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10/31/23

Tumor-targeted therapies such as trastuzumab have led to significant improvements in survival of human epidermal growth factor receptor 2

Abstract

Tumor-targeted therapies such as trastuzumab have led to significant improvements in survival of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, these therapies have also been associated with significant left ventricular dysfunction. The incidence of trastuzumab-induced heart failure has decreased significantly since the initial reports, in large part due to improved screening, closer monitoring for early changes in left ventricular function, and a significant decrease in the concurrent administration of anthracyclines. The mechanism of trastuzumab cardiotoxicity is still not well understood, but current knowledge suggests that ErbB2 inhibition in cardiac myocytes plays a key role. In addition to trastuzumab and other HER2-targeted agents, vascular endothelial growth factor inhibitors, proteasome inhibitors, and immune checkpoint inhibitors are all additional classes of drugs used with great success in the treatment of solid tumors and hematologic malignancies. Yet these, too, have been associated with cardiac toxicity that ranges from a mild asymptomatic decrease in ejection fraction to fulminant myocarditis. In this review, we summarize the cardiotoxic effects of tumor-targeted and immunotherapies with a focus on HER2 antagonists.

PMID: 31988685 [PubMed - in process]

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The Burgeoning Field of Cardio-Oncology.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):241-242

Authors: Trachtenberg BH

PMID: 31988683 [PubMed - in process]

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Barry H. Trachtenberg Leads Issue on Cardio-Oncology.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):240

Authors:

PMID: 31988682 [PubMed - in process]

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Late cardiac adverse events in patients with cancer treated with immune checkpoint inhibitors.

J Immunother Cancer. 2020 Jan;8(1):

Authors: Dolladille C, Ederhy S, Allouche S, Dupas Q, Gervais R, Madelaine J, Sassier M, Plane AF, Comoz F, Cohen AA, Thuny FR, Cautela J, Alexandre J

Innovations and discoveries in cancer therapeutics have improved survival rates in patients with various types of malignancies. At the same time

Abstract

Innovations and discoveries in cancer therapeutics have improved survival rates in patients with various types of malignancies. At the same time, physicians are identifying an increased number of patients with treatment-related cardiotoxicity. It is imperative that physicians recognize early treatment-related adverse effects to determine the safest therapeutic options for patients with cancer. This manuscript evaluates the role of cardiovascular imaging and biomarkers in identifying cardiotoxicity trigged by various chemotherapeutic agents and summarizes expert consensus statements regarding cardiotoxicity monitoring.

PMID: 31988686 [PubMed - in process]

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Heart Failure in Relation to Tumor-Targeted Therapies and Immunotherapies.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):250-257

Authors: Agunbiade TA, Zaghlol RY, Barac A

Recent decades have seen an increase in survival rates for cancer patients, partially explained by earlier diagnoses and new chemotherapeutic

Abstract

Recent decades have seen an increase in survival rates for cancer patients, partially explained by earlier diagnoses and new chemotherapeutic agents. However, chemotherapy may be associated with adverse cardiovascular events, including hypertension and pulmonary hypertension, supraventricular and ventricular arrhythmias, cardiomyopathy, and other forms of cardiovascular disease. For patients, the benefits of chemotherapy may be partially obfuscated by deleterious effects on the cardiovascular system, resulting in a significant increase in morbidity and mortality. In this article, we review strategies for prevention and treatment of chemotherapy-related cardiotoxicity.

PMID: 31988687 [PubMed - in process]

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The Role of Cardiovascular Imaging and Serum Biomarkers in Identifying Cardiotoxicity Related to Cancer Therapeutics.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):258-266

Authors: Agha A, Zarifa A, Kim P, Iliescu C, Gladish G, Hassan S, Palaskas N, Durand JB, Lu Y, Lopez-Mattei J

As cancer survival outcomes improve, there is a growing focus on survivorship and long-term morbidity after cancer treatment

Abstract

As cancer survival outcomes improve, there is a growing focus on survivorship and long-term morbidity after cancer treatment. In particular, there has been concern about the long-term effects of radiotherapy on cardiac function. In this review, we discuss the cardiac effects of radiotherapy in the context of potential confounding factors, examine the potential parameters of interest when studying and modeling cardiac injury, highlight current treatment techniques to minimize radiation to the heart, and consider future areas of improvement and study.

PMID: 31988688 [PubMed - in process]

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Prevention and Treatment of Chemotherapy-Induced Cardiotoxicity.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):267-273

Authors: Avila MS, Siqueira SRR, Ferreira SMA, Bocchi EA

The acknowledgement of cardiovascular disease as one of the leading causes of mortality and morbidity among cancer survivors is the cornerstone of the growing

Abstract

The acknowledgement of cardiovascular disease as one of the leading causes of mortality and morbidity among cancer survivors is the cornerstone of the growing field of cardio-oncology. Although standardizing treatment for any given disease is often considered ideal, it is important to recognize the value of pursuing a practical and personalized approach when caring for an oncology patient to minimize the risk of treatment-related cardiotoxicity. We hereby discuss a series of cases that illustrate the ways vascular toxicity can manifest in patients with cancer and, when appropriate, provide scientific evidence that supports clinical decision making. We also raise questions about the complex management of these patients while shedding light on future research in this growing field.

PMID: 31988690 [PubMed - in process]

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Electrophysiologic Complications in Cancer Patients.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):282-288

Authors: Lee DH, Chandrashekhar S, Fradley MG

Abstract

In recent years, dramatic advances in both cancer diagnosis and treatment have led to significantly increased survival rates. As such, cardiovascular toxicities due to oncologic treatments are more frequently identified. Although heart failure and cardiomyopathy have historically been the cardiotoxicities most associated with cancer therapeutics, it is now recognized that all components of the cardiovascular system can be affected. In this review, we discuss electrophysiologic complications of cancer treatments, including atrial and ventricular tachyarrhythmias as well as bradyarrhythmias, and recommend a multidisciplinary approach with both cardiologists and oncologists to provide safe and effective care to these patients.

PMID: 31988689 [PubMed - in process]

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Cardiovascular Toxicities of Radiation Therapy.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):274-281

Authors: Lewis GD, Farach A

SIGNIFICANCE: The cardiac side effects of hematological treatments are a major issue of the growing population of cancer survivors, often affecting

Abstract

SIGNIFICANCE: The cardiac side effects of hematological treatments are a major issue of the growing population of cancer survivors, often affecting patient survival even more than the tumor for which the treatment was initially prescribed. Among the most cardiotoxic drugs are anthracyclines, highly potent anti-tumor agents, which still represent a mainstay in the treatment of hematological and solid tumors. Unfortunately, diagnosis, prevention and treatment of cardiotoxicity are still unmet clinical needs which call for a better understanding of the molecular mechanism behind the pathology. Recent Advances: This review article will discuss recent findings on the pathomechanisms underlying the cardiotoxicity of anthracyclines, spanning from DNA and mitochondrial damage to calcium homeostasis, autophagy and apoptosis. Special emphasis will be given to the role of reactive oxygen species and their interplay with major signaling pathways.

CRITICAL ISSUES: Although new promising therapeutic targets and new drugs have started to be identified, their efficacy has been mainly proven in preclinical studies and requires clinical validation.

FUTURE DIRECTIONS: Future studies are awaited to confirm the relevance of recently uncovered targets, as well as identifying new druggable pathways, in more clinically relevant models, including for example human induced pluripotent stem cell-derived cardiomyocytes.

PMID: 31989842 [PubMed - as supplied by publisher]

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Future Directions in Cardio-Oncology.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):300-302

Authors: Trachtenberg BH

PMID: 31988691 [PubMed - in process]

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Vascular Toxicity in Patients with Cancer: Is There a Recipe to Clarify Treatment? CME.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):289-299

Authors: Alvarez-Cardona J, Mitchell J, Lenihan D

Abstract

CRITICAL ISSUES: Although new promising therapeutic targets and new drugs have started to be identified, their efficacy has been mainly proven in preclinical studies and requires clinical validation.

