Chemotherapy-related Cardiomyopathy Research Articles

Possibilities of dapagliflozin-induced cardioprotection on doxorubicin + cyclophosphamide mode of chemotherapy-induced cardiomyopathy

RationaleThe global burden of cardiovascular (CV) and oncological diseases continues to increase. In this regard, the prevention of CV diseases (CVD) before and after cancer treatment is an urgent and unsolved problem in medicine. For this reason, our research group aimed to investigate the possibility of dapagliflozin-related cardioprotection, using an experimental model of chronic Doxorubicin (Adriamycin) + Cyclophosphamide (AC)-mode of chemotherapy-induced cardiomyopathy. ObjectiveThe redox balance, lipid metabolism, endothelial dysfunction, and myocardial damage parameters were measured to evaluate the pathways of dapagliflozin-induced stabilization of CV homeostasis. MethodsFor this study, 80 inbred Wistar rats were randomly assigned to four equally sized groups. A model of chronic cardiotoxicity was attained by using doxorubicin and cyclophosphamide co-administration. In the case, the markers of redox-balance, cholesterol metabolism, endothelial dysfunction, myocardial alteration, and morphological examination were assessed. ResultsFor all parameters, statistically significant deviations were obtained, emphasizing the sequel of AC-mode chemotherapy-related detergent effect on CV system (group 2). Moreover, the data obtained from dapagliflozin-treated groups (group 3) showed that this strategy provide limitation of lipid peroxidation, cholesterol metabolism and endothelial function normalization, with subsequent morphological preservation of myocardium. ConclusionDapagliflozin has a broad spectrum of pleiotropic influences, namely cholesterol-lowering, anti-inflammatory, and endothelium-stabilizing properties. These properties provide a favorable environment for the prevention of chemotherapy-related cardiomyopathy.

Severe Cardiac Toxicity Induced by Cancer Therapies Requiring Intensive Care Unit Admission

A steadying increase of cancer survivors has been observed as a consequence of more effective therapies. However, chemotherapy regimens are often associated with significant toxicity, and cardiac damage emerges as a prominent clinical issue. Many mechanisms sustain chemotherapy-induced cardiac toxicity: direct myocyte damage, arrhythmia induction, coronary vasospasm, and accelerated atherosclerosis. Anthracyclines are the most studied cardiotoxic drugs and represent a clinical model for cardiac damage induced by chemotherapy. In patients suffering from advanced heart failure (HF) because of chemotherapy-related cardiomyopathy, when refractory to optimal medical therapy, mechanical circulatory support or heart transplantation represents an effective treatment. Here, the main mechanisms of cardiac toxicity induced by cancer therapies are analyzed, with a focus on patients requiring intensive care unit (ICU) admission during the course of the disease because of acute cardiac toxicity, takotsubo syndrome, and acute-on-chronic HF in patients suffering from chemotherapy-induced cardiomyopathy. In a subset of patients, cardiac toxicity can be acute and life-threatening, leading to overt cardiogenic shock. The management of critically ill cancer patients poses a unique challenge and requires a multidisciplinary approach. Moreover, no etiologic therapy is available, and only supportive measures can be implemented.

Medical Decision Making among Adolescents and Young Adults with Heart Failure

Purpose In pediatric chronic illness groups, adolescent and young adult (AYA) medical decision making (DM) involvement is associated with important physical and psychosocial outcomes. Despite high morbidity, mortality, and treatment burden in AYAs with heart failure, their DM preferences and level of involvement are largely unknown. This study aimed to: 1) describe AYA DM preferences, 2) determine the degree of AYA DM involvement related to heart disease management, and 3) examine patient and disease characteristics associated with DM involvement. Methods AYAs (12-24 years) with heart failure or a significant post-heart transplant complication and a parent were enrolled at a single center. AYA/parent dyads completed a validated DM preferences item and Decision Making Involvement Scale. Standard descriptive statistics were reported and univariate comparisons were conducted. Results 46 patients and 44 parents participated. Patients were 63% male; 76% White. Dilated cardiomyopathy (28%), chemotherapy-related cardiomyopathy (24%), and single ventricle heart disease (17%) were the most common diagnoses. Disease burden was high with 59% having ≥6 hospitalizations, 50% having ≥3 cardiac surgeries, and 39% having extra-cardiac disease. Nearly half (48%) of AYAs reported a preference for active, patient-led DM; 24% desired shared DM with parent/medical team. Conversely, 36% of parents felt that they and the medical team should make decisions together without child involvement with a smaller group preferring shared DM with their child (25%) or patient-led DM (11%). AYA-parent dyads were highly discordant in DM preferences (P=0.004). Parents perceived seeking their child's opinion more than AYA report of such behavior (P=0.01). Greater time since diagnosis (P=0.01) and higher NYHA class (P=0.02) were associated with AYA preference for more active, patient-led DM. Older AYA age (P=0.04), congenital heart disease diagnosis (P=0.03), and transplant history (P=0.04) were associated with greater involvement in a recent heart disease management decision. Conclusion Most AYAs with heart failure desire involvement in their medical DM, often to a degree greater than what their parent(s) perceives. Interventions to enhance AYA engagement in their own medical DM are needed, along with future study of the associations of AYA DM involvement with physical and psychosocial outcomes.

