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Pubblicazioni recenti - cardio-oncology
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The epigenetics changes associated with anthracyclines induced cardiotoxicity.
Clin Transl Sci2020 Aug;():. doi: 10.1111/cts.12857.
Tantawy Marwa, Pamittan Frances G, Singh Sonal, Gong Yan,
Abstract
Advances in cancer treatment have significantly improved the survival of cancer patients, but unfortunately, many of these treatments also have long-term complications. Cancer treatmement related cardiotoxicities is becoming a significant clinical problem that a new discipline, Cardio-Oncology, was established to advance the cardiovascular care of growing cancer patient populations. Anthracyclines are a class of chemotherapeutic agents used to treat many cancers in adults and children. Their clinical use is limited by anthracycline-induced cardiotoxicity (AIC), which can lead to heart failure (HF). Early-onset cardiotoxicity appears within a year of treatment, while late-onset cardiotoxicity occurs more than one year and even up to decades after treatment completion. The pathophysiology of AIC was hypothesized to be caused by generation of reactive oxygen species (ROS) that lead to lipid peroxidation, defective mitochrondrial biogenesis, and DNA damage of the cardiomyocytes. The accumulation of anthracycline metabolites was also proposed to cause mitochondrial damage and the induction of cardiac cell apoptosis, which induces arrhythmias, contractile dysfunction, and cardiomyocyte death. This article will provide a general overview of cardiotoxicity focusing on the effect of anthracyclines and their epigenetic molecular mechanisms on cardiotoxicity.
This article is protected by copyright. All rights reserved.
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Sex-Related Differences in Dilated Cardiomyopathy with a Focus on Cardiac Dysfunction in Oncology.
Curr Cardiol Rep2020 Aug;22(10):102. doi: 10.1007/s11886-020-01377-z.
D'Amario Domenico, Camilli Massimiliano, Migliaro Stefano, Canonico Francesco, Galli Mattia, Arcudi Alessandra, Montone Rocco Antonio, Borovac Josip Andjelo, Crea Filippo, Savarese Gianluigi,
Abstract
PURPOSE OF REVIEW:
The aim of this report is to describe the main aspects of sex-related differences in non-ischemic dilated cardiomyopathies (DCM), focusing on chemotherapy-induced heart failure (HF) and investigating the possible therapeutic implications and clinical management applications in the era of personalized medicine.
RECENT FINDINGS:
In cardio-oncology, molecular and multimodality imaging studies confirm that sex differences do exist, affecting the therapeutic cardioprotective strategies and, therefore, the long-term outcomes. Interestingly, compelling evidences suggest that sex-specific characteristics in drug toxicity might predict differences in the therapeutic response, most likely due to the tangled interplay between cancer and HF, which probably share common underlying mechanisms. Cardiovascular diseases show many sex-related differences in prevalence, etiology, phenotype expression, and outcomes. Complex molecular mechanisms underlie this diverse pathological manifestations, from sex-determined differential gene expression to sex hormone interaction with their receptors in the heart. Non-ischemic DCM is an umbrella definition that incorporates several etiologies, including chemotherapy-induced cardiomyopathies. The role of sex as a risk factor for cardiotoxicity is poorly explored. However, understanding the various features of disease manifestation and outcomes is of paramount importance for a prompt and tailored evaluation.
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The Role of Biomarkers to Evaluate Cardiotoxicity.
Curr Treat Options Oncol2020 Aug;21(10):79. doi: 10.1007/s11864-020-00777-1.
Upshaw Jenica N,
Abstract
OPINION STATEMENT:
Moderate-level evidence suggests that cardiac troponin and natriuretic peptides are useful for risk stratification and early identification of anthracycline cardiotoxicity; however, many of these studies used older chemotherapy regimens, and thus, the applicability to current anthracycline treatment regimens is uncertain. Further research is needed to determine optimal timing and thresholds for troponin and natriuretic peptides in anthracycline-treated patients and evaluate these and other promising biomarkers for anti-HER2 therapies, thoracic radiation, anti-VEGF therapy, and fluoropyrimidine therapy-related cardiotoxicity. Risk tools that combine cardiac risk factors, cancer treatment variables, biomarkers, and imaging parameters are most likely to accurately identify individuals at highest risk for cancer therapy cardiotoxicity. Clinical trials focusing cardioprotective strategies on high-risk individuals are more likely to result in clinically significant results compared with primary prevention cardioprotective approaches.