PMID: 31989842 [PubMed - as supplied by publisher]

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Future Directions in Cardio-Oncology.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):300-302

Authors: Trachtenberg BH

PMID: 31988691 [PubMed - in process]

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Vascular Toxicity in Patients with Cancer: Is There a Recipe to Clarify Treatment? CME.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):289-299

Authors: Alvarez-Cardona J, Mitchell J, Lenihan D

BACKGROUND: Primary Hepatic Epithelioid Haemangioendothelioma (HEHE) and Primary Hepatic Angiosarcoma (PHA) are rare mesenchymal

Abstract

BACKGROUND: Primary Hepatic Epithelioid Haemangioendothelioma (HEHE) and Primary Hepatic Angiosarcoma (PHA) are rare mesenchymal tumours with different malignant potential. Whereas HEHE demonstrates low to intermediate malignant potential, PHA is an aggressive malignancy with poor prognosis. The knowledge of typical imaging features of these lesions may facilitate correct diagnosis; however, the ultimate diagnosis of HEHE and PHA is based on histopathologic examination.

DISCUSSION: The most typical findings helpful in diagnosing HEHE are: Presence of multiple, confluent nodules located at the liver periphery (in young to middle-aged woman), retraction of the liver capsule, marked hyperintensity on T2-weighted images, "target-sign" appearance, progressive centripetal contrast enhancement, and relatively high Apparent Diffusion Coefficient (ADC) values. More than ≥50% of nodules are hyper- or isointense on Hepatobiliary Phase (HBP) images.

CONCLUSION: The imaging features suggestive of PHA are: Occurrence of metastases (lungs, spleen) at the time of diagnosis, presence of a large dominant mass with smaller satellites, heterogeneity and areas of haemorrhage in a dominant mass, progressive contrast enhancement, slightly elevated ADC values as compared to other malignant liver tumours.

PMID: 31989904 [PubMed - in process]

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Signaling pathways underlying anthracycline cardiotoxicity.

Antioxid Redox Signal. 2020 Jan 28;:

Authors: Sala V, Della Sala A, Hirsch E, Ghigo A

BACKGROUND AND PURPOSE: We conducted a phase I trial of alisertib, an oral aurora kinase inhibitor, with fractionated stereotactic

Abstract

BACKGROUND AND PURPOSE: We conducted a phase I trial of alisertib, an oral aurora kinase inhibitor, with fractionated stereotactic re-irradiation therapy (FSRT) for patients with recurrent high grade glioma (HGG).

MATERIALS AND METHODS: Adult patients with recurrent HGG were enrolled from Feb 2015 to Feb 2017. Patients were treated with concurrent FSRT and alisertib followed by maintenance alisertib. Concurrent alisertib dose was escalated from 20 mg to 50 mg twice daily (BID).

RESULTS: 17 patients were enrolled. Median follow-up was 11 months. Median FSRT dose was 35 Gy. There were 6, 6, 3, and 2 patients enrolled in 20 mg, 30 mg, 40 mg, and 50 mg cohort, respectively. Only one DLT was observed. One patient in the 20 mg cohort had severe headache (Grade 3) resolved with steroids. There was no non-hematological grade 3 or higher toxicity. There were two Grade 4 late toxicities (one with grade 4 neutropenia and leukopenia, one with pulmonary embolism). One patient developed radiation necrosis (Grade 3). Sixteen patients finished concurrent treatment and received maintenance therapy (median cycles was 3, range 1-9). OS for all cohorts at 6 months was 88.2% with median survival time of 11.1 months. PFS at 6 months was 35.3% with median time to progression of 4.9 months. The trial stopped early due to closure of alisertib program with only 2 of 3 planned patients enrolled in the 50 mg cohort.

CONCLUSION: Re-irradiation with FSRT combined with alisertib is safe and well tolerated for HGG with doses up to 40 mg BID. Although no DLT observed in the 50 mg cohort, this cohort was not fully enrolled and MTD was not reached. Clinical outcomes appear comparable to historical results. (NCT02186509).

PMID: 30825962 [PubMed - indexed for MEDLINE]

15:59

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Magnetic Resonance Imaging of Uncommon Hepatic Mesenchymal Tumours: Haemangioendothelioma and Angiosarcoma.

Curr Med Imaging Rev. 2019;15(4):362-368

Authors: Cieszanowski A, Anysz-Grodzicka A, Podgorska J, Jagielska B, Pałucki J

The risk of venous thromboembolism (VTE) is higher in myeloma patients receiving immunomodulatory compounds. A VTE

Abstract

The risk of venous thromboembolism (VTE) is higher in myeloma patients receiving immunomodulatory compounds. A VTE prophylaxis using low-molecular-weight heparin or aspirin is therefore proposed. Apixaban is an oral direct anti-Xa. Several studies have shown the efficacy and safety of apixaban in VTE prophylaxis compared to enoxaparin. The objective of this prospective phase 2 pilot study was to assess the risk of VTE and bleeding in patients with myeloma treated with immunomodulatory compounds lenalidomide (len) or thalidomide (thal), using apixaban in a preventive scheme. Myeloma patients requiring Melphalan-Prednisone-Thalidomide in the first line, or Lenalidomide-Dexamethasone in the relapse setting received apixaban, 2.5 mg x 2/day for 6 months. Venous (pulmonary embolism-PE, or symptomatic proximal or distal deep vein thrombosis-DVT, or all proximal asymptomatic events detected by systematic proximal bilateral compression ultrasound) or arterial thrombotic events, and bleeding events (ISTH 2005) were registered. One hundred and four patients were enrolled (mean age 69.8 ± 7.8 years), 11 in first line and 93 in relapse. Two venous thrombotic events were observed, for example, an asymptomatic proximal DVT and a symptomatic distal DVT, in the context of apixaban stopped 14 days before, due to lenalidomide-induced thrombocytopenia. No PE or arterial cardiovascular events were reported. Only one major and 11 CRNM hemorrhages were reported. These data must now be confirmed on a randomized large study.

PMID: 30859608 [PubMed - indexed for MEDLINE]

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Phase I trial of alisertib with concurrent fractionated stereotactic re-irradiation for recurrent high grade gliomas.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

Phase I trial of alisertib with concurrent fractionated stereotactic re-irradiation for recurrent high grade gliomas.

Radiother Oncol. 2019 03;132:135-141

Authors: Song A, Andrews DW, Werner-Wasik M, Kim L, Glass J, Bar-Ad V, Evans JJ, Farrell CJ, Judy KD, Daskalakis C, Zhan T, Shi W

Older patients, especially those with malignancy, may have an increased risk of pulmonary embolism (PE). However, few studies have evaluated the clinical

Abstract

Older patients, especially those with malignancy, may have an increased risk of pulmonary embolism (PE). However, few studies have evaluated the clinical characteristics and prognosis of older patients. We evaluated the clinical characteristics, prognosis, and risk factors in older patients with lung cancer complicated with PE. This was a single-center, prospective cohort study. Older patients (≥65 years) with lung cancer admitted in Beijing Hospital from January 2006 to December 2016 were enrolled. The patients were divided into two groups according to the presence of PE using propensity score matching (PSM). After PSM, one hundred and six patients (53 per group) with an average age of (77.3 ± 10.9) years were enrolled. Adenocarcinoma was the most common histology in patients with PE (52.8%, n = 28), and most lung cancer patients were in stages III and IV (59.4%, n = 63). Patients with PE were stratified to low risk (52.8%, n = 28), intermediate-low risk (24.5%, n = 13), intermediate-high risk (15.1%, n = 8), high-risk (7.5%, n = 4) subgroups. Most PE patients presented with dyspnea (75.5%), and the majority of patients (86.8%, n = 46) developed PE within 3 months after the diagnosis of cancer. The median follow-up time was 23.7 months (12.0-62.0 months), and 7 patients (6.6%) were lost to follow-up. During the follow-up period, 92 patients (86.8%) died, including 8 cases (8.7%) of PE-related death, 73 (79.3%) of tumor death, and 11 (11.9%) of unknown cause. There were significant differences in all-cause mortality (94.3% vs. 83.0%) and PE-related mortality (15.1% vs. 0) between the PE and control groups, but the rate of tumor-related mortality (75.5% vs. 66.0%) was comparable between the groups. Among the 92 patients who died, the mortality rates at 3, 6, 12, and > 12 months after tumor diagnosis were 33.0% (33/106), 57.5% (61/106), 78.3% (83/106), and 89.6% (95/106), respectively. Kaplan-Meier survival analysis showed that the median overall survival time was significantly different between the PE and the control groups (4.3 vs. 9.2 months, P = 0.0015). Multivariate stepwise logistic regression analysis showed that age ≥ 77 years (OR = 2.58, 95%CI: 1.66-4.01), clinical stage III-IV (OR = 2.21, 95%CI: 1.03-4.74), adenocarcinoma (OR = 3.24, 95%CI: 1.75-6.00), high D-dimer (≥600 mg/L) (OR = 2.73, 95%CI: 1.25-5.96), and low partial pressure of oxygen (PaO2; <75 mmhg)

PMID: 31988400 [PubMed - in process]

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Apixaban for the prevention of thromboembolism in immunomodulatory-treated myeloma patients: Myelaxat, a phase 2 pilot study.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7388-69-wiley-full-text.png Related Articles

Apixaban for the prevention of thromboembolism in immunomodulatory-treated myeloma patients: Myelaxat, a phase 2 pilot study.

