythmias and Cardiac Dysfunction in Paclitaxel-Treated Mice

In the past two decades, chemotherapy-related cardiac dysfunction (CRCD) has emerged as a dangerous complication in cancer survivors. Despite recent advancements, the mechanisms underlying the development and progression of CRCD remain poorly understood. Paclitaxel (PTX), an antimicrotubular agent, is known to produce dysrhythmia in 29% of patients when used as monotherapy. Since cardiac stress via β-adrenergic signaling is known to exacerbate arrhythmias, here we examine the action of a single isoproterenol (ISO) injection in wild-type mice treated with low and high therapeutic doses of PTX (8mg/kg and 12.5mg/kg, respectively). Male mice were treated with 4 intraperitoneal (IP) injections of PTX or vehicle (1:1:4 ratio of ethanol: Kolliphor: saline) per week for 4 weeks and a remote telemetry device was surgically implanted. Following treatment, mice were challenged with one IP injection of 5mg/kg ISO and ambulatory electrocardiography was performed. Over the course of PTX treatment, low- and high-dose PTX-treated mice displayed significant weight loss compared to vehicle-treated mice (-9.65% vs -0.52%, p=0.0018 and -10.99% vs 0.93%, p=0.0016, respectively). While low-dose PTX-treated mice did not show statistically significant differences in heart weight to body weight ratio compared to vehicle-treated mice (5.56mg/g vs 5.16mg/g, p=0.14), high-dose PTX-treated males showed increased cardiac hypertrophy compared to vehicle-treated mice (5.20mg/g vs 4.89mg/g, p=0.081). Prior to ISO challenge, there was no difference in arrhythmia severity between groups (0.0 vs 0.0, p=0.45 and 0.0 vs 1.0, p=0.99). One hour following ISO challenge, all mice treated with either a low or high dose of PTX showed higher arrhythmia severity than vehicle-treated mice (4.0 vs 2.5, p=0.0087 and 4.0 vs 3.0, p=0.0079, respectively). Additionally, low and high-dose PTX-treated mice experienced more atrioventricular block than vehicle-treated mice in the first hour following ISO challenge (9.17 vs 0.67, p=0.01 and 4.0 vs 1.0, p=0.06, respectively). After 24-hours, differences in arrhythmia severity returned to baseline (0.5 vs 1.0, p=0.99 and 1.0 vs 0.0, p=0.4). Our data indicates that chronic treatment of male mice with therapeutic levels of PTX predisposes to cardiac stress-induced atrial arrhythmias. This finding might have important implications for the treatment of CRCD. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Incidence of chemotherapy-related cardiac dysfunction in cancer patients.

Cancer patients are increasingly affected by chemotherapy-related cardiac dysfunction. The reported incidence of this condition vary significantly across different studies. A better comprehensive understanding of chemotherapy-related cardiac dysfunction incidence in cancer patients is imperative. Therefore, we performed a meta-analysis to establish the overall incidence of chemotherapy-related cardiac dysfunction in cancer patients. We searched articles in PubMed and EMBASE from database inception to May 1, 2023. Studies that reported the incidence of chemotherapy-related cardiac dysfunction in cancer patients were included. A total of 53 studies involving 35 651 individuals were finally included in the meta-analysis. The overall pooled incidence of chemotherapy-related cardiac dysfunction in cancer patients was 63.21 per 1000 person-years (95% CI: 57.28-69.14). The chemotherapy-related cardiac dysfunction incidence increased steeply within half a year of cancer chemotherapy. Also, the trend of chemotherapy-related cardiac dysfunction incidence appeared to have plateaued after a longer duration of follow-up. In addition, chemotherapy-related cardiac dysfunction incidence rates are significantly higher among patients with age ≥50 years versus patients with age <50 years (99.96 vs. 34.48 per 1000 person-years). The incidence rate of cardiac dysfunction was higher among breast cancer patients (72.97 per 1000 person-years), leukemia patients (65.21 per 1000 person-years), and lymphoma patients (55.43 per 1000 person-years). Our meta-analysis unveiled a definitive overall incidence rate of chemotherapy-related cardiac dysfunction in cancer patients. In addition, it was found that the risk of developing this condition escalates within the initial 6 months postchemotherapy, subsequently tapering off to become statistically insignificant after a duration of 6 years.