Palliative and End of Life Care Preferences in Adolescents and Young Adults with Heart Failure

Purpose Nearly 14,000 children experience heart failure (HF) related hospitalizations annually in the US. Death occurs in 7% of these cases with costly and invasive interventions being common near the end of life (EOL). Yet, youth with HF are less likely to receive palliative care services compared to other pediatric illness groups, with little research focusing on EOL care needs. This study aimed to describe palliative and EOL care preferences in adolescents and young adults (AYAs) with HF. Methods AYAs (12-24 years) with HF or a significant post-heart transplant complication and a parent were enrolled at a single center. AYA/parent dyads completed the Lyon Family-Centered Advance Care Planning Survey. Standard descriptive statistics were reported. Results 46 patients and 44 parents participated. Patients were 63% male; 76% White. Dilated cardiomyopathy (28%), chemotherapy-related cardiomyopathy (24%), and single ventricle heart disease (17%) were the most common diagnoses. Of patients 18 or over, only 24% had completed a Durable Power of Attorney. The majority of patients (57%) had not discussed their EOL care wishes with anyone. Most AYAs (80%) and parents (93%) desired parental involvement in EOL decisions if critically ill. Fewer AYAs (50%) and parents (57%) desired physician involvement in EOL decisions. Preferred timing for EOL discussions varied with nearly 1/3 stating discussions should occur when there is no chance of cure or survival. A quarter (26%) of AYAs preferred to have EOL discussions before getting too sick. Both AYAs and parents commonly endorsed that conversations about EOL wishes should be initiated by the following people: parent, cardiologist, psychologist/therapist, sibling, family physician. While many patients (37%) reported no barriers to discussing EOL wishes, 39% endorsed discomfort with discussions, and 15% stated their doctor never brings it up. Among participants, 13% of AYAs and 41% of parents perceived patient's heart disease to result in shortened life. Overall, AYAs (72%) and parents (66%) did not find participation in this study to be stressful. Conclusion Most AYAs with HF in this study had clear preferences regarding discussions about their EOL wishes; however, the majority had not discussed their wishes with anyone. Interventions to meet the individualized EOL communication needs of young patients with HF are needed.

Echocardiographic measures associated with the presence of left ventricular thrombus in patients with chemotherapy-related cardiac dysfunction.

Previous studies have not evaluated the prevalence and specific risk factors for the development of left ventricular (LV) thrombus in patients with severely reduced left ventricular dysfunction due to chemotherapy-related cardiomyopathy. We sought to evaluate the prevalence and potential markers of LV thrombus in this patient population. From January 2009 to December 2013, patients with chemotherapy-related severe LV dysfunction (LV ejection fraction [LVEF]≤30%) identified from MD Anderson Cancer Center database were reviewed. Patient characteristics and echocardiographic parameters were analyzed to determine potential risk factors for LV thrombus. A total of 121 patients met inclusion criteria (age 54.8±15.2years; female 63.6%; LVEF 26.3±4%). LV thrombus was present in 9 patients (7.4%). Patients with LV thrombus have significantly lower LVEF compared to those without (18.7±3.8% vs 26.9±3.4%, P<.0001). Prevalence of LV thrombus increased as LVEF decreased and was the highest in patients with LVEF<20%. By univariate analysis, decreased LVEF, particularly LVEF<20% (OR 36.30, 95% CI 7.35-179.25, P<.0001) and restrictive LV filling pattern (OR 18.13, 95% CI 4.17-78.89, P=.0001) were associated with presence of LV thrombus. In patients with severely reduced LV systolic function due to chemotherapy-induced cardiomyopathy, LV thrombus was found in 7.4% of subjects. Severely decreased LVEF (<20%) and restrictive LV filling pattern were associated with the presence of LV thrombus.

