Project description:Echocardiographic imaging is crucial for patient management during cardiotoxic cancer therapy. Left ventricular ejection fraction is the most commonly used parameter for identifying left ventricular dysfunction. However, it lacks sensitivity to detect subclinical changes in cardiac function due to cardiotoxic treatment. Global longitudinal strain (GLS) is the best studied strain parameter with established diagnostic and prognostic value. Multiple studies have demonstrated changes in GLS as an early marker of cardiotoxicity. This document serves as a primer to help clinicians in the acquisition and interpretation of strain in cardio-oncology. Cases with embedded videos illustrate a step-by-step approach to obtaining GLS measurements and common pitfalls to avoid. The document includes a concise summary of the indications of GLS in cardio-oncology and its role in guiding oncological therapy. Practical approaches on how to implement strain in the echo laboratory with guidance on training and quality assurance are also discussed.
Project description:BackgroundChemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracyclines (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 therapeutics related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (LVEF) reduction of > 10%, to a value below 53%. The aim of our study was to estimate the prevalence of CTRCD in patients diagnosed with sarcoma and to describe the baseline risk factors and echocardiography parameters among that population.MethodsData were collected as part of the Israel Cardio-Oncology Registry (ICOR), enrolling all patients evaluated in the cardio-oncology clinic at our institution. The registry was approved by the local ethics committee and is registered in clinicaltrials.gov (Identifier: NCT02818517). All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. non-CTRCD group.ResultsAmong 43 consecutive patients, 6 (14%) developed CTRCD. Baseline cardiac risk factors were more frequent among the non-CTRCD group. Elevated left ventricular end systolic diameter and reduced Global Longitudinal Strain were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the non-CTRCD group.ConclusionsCTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.
Project description:Serial transthoracic echocardiographic (TTE) assessment of 2D left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) are the gold standard screening methods for cancer therapeutics-related cardiac dysfunction (CTRCD). Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages to evaluate the impact of cardiotoxic treatments on heart function. We prospectively assessed breast cancer female patients undergoing cancer therapy through serial monitoring by 2D and 3D TTE. Patients were evaluated at T0, T1 and T2 (before, 4-6 and 12-14 months after starting therapy, respectively). Through PSL analysis, MW indices were calculated. A total of 122 patients, with a mean age of 54.7 years, who received treatment with anthracyclines (77.0%) and anti-HER2 (75.4%) were included. During a mean follow-up of 14.9 ± 9.3 months, LVEF and GLS were significantly diminished, and 29.5% developed CTRCD. All MW indices were significantly reduced at T1 compared with baseline and tended to return to baseline values at T2. Global work index and global work efficiency showed a more pronounced variation in patients with CTRCD. The presence of more than one cardiovascular risk factor, obesity and baseline left atrium volume were predictors of changes in MW parameters. In conclusion, breast cancer treatment was associated with LV systolic dysfunction as assessed by MW, with its peak at 4-6 months and a partial recovery afterwards. Assessment of myocardial deformation parameters allows a more detailed characterization of cardiac remodelling and could enhance patient screening and selection for cardioprotective therapeutics.
Project description:Heart disease and cancer are the leading causes of death in older adults. Many first-line cancer treatments have the potential for cardiotoxicity. Age-related risk factors, pre-existing cardiac disease, and a high prevalence of comorbidities are reasons for increased cardiotoxicity in older adults. Concerns regarding cardiotoxicity may lead to frailty bias and undertreatment, resulting in suboptimal outcomes. There is an urgent need for geriatric-specific evidence and guidelines to help tailor care for this vulnerable group. A multi-disciplinary approach based on close collaboration between oncologists, cardiologists, and geriatricians, among other specialist clinicians is essential.
Project description:Recent advances in treatment have transformed the management of cancer. Despite these advances, cardiovascular disease remains a leading cause of death in cancer survivors. Cardio-oncology has recently evolved as a subspecialty to prevent, diagnose, and manage cardiovascular side effects of antineoplastic therapy. An emphasis on optimal management of comorbidities and close attention to drug interactions are important in cardio-oncologic care. With interdisciplinary collaboration among oncologists, cardiologists, and pharmacists, there is potential to prevent and reduce drug-related toxicities of treatments. The cytochrome P450 (CYP450) family of enzymes and the P-glycoprotein (P-g) transporter play a crucial role in drug metabolism and drug resistance. Here we discuss the role of CYP450 and P-g in drug interactions in the field of cardio-oncology, provide an overview of the cardiotoxicity of a spectrum of cancer agents, highlight the role of precision medicine, and encourage a multidisciplinary treatment approach for patients with cancer.
Project description:Cardio-oncology (the cardiovascular care of cancer patients) has developed as a new translational and clinical field based on the expanding repertoire of mechanism-based cancer therapies. Although these therapies have changed the natural course of many cancers, several may also lead to cardiovascular complications. Many new anticancer drugs approved over the past decade are "targeted" kinase inhibitors that interfere with intracellular signaling contributing to tumor progression. Unexpected cardiovascular and cardiometabolic effects of patient treatment with these inhibitors have provided unique insights into the role of kinases in human cardiovascular biology. Today, an ever-expanding number of cancer therapies targeting novel kinases and other specific cellular and metabolic pathways are being developed and tested in oncology clinical trials. Some of these drugs may affect the cardiovascular system in detrimental ways and others perhaps in beneficial ways. We propose that the numerous ongoing oncology clinical trials are an opportunity for closer collaboration between cardiologists and oncologists to study the cardiovascular and cardiometabolic changes caused by the modulation of these pathways in patients. In this regard, cardio-oncology represents an opportunity and a novel platform for basic and translational investigation and can serve as a potential avenue for optimization of anticancer therapies and for cardiovascular research and drug discovery.
Project description:The genomic predisposition to oncology-drug-induced cardiovascular toxicity has been postulated for many decades. Only recently has it become possible to experimentally validate this hypothesis via the use of patient-specific human-induced pluripotent stem cells (hiPSCs) and suitably powered genome-wide association studies (GWAS). Identifying the individual single nucleotide polymorphisms (SNPs) responsible for the susceptibility to toxicity from a specific drug is a daunting task as this precludes the use of one of the most powerful tools in genomics: comparing phenotypes to close relatives, as these are highly unlikely to have been treated with the same drug. Great strides have been made through the use of candidate gene association studies (CGAS) and increasingly large GWAS studies, as well as in vivo whole-organism studies to further our mechanistic understanding of this toxicity. The hiPSC model is a powerful technology to build on this work and identify and validate causal variants in mechanistic pathways through directed genomic editing such as CRISPR. The causative variants identified through these studies can then be implemented clinically to identify those likely to experience cardiovascular toxicity and guide treatment options. Additionally, targets identified through hiPSC studies can inform future drug development. Through careful phenotypic characterization, identification of genomic variants that contribute to gene function and expression, and genomic editing to verify mechanistic pathways, hiPSC technology is a critical tool for drug discovery and the realization of precision medicine in cardio-oncology.
Project description:Cardiovascular disease is a common problem in cancer patients that is becoming more widely recognized. This may be a consequence of prior cardiovascular risk factors but could also be secondary to the anticancer treatments. With the goal of offering a multidisciplinary approach to guaranteeing optimal cancer therapy and the early detection of related cardiac diseases, and in light of the recent ESC Cardio-Oncology Guideline recommendations, we developed a Cardio-Oncology unit devoted to the prevention and management of these specific complications. This document brings together important aspects to consider for the development and organization of a Cardio-Oncology program through our own experience and the current evidence.