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Nano-Encapsulation of Coenzyme Q10 in Secondary and Tertiary Nano-Emulsions for Enhanced Cardioprotection and Hepatoprotection in Human Cardiomyocytes and Hepatocytes During Exposure to Anthracyclines and Trastuzumab.
Int J Nanomedicine2020 ;15():4859-4876. doi: 10.2147/IJN.S245170.
Quagliariello Vincenzo, Vecchione Raffaele, De Capua Alberta, Lagreca Elena, Iaffaioli Rosario Vincenzo, Botti Gerardo, Netti Paolo A, Maurea Nicola,
Abstract
Introduction:
CoenzymeQ (CoQ) is a well-known antioxidant and anti-inflammatory agent with cardioprotective properties. However, clinical trials based on its oral administration have failed to provide significant effect on cardiac functionality. The main limitation of CoQ is based on its very low oral bioavailability and instability that limit dramatically its effects as a cardioprotective agent. Herein, we loaded CoQ in high bioavailable nano-emulsions (NEs) coated with chitosan or chitosan and hyaluronic acid in order to improve its performance.
Methods:
We tested cardioprotective and hepatoprotective effects of CoQ-loaded nano-carriers against Doxorubicin and Trastuzumab toxicities in cardiomyocytes and liver cells through analysis of cell viability, lipid peroxidation, expression of leukotrienes, p65/NF-kB and pro-inflammatory cytokines involved in anticancer-induced cardio and hepatotoxicity.
Results:
Nano-carriers showed high stability and loading ability and increased cell viability both in hepatocytes and cardiomyocytes during anticancer treatments. We observed that these effects are mediated by the inhibition of lipid peroxidation and reduction of the inflammation. CoQ-loaded nano-emulsions showed also strong anti-inflammatory effects reducing leukotriene B4 and p65/NF-?B expression and Interleukin 1? and 6 production during anticancer treatments.
Discussion:
Anthracyclines and Human epidermal growth factor receptor (HER2) inhibitors have shown significant anticancer effects in clinical practice but their use is characterized by cardiotoxicity and hepatotoxicity. Nano-carriers loaded with CoQ showed cardio and hepatoprotective properties mediated by reduction of oxidative damages and pro-inflammatory mediators. These results set the stage for preclinical studies of cardio and hepatoprotection in HER2+ breast cancer-bearing mice treated with Doxorubicin and Trastuzumab.
© 2020 Quagliariello et al.
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Adjuvant treatment with 5-FU and oxaliplatin does not influence cardiac function neurovascular control, and physical capacity in patients with colon cancer.
Oncologist2020 Aug;():. doi: 10.1634/theoncologist.2020-0225.
Groehs Raphaela V, Negrao Marcelo V, Hajjar Ludhmila A, Jordão Camila P, Carvalho Bruna P, Toschi-Dias Edgar, Andrade Ana C, Hodas Fabiana P, Alves Maria Jnn, Sarmento Adriana O, Testa Laura, Hoff Paulo M G, Negrão Carlos E, Filho Roberto Kalil,
Abstract
BACKGROUND:
Adjuvant chemotherapy with fluorouracil (5-FU) and oxaliplatin increases recurrence-free and overall survival in patients with colon adenocarcinoma. It is known that these drugs have been associated with cardio- and neurotoxicity. We investigated the effects of 5-FU+/-oxaliplatin on cardiac function, vascular responses, neurovascular control, and physical capacity in patients with colon cancer.
METHODS:
Twenty-nine patients with prior colectomy for stage II-III adenocarcinoma and clinical indication for adjuvant chemotherapy were allocated to receive 5-FU (n=12) or 5-FU+oxaliplatin (n=17), according to the oncologist's decision. All the analyses were performed just before and after the end of chemotherapy. Cardiac function was assessed by echocardiography and speckle-tracking and cardiac autonomic control by heart rate variability (HRV). Vascular endothelial function was assessed by flow-mediated dilation (FMD). Muscle sympathetic nerve activity (MSNA) was directly recorded by microneurography technique and muscle blood flow by venous occlusion plethysmography. Physical capacity was evaluated by cardiopulmonary exercise test.