Incidence and outcomes of cancer treatment-related cardiomyopathy among referrals for advanced heart failure

BackgroundApproximately 2–3% of patients undergoing advanced heart failure therapies such as left ventricular assist devices (LVAD) and orthotropic heart transplantation (OHT) have chemotherapy-related cardiomyopathy, according to analyses of large databases such as United Network for Organ Sharing (UNOS) or Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registries. While these studies have shown similar survival outcomes post-interventions, these databases by definition exclude patients referred for advanced therapies but do not receive them, and thus there is little data on overall outcomes of such patients. Given the lack of nuance in the diagnoses in large registries and the possibility that many cancer treatment-related cardiomyopathy (CCMP) patients might be misclassified by the generic “non-ischemic” or “dilated” cardiomyopathies, we investigated the incidence and clinical outcomes of CCMP patients among advanced heart failure (HF) referrals at a single high volume institution.MethodsAll referrals from 2013 to 2016 were evaluated for type of cardiomyopathy, with careful chart review. Outcomes such as LVAD, OHT and death were compared between CCMP and other cardiomyopathies.ResultsOf 553 referrals for advanced HF, 19 (3.4%) were for CCMP. There was a higher percentage of patients receiving advanced therapies in the CCMP vs. non-ischemic cardiomyopathy (NICMP) and ischemic cardiomyopathy (ICMP) (42.1% vs 30.2% vs 33.6%, not significant). Of the CCMP patients, 3 had OHT directly, 2 had LVAD followed by OHT, and 3 had LVADs as bridge to candidacy or destination therapy. Fifty-eight percent of the CCMP did not receive LVAD or OHT compared to 69.8% and 66.3 of the NICMP and ICMP, respectively (p = 0.0388). Independent of type of advanced therapy, survival was significantly higher in the CCMP group compared to NICMP and ICMP (93.3% vs 84.8% vs 73.8%, respectively P = 0.0021 for 1 year, 93.3% vs 76.2% vs 58.3%, respectively, P = < 0.0001 for 3 year).ConclusionsIn a single institution, CCMP accounts for more than 3% of all referrals for advanced HF therapies and almost 8% of NICMP. Contrary to concerns for previous cancer and sequelae of cancer treatment excluding patients for advanced therapies, a higher percentage of CCMP underwent advanced HF therapies and with similar outcomes. This is the first study to show that among patients referred for advanced therapies, CCMP patients do not have inferior outcomes compared to other cardiomyopathies regardless of the selected management strategy.

Multi-Modality Imaging in the Setting of Her-2-Negative Breast Cancer Therapy Over 1 Year in the Contemporary Era

Background: Contemporary breast cancer therapies have improved survival; however, there is increased identification of chemotherapy-related cardiomyopathy. We sought to correlate contemporary transthoracic echocardiographic (TTE) imaging, including global longitudinal strain (GLS), with cardiac magnetic resonance imaging (cMRI) to assess the effects of chemotherapy and characterise subclinical cardiomyopathy.

The Positive Effects of Exercise in Chemotherapy-Related Cardiomyopathy.

Anthracyclines such as doxorubicin, daunorubicin, epirubicin, mitoxantrone and idarubicin, are powerful chemotherapeutic drugs used both in children and adult populations. Their properties made them particularly suitable for a large variety of neoplasms including breast adenocarcinoma, small cell lung cancer and acute leukemia. Early and late anthracycline-induced cardiotoxicity is a well-known phenomenon, and the incidence of heart failure in patients receiving doxorubicin is 2.2%, with a mortality rate over 60% at 2years. Prognosis can be improved by prevention, early detection and treatment. A specific treatment for anthracycline-induced cardiotoxicity is not yet available, but non-pharmacological measures such as exercise, lifestyle changes and control of risk factors have shown a cardioprotective effect. Exercise training represents a viable non-pharmacological treatment as it increases cardiovascular reserve and endothelial function, regulates proapoptotic signaling, protects against reactive oxygen species (ROS), and decreases autophagy/lysosomal signaling. However, no current guidelines are available for prevention management in cancer patients. Pharmacological measures both for prevention and treatment are those used for heart failure (β-blockers, angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors, statins, dexrazoxane and aldosteron antagonists). In this chapter, we will discuss how the evaluation, monitoring and prevention of chemotherapy-related cardiomyopathy is correlated with physical exercise.