A prospective randomized controlled trial to determine the safety and efficacy of extracorporeal shock waves therapy for primary prevention of subclinical cardiotoxicity in breast cancer patients without a cardiovascular risk treated with doxorubicin.

Doxorubicin is a highly effective anti-cancer drug that causes left ventricular (LV) dysfunction and induces late-onset cardiomyopathy. However, an effective and clinically applicable preventive treatment is yet to be discovered. Cardiac-Extracorporeal shockwave therapy (C-ESWT) has been suggested to treat inflammatory and ischemic diseases and protect cardiomyocytes from doxorubicin-induced cardiomyopathy. This study aims to assess the safety and efficacy of C-ESWT in the prevention of subclinical cardiotoxicity. We enrolled 64 breast cancer patients. C-ESWT group 33 patients were treated with our C-ESWT (200 shots/spot at 0.09 mJ/mm2 for 20 spots, 3 times every six weeks). The efficacy endpoints were the difference in left ventricular global longitudinal strain (LVGLS) change by 2D speckle tracking echocardiography and chemotherapy-related cardiac dysfunction (CTRCD). Echocardiography was performed on the baseline line and every 4 cycles of chemotherapy, followed by a follow-up 3,6 months after chemotherapy to compare the incidence of cardiomyopathy of subclinical LV dysfunction due to chemotherapy between the two groups. Participants averaged 50 ± 9 years in age, 100% female. In the results of follow-up 6 months after the end of chemotherapy, there was a significant difference in delta LVGLS between the C-ESWT group and the control group (LVGLS; -1.1 ± 10.9% vs. -11.5 ± 11.6% p-value; <0.001). A total of 23% (15 patients) of patients developed CTRCD (Control group; 13 vs. C-ESWT group; (2). C-ESWT was performed safely without any serious adverse events. In this prospective study, C-ESWT established efficacy in preventing subclinical cardiotoxicity, especially in breast cancer patients using doxorubicin chemotherapy, and the safety of C-ESWT. ClinicalTrials.gov, identifier (NCT05584163).

The added value of the HFA/ICOS score in the prediction of chemotherapy-related cardiac dysfunction in breast cancer.

The 2022 ESC Guidelines on Cardio-Oncology recommend baseline cardiovascular risk stratification before starting anticancer drugs, using the new risk assessment tools proposed by the Heart Failure Association (HFA) and the International Cardio-Oncology Society (ICOS).Our study aimed to assess the clinical application of HFA/ICOS risk score in breast cancer patients undergoing chemotherapy and its usefulness in predicting the development of chemotherapy-related cardiac dysfunction (CTRCD). A prospective multicentric study enrolled 109 breast cancer patients treated with anthracyclines with or without trastuzumab. A cardiological evaluation, including ECG and echocardiogram at baseline (T0), 3 (T1), 6 (T2), and 12 months (T3) after starting treatment was performed. HFA/ICOS score was assessed in all patients. The population was divided into low, medium, high, and very-high risk.During follow-up, CTRCD and other cardiovascular events have been evaluated. 61 patients were low risk, 37 medium, 9 high, 2 very-high risk criteria. We found a significantly higher incidence of overall cardiotoxicity (CTRCD and other cardiovascular events) in the very-high risk group (100%) compared with the medium (29%) and low risk groups (13%). CTRCD incidence was also significantly higher in the high risk group (55%). CTRCD resulted as being associated with baseline arterial hypertension and baseline HFA/ICOS risk score of high ( p = 0.006) or very-high ( p < 0.0001). Our study confirms the HFA/ICOS score's ability to predict cardiovascular toxicity in breast cancer women and the need for close monitoring especially in high and very-high risk patients.