RESULTS:
Chemotherapy (pooled data) did not significantly change left ventricular ejection fraction (58±1 vs 55±2%, P=0.14), longitudinal strain (-18±1 vs -18±1%, P=0.66) and HRV. Likewise, chemotherapy did not significantly change FMD and muscle blood flow, and MSNA (33±2 vs 32±1 bursts/min, P=0.31). Physical capacity was not significantly change in both groups. Similar findings were observed when the patients were subdivided in 5-FU and 5-FU+oxaliplatin. 5-FU and 5-FU+oxaliplatin did not significantly change cardiac function, HRV, vascular responses, MSNA and physical capacity.
CONCLUSION:
This study provides evidence that adjuvant treatment with 5-FU+/-oxaliplatin is well tolerated and does not promote changes compatible with long-term cardiotoxicity.
IMPLICATIONS FOR PRACTICE:
Adjuvant chemotherapy with fluorouracil (5-FU) and oxaliplatin increases recurrence-free and overall survival in patients with colon adenocarcinoma, however these drugs have been associated with cardio- and neurotoxicity. We investigated the effects of these drugs on cardiac function, vascular responses, neurovascular control, and physical capacity in patients with colon cancer. And we found that 5-FU and oxaliplatin did not significantly change cardiac function, cardiac autonomic control, vascular endothelial function, muscle sympathetic nerve activity and physical capacity. This study provides evidence that adjuvant treatment with 5-FU+/-oxaliplatin is well tolerated and does not promote changes compatible with long-term cardiotoxicity.
© AlphaMed Press 2020.
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Doxorubicin metabolism moderately attributes to putative toxicity in prodigiosin/doxorubicin synergism in vitro cells.
Mol Cell Biochem2020 Aug;():. doi: 10.1007/s11010-020-03864-x.
Lin Shian-Ren, Lin Chun-Shu, Chen Ching-Cheng, Tseng Feng-Jen, Wu Tsung-Jui, Weng Lebin, Weng Ching-Feng,
Abstract
Doxorubicin (Dox) is a widely neoplasm chemotherapeutic drug with high incidences of cardiotoxicity. Prodigiosin (PG), a red bacterial pigment from Serratia marcescens, has been demonstrated to potentiate Dox's cytotoxicity against oral squamous cell carcinoma cells through elevating Dox influx and identified as a Dox enhancer via PG-induced autophagy; however, toxicity of normal cell remains unclear. This study is conducted to evaluate putative cytotoxicity features of PG/Dox synergism in the liver, kidney, and heart cells and further elucidate whether PG augmented Dox's effect via modulating Dox metabolism in normal cells. Murine hepatocytes FL83B, cardio-myoblast h9c2, and human kidney epithelial cells HK-2 were sequentially treated with PG and Dox by measuring cell viability, cell death characteristics, oxidative stress, Dox flux, and Dox metabolism. PG could slightly significant increase Dox cytotoxicity in all tested normal cells whose toxic alteration was less than that of oral squamous carcinoma cells. The augmentation of Dox cytotoxicity might be attributed to the increase of Dox-mediated ROS accumulation that might cause slight reduction of Dox influx and reduction of Dox metabolism. It was noteworthy to notice that sustained cytotoxicity appeared in normal cells after PG and Dox were removed. Taken together, moderately metabolic reduction of Dox might be ascribed to the mechanism of increase Dox cytotoxicity in PG-induced normal cells; nevertheless, the determination of PG/Dox dose with sustained cytotoxicity in normal cells needs to be comprehensively considered.
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p53-Mediated Repression of the PGC1A (PPARG Coactivator 1?) and APLNR (Apelin Receptor) Signaling Pathways Limits Fatty Acid Oxidation Energetics: Implications for Cardio-oncology.
J Am Heart Assoc2020 Aug;9(15):e017247. doi: 10.1161/JAHA.120.017247.
Saleme Bruno, Das Subhash K, Zhang Yongneng, Boukouris Aristeidis E, Lorenzana Carrillo Maria Areli, Jovel Juan, Wagg Cory S, Lopaschuk Gary D, Michelakis Evangelos D, Sutendra Gopinath,
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Metabolic syndrome parameters, determinants, and biomarkers in adult survivors of childhood cancer: methodology of the Dutch Childhood Cancer Survivor Study Metabolic Syndrome (Dutch LATER METS Study).
JMIR Res Protoc2020 Aug;():. doi: 10.2196/21256.