Erratum to: The Positive Effects of Exercise in Chemotherapy-Related Cardiomyopathy.

Erratum to: The Positive Effects of Exercise in Chemotherapy-Related Cardiomyopathy.

Chemotherapy-related Cardiomyopathy.

Advances in chemotherapeutic agents have resulted in significantly improved cancer survival rates. Cardiac toxicity, however, has emerged as a leading cause of morbidity, both during and years after treatment. One of the most common manifestations of cardiotoxicity is that of heart failure and left ventricular systolic dysfunction. In this review, current opinions and guidelines in this field are discussed, with particular focus on the most common culprits, the anthracyclines, and the monoclonal antibody, trastuzumab.

Chemotherapy-related cardiomyopathy: a neglected aspect of cancer survivorship.

Improvements in survival from cancer have led to a large population who are at risk of late complications of chemotherapy. One of the most serious cardiovascular complications is chemotherapy-related cardiomyopathy (CRC), which may become clinically overt years or even decades after treatment and has over threefold higher mortality rate compared with idiopathic dilated cardiomyopathy. The early stages of this condition appear to respond well to cardioprotective medications (i.e. angiotensin-converting enzyme inhibitors, β-blockers). Periodic cardiac monitoring is necessary in this population to identify patients who would benefit from treatment. Cardio-oncology clinics have been established in recognition of this hazard in survivorship. This review summarises the epidemiology and pathophysiology of CRC, the evidence base for different non-invasive imaging modalities for screening and diagnosis and the rationale for treatment.

PREVALENCE AND RISK FACTORS OF LEFT VENTRICULAR THROMBUS IN NONISCHEMIC CARDIOMYOPATHY PATIENTS WITH SEVERE LEFT VENTRICULAR SYSTOLIC DYSFUNCTION

Previous studies have not evaluated the prevalence and the presence of specific risk factors for the development of left ventricular thrombus (LVT) among chemotherapy related cardiomyopathy (CRC) patients who develop severe left ventricular (LV) systolic dysfunction. We used echocardiographic and

Heart Transplant Survival Outcomes for Adriamycin-Dilated Cardiomyopathy

In 2015, there will be an estimated 11.3 million cancer survivors. With an increasing population of cancer survivors, it is imperative to understand the treatment options available and outcomes for chemotherapy-related cardiomyopathy. Anthracycline-based chemotherapy causes heart failure in approximately 5% of patients. Orthotopic heart transplantation (OHT) is an option for cancer survivors in complete remission who develop end-stage heart failure. We examined retrospective OHT data collected from the United Network of Organ Sharing from 1987 to 2011. The primary aim was to characterize the survival in patients with either the primary diagnosis of "dilated cardiomyopathy: Adriamycin" (DCA) versus "all other" causes of cardiomyopathy. The secondary aim was to define the differences in the primary cause of death and to describe the temporal relationship of DCA OHT. The United Network of Organ Sharing database identified 453 OHTs for the diagnosis of DCA and 51,312 OHTs for all other causes of cardiomyopathy. The DCA group was significantly younger with a greater percentage of women. After adjusting for age, gender, and history of malignancy, the 10-year survival curves showed that patients with DCA have an improved survival compared to those with all other causes of cardiomyopathy (hazard ratio 1.28, p= 0.026). No difference was found in the primary cause of death between the 2 groups. Astatistically significant increasing temporal trend was seen in the number of OHTs for the diagnosis DCA. In conclusion, patients who undergo OHT for DCA have favorable 10-year survival, making OHT a good therapeutic option for end-stage heart failure due to anthracyclines. Additionally, no increased risk of cancer-related deaths was found in the DCA group, demonstrating that recurrent malignancy does not affect long-term survival. The temporal trends demonstrated that DCA remains a significant problem for cancer survivors.

Reversibility of Left Ventricular Dysfunction Resulting from Chemotherapy: Can This Be Expected?

Recent advances in cancer management have improved long-term survival. Increased longevity has been accompanied by a rise in the frequency of age-related cardiovascular disease and treatment-related cardiotoxicity. Chemotherapy-related left ventricular dysfunction has historically been considered resistant to conventional therapy and to carry a poorer prognosis than other cardiomyopathies. However, these conclusions were drawn primarily from trials that predate contemporary heart failure therapy and where treatment was often initiated only after the development of symptoms. More recent data suggest that selected forms of chemotherapy-related cardiomyopathy are, to some degree, reversible, but response is dependent on early detection and prompt intervention. This challenges us to develop more sophisticated risk stratification and monitoring strategies that include symptom detection, noninvasive imaging, and carefully applied biomarkers. This paradigm also suggests that a multidisciplinary team of cardiologists and oncologists may provide more comprehensive care to this complex patient population.