Am J Hematol. 2019 06;94(6):635-640

Authors: Pegourie B, Karlin L, Benboubker L, Orsini-Piocelle F, Tiab M, Auger-Quittet S, Rodon P, Royer B, Leleu X, Bareau B, Cliquennois M, Fuzibet JG, Voog E, Belhadj-Merzoug K, Decaux O, Rey P, Slama B, Leyronnas C, Zarnitsky C, Boyle E, Bosson JL, Pernod G, IFM Group

The acknowledgement of cardiovascular disease as one of the leading causes of mortality and morbidity among cancer survivors is the cornerstone of the

Abstract

PMID: 31988690 [PubMed - in process]

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Prognosis and risk factors in older patients with lung cancer and pulmonary embolism: a propensity score matching analysis.

Sci Rep. 2020 Jan 27;10(1):1272

Authors: Junjun L, Pei W, Ying Y, Kui S

Background: The propensity to develop venous thromboembolism (VTE) on the basis of individual tumor biological features remains unknown.

Abstract

Background: The propensity to develop venous thromboembolism (VTE) on the basis of individual tumor biological features remains unknown.

Objectives: We conducted a whole transcriptome RNA sequencing strategy, focusing on a single cancer type (lung cancer), to identify biomarkers of cancer-associated VTE.

Methods: Twelve propensity-matched patients, 6 each with or without VTE, were identified from a prospective institutional review board-approved registry at the Cleveland Clinic with available tissue from surgical excision of a primary lung mass between 2010 and 2015. Patients were propensity matched based on age, sex, race, history of prior cancer, date of cancer diagnosis, stage, histology, number of lines of chemotherapy, and length of follow-up. RNA sequencing was performed on tumor tissue, and gene set enrichment analysis (GSEA) was performed on differentially expressed genes.

Results: We identified 1037 genes with differential expression. In patients with VTE, 869 genes were overexpressed and 168 were underexpressed compared to patients without VTE. Of these, 276 overexpressed and 35 underexpressed were significantly different (Q < 0.05).

Conclusions: These differentially expressed genes and associated pathways provide biologic insights into cancer-associated VTE and may provide insignts to develop new risk stratification schemes, prevention, or treatment strategies.

PMID: 31989093 [PubMed]

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Vascular Toxicity in Patients with Cancer: Is There a Recipe to Clarify Treatment? CME.

Methodist Debakey Cardiovasc J. 2019 Oct-Dec;15(4):289-299

Authors: Alvarez-Cardona J, Mitchell J, Lenihan D

Background: Pulmonary embolism (PE) in children carries a significant morbidity and mortality. We examined previously described factors in

Abstract

Background: Pulmonary embolism (PE) in children carries a significant morbidity and mortality. We examined previously described factors in 2 cohorts of children tested for PE and identified novel factors.

Methods: We combined data from 2 retrospective cohorts. Patients up to age 21 years were included who underwent imaging or D-dimer testing for PE, with positive radiologic testing being the gold standard. Combined predictor variables were examined by univariate analysis and then forward stepwise multivariable logistic regression.

Results: The combined data set yielded 1103 patients with 42 unique predictor variables, and 93 PE-positive patients (8.4%), with a median age of 16 years. Univariate analysis retained 17 variables, and multivariable logistic regression found 9 significant variables with increased probability of PE diagnosis: age-adjusted tachycardia, tachypnea, hypoxia, unilateral limb swelling, trauma/surgery requiring hospitalization in previous 4 weeks, prior thromboembolism, cancer, anemia, and leukocytosis.

Conclusion: This combined data set of children with suspected PE discovered factors that may contribute to a diagnosis of PE: hypoxia, unilateral limb swelling, trauma/surgery requiring hospitalization in previous 4 weeks, prior thromboembolism, and cancer, age-adjusted tachycardia, tachypnea, anemia, and leukocytosis. Prospective testing is needed to determine which criteria should be used to initiate diagnostic testing for PE in children.

PMID: 31989094 [PubMed]

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RNA expression and risk of venous thromboembolism in lung cancer.

Res Pract Thromb Haemost. 2020 Jan;4(1):117-123

Authors: Sussman TA, Abazeed ME, McCrae KR, Khorana AA

Introduction: Previous research from the United Kingdom and Spain has identified several areas of unmet clinical and support need for cancer patients

Abstract

Introduction: Previous research from the United Kingdom and Spain has identified several areas of unmet clinical and support need for cancer patients diagnosed with venous thromboembolism. It is not known whether such experiences are restricted to those countries health care systems and culture. We therefore evaluated patients' experience of cancer-associated thrombosis (CAT) within a Canadian setting.

Methods: Purposive sampling of patients with CAT attending a regional thrombosis clinic in Vancouver was undertaken. Semistructured interviews were audio recorded, transcribed, and coded using NVivo software. A deductive approach was taken by applying the framework matrix from the original study to these data on a case-by-case basis.

Results: Twenty patients (10 male, 10 female) aged 39 to 74 (mean, 63) representing a breadth of different cancers participated. Commonalities between the UK and Canadian patients included the traumatic nature of experiencing CAT, the need for information, and adaptive behaviors through ritualization. Two new themes were identified: (1) Patients with incidental pulmonary emboli (iPE) were usually telephoned about their thrombus with little support and suboptimal communication; and (2) cost implications of accessing low-molecular-weight heparin varied according to insurance cover. Patients were sometimes converted to warfarin for financial reasons.

Conclusion: The distress associated with CAT is a common experience across different populations but may be ameliorated by early access to specialist services, information, and support. The current process for managing iPE could be improved with better communication and a dedicated clinical pathway. Funding issues may influence choice of anticoagulant.

PMID: 31989097 [PubMed]

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Clinical variables that increase the probability of pulmonary embolism diagnosis in symptomatic children.

Res Pract Thromb Haemost. 2020 Jan;4(1):124-130

Authors: Hennelly KE, Ellison AM, Neuman MI, Kline JA

Heparin-induced thrombocytopenia (HIT)

Abstract

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction to heparin products characterized by thrombocytopenia with or without thrombosis. This study aimed to determine the incidence, morbidity, mortality and economic burden of HIT in solid-malignancy-related hospitalizations. We analyzed the National Inpatient Sample Database (NIS), the largest public database of hospital admissions in the United States, from January 2012 to September 2015. The primary outcome of the study was the incidence of HIT. Secondary outcomes included incidence of venous thrombosis (acute deep venous thrombosis and pulmonary embolism), arterial thrombosis (thrombotic stroke, myocardial infarctions and other arterial thromboembolism), mortality associated with HIT, length of stay, total hospital charges and disposition. During the study period, 7 437 049 hospitalizations had an associated diagnosis of solid malignancy. Approximately 0·08% (n = 6225) hospitalizations had a secondary diagnosis of HIT in this population. The standardized incidence of total thrombotic events was higher in the solid malignancy with HIT compared to the solid malignancy without HIT group (24·7% vs. 6·8%, P < 0·001).< 0·001).

PMID: 31990984 [PubMed - as supplied by publisher]

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Patient Experience of Living With Cancer-Associated Thrombosis in Canada (PELICANADA).

Res Pract Thromb Haemost. 2020 Jan;4(1):154-160

Authors: Noble S, Nelson A, Scott J, Berger A, Schmidt K, Swarnkar P, Lee A

OBJECTIVES: To examine and summarize current international guidelines regarding cardiovascular risk reduction before and during cancer

Abstract

OBJECTIVES: To examine and summarize current international guidelines regarding cardiovascular risk reduction before and during cancer therapy, and to discuss the emerging role of cardio-oncology as a subspecialty in cancer care and the role of cardio-oncology rehabilitation.

DATA SOURCES: Published articles and guidelines.

CONCLUSION: With improvements in cancer detection and the use of novel adjuvant therapies, an increasing number of individuals now survive a cancer diagnosis. However, for some the cost is high - many survivors are now at higher risk of death from cardiovascular disease than from recurrent cancer. Cardiovascular morbidity and mortality are common and associated with common cancer therapies serially administered in adult oncology care.