Pluimakers Vincent, Fiocco Marta, Van Atteveld Jenneke, Hobbelink Monique, Bresters Dorine, Van Dulmen-den Broeder Eline, Van der Heiden-van der Loo Margriet, Janssens Geert, Kremer Leontien, Loonen Jacqueline, Louwerens Marloes, Van der Pal Heleen, Ronckers Ceciel, Van Santen Hanneke, Versluijs Birgitta, De Vries Andrica, Van den Heuvel-Eibrink Marry, Neggers Sebastian,
Abstract
BACKGROUND:
Potential long-term effects of treatment for childhood cancer include adiposity, insulin resistance, dyslipidemia and hypertension. These risk factors cluster together as metabolic syndrome (MetS) and increase the risk for development of diabetes mellitus and cardio- and cerebrovascular disease. Knowledge on risk factors, timely diagnosis and preventive strategies is of importance to prevent cardio- and cerebrovascular complications and improve quality of life. Currently, no studies in national cohorts on prevalence and determinants of MetS in childhood cancer survivors including biomarkers and genetic predisposition are available.
OBJECTIVE:
Describe the methodology of the Dutch LATER METS study on prevalence and risk factors of metabolic syndrome in adult survivors of childhood cancer, treated between 1963 and 2002.
METHODS:
The current study is a cross-sectional study, based on recruitment of a national cohort of adult long-term survivors, that will assess 1) prevalence as well as disease- and treatment-related and genetic risk factors of MetS and its separate components, compared to available normative data, and 2) diagnostic value of biomarkers. Metabolic syndrome will be classified according to the definitions of the National Cholesterol Education Program (NCEP-ATPIII) as well as the International Diabetes Federation (IDF), and DXA-scans will be performed to assess body composition in more detail.
RESULTS:
Patient accrual started in 2016 and lasted until April 2020. A total of 2380 survivors has participated, in seven pediatric oncology hospitals. From July 2020, biomarker testing, SNP-analysis and data analysis will be performed.
CONCLUSIONS:
The Dutch LATER METS study will provide knowledge on clinical and genetic determinants of MetS, and the diagnostic value of biomarkers, in survivors. The results of this study will be used to optimize surveillance guidelines for MetS in survivors, and improve follow-up of survivors.
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Hypertension management in cardio-oncology.
J Hum Hypertens2020 Aug;():. doi: 10.1038/s41371-020-0391-8.
Essa Hani, Dobson Rebecca, Wright David, Lip Gregory Y H,
Abstract
Cancer is one of the leading causes of death worldwide. During the last few decades prognosis has improved dramatically and patients are living longer and suffering long-term cardiovascular consequences of chemotherapeutic agents. Cardiovascular disease is a leading cause of morbidity and mortality in cancer survivors second only to recurrent cancer. In some types of cancer, cardiovascular disease is a more common cause of death than the cancer itself. This has led to a new sub-specialty of cardiology coined cardio-oncology to manage this specific population. Hypertension is one of the most common cardiovascular disease seen in this cohort. The aetiology of hypertension in cardio-oncology is complex and multifactorial based on the type of chemotherapy, type of malignancy and intrinsic patient factors such as age and pre-existing comorbidities. A variety of different oncological treatments have been implicated in causing hypertension. The effect can be transient whilst undergoing treatment or can be delayed occurring decades after treatment. A tailored management plan is recommended given the plethora of agents and their differing underlying mechanisms and speed of this mechanism in causing hypertension. Management by a multidisciplinary team consisting of oncology, general practice and cardiology is advised. There are currently no trials comparing antihypertensives in this specific cohort of patients. In the absence of evidence demonstrating otherwise, hypertension in cardio-oncology should be managed utilising the same treatment guidelines for the general population.
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Assessment of coronary artery disease during hospitalization for cancer treatment.
Clin Res Cardiol2020 Aug;():. doi: 10.1007/s00392-020-01719-5.
Mrotzek Simone M, Lena Alessia, Hadzibegovic Sara, Ludwig Ria, Al-Rashid Fadi, Mahabadi Amir A, Mincu Raluca I, Michel Lars, Johannsen Laura, Hinrichs Lena, Schuler Martin, Keller Ulrich, Anker Stefan D, Landmesser Ulf, Rassaf Tienush, Anker Markus S, Totzeck Matthias,
Abstract
BACKGROUND:
With improvement of cancer-specific survival, comorbidities and treatment-related side effects, particularly cardiovascular toxicities, need close attention. The aim of the present study was to evaluate clinical characteristics and outcomes of cancer patients requiring coronary angiography during inpatient care.