Clinical Outcome of Patients with Follicular Lymphoma and Bulky Disease After Rituximab-CHOP Immunochemotherapy with and without Consolidating Radiotherapy.

Abstract 2722Poster Board II-698 Background:As the clinical management of patients with bulky disease remains challenging, many centres apply involved-field radiotherapy (IF-RT) after completion of immunochemotherapy. This strategy remains controversial. Patients and Methods:To evaluate the benefit of consolidating IF-RT in addition to immunochemotherapy, we retrospectively analyzed relapse patterns and survival of patients presenting with bulky follicular lymphoma (FL). Bulky disease was defined as abdominal/ mediastinal lymphoma mass >7.5 cm and/ or peripheral lymphoma mass >5 cm. All patients were treated within a prospective randomized trial on 126 patients with FL with six cycles of standard CHOP-chemotherapy in combination with 1, 3 or 6 cycles of Rituximab, followed by consolidating IF-RT in patients with bulky disease. 42 eligible patients with bulky disease were identified and form the foundation of this analysis, of which 26 were irradiated and 16 were not, violating the protocol. Results:With the exception of number of affected nodal regions, there was no significant difference between the irradiated and the non-irradiated group with regards to presenting characteristics (p > .05). Among all patients, bulks were located below the diaphragm in 91%. A second tumour bulk was present in 9 patients (22%). Female to male ratio was 1.3:1, and the median age at diagnosis was 54 years (range 23–73). According to FLIPI, 10% were classified as low risk (0–1), 45% as intermediate risk (2), and 45% as high risk (3–5). B symptoms were absent in 69%. Eleven patients (26 %) had received one course of Rituximab, 17 (41%) three courses and 14 (33%) six courses. There was no significant difference between the irradiated and the non-irradiated group with regards to previous exposure to immunochemotherapy (p = .628). After a median follow-up of 60 months, a total of 21 patients (50%) had progressed or relapsed and 9 patients (21%) had died. With the exception of one patient who died from congestive heart failure following chemotherapy-related cardiomyopathy, the main cause of death was disease progression or relapse. Highly malignant transformation into diffuse large B-cell lymphoma was observed in 5 cases. In the irradiated group, relapse occurred in 12 of 26 patients. Half of these relapses were located within the original bulk or within the bulk plus a new location, and 50% at a new location altogether; 42% occurred within the previously irradiated area. In the non-irradiated group, 9 of 16 patients relapsed. The corresponding rates regarding relapse location were 67% for original plus new location and 33% for new location only. There was no statistically significant difference between exposure to radiotherapy after immunochemotherapy and the likelihood of a relapse per se (p = .751) or at a specific location (p = .66). At the last follow-up, 31% of irradiated patients had achieved CR and 23% PR. Among the non-irradiated group, the corresponding rates were 25% and 19%. There was no significant difference in remission rates at any staging examination throughout the clinical trial between the two treatment groups (p > .05). 6-year progression-free- and overall survival rates were 52% and 80% after IF-RT and 48% and 73% without IF-RT (p = 1.00, p = .68 respectively). Conclusion:In this analysis, there was no difference in relapse rate, relapse location, PFS and OS between patients with bulky FL treated with and without consolidating IF-RT. Although patient numbers are limited, this is the first analysis of its kind conducted in the Rituximab era. Disclosures:No relevant conflicts of interest to declare.

Chemotherapy‐Related Cardiomyopathy: All That Glitters Is Not Gold

As long-term morbidity with chemotherapeutic exposure becomes a clinical reality, the development of cardiomyopathy with heart failure is rapidly growing. The type of chemotherapy agent, dose, rate of administration, use of combination chemotherapy, and concomitant radiation therapy are major factors that define the propensity to cardiotoxicity. Chemotherapy-related cardiomyopathy is multifactorial in origin and requires a diligent etiologic survey to arrive at the appropriate diagnosis. A contemporary discussion of chemotherapy-related cardiomyopathy with particular emphasis on the pathogenesis and ameliorative targets of this unique clinical disorder are described in this report.