IMPLICATIONS FOR NURSING PRACTICE: Timely risk-reduction interventions hold promise in reducing cardiovascular morbidity and mortality. Oncology nurses are the key providers to identify baseline risks, perform necessary referrals, provide individualized teaching, and support the patient within the family and community.

PMID: 31983487 [PubMed - as supplied by publisher]

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Modulating the cardiotoxic behaviour of immunoglobulin light chain dimers through point mutations.

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Modulating the cardiotoxic behaviour of immunoglobulin light chain dimers through point mutations.

Amyloid. 2019;26(sup1):105-106

Authors: Maritan M, Ambrosetti A, Oberti L, Barbiroli A, Diomede L, Romeo M, Lavatelli F, Sormanni P, Palladini G, Bolognesi M, Merlini G, Ricagno S

PMID: 31343361 [PubMed - indexed for MEDLINE]

29 January 2020

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Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Incidence and outcomes of heparin-induced thrombocytopenia in solid malignancy: an analysis of the National Inpatient Sample Database.

Br J Haematol. 2020 Jan 28;:

Authors: Kumar R, Bhandari S, Singh SRK, Malapati S, Cisak KI

Abstract

BACKGROUND: Described variations of tentorial venous anatomy impact surgical sectioning of the tentorium in skull base approaches; however, described configurations do not consistently explain postoperative complications. To understand the outcomes of 2 clinical cases we studied the tentorial venous anatomy of 2 cadavers.

METHODS: The venous anatomy of the tentorium isolated in 2 uninjected fresh cadaver head specimens with preserved bridging veins was observed by transillumination before and after methylene blue injection of the dural sinuses and tentorial veins. Our findings in cadavers were applied to explain the clinical and radiologic (magnetic resonance imaging and computed tomographic venography) findings in the 2 cases presented.

RESULTS: A consistent transtentorial venous system, arising from transverse and straight sinuses, communicating with supra- and infratentorial bridging veins was seen in the cadaver and patient radiography (magnetic resonance imaging and computed tomographic venography). Our first patient had a cerebellar venous infarct from compromise of the venous drainage from the adjacent brain after ligation of a temporal lobe bridging vein to the tentorium. Our second patient suffered no clinical effects from bilateral transverse sinus occlusion due to drainage through the accessory venous system within the tentorium.

CONCLUSIONS: Herein, we elaborate on transtentorial venous anatomy. These veins, previously reported to obliterate in completed development of the tentorium, remain patent with consistent observed configuration. The same transtentorial venous system was observed in both cases and provided insight to their outcomes. These findings emphasize the importance of the transtentorial venous system physiologically and in surgical approaches.

PMID: 31295599 [PubMed - indexed for MEDLINE]

14:44

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Rehabilitation Needs in Cancer Treatment-Related Cardiotoxicity.

Semin Oncol Nurs. 2020 Jan 23;:150986

Authors: Pituskin E, Kirkham AA, Cox-Kennett N, Dimitry R, Dimitry J, Paterson I, Gyenes GT

Abstract

BACKGROUND: Clinically unsuspected venous thromboembolic events (uVTE) detected during routine imaging pose a management challenge due to limited knowledge about their clinical significance. Unsuspected VTE are often referred as "asymptomatic", "incidental" or "clinically silent/occult" VTE.

OBJECTIVE: Understand the epidemiology, management, and outcomes of uVTE in children.

METHODS: A systematic review was performed according to PRISMA guidelines. The search criteria included controlled vocabulary and keywords for VTE, incidental findings, and children (ages ≤21 years).

RESULTS: Among 10,875 articles, 51 studies (7597 children with 758 uVTE) were selected. The studies were heterogeneous, I2 96%; p <.0001.

CONCLUSION: Clinically uVTE were predominantly diagnosed with CVL and their outcomes were generally favorable implying limited benefit of routine surveillance and thromboprophylaxis. Prospective research is needed to clarify the optimal management of iVTE.

PMID: 31984669 [PubMed - as supplied by publisher]

13:19

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Tentorial Venous Anatomy: Cadaveric and Radiographic Study with Discussion of Origin and Surgical Significance.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

Tentorial Venous Anatomy: Cadaveric and Radiographic Study with Discussion of Origin and Surgical Significance.

World Neurosurg. 2019 Nov;131:e38-e45

Authors: Rosenblum JS, Neto M, Essayed WI, Bi WL, Patel NJ, Aziz-Sultan MA, Heiss JD, Al-Mefty O

Background: Venous thromboembolism (VTE)

Abstract

Background: Venous thromboembolism (VTE) is a common complication in cancer patients. We aim to evaluate the effect and safety of direct oral anticoagulants (DOACs) as primary prophylaxis in ambulatory cancer patients.Methods: We conducted a literature search in PubMed, EMBASE and ClinicalTrials for studies that evaluated DOACs for thromboprophylaxis in cancer patients. RevMan 5.3 software was used for this meta-analysis.Results: Three randomized controlled trials (RCTs) with a total of 1465 patients were pooled in the meta-analysis. DOACs significantly reduced the symptomatic VTE incidence during intervention period (RR 0.23, CI 0.11-0.47, P<0.0001,

PMID: 31984870 [PubMed - in process]

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Epidemiology and outcomes of clinically unsuspected venous thromboembolism in children: a systematic review.

J Thromb Haemost. 2020 Jan 27;:

Authors: Sharathkumar AA, Biss T, Kulkarni K, Ahuja S, Regan M, Male C, Revel-Vilk S

In this concise review, we discuss some common clinical challenges in the management of patients with cancer-associated venous thromboembolism (VTE

Abstract

In this concise review, we discuss some common clinical challenges in the management of patients with cancer-associated venous thromboembolism (VTE), a frequent complication in patients with cancer that increases morbidity and mortality. While direct oral anticoagulants (DOACs) have been established in clinical practice for anticoagulation in patients with VTE without cancer, their efficacy and safety in patients with cancer have not been assessed in randomized controlled trials until recently. The choice of the appropriate anticoagulant agent in the era of DOACs to treat patients with cancer-associated VTE is based on balancing the risk of recurrence against the risk of bleeding, and potential drug-drug interactions. However, the management of patients is challenged by special scenarios such as incidentally diagnosed pulmonary embolism and catheter-related thrombosis, and sometimes complicated by concomitant thrombocytopenia. We provide guidance for management of cancer-associated VTE in different clinical scenarios in a case-based manner and briefly review recent clinical studies and guidelines to explain our approach to management of the cases.

PMID: 31986545 [PubMed - as supplied by publisher]

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Pharmacology Focus: Direct Oral Anticoagulants for the Treatment of Cancer-Associated Venous Thromboembolism.

S D Med. 2019 Nov;72(11):537-538

Authors: Lund J, Strain J

PMID: 31985908 [PubMed - in process]

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Direct oral anticoagulants for thromboprophylaxis in ambulatory patients with cancer.

Hematology. 2020 Dec;25(1):63-70

Authors: Wang Y, Wang M, Ni Y, Liang Z

PURPOSE: To evaluate ultrasound-accelerated, catheter-directed thrombolysis (CDT) for treatment of acute submassive pulmonary embolism (PE).

Abstract

PURPOSE: To evaluate ultrasound-accelerated, catheter-directed thrombolysis (CDT) for treatment of acute submassive pulmonary embolism (PE).

MATERIALS AND METHODS: This single-center, retrospective study included patients who underwent CDT for acute submassive PE (N = 113, 52% men/48% women) from 2013 to 2017. Baseline characteristics included history of deep venous thrombosis (12%), history of PE (6%), and history of cancer (18%). Of cohort patients, 88% (n=99) had a simplified PE severity index score of ≥ 1 indicating a high risk of mortality.

RESULTS: A technical success rate of 100% was achieved with 84% of patients having bilateral catheter placements. Average tissue plasminogen activator (tPA) therapy duration was 20.7 hours ± 1.5, and median tPA dose was 21.5 mg. Three patients (2.6%) experienced minor hemorrhagic complications. Mean hospital length of stay was 6 days. Mean pulmonary arterial pressure decreased from 55 mm Hg on presentation to 37 mm Hg (P < .01) 1 day following initiation of thrombolytic therapy. All-cause mortality rate of 4% (n = 4) was noted on discharge, which increased to 6% (n = 7) at 6 months. At 6-month follow-up compared with initial presentation, symptom improvements (93%), physiologic improvements (heart rate 72 beats/min vs 106 beats/min, P < .01), oxygen requirement improvements (fraction of inspired oxygen 20% vs 28%, P < .01), and right ventricular systolic pressure improvements by echocardiography (30 mm Hg vs 47 mm Hg, P < .01) were observed.