METHODS:
We performed a retrospective analysis of patients hospitalized between 02/2011 and 02/2018 in our two university hospital cancer centers. From a cohort of 60,676 cancer patients, we identified 153 patients (65.7?±?11.6 years, 73.2% male), who underwent coronary angiography and were eligible for analysis. These were compared to a control group of 153 non-cancer patients pair-matched with respect to age, sex, and indication for catheterization.
RESULTS:
Cancer patients presented in 66% with an acute coronary syndrome (ACS). The most prevalent cancer entities were lymphoma (19%) and lung cancer (18.3%). The rate of primary percutaneous coronary interventions (PCI) was significantly lower in the cancer cohort (40.5% vs. 53.6%, p?=?0.029), although manifestation of coronary artery disease (CAD) and PCI results were comparable (SYNergy between PCI with TAXus and cardiac surgery (SYNTAX)-score, delta pre- and post-PCI -?9.8 vs. -?8.0, p?=?0.2). Mortality was remarkably high in cancer patients (1-year mortality 46% vs. 8% in non-cancer patients, p?
CONCLUSION:
Strategies to effectively control cardiovascular risks in cancer patients are needed. Additionally, suspected CAD in cancer patients should not prevent prompt diagnostic clarification and optimal revascularization as PCI results in cancer patients are comparable to non-cancer patients and occurrence of troponin-positive ACS leads to a significantly increased risk of mortality.
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Quantitative assessment of cardiovascular autonomic impairment in cancer survivors: a single center case series.
Cardiooncology2020 ;6():11. doi: 10.1186/s40959-020-00065-9.
Noor Benjamin, Akhavan Shannel, Leuchter Michael, Yang Eric H, Ajijola Olujimi A,
Abstract
Background:
Cardiovascular autonomic dysfunction in cancer survivors is poorly understood.
Objectives:
To better characterize the clinical characteristics and types of autonomic dysfunction in this population.
Methods:
A retrospective analysis of cancer survivors within an academic cardio-oncology program referred for suspected autonomic dysfunction was performed. Autonomic reflex testing of adrenergic, cardiovagal, and sudomotor function was done. Autonomic impairment was graded on severity based on the Composite Autonomic Severity Score system. Patients with pre-existing autonomic dysfunction prior to their cancer diagnosis were excluded.
Results:
Of approximately 282 total patients in the UCLA Cardio-Oncology program, 24 were referred for suspected autonomic dysfunction and met the inclusion criteria. 22 had autonomic impairment on autonomic reflex testing. Eight patients were female, and the mean age at time of autonomic testing was 51.3?years. The average duration from cancer diagnosis to autonomic testing was 10.3?years. The reasons for referral included dizziness, tachycardia, palpitations, and syncope. The majority of patients (75%) had hematologic disorders. The most common chemotherapies administered were vinca alkaloids (54.2%), alkylating agents (66.7%), and anthracyclines (54.2%). Most patients received radiation to the thorax (66.7%) and neck (53.3%). Eleven patients had mild autonomic impairment, 7 had moderate, and 4 had severe autonomic impairment. Dysfunction was commonly present in the sympathetic and parasympathetic branches, but most pronounced in the sympathetic system. The majority of patients were diagnosed with orthostatic hypotension (50%), inappropriate sinus tachycardia (20.8%), and postural orthostatic tachycardia syndrome (12.5%) and had subjective improvement with treatment.
Conclusion:
Cardiovascular autonomic dysfunction occurs in cancer survivors, and commonly affects both the sympathetic and parasympathetic systems. Symptom recognition in patients should prompt autonomic testing and treatment where appropriate.
© The Author(s) 2020.
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Cardio-Oncology rehabilitation- challenges and opportunities to improve cardiovascular outcomes in cancer patients and survivors.
J Cardiol2020 Jul;():. doi: S0914-5087(20)30255-0.