Clinical application of the HFA/ICOS score in breast cancer women: its added value in the prediction of chemotherapy-related cardiac dysfunction

Abstract Background Breast cancer is the most common malignancy in women. It is known that anti-cancer drugs can cause cardiovascular complications. Chemotherapy-related cardiac dysfunction (CTRCD) is the main complication of a treatment with anthracyclines, used to treat breast cancer. Echocardiography is fundamental in the evaluation of the left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) to define CTRCD as mild, moderate or severe, in accordance with 2022 ESC Guidelines on Cardio-Oncology. These guidelines recommend cardiovascular baseline risk stratification using the HFA/ICOS score, in order to plan the most appropriate surveillance program and implement cardioprotective strategies. Purpose to assess the usefulness of HFA/ICOS score in patients with breast cancer undergoing treatment with anthracyclines, in predicting the development of CTRCD. Methods A retrospective study was carried out enrolling 109 patients with breast cancer treated with anthracyclines. We performed a cardiological visit with an ECG and echocardiogram at baseline (T0), three months (T1), and six months (T2) after starting treatment. Baseline cardiovascular risk was assessed in all patients, using HFA/ICOS score and patients were classified into 4 groups: low-risk patients, medium-risk patients, high and very high risk patients. During the follow-up, we assessed the development of CTRCD analyzing changes in LVEF and in GLS. Results At baseline, 61 patients had low risk of developing cardiotoxicity, 34 patients had medium risk, 14 patients had high risk, no patients had very high risk. Analyzing the development of CTRCD, 21 patients (20,5%) developed asymptomatic mild CTRCD at T1 and 13 patients (14%) at T2. 1 patient developed moderate asymptomatic CTRCD at T1 and 1 patient at T2. No patient developed severe CTRCD. We found a significantly higher proportion of CTRCD in the high-risk group (57%, pvalue 0,03) than in the medium (41%) and low risk group (32%). In a subanalysis we found a correlation between the development of asymptomatic CTRCD and the presence of LVEF between 50-54% or arterial hypertension in intermedium/low risk patients. Conclusion our study confirms the usefulness of the HFA/ICOS score in the prediction of CTRCD in high risk breast cancer women; however the evidence of a correlation between the presence of LVEF 50-54% or arterial hypertension and the development of asymptomatic CTRCD emphasises the importance of cardiovascular monitoring also in intermediate risk patients, in which chemotherapy plays an additional role of developing CRTD.

Effect of increase in heart rate after anthracycline chemotherapy on subsequent left ventricular dysfunction

BackgroundAnthracycline chemotherapy-related cardiac dysfunction is believed to be refractory to conventional pharmacological therapy and is associated with a poor prognosis. Increased heart rate (HR) is a known marker of cardiovascular outcomes for various categories of heart failure (HF). However, little interest has been expressed regarding increased HR after anthracycline chemotherapy. Aim of this study was to investigate the effect of increased HR soon after completion of anthracycline chemotherapy on subsequent left ventricular (LV) ejection fraction (LVEF) in cancer patients. MethodsWe studied 172 patients with breast cancer and malignant lymphoma with preserved LVEF (≥ 50 %) and sinus rhythm treated with anthracyclines. Electrocardiography was performed before and soon after completion of anthracycline chemotherapy (2.3 months), and echocardiography before and late after completion of anthracycline chemotherapy (10.5 months). ResultsHR significantly increased from 74.2 ± 14.2 bpm to 75.9 ± 13.2 bpm (P = 0.05) soon after completion of anthracycline chemotherapy, while LVEF subsequently significantly decreased from 65.3 ± 5.5 % to 62.4 ± 6.1 % (P < 0.01) late after completion of anthracycline chemotherapy. Patients whose HR increased ≥10 bpm subsequently showed a significantly greater decrease in LVEF than those whose HR increased <10 bpm [−4.9 % (−32.7 % - 10.8 %) vs. -2.2 % (−21.2 % - 12.9 %), p = 0.04]. Multivariable logistic regression analysis showed that an increase in HR soon after completion of anthracycline chemotherapy was independently associated with a subsequent decrease in LVEF (odds ratio: 1.022, 95 % confidential interval; 1.008–1.037, P = 0.002). ConclusionsOur findings may have a novel effect on the management of cancer patients scheduled for anthracycline chemotherapy.