CONCLUSIONS: CDT for acute submassive PE was associated with low complications and mortality, decreased right ventricular systolic pressure, high rates of clinical improvement, and improved intermediate-term clinical outcomes.

PMID: 31982316 [PubMed - as supplied by publisher]

28 January 2020

13:19

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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How I Manage Cancer-Associated Thrombosis.

Hamostaseologie. 2020 Jan 27;:

Authors: Moik F, Ay C

Abstract

In 2011, the Spanish Society of Medical Oncology (SEOM) first published a clinical guideline of venous thromboembolism (VTE) and cancer. This guideline was updated in 2014, and since then, multiple studies and clinical trials have changed the landscape of the treatment and prophylaxis of VTE in cancer patients. To incorporate the most recent evidence, including data from direct oral anticoagulants (DOACs) randomized clinical trials, SEOM presents a new update of the guideline.

PMID: 31981080 [PubMed - as supplied by publisher]

27 January 2020

16:23

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Ultrasound-Accelerated, Catheter-Directed Thrombolysis for Submassive Pulmonary Embolism: Single-Center Retrospective Review with Intermediate-Term Outcomes.

J Vasc Interv Radiol. 2020 Jan 22;:

Authors: Makary MS, Fogler BD, Dube PP, Flanders VL, Natarajan K, Garcia-Cortes R, Foster T, Dowell JD

Abstract

BACKGROUND AND OBJECTIVES: Doxorubicin plays an essential role in the treatment of paediatric cancers. Defining genotypes with a higher risk for developing anthracycline-induced cardiotoxicity could help to reduce cardiotoxicity.

METHODS: Data originated from a phase II study assessing the pharmacokinetics of doxorubicin in 100 children. Studied patients (0-17 years) were treated for solid tumours or leukaemia. Two cycles of doxorubicin were studied. Concentrations of natriuretic peptides proANP, BNP and NT-proBNP and cardiac troponins T and I were measured at five time points before, during and after two cycles of doxorubicin treatment. Genotypes of 17 genetic polymorphisms in genes encoding for anthracycline metabolizing enzymes and drug transporters were determined for each patient. We analysed the influence of genotypes on cardiac biomarker concentrations at different time points by a Kruskal-Wallis test. To perform a pairwise comparison significant genetic polymorphisms with more than two genotypes were analysed by a post hoc test.

RESULTS: The Kruskal-Wallis tests and the post hoc-tests showed a significant association for seven genetic polymorphisms (ABCB1-rs1128503, ABCB1-rs1045642, ABCC1-rs4148350, CBR3-rs8133052, NQO2-in/del, SLC22A16-rs714368 and SLC22A16-rs6907567) with the concentration of at least one biomarker at one or more time points. We could not identify any polymorphism with a consistent effect on any biomarker over the whole treatment period.

CONCLUSIONS: In this study of patients treated with doxorubicin for different tumour entities, seven genetic polymorphisms possibly influencing the pharmacokinetics and pharmacodynamics of doxorubicin could lead occasionally to differences in the concentration of cardiac biomarkers. Since, the role of cardiac biomarkers for monitoring anthracycline-induced cardiotoxicity has not yet been clarified, further trials with a long follow-up time are required to assess the impact of these genetic polymorphisms on chemotherapy-related cardiotoxicity.

TRIAL REGISTRATION: EudraCT number: 2009-011454-17.

PMID: 31981210 [PubMed - as supplied by publisher]

14:50

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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SEOM clinical guideline of venous thromboembolism (VTE) and cancer (2019).

Clin Transl Oncol. 2020 Jan 24;:

Authors: Muñoz Martín AJ, Gallardo Díaz E, García Escobar I, Macías Montero R, Martínez-Marín V, Pachón Olmos V, Pérez Segura P, Quintanar Verdúguez T, Salgado Fernández M

Abstract

Although artesunate (ART) is generally accepted as a safe and well-tolerated first-line treatment of severe malaria, cases of severe side effects and toxicity of this compound are also documented. This study applied larval zebrafishes to determine the acute toxicity and efficacy of ART and performed RNA-sequencing analyses to unravel the underlying signaling pathways contributing to ART's activities. Results from acute toxicity assay showed that a single-dose intravenous injection of ART from 3.6 ng/fish (1/9 maximum nonlethal concentration) to 41.8 ng/fish (lethal dose 10%) obviously induced pericardial edema, circulation defects, yolk sac absorption delay, renal edema, and swim bladder loss, indicating acute cardiotoxicity, nephrotoxicity, and developmental toxicity of ART. Efficacy assay showed that ART at 1/2 lowest observed adverse effect level (LOAEL) exerted cardioprotective effects on zebrafishes with verapamil-induced heart failure. Artesunate significantly restored cardiac malformation, venous stasis, cardiac output decrease, and blood flow dynamics reduction. No adverse events were observed with this treatment, indicating that ART at doses below LOAEL was effective and safe. These results indicate that ART at low doses was cardioprotective, but revealed cardiotoxicity at high doses. RNA-sequencing analysis showed that gene expression of frizzled class receptor 7a (fzd7a) was significantly upregulated in zebrafishes with verapamil-induced heart failure and significantly downregulated if ART at 1/2 LOAEL was coadministrated, indicating that fzd7a-modulated Wnt signaling may mediate the cardioprotective effect of ART. For the first time, this study revealed the biphasic property of ART, providing in-depth knowledge on the pharmacological efficacy-safety profile for its therapeutic and safe applications in clinic.

PMID: 31975974 [PubMed]

15:42

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The Limits of the Linear Quadratic (LQ) Model for Late Cardiotoxicity Prediction: Example of Hypofractionated Rotational Intensity Modulated Radiation Therapy (IMRT) for Breast Cancer.

Int J Radiat Oncol Biol Phys. 2020 Jan 20;:

Authors: Loap P, Fourquet A, Kirova Y

PMID: 31973883 [PubMed - as supplied by publisher]

26 January 2020

12:06

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Genetic Polymorphisms Affecting Cardiac Biomarker Concentrations in Children with Cancer: an Analysis from the "European Paediatric Oncology Off-patents Medicines Consortium" (EPOC) Trial.

Eur J Drug Metab Pharmacokinet. 2020 Jan 24;:

Authors: Hellmann F, Völler S, Krischke M, Jamieson D, André N, Bisogno G, Boddy A, Hempel G

: Cancer patients are increasingly referred for cardiology evaluations. These patients differ from those routinely seen in cardiology clinic

Abstract

: Cancer patients are increasingly referred for cardiology evaluations. These patients differ from those routinely seen in cardiology clinics because of their psychological burden and because the therapies and cancer itself can cause cardiac symptoms. A humane approach is critical to managing these patients. Cardiologists may see patients who are newly diagnosed with cancer or are in various phases of treatment; these patients may or may not have preexisting cardiac disease, and may develop cardiotoxicity from chemoimmunotherapy or radiotherapy. Each of these situations presents unique communication challenges for cardiologists. Although some oncology centers provide training in communication skills for their personnel, including cardiologists, this training is not widely available to physicians in general hospitals or private practice. This article examines the psychological aspects of cardio-oncology. It offers practical suggestions on how to best communicate with cancer patients in different phases of oncology care, and discusses when professional psychological help is needed.

PMID: 31977538 [PubMed - as supplied by publisher]

15:42

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Cardiotoxicity and Cardioprotection by Artesunate in Larval Zebrafish.

Dose Response. 2020 Jan-Mar;18(1):1559325819897180

Authors: Zheng C, Shan L, Tong P, Efferth T

This study aimed to compare the predictive value of 2009 and 2013 version of Caprini risk assessment models (RAM) for venous

Abstract

This study aimed to compare the predictive value of 2009 and 2013 version of Caprini risk assessment models (RAM) for venous thromboembolism (VTE) in cancer patients by receiver operating characteristic (ROC) analysis. This retrospective study reviewed a total of 1439 VTE and 1439 non-VTE Chinese cancer inpatients. The baseline demographic data of these patients were recorded. 2009 and 2013 versions Caprini RAMs were applied, and cumulative risk scores were obtained by adding the scores of each risk factor. The specificity, sensitivity, positive predictive value and negative predictive value of these two models were analyzed. ROC curve was drawn to calculate the area under the curve (AUC) and the Youden index. Significant differences were observed in the risk factors between VTE and non-VTE Group. The specificity and negative predictive value of 2013 version were higher than those of 2009 version (P < 0.05).0.05). The AUC and Youden index of 2013 Caprini RAM were significantly higher than those of 2009 Caprini RAM (P < 0.001),< 0.05).