Sase Kazuhiro, Kida Keisuke, Furukawa Yutaka,
Abstract
While the number of cancer patients is increasing with the arrival of the super-aging society, the age-adjusted mortality rate of cancer decreases due to medical advances, and the number of cancer survivors is growing rapidly. Cardiovascular disease (CVD) is one of the most important causes of death among cancer survivors. In recent years, the number of cancer patients with CVD risk factors has increased. Also, the emergence of new drugs has led to the emergence of a new condition called cancer treatment-related cardiovascular disease (CTRCD). Cardio-oncology (onco-cardiology) is a new multidisciplinary field with the common goal of completing cancer treatment and improving the prognosis of cancer patients and survivors, including the prevention, diagnosis, and treatment of CTRCD. Cardio-oncology rehabilitation (CORE) is a new concept that aims to reduce the risk of CVD and improve cardiopulmonary fitness in cancer survivors by providing exercise prescriptions and cardiac rehabilitation in addition to so-called cancer rehabilitation during and after cancer treatment. This review provides an overview of the theoretical background, feasibility, challenges, and opportunities of CORE, including a series of recent white papers and scientific statements released by the American Heart Association.
Copyright © 2020. Published by Elsevier Ltd.
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[The cardiovascular impact of cancer control therapy].
Rev Med Chil2020 Jan;148(1):93-102. doi: S0034-98872020000100093.
Ríos Juvenal A, Rojo Pamela, Schuster AndréS, Gormaz Juan G, Carrasco Rodrigo, Neira Carolina, Becerra Sergio, Labbé Tomas P,
Abstract
Cardiovascular diseases and cancer account for 27 and 25% of mortality in Chile, respectively. In the last decades, survival of people with cancer has improved due to preventive programs, early detection strategies, advances in technology and development of new antineoplastic therapies. Consequently, a progressive number of cancer-surviving patients have been generated, who may develop cardiovascular diseases, secondary to the same cancer therapy. Cardio-Oncology has emerged as the necessary link between both specialties to promote the prevention and early detection of cardiac complications, in patients undergoing oncological therapies. The aim is to curb cardiovascular complications. Also, to acquire knowledge about the mechanisms and effects of drugs that lead to heart damage aiming to develop efficient cardioprotective therapies. In this article we review and propose a didactic organization and classification of the main cardiovascular effects of cancer control therapy. We recognize that there is still a knowledge gap in basic sciences about the mechanisms that underlie these alterations.
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Cancer Therapeutics-Related Cardiac Dysfunction?- Insights From Bench and Bedside of Onco-Cardiology.
Circ J2020 Jul;():. doi: 10.1253/circj.CJ-20-0467.
Kadowaki Hiroshi, Akazawa Hiroshi, Ishida Junichi, Komuro Issei,
Abstract
Improvements in the long-term survival of cancer patients have led to growing awareness of the clinical importance of cancer therapeutics-related cardiac dysfunction (CTRCD), which can have a considerable effect on the prognosis and quality of life of cancer patients and survivors. Under such circumstances, onco-cardiology/cardio-oncology has emerged as a new discipline, with the aim of best managing cardiovascular complications, including CTRCD. Despite the recent accumulation of epidemiological and clinical information regarding CTRCD, the molecular mechanisms underlying the pathogenesis of CTRCD by individual drugs remain to be determined. To achieve the goal of preventing cardiovascular complications in cancer patients and survivors, it is important to elucidate the pathogenic mechanisms and to establish diagnostic strategies with risk prediction and mechanism- and evidence-based therapies against CTRCD.
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Sympathetic activation and outcomes in chronic heart failure: Does the neurohormonal hypothesis apply to mid-range and preserved ejection fraction patients?
Eur J Intern Med2020 Jul;():. doi: S0953-6205(20)30288-0.
Jimenez-Marrero Santiago, Moliner Pedro, Rodríguez-Costoya Iris, Enjuanes Cristina, Alcoberro Lidia, Yun Sergi, Gonzalez-Costello Jose, Garay Alberto, Tajes Marta, Calero Esther, Hidalgo Encarnación, Guerrero Carmen, García-Romero Elena, Díez-López Carles, Cainzos-Achirica Miguel, Comin-Colet Josep,
Abstract
BACKGROUND:
Sympathetic activity (SA) is increased in patients with heart failure and reduced ejection fraction (HFrEF) and is associated with poor outcomes. However, its clinical implications are less understood in HF with mid-range (HFmrEF) and preserved ejection fraction (HFpEF). We aimed to study SA across left ventricle ejection fraction (LVEF) groups and its association with clinical outcomes.