Statins for Primary Prevention of Anthracycline Chemotherapy-Related Cardiac Dysfunction: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Statins for Primary Prevention of Anthracycline Chemotherapy-Related Cardiac Dysfunction: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Prognostic value of coronary atherosclerosis and CAC score for the risk of chemotherapy-related cardiac dysfunction (CTRCD): The protocol of ANTEC study.

Cardiological complications of oncological treatment, including the most serious one, heart failure, constitute a significant and still unsolved clinical problem. A history of dyslipidemia and complications of atherosclerosis, including coronary artery disease, are established risk factors for cardiotoxicity in cancer patients. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. This protocol describes a study aiming to assess the prognostic value of coronary atherosclerosis burden and the CAC score on the onset of cardiac dysfunction associated with cancer therapy. ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a single-site, prospective, observational study to evaluate the influence of the coronary atherosclerosis and CAC score assessed by computed tomography on the development of left ventricular systolic dysfunction in cancer patients with at least moderate cardiotoxicity risk. A group of 80 patients diagnosed with cancer prior to high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 body weight or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. Patient follow-up is planned for 12 months. In all patients, coronary computed tomographic angiography (CCTA) will be performed once at the beginning of the study. The primary endpoint is the onset of cancer therapy-related cardiovascular toxicity, defined as mild, moderate, severe and very severe according to ESC 2022 Cardio-oncology guidelines. During follow up, echocardiography with GLS assessment will be performed every three months. Additionally, new biomarkers of atherosclerosis (IL-6, MPO, TNF-alpha) will be measured every 6 months. The study registration identifier on clinicaltrials.gov is NCT05118178. This study is listed on cinicaltrials.gov with identifier NCT05118178.

Chemotherapy-related cardiac dysfunction: the usefulness of myocardial work indices.

The role of left ventricular global longitudinal strain (GLS) in the diagnosis of subclinical cardiac damage induced by anticancer drugs is now consolidated. Considering some strain disadvantages such as the dependence on the haemodynamic loading conditions, the aim of our study was to investigate the usefulness of non-invasive myocardial work indices (MWI) derived from pressure-strain analysis, in the early diagnosis of cardiotoxicity. We enrolled 61 consecutive patients with breast cancer undergoing adjuvant treatment with anthracycline-containing chemotherapy followed by taxane + trastuzumab. Patients underwent a cardiological evaluation with 2D echocardiography including measurement of the left ventricular ejection fraction (LVEF) and other conventional parameters of systolic and diastolic function, GLS and MWI at baseline (T0), 3 months (T1) and 6 months (T2) after starting chemotherapy. At T1 and T2, we did not find a significant reduction in LVEF but we found a significant reduction in GLS and MWI (p value < 0.05). In addition, at T2, 31% of patients developed subclinical cardiac dysfunction defined as a relative decrease ≥ 12% of GLS from baseline. Global work index (GWI), global constructive work (GCW) and global work efficiency (GWE) decreased significantly in both patients with subclinical dysfunction and in those without subclinical dysfunction (p value < 0.05). Patients with subclinical dysfunction at T2 showed lower values of GCW at T0. MWI changed significantly during chemotherapy and appeared to alter precociously compared to GLS. Therefore, a multiparametric approach including left ventricular GLS and MWI measurements should be used in the evaluation of patients undergoing cardiotoxic antineoplastic treatment.

Comparing Renin-Angiotensin-Aldosterone Blockade Regimens for Long-Term Chemotherapy-Related Cardiac Dysfunction: A Network Meta-Analysis.