PMID: 31975322 [PubMed - as supplied by publisher]

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15:42

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Cancer patients in cardiology: how to communicate with patients with special psychological needs and manage their cardiac problems in daily clinical practice.

J Cardiovasc Med (Hagerstown). 2020 Jan 20;:

Authors: Lestuzzi C, Annunziata MA, Nohria A, Muzzatti B, Bisceglia I, Ewer MS

RATIONALE: Aberrant formation of blood vessels precedes a broad spectrum of vascular complications; however,

Abstract

RATIONALE: Aberrant formation of blood vessels precedes a broad spectrum of vascular complications; however, the cellular and molecular events governing vascular malformations are not yet fully understood.

OBJECTIVE: Here, we investigated the role of CDC42 (cell division cycle 42) during vascular morphogenesis and its relative importance for the development of cerebrovascular malformations.

METHODS AND RESULTS: To avoid secondary systemic effects often associated with embryonic gene deletion, we generated an endothelial-specific and inducible knockout approach to study postnatal vascularization of the mouse brain. Postnatal endothelial-specific deletion of Cdc42 elicits cerebrovascular malformations reminiscent of cerebral cavernous malformations (CCMs). At the cellular level, loss of CDC42 function in brain endothelial cells (ECs) impairs their sprouting, branching morphogenesis, axial polarity, and normal dispersion within the brain tissue. Disruption of CDC42 does not alter EC proliferation, but malformations occur where EC proliferation is the most pronounced during brain development-the postnatal cerebellum-indicating that a high, naturally occurring EC proliferation provides a permissive state for the appearance of these malformations. Mechanistically, CDC42 depletion in ECs elicited increased MEKK3 (mitogen-activated protein kinase kinase kinase 3)-MEK5 (mitogen-activated protein kinase kinase 5)-ERK5 (extracellular signal-regulated kinase 5) signaling and consequent detrimental overexpression of KLF (Kruppel-like factor) 2 and KLF4, recapitulating the hallmark mechanism for CCM pathogenesis. Through genetic approaches, we demonstrate that the coinactivation of Klf4 reduces the severity of vascular malformations in Cdc42 mutant mice. Moreover, we show that CDC42 interacts with CCMs and that CCM3 promotes CDC42 activity in ECs.

CONCLUSIONS: We show that endothelial-specific deletion of Cdc42 elicits CCM-like cerebrovascular malformations and that CDC42 is engaged in the CCM signaling network to restrain the MEKK3-MEK5-ERK5-KLF2/4 pathway.

PMID: 30732528 [PubMed - indexed for MEDLINE]

25 January 2020

14:20

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Comparison of 2013 and 2009 versions of Caprini risk assessment models for predicting VTE in Chinese cancer patients: a retrospective study.

J Thromb Thrombolysis. 2020 Jan 23;:

Authors: Shang MM, Yan R, Wang XL, Gong WP, Guo ZQ

Background: This study evaluated the cardioprotective effect of Ajwa nano-preparation against doxorubicin-associated cardiotoxicity

Abstract

Background: This study evaluated the cardioprotective effect of Ajwa nano-preparation against doxorubicin-associated cardiotoxicity. Methods: Twenty-four male Wistar rats (200-250 g) were divided into 3 groups. One group was given the nanopreparation containing both Ajwa fruit and pit in a dose of 1.4 g/kg orally 1 hour before doxorubicin infusion (Dates-DOX group). Another group was given the vehicle for 1 hour before doxorubicin infusion (DOX group). The third group received the vehicle but no DOX infusion (time control). Cardiac hemodynamics, blood pressure, cardiac contractility, and conductivity were recorded before and after 45 minutes of infusion of doxorubicin (15 mg/kg, slow intravenous over 45 minutes). Blood samples were collected before and after doxorubicin infusion. Heart tissue samples were collected and snap frozen until assay of reduced glutathione. Results: Rats pre-administered Ajwa nanopreparation were protected from doxorubicin-associated systolic and diastolic dysfunction based on the significant elevation in the rate of rise in left ventricular pressure (dp/dtmax) and (dp/dtmin) compared with the DOX group. In addition, it prevented the doxorubicin-associated ischemia based on the significant shortening in QT interval, JT interval, and Tpeak-Tend interval versus the DOX group. There was no effect on atrial conductivity (PR interval and P duration). Ajwa pretreatment increased the antioxidant capacity of cardiac tissue, as evidenced by increasing the cardiac content of reduced glutathione compared with the untreated doxorubicin group. Conclusion: Ajwa nanopreparation protects from doxorubicin-associated cardiotoxicity through alleviating cardiac ischemia and increasing cardiac antioxidant capacity.

PMID: 31282195 [PubMed - indexed for MEDLINE]

15:13

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CDC42 Deletion Elicits Cerebral Vascular Malformations via Increased MEKK3-Dependent KLF4 Expression.

Circ Res. 2019 04 12;124(8):1240-1252

Authors: Castro M, Laviña B, Ando K, Álvarez-Aznar A, Abu Taha A, Brakebusch C, Dejana E, Betsholtz C, Gaengel K

Androgen deprivation therapy is a central part of prostate cancer treatment. Pharmacological androgen deprivation includes gonadotropin

Abstract

Androgen deprivation therapy is a central part of prostate cancer treatment. Pharmacological androgen deprivation includes gonadotropin-releasing hormone agonism and antagonism, AR (androgen receptor) inhibition, and CYP17 inhibition. Studies in the past decade have raised concerns about the potential for androgen deprivation therapy to increase the risk of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular mortality, possibly by exacerbating cardiovascular risk factors. In this review, we summarize existing data on the cardiovascular effects of androgen deprivation therapy. Among the therapies, abiraterone stands out for increasing risk of cardiac events in meta-analyses of both randomized controlled trials and observational studies. We find a divergence between observational studies, which show consistent positive associations between androgen deprivation therapy use and cardiovascular disease, and randomized controlled trials, which do not show these associations reproducibly.

PMID: 31969015 [PubMed - as supplied by publisher]

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Ajwa Nanopreparation Prevents Doxorubicin-Associated Cardiac Dysfunction: Effect on Cardiac Ischemia and Antioxidant Capacity.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--journals.sagepub.com-pb-assets-sage-pubmed-sage.png //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

Ajwa Nanopreparation Prevents Doxorubicin-Associated Cardiac Dysfunction: Effect on Cardiac Ischemia and Antioxidant Capacity.

Integr Cancer Ther. 2019 Jan-Dec;18:1534735419862351

Authors: Al-Jaouni S, Abdul-Hady S, El-Bassossy H, Salah N, Hagras M

BACKGROUND: Doxorubicin (DX) is used for the treatment of many types of cancer; however, a side effect of this agent is cardiotoxicity,

Abstract

BACKGROUND: Doxorubicin (DX) is used for the treatment of many types of cancer; however, a side effect of this agent is cardiotoxicity, which may lead to cardiomyopathy or cardiac failure. Oxidative stress is thought to play a major role in the development of cardiotoxic effects. Proanthocyanidins found in grapeseed (GS) extract may inhibit chemically induced lipid peroxidation and apoptosis caused by oxidative stress. We aimed to investigate the cardioprotective effects of GS extract against DX-induced cardiotoxicity.

METHODS: A total of 28 male Sprague Dawley rats were grouped to receive: (a) standard nutrition (n = 7); (b) standard nutrition with an additional dose of 10 mg/kg DX (n = 7); (c) standard nutrition plus 100 mg/kg/day of GS (n = 7); (d) standard nutrition with 100 mg/kg/day of GS plus a single dose of 10 mg/kg DX. After 35 days the rats were decapitated and blood samples were taken for biochemical testing. Cardiac tissue samples were prepared for microscopy and histopathological evaluation.

RESULTS: Rats in the DX group exhibited significant elevations in biomarkers such as troponin and NT-proBNP as well as in oxidative stress markers compared with all other groups. Histopathological examination corroborated these findings by demonstrating significant and severe structural injury in the cardiac tissue of DX rates. Moreover, rats in the DX + GS group had significantly lower cardiac injury than rats in the DX group according to both biochemical (troponin and NT-proBNP) and histopathological analyses. Serum malondialdehyde levels (a marker of oxidative stress) in the DX + GS rats were significantly lower than in the DX rats.