METHODS AND RESULTS:
SA estimated by norepinephrine (NE) levels was determined in 742 consecutive outpatients with chronic HF: 348 (47%) with HFrEF, 116 (16%) HFmrEF, and 278 (37%) HFpEF. After a mean follow-up of 15 months, 17% died. Adjusted analyses showed that patients with HFpEF and HFmrEF had lower estimated marginal means of NE levels compared to HFrEF (278 and 116 pg/mL, respectively, vs. 348 pg/mL; p-value=0.005). Adjusted Cox regression analyses showed that high norepinephrine levels independently predicted all-cause mortality (ACM) in all 3 groups. The strongest associations between high NE levels and cardiovascular mortality (CVM) were observed in HFmrEF (HR: 4.7 [1.33-16.68]), while the weakest association was in HFpEF (HR: 2.62 [1.08-6.35]).
CONCLUSIONS:
Adjusted analyses showed that HFpEF and HFmrEF were associated with lower SA compared to HFrEF. Nevertheless, increasing NE levels were independently associated with ACM and CVM in all three LVEF groups. The strongest association between high NE levels and CVM was present in HFmrEF patients, while the weakest was seen in HFpEF. These findings could explain why the response to neurohormonal therapies in patients with HFmrEF is similar to that of patients with HFrEF rather than with HFpEF.
Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
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Assessing cardiovascular risk in cancer patients: opportunities and challenges.
Eur J Prev Cardiol2020 Jul;():2047487320943002. doi: 10.1177/2047487320943002.
Guha Avirup, Desai Nihar R, Weintraub Neal L,
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Heart Failure with Carfilzomib in Patients with Multiple Myeloma: A Meta-analysis of Randomized Controlled Trials.
J Card Fail2020 Jul;():. doi: S1071-9164(20)30870-8.
Rahman M Rubayat, Ball Somedeb, Bandyopadhyay Dhrubajyoti, Paz Pablo, Elmassry Mohamed, Vutthikraivit Wasawat, Lavie Carl J, Fonarow Gregg C,
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Prediction of doxorubicin cardiotoxicity by early detection of subclinical right ventricular dysfunction.
Cardiooncology2020 ;6():10. doi: 10.1186/s40959-020-00066-8.
Planek Maria Isabel Camara, Manshad Ahmad, Hein Kyaw, Hemu Mohamad, Ballout Fatima, Varandani Rajiv, Venugopal Parameswaran, Okwuosa Tochukwu,
Abstract
Background:
Doxorubicin remains one of the most common causes of cardiotoxicity in patients with lymphoma, leading to significant morbidity and mortality. Early decline in left ventricular (LV) ejection fraction predicts chemotherapy-induced cardiotoxicity and mortality, but limited data exist on doxorubicin-induced subclinical right ventricular (RV) dysfunction. We investigated dose-dependent subclinical doxorubicin-induced RV dysfunction in lymphoma patients.
Methods:
Thirty-five patients with adult lymphoma treated with doxorubicin were studied. All patients had normal baseline LV ejection fraction (LVEF >?55%), and no known cardiopulmonary disease. We studied the dose-dependent effect of doxorubicin on RV strain by 2D speckle-tracking echocardiography (STE) using a vendor-independent software (TomTec). Images were analyzed offline by two independent observers blinded to the clinical characteristics of the study population. Baseline LVEF, RV fractional area change (RV FAC), RV free wall strain (RV FWS), and RV global longitudinal strain (RV GLS) were measured prior to chemotherapy initiation and compared with echo studies obtained at a 6-month follow-up interval. Patients served as their own controls. Comparisons between pre- and post-therapy were achieved using paired Student's t-tests or Chi-Square test.
Results:
The Interobserver Intraclass Correlation Coefficient for RV GLS, RV FAC and RV FWS, was 0.87, 0.81 and 0.79, respectively. The mean age was 51?±?13?years, 40% women, 60% white. The mean cumulative doxorubicin dose was 239?±?104?mg?m. There was there was significant decline in RV FAC (47.3?±?4.4% vs. 43.7?±?3.9%), RV FWS (-?24.9?±?3.3 vs. -22.2?±?2.9), and RV GLS (-?22.4?±?4.1 vs. -20.6?±?3.4) (all ?
Conclusion:
In this cohort of adult lymphoma patients, doxorubicin-based therapy was associated with subclinical RV dysfunction, but not LV dysfunction, at a cumulative dose ?200?mg?m. Additional studies evaluating the long-term prognostic implications of RV dysfunction in this population are essential.