Cancer therapies including trastuzumab and anthracyclines are cardiotoxic and cause cardiac dysfunction. To prevent cardiotoxicity, pharmacological agents used in heart failure have been administered concomitantly with cardiotoxic cancer therapy, but few studies to date have performed a head-to-head comparison of these different agents. This systematic review and network meta-analysis of randomized-controlled trials aims to evaluate the efficacy of renin-angiotensin-aldosterone system (RAAS) blockers, namely angiotensin-converting enzyme inhibitors (ACE-Is), aldosterone receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), in primary prevention against chemotherapy-related cardiac dysfunction in patients receiving anthracyclines and/or trastuzumab. A systematic search was performed in major web databases for studies from inception to 15 September 2022. A Bayesian network meta-analysis model was used to assess the relative effects of competing treatments on the primary outcomes of risk of significant decline in left ventricular ejection fraction (LVEF) and mean LVEF decline. Secondary outcomes included left ventricular diastolic function, global longitudinal strain, and cardiac biomarkers. This study is registered with PROSPERO, CRD42022357980. Nineteen studies reported the effects of 13 interventions (N = 1905 patients). Only enalapril (RR 0.05, 95% CI 0.00-0.20) was associated with reduced risk of patients developing significant decline in LVEF relative to placebo. Subgroup analysis showed that the beneficial effect of enalapril was driven by protection against anthracycline-associated toxicity. In addition, no RAAS-inhibiting agents showed efficacy in protection against treatment with both anthracycline and trastuzumab. The use of RAAS inhibition therapy did not conclusively impact on other markers of cardiac function, including left ventricular diastolic function and cardiac biomarkers.

Chemotherapy-Related Cardiac Dysfunction: Quantitative Cardiac Magnetic Resonance Image Parameters and Their Prognostic Implications.

To quantitatively analyze the cardiac magnetic resonance imaging (CMR) characteristics of chemotherapy-related cardiac dysfunction (CTRCD) and explore their prognostic value for major adverse cardiovascular events (MACE). A total of 145 patients (male:female = 76:69, mean age = 63.0 years) with cancer and heart failure who underwent CMR between January 2015 and January 2021 were included. CMR was performed using a 3T scanner (Siemens). Biventricular functions, native T1 T2, extracellular volume fraction (ECV) values, and late gadolinium enhancement (LGE) of the left ventricle (LV) were compared between those with and without CTRCD. These were compared between patients with mild-to-moderate CTRCD and those with severe CTRCD. Cox proportional hazard regression analysis was used to evaluate the association between the CMR parameters and MACE occurrence during follow-up in the CTRCD patients. Among 145 patients, 61 had CTRCD and 84 did not have CTRCD. Native T1, ECV, and T2 were significantly higher in the CTRCD group (1336.9 ms, 32.5%, and 44.7 ms, respectively) than those in the non-CTRCD group (1303.4 ms, 30.5%, and 42.0 ms, respectively; P = 0.013, 0.010, and < 0.001, respectively). They were not significantly different between patients with mild-to-moderate and severe CTRCD. Indexed LV mass was significantly smaller in the CTRCD group (65.0 g/m² vs. 78.9 g/m²; P < 0.001). According to the multivariable Cox regression analysis, T2 (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.01-1.27; P = 0.028) and quantified LGE (HR: 1.07, 95% CI: 1.01-1.13; P = 0.021) were independently associated with MACE in the CTRCD patients. Quantitative parameters from CMR have the potential to evaluate myocardial changes in CTRCD. Increased T2 with reduced LV mass was demonstrated in CTRCD patients even before the development of severe cardiac dysfunction. T2 and quantified LGE may be independent prognostic factors for MACE in patients with CTRCD.