CONCLUSION: Our findings suggest that GS may reduce the severity of DX-induced cardiotoxicity and thus has the potential to prevent cardiac injury in this setting.

PMID: 31970462 [PubMed - as supplied by publisher]

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Cardiovascular Effects of Androgen Deprivation Therapy in Prostate Cancer.

Arterioscler Thromb Vasc Biol. 2020 Jan 23;:ATVBAHA119313046

Authors: Hu JR, Duncan MS, Morgans AK, Brown JD, Meijers WC, Freiberg MS, Salem JE, Beckman JA, Moslehi JJ

OBJECTIVE: The American Society of Clinical Oncology (ASCO) 2017 guidelines on cardiac monitoring during cancer treatments

Abstract

OBJECTIVE: The American Society of Clinical Oncology (ASCO) 2017 guidelines on cardiac monitoring during cancer treatments identified patients receiving thoracic radiation (TRT) ≥30 Gy (heart in field) at increased risk for developing radiation-induced heart disease (RIHD). ASCO encouraged clinicians to actively screen and monitor for baseline modifiable cardiac risk factors and therapy-induced cardiotoxicity in this high-risk population. Coronary artery calcium (CAC) is an independent risk factor for adverse cardiac events that can be mitigated with preventative medical therapy. It is unclear whether radiation oncologists (ROs) are aware of ASCO guidelines or the implications of CAC observed on computed tomographic scans. We report on practice patterns, perceptions, and experiences of cardiac monitoring for patients receiving definitive TRT, excluding breast patients.

MATERIALS AND METHODS: A 28-question survey was emailed to United States ROs 3 times from September 2018 to January 2019.

RESULTS: There were 162 respondents from 42 states, 51% in academic practice. Most ROs (81%) were not aware of the ASCO guidelines. Only 24% agreed with the guidelines, only 27% believed symptomatic RIHD could manifest within 2 years of TRT, and 69% thought there was a lack of strong evidence for type and timing of cardiac monitoring tests. If CAC was evident on computed tomographic scans, 40% took no further action to inform the patient or referring doctor.

CONCLUSIONS: This survey highlights a critical gap in knowledge about cardiac monitoring and potentially life-saving opportunities for preventive cardiac medical management. Future studies focusing on timing and detection of RIHD may elucidate the utility of cardiac monitoring for TRT patients.

PMID: 31972567 [PubMed - as supplied by publisher]

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Effects of grapeseed extract on doxorubicin-induced cardiotoxicity in rats.

Herz. 2020 Jan 22;:

Authors: Adıyaman MŞ, Adıyaman ÖA, Dağlı AF, Karahan MZ, Kaya İ, Dağlı MN

BACKGROUND: Pulmonary embolism (PE) is frequently associated with cancer. This study aimed to assess patients with acute PE and identify

Abstract

BACKGROUND: Pulmonary embolism (PE) is frequently associated with cancer. This study aimed to assess patients with acute PE and identify diagnostic predictors of new cancer after 1 year of follow-up.

METHODS: One hundred and twenty-one patients with PE were enrolled consecutively from the emergency department of a single medical center in Taiwan. Data from computed tomography angiography, echocardiogram, electrocardiogram and for baseline comorbidities, clinical presentation, and laboratory parameters were recorded. The surviving discharged patients without a cancer diagnosis were followed-up for 1 year, and new malignancies were recorded.

RESULTS: Of 121 patients with acute PE, 44 (36 %) had an underlying cancer history (cancer group), and 77 (64 %) did not (non-cancer group). Baseline demographic characteristics, comorbidities, clinical symptoms, biochemical parameters, echocardiogram data, and electrocardiogram data of the two groups were similar except for a higher hospital mortality rate (56.8 % vs. 9.1 %, p<0.001),<0.01),

CONCLUSION: This study suggests that the CK-MB level is associated with future malignancy in patients with PE. Patients with cancer-related PE had a worse 30-day survival rate.

PMID: 31972832 [PubMed - as supplied by publisher]

15:13

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Cardiac Monitoring for Thoracic Radiation Therapy: Survey of Practice Patterns in the United States.

Am J Clin Oncol. 2020 Jan 17;:

Authors: Amin NP, Desai N, Kim SM, Agarwal M, Amin NP

As many novel cancer therapies continue to emerge, the field of Cardio-Oncology (or onco-cardiology) has become crucial to prevent

Abstract

As many novel cancer therapies continue to emerge, the field of Cardio-Oncology (or onco-cardiology) has become crucial to prevent, monitor and treat cancer therapy-related cardiovascular toxicity. Furthermore, given the narrow therapeutic window of most cancer therapies, drug-drug interactions are prevalent in the cancer population. Consequently, there is an increased risk of affecting drug efficacy or predisposing individual patients to adverse side effects. Here we review the role of cytochrome P450 (CYP450) enzymes in the field of Cardio-Oncology. We highlight the importance of cardiac medications in preventive Cardio-Oncology for high-risk patients or in the management of cardiotoxicities during or following cancer treatment. Common interactions between Oncology and Cardiology drugs are catalogued, emphasizing the impact of differential metabolism of each substrate drug on unpredictable drug bioavailability and consequent inter-individual variability in treatment response or development of cardiovascular toxicity. This inter-individual variability in bioavailability and subsequent response can be further enhanced by genomic variants in CYP450, or by modifications of CYP450 gene, RNA or protein expression or function in various 'omics' related to precision medicine. Thus, we advocate for an individualized approach to each patient by a multidisciplinary team with clinical pharmacists evaluating a treatment plan tailored to a practice of precision Cardio-Oncology. This review may increase awareness of these key concepts in the rapidly evolving field of Cardio-Oncology.

PMID: 31963461 [PubMed - in process]

24 January 2020

13:50

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Clinical features and diagnosis of new malignancy in patients with acute pulmonary embolism and without a history of cancer.

J Chin Med Assoc. 2020 Jan 14;:

Authors: Lin YC, Chen SC, Huang CM, Hu YF, Chen YY, Chang SL, Lo LW, Lin YJ, Chen SA

Cardiovascular disease (CVD) and cancer represent the two main causes of death in industrialised countries. Both share common risk

Abstract

Cardiovascular disease (CVD) and cancer represent the two main causes of death in industrialised countries. Both share common risk factors (diabetes, obesity, hypertension, diet, smoking, etc.). The associated timing of CVD and cancer onset is thus largely influenced by modifiable risk factors. Advances in cancer treatment have extended the lives of patients with cancer, but for some at the cost of adverse cardiovascular events. The rapidly growing number of patients surviving cancer, often in the setting of advanced age, new or pre-existing CV disease and risk factors, the management of these patients has become the concern of experts in cardio-oncology. The goal of cardio-oncology is to provide optimal care for patients with cancer and/or at risk of cardiovascular disease. To date, no specific cardio-oncology teaching programme is available in Belgium. The present paper reports the results of the Belgian Society of Cardiology (BSC) survey on cardio-oncology. The vast majority of respondents (154/159, 97%) are in favour of organising courses or educational meetings on cardio-oncology. A dedicated cardio-oncology clinic was present in only 40% of the hospitals that participated in the survey. Compared to the data collected by the European Society of Cardiology, the number of respondents considering themselves as experts in the management of left ventricular dysfunction or atrial fibrillation complicating cancer treatment was much lower in Belgium (11% vs. 30%).

PMID: 31967938 [PubMed - as supplied by publisher]

14:38

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The Role of CYP450 Drug Metabolism in Precision Cardio-Oncology.

Int J Mol Sci. 2020 Jan 17;21(2):

Authors: Fatunde OA, Brown SA

BACKGROUND: Current data suggests that decreasing VTE incidence may require focus on other factors. This study aimed to identify

Abstract

BACKGROUND: Current data suggests that decreasing VTE incidence may require focus on other factors. This study aimed to identify perioperative risk factors for VTE in patients undergoing surgery for gastrointestinal (GI) malignancy.

METHODS: Patients undergoing surgery for GI malignancy from 2013 to 2016 were grouped according to whether or not they developed a postoperative VTE, and groups were compared along demographic, perioperative, and outcome variables.

RESULTS: Patients who developed VTE were more likely to be older (67 ± 11 VTE vs. 61 ± 10 no VTE, p = 0.04), male (92% vs. 59%, p = 0.02), and have a history of atrial fibrillation (39% vs. 11%, p = 0.01). They also experienced higher intraoperative blood loss (328 ± 724 mL no VTE vs. 918 ± 1885 mL VTE, p = 0.01). On multivariable analysis, history of atrial fibrillation was independently associated with development of postoperative VTE (odds ratio = 3.83, 95% confidence interval = 1.13-13.05, p = 0.03).