© The Author(s) 2020.
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Cardio-Oncology in Era of the COVID-19 Pandemic and Beyond.
J Am Heart Assoc2020 Jul;():e05456. doi: 10.1161/JAHA.120.017787.
Addison Daniel, Campbell Courtney M, Guha Avirup, Ghosh Arjun K, Dent Susan F, Jneid Hani,
Abstract
Coronavirus 2019 (COVID-19) has emerged as a global pandemic and public health crisis. Increasing waves of intermittent infectious outbreaks have dramatically influenced care among broad populations. Over the last two decades, there has been a rapid increase in cancer survival, with >400,000 new survivors each year. The increasingly common presence of cardiovascular disease in patients during or after cancer treatment led to the rapid growth of the field of cardio-oncology with a mandate of identifying, treating, and preventing the various forms of cardiovascular disease seen among this population. This review evaluates the implications of the pandemic on the practice and study of cardio-oncology. The evolving understanding of the relationship between comorbid disease and clinical outcomes among this population is assessed. With the impetus of the pandemic, cardio-oncology can be deliberate in embracing changes to cardiac screening, monitoring, and intervention during oncology care. Bridging two specialties, consideration of the lessons learned in cancer and cardiovascular may pivotally inform ongoing therapeutic efforts. Further, the development of multi-center registries focused on understanding and optimizing outcomes among these patients should be considered. Together, these insights may critically inform strategies for the care of cardio-oncology patients in future phases of the COVID-19 pandemic and beyond.
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Myocardial F-FDG Uptake Pattern for Cardiovascular Risk Stratification in Patients Undergoing Oncologic PET/CT.
J Clin Med2020 Jul;9(7):. doi: E2279.
Haider Ahmed, Bengs Susan, Schade Katharina, Wijnen Winandus J, Portmann Angela, Etter Dominik, Fröhlich Sandro, Warnock Geoffrey I, Treyer Valerie, Burger Irene A, Fiechter Michael, Kudura Ken, Fuchs Tobias A, Pazhenkottil Aju P, Buechel Ronny R, Kaufmann Philipp A, Meisel Alexander, Stolzmann Paul, Gebhard Catherine,
Abstract
OBJECTIVE:
Positron emission tomography/computed tomography with F-fluorodeoxy-glucose (F-FDG-PET/CT) has become the standard staging modality in various tumor entities. Cancer patients frequently receive cardio-toxic therapies. However, routine cardiovascular assessment in oncologic patients is not performed in current clinical practice. Accordingly, this study sought to assess whether myocardial F-FDG uptake patterns of patients undergoing oncologic PET/CT can be used for cardiovascular risk stratification.
METHODS:
Myocardial F-FDG uptake pattern was assessed in 302 patients undergoing both oncologic whole-body F-FDG-PET/CT and myocardial perfusion imaging by single-photon emission computed tomography (SPECT-MPI) within a six-month period. Primary outcomes were myocardial F-FDG uptake pattern, impaired myocardial perfusion, ongoing ischemia, myocardial scar, and left ventricular ejection fraction.
RESULTS:
Among all patients, 109 (36.1%) displayed no myocardial F-FDG uptake, 77 (25.5%) showed diffuse myocardial F-FDG uptake, 24 (7.9%) showed focal F-FDG uptake, and 92 (30.5%) had a focal on diffuse myocardial F-FDG uptake pattern. In contrast to the other uptake patterns, focal myocardial F-FDG uptake was predominantly observed in patients with myocardial abnormalities (i.e., abnormal perfusion, impaired LVEF, myocardial ischemia, or scar). Accordingly, a multivariate logistic regression identified focal myocardial F-FDG uptake as a strong predictor of abnormal myocardial function/perfusion (odds ratio (OR) 5.32, 95% confidence interval (CI) 1.73-16.34, = 0.003). Similarly, focal myocardial F-FDG uptake was an independent predictor of ongoing ischemia and myocardial scar (OR 4.17, 95% CI 1.53-11.4, = 0.005 and OR 3.78, 95% CI 1.47-9.69, = 0.006, respectively).
CONCLUSIONS:
Focal myocardial F-FDG uptake seen on oncologic PET/CT indicates a significantly increased risk for multiple myocardial abnormalities. Obtaining and taking this information into account will help to stratify patients according to risk and will reduce unnecessary cardiovascular complications in cancer patients.
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