PSY3-1 Cardiac energy metabolism as a therapeutic target against chemotherapy-related cardiac dysfunction (CTRCD)

Due to the recent advances in cancer therapy, prognosis of cancer patient has improved, and the number of cancer survivors has increased. Anthracycline-induced cardiotoxicity has been the most well-known cardiac problem associated with cancer treatment. However, with the advent of molecularly targeted therapy and other advances in cancer treatment, new cancer treatment-related cardiovascular diseases have been reported. In addition to heart failure due to reduced cardiac function, vascular thromboembolism, and immune checkpoint inhibitor -associated myocarditis have also been reported (Nishi et al.

Deterioration in myocardial work indices precedes changes in global longitudinal strain following anthracycline chemotherapy

BackgroundLeft ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) have conventionally been used for surveillance of cardiac function after cancer therapy, but indices of myocardial work (MW) are potentially superior for this purpose because they take into account both myocardial deformation and loading conditions. ObjectivesWe aimed to investigate the usefulness of MW in the follow-up of children and young adults following anthracycline chemotherapy. MethodsConventional markers of LV function (LV fractional shortening [LVFS], LVEF, GLS) and MW indices (global work index [GWI], global constructive work [GCW], global wasted work [GWW], and global work efficiency [GWE]) were obtained from 2342 echocardiographic examinations in 598 patients (354 male, 12.2 [4.7–17.3] years at initiation of chemotherapy). ResultsGWI, GCW, GLS, LVFS, and LVEF all deteriorated significantly during and after anthracycline chemotherapy, while GWW decreased and GWE was preserved. On multivariable analysis, MW indices were correlated with conventional markers of LV function and with clinical information relating to underlying malignancy and chemotherapy. Cox regression analysis revealed that similar levels of deterioration in GWW, GWI, and GCW preceded those in GLS, LFS, and LVEF. ConclusionsNon-invasive MW indices correlate well with conventional markers of LV function. Indices of MW appear to provide an earlier and more sensitive marker of progression towards chemotherapy-related cardiac dysfunction. Future studies are warranted to validate whether the incorporation of non-invasive MW into the routine clinical surveillance in patients after chemotherapy would improve outcomes.

Higher Incidence of Chemotherapy-Related Cardiac Dysfunction after Third Wave COVID-19 Pandemic: A Single Cardioncology Centre Experience

Higher Incidence of Chemotherapy-Related Cardiac Dysfunction after Third Wave COVID-19 Pandemic: A Single Cardioncology Centre Experience

The Utility of Intraventricular Pressure Gradient for Early Detection of Chemotherapy-Induced Subclinical Cardiac Dysfunction in Dogs.

Simple SummaryCardiotoxicity is a serious side effect of doxorubicin in cancer patients due to the risk of development of heart failure. Early detection of doxorubicin-induced cardiomyopa-thy (DXR-ICM) has become a major objective to reduce heart failure in cancer patients. Echocar-diography is the gold standard method to diagnose cardiac diseases when cardiac dysfunction is prominent; however, it still cannot predict or early diagnose heart failure before functional de-cline. The intraventricular blood flow is characterized by intraventricular pressure gradients (IVPG) that created due to the suction of blood by the ventricles. Currently, advanced imaging techniques allow non-invasive assessment of IVPG from color M-mode echocardiography (CMME) after image processing for the clinical setting. Studies revealed that IVPG indices are promising for the early diagnosis of cardiac dysfunction. In this study, we aimed to investigate the usefulness of IVPG to detect cardiac function changes after DXR administration in dogs. Early detection of doxorubicin (DXR)-induced cardiomyopathy (DXR-ICM) is crucial to improve cancer patient outcomes and survival. In recent years, the intraventricular pressure gradient (IVPG) has been a breakthrough as a sensitive index to assess cardiac function. This study aimed to evaluate the usefulness of IVPG for the early detection of chemotherapy-related cardiac dysfunction. For this purpose, six dogs underwent conventional, speckle tracking, and color M-mode echocardiography concomitantly with pressure-and-volume analysis by conductance catheter. The cardiac function measurements were assessed before DXR administration (baseline, Pre), at the end of treatment protocol (Post), and at 1.5 years follow-up (Post2). The result showed a significant reduction in the left ventricular end-systolic pressure-volume (Emax: 4.4 ± 0.7, 6.1 ± 1.6 vs. 8.4 ± 0.8 mmHg/mL), total-IVPG (0.59 ± 0.12, 0.62 ± 0.15 vs. 0.86 ± 0.12 mmHg), and mid-IVPG (0.28 ± 0.12, 0.31 ± 0.11 vs. 0.48 ± 0.08 mmHg), respectively in Post2 and Post compared with the baseline (p < 0.05). Mid-to-apical IVPG was also reduced in Post2 compared with the baseline (0.29 ± 0.13 vs. 0.51 ± 0.11). Meanwhile, the fraction shortening, ejection fraction, and longitudinal strain revealed no change between groups. Total and mid-IVPG were significantly correlated with Emax (R = 0.49; p < 0.05, both) but only mid-IVPG was a predictor for Emax (R2 = 0.238, p = 0.040). In conclusion, this study revealed that impairment of contractility was the initial changes observed with DXR-ICM in dogs and only IVPG could noninvasively detect subclinical alterations in cardiac function. Color M-mode echocardiography-derived IVPG could be a potential marker for the early detection of doxorubicin cardiomyopathy.

What Does a Cardio-oncology Service Offer to the Oncologist and the Haematologist?

Cardio-oncology is an emerging subspecialty arising from the need for multidisciplinary collaboration to address the increasing prominence of cardiovascular disease (CVD) among cancer patients. This overview outlines the case for establishing cardio-oncology services and defines the ways in which these services benefit cancer patients. The primary objective of cardio-oncology is to manage CVDs in order to allow cancer patients to complete the best cancer treatments safely and with minimal interruption. In the decades since the first discovery of heart failure induced by anthracycline chemotherapy, both cardiovascular and oncological science have advanced considerably. Cardio-oncology services aim to bring together expertise from these two fast moving fields in order to provide optimal evidence-based care for cancer patients with CVDs. Here we discuss the basis of cardio-oncology services by presenting their rationale and key components, as well as their essential roles in education, training and research. At each stage of the cancer care pathway, a cardio-oncology service can add value by ensuring cancer patients have timely access to specialist care backed up by cutting edge diagnostic tools and treatment options, as well as holistic supports. We highlight areas of recent and upcoming developments in the field that are likely to change established clinical practice. Improved cardiac imaging modalities can detect chemotherapy-related cardiac dysfunction earlier and are also essential for the prompt diagnosis of an expanding range of cardiovascular effects complicating newer cancer therapeutics, such as immune checkpoint inhibitors and other targeted therapies. Modern cancer therapy has dramatically improved cancer survival and as such CVD is becoming one of the principal determinants of overall outcome for cancer patients. A dedicated cardio-oncology service can facilitate the optimisation of cardiovascular treatment and enable the completion of cancer therapy. A multidisciplinary collaborative approach is key to achieving these objectives.

Assessment of Subclinical Deterioration of Right Ventricular Function by Three-Dimensional Speckle Tracking Echocardiography in Breast Cancer Patients Undergoing Anthracycline-Based Chemotherapy.

ObjectiveThis study was aimed at assessing the longitudinal strain changes of RV function using three-dimensional speckle tracking echocardiography (3D STE) in breast cancer patients receiving anthracycline chemotherapy.Patients and MethodsA total of 95 women with breast cancer receiving epirubicin (360 mg/m2) underwent 3D STE at baseline, the end of chemotherapy and 12 months after chemotherapy. 3D STE assessment included RV ejection fraction (EF), LV global longitudinal strain (GLS), RV GLS, and RV free wall longitudinal strain (RV FWLS). Meanwhile, serum hs‐cTnI and NT-proBNP were measured. Chemotherapy-related cardiac dysfunction (CTRCD) was defined as an absolute decrease in 3D LVEF > 10% to a value <50%, while a percent reduction of 3D LV GLS > 15% indicated subclinical CTRCD.ResultsSubclinical CTRCD occurred in 10 (10.5%) patients during follow-up. Compared to baseline, the 3D GLS of LV and GLS and FWLS of RV decreased significantly at 12months after chemotherapy (all p<0.01). Variations of 3D RV GLS and RV FWLS had a good discrimination for predicting subclinical CTRCD. The variation of 3D RV FWLS was the only independent predictor of subclinical CTRCD (OR, 1.37; 95% CI, 1.12–2.87; p = 0.028) in multivariate analysis. The cutoff value with −17.5% of 3D RV FWLS variation had a high predictive accuracy for subclinical CTRCD, with an AUC of 0.74, 80.5% sensitivity and 65.8% specificity. The association between 3D RV FWLS and the cumulative dose of anthracyclines was calculated by Spearman’s test (r = −0.71, p < 0.001).ConclusionLongitudinal strain analysis by 3D STE allows the identification of subclinical RV dysfunction when conventional indices of RV function are unaffected. 3D RV FWLS was superior to other parameters in early detection of the development of CTRCD in breast cancer patients receiving epirubicin therapy.

Cardiotoxicity of Novel Targeted Hematological Therapies.

Chemotherapy-related cardiac dysfunction, also known as cardiotoxicity, is a group of drug-related adverse events negatively affecting myocardial structure and functions in patients who received chemotherapy for cancer treatment. Clinical manifestations can vary from life-threatening arrythmias to chronic conditions, such as heart failure or hypertension, which dramatically reduce quality of life of cancer survivors. Standard chemotherapy exerts its toxic effect mainly by inducing oxidative stress and genomic instability, while new targeted therapies work by interfering with signaling pathways important not only in cancer cells but also in myocytes. For example, Bruton’s tyrosine kinase (BTK) inhibitors interfere with class I phosphoinositide 3-kinase isoforms involved in cardiac hypertrophy, contractility, and regulation of various channel forming proteins; thus, off-target effects of BTK inhibitors are associated with increased frequency of arrhythmias, such as atrial fibrillation, compared to standard chemotherapy. In this review, we summarize current knowledge of cardiotoxic effects of targeted therapies used in hematology.

Abstract 17413: Determination of Etiology of Left Ventricular Ejection Fracture Decline in Chemotherapy Related Cardiac Dysfunction

Introduction: Chemotherapy related cardiac dysfunction (CTRCD) is an undesired complication of anticancer treatment, roughly affecting 10% of patients undergoing therapy. The American Society of Echocardiography (ASE) and the European Association of Cardiovascular imaging (EACVI) defines CTRCD as a decrease in left ventricular ejection fraction (LVEF) greater than 10% from the lower limit of normal. Using this definition, several patients are diagnosed with CTRCD. Our study aims to understand the context of LVEF decline to help delineate the etiology of LVEF dysfunction in these patients. Methods: A retrospective descriptive study was conducted on registry of adult cancer patients (N=6754) referred to cardio-oncology clinic at the Cleveland Clinic between January 2011 and June 2018. The context of each LVEF decline event was independently adjudicated into one of nine categories: Chemotherapy induced, Valvular Heart Disease, Arrhythmia, Ischemia, Acute Hospitalization, Infiltrative disease, Misdiagnosed, Undifferentiated, or Other. Results: A cohort of patients (N=616) were identified to have CTRCD based on the ASE/EACVI definition. This cohort was 54% female and 80% Caucasian, with a median age of 58 years. In terms of therapy, 50% were exposed to anthracyclines, 15% exposed to HER2 neu inhibitors, 24% exposed to VEGF inhibitors. Upon adjudication of LVEF decline events, 31% of patients had isolated chemotherapy related decline, 24% caused by acute hospitalizations. 13% of events were multifactorial/undifferentiated and 11% of reported events were misdiagnosed. Conclusion: Our findings suggest left ventricular dysfunction in patients undergoing anticancer therapies can be multifaceted. Moreover, only a small proportion of reported CTRCD events were solely due to chemotherapy.