CONCLUSION: A prior history of atrial fibrillation independently predicts increased risk of developing VTE after surgery for GI malignancy. Improving understanding of the underlying VTE pathophysiology in these patients can help guide effective prevention strategies.

PMID: 30795857 [PubMed - indexed for MEDLINE]

14:38

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Cardio-oncology: where do we stand for in Belgium?

Acta Cardiol. 2020 Jan 22;:1-5

Authors: Lancellotti P, De Pauw M, Claeys M

Abstract

OBJECTIVE: Venous thromboembolism (VTE) often is encountered in patients with high-grade gliomas. The underlying mechanisms are unclear, as is the optimal prophylactic protocol. The purpose of the present study was to identify risk factors of VTE and examine the validity of early VTE detection in high-grade gliomas.

METHODS: We reviewed the medical records of 165 patients with newly diagnosed high-grade glioma treated at Niigata University Hospital during the years 2009 to 2016. If the serum D-dimer levels increased to 5.0 μg/mL or more, computed tomography was performed to detect VTE. Furthermore, immunohistochemistry with antibodies against podoplanin was performed on available 101 tumor tissues.

RESULTS: Of the 165 patients, 44 (26.7%) developed VTE. Of the 44 patients, 34 (79.5%) developed VTE within 7 days after surgery. No fatal VTE occurred and major complications secondary to anticoagulation occurred in only 2 (1.2%) patients. On multivariate analysis, lower Karnofsky Performance Scale status, podoplanin expression, and isocitrate dehydrogenase-wildtype status were independently associated with the risk of VTE (P < 0.05).

CONCLUSIONS: We found that most VTEs occurred early in the postoperative period and commonly in patients with lower Karnofsky Performance Scale status and isocitrate dehydrogenase-wildtype gliomas, which expressed podoplanin.

PMID: 31100523 [PubMed - indexed for MEDLINE]

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Identifying risk factor for development of perioperative venous thromboembolism in patients with gastrointestinal malignancy.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

Identifying risk factor for development of perioperative venous thromboembolism in patients with gastrointestinal malignancy.

Am J Surg. 2019 08;218(2):311-314

Authors: Bhutiani N, Quinn SA, Mercer MK, Hong YK, Stevenson M, Egger ME, Philips P, McMasters KM, Martin RCG, Scoggins CR

Abstract

Hypodysfibrinogenemia, the least frequently reported congenital fibrinogen disorder is characterized by low circulating levels of a dysfunctional protein, and is associated with phenotypic features of both hypo- and dysfibrinogenemia. Herein, we report an adolescent male with unprovoked venous thromboembolism and hypodysfibrinogenemia. Patient had recurrent, progressive thrombosis despite therapeutic anticoagulation with both low molecular weight heparin and warfarin. He had clinical and radiological improvement after transition to a direct thrombin inhibitor. Sequencing of the FGG gene identified a novel heterozygous mutation, c.1075G>T. Structural visualization of the identified variant was pursued and suggested that the mutation likely destabilizes the Ca2+ -binding site of fibrinogen resulting in pathogenicity.

PMID: 31131962 [PubMed - indexed for MEDLINE]

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Podoplanin Expression and IDH-Wildtype Status Predict Venous Thromboembolism in Patients with High-Grade Gliomas in the Early Postoperative Period.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

Podoplanin Expression and IDH-Wildtype Status Predict Venous Thromboembolism in Patients with High-Grade Gliomas in the Early Postoperative Period.

World Neurosurg. 2019 Aug;128:e982-e988

Authors: Watanabe J, Natsumeda M, Okada M, Kanemaru Y, Tsukamoto Y, Oishi M, Kakita A, Fujii Y

Venous thromboembolism is a significant cause of mortality1, yet its genetic determinants are incompletely defined. We performed

Abstract

Venous thromboembolism is a significant cause of mortality1, yet its genetic determinants are incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank, with testing of approximately 13 million DNA sequence variants for association with venous thromboembolism (26,066 cases and 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 venous thromboembolism cases and 167,295 controls. We identified 22 previously unknown loci, bringing the total number of venous thromboembolism-associated loci to 33, and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for venous thromboembolism that identifies 5% of the population at an equivalent incident venous thromboembolism risk to carriers of the established factor V Leiden p.R506Q and prothrombin G20210A mutations. Our data provide mechanistic insights into the genetic epidemiology of venous thromboembolism and suggest a greater overlap among venous and arterial cardiovascular disease than previously thought.

PMID: 31676865 [PubMed - indexed for MEDLINE]

13:07

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Fibrinogen Columbus II: A novel c.1075G>T mutation in the FGG gene causing hypodysfibrinogenemia and thrombosis in an adolescent male.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7388-69-wiley-full-text.png Related Articles

Fibrinogen Columbus II: A novel c.1075G>T mutation in the FGG gene causing hypodysfibrinogenemia and thrombosis in an adolescent male.

Pediatr Blood Cancer. 2019 09;66(9):e27832

Authors: Kumar R, Dawson J, Varga E, Canini JT, Monda KL, Dunn AL

BACKGROUND: There is significant variation in rectal cancer outcomes in the USA, and reported outcomes have been inferior to those in other

Abstract

BACKGROUND: There is significant variation in rectal cancer outcomes in the USA, and reported outcomes have been inferior to those in other countries. In recognition of this fact, the American College of Surgeons (ACS) recently launched the Commission on Cancer (CoC) National Accreditation Program for Rectal Cancer (NAPRC) in an effort to further optimize rectal cancer care. Large surgical databases will play an important role in tracking surgical and oncologic outcomes. Our study sought to explore the trends in surgical outcomes over the decade prior to the NAPRC using a large national database.

METHODS: The ACS National Surgical Quality Improvement Program (NSQIP) database from 2005 to 2017 was used to select colorectal cancer cases which were divided into abdominal-colonic (AC) and pelvic-rectal (PR) cohorts based upon the operation performed. Outcomes of interest were occurrence of any major surgical complication, mortality within 30 days of procedure, and postoperative length of stay (LOS). Chi-square and two sample t-tests were used to evaluate association between various risk factors and outcomes. Modified Poisson regression was used to compare and estimate the unadjusted and adjusted effect of procedure type on the outcomes. STATA 15.1 was used for analysis and statistical significance was set at 0.05.

RESULTS: A total of 34,159 patients were analyzed. AC cases constituted 50.7% of the overall cohort. The two groups were relatively similar in demographic distribution, but the PR patients had higher rates of hypoalbuminemia and were sicker (ASA class 3 or greater). Rates of non-sphincter preserving operations ranged from 30 to 34%. Higher complication rates in the PR cohort were mainly infectious and surgical site complications, while rates of deep vein thrombosis and pulmonary embolism were similar between the two cohorts. On bivariate analysis, rates of mortality were similar between the two groups (AC: 1.02% vs PR: 0.91%, p = 0.395), while PR patients were found to be 1.36 times (95% CI: 1.32-1.41) more likely to have major complications and 1.40 times (95% CI: 1.35-1.44) more likely to have an extended LOS as compared to the AC patients. After multivariable analysis, PR patients continued to have a higher likelihood of major complications (IRR: 1.31, 95% CI 1.25-1.36) and extended LOS (IRR: 1.38, 95% CI: 1.33-1.43). 10-year trends showed a significant reduction in the percentage of patients with prolonged lengths of hospitalization as well as a reduction of nearly 20% in the mean LOS, but without improvement in morbidity or mortality.

CONCLUSIONS: Patients undergoing PR operations were more likely to have had major complications than were patients who underwent AC procedures; unfortunately no improvement in the rate of these complications or in mortality occurred. Perhaps the significant reduction in LOS is due in part to an increased prevalence of minimally invasive surgery and/or enhanced recovery protocols. Data were found to be lacking within NSQIP for several important variables including key oncologic data, stratification by surgical volume, and patient geographic location. We anticipate that the NAPRC should help improve PR surgical and oncologic outcomes including decreasing morbidity and mortality rates during the next decade.

PMID: 31964524 [PubMed - as supplied by publisher]

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Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.nature.com-images-lo_ng.gif Related Articles

Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease.

Nat Genet. 2019 11;51(11):1574-1579

Authors: Klarin D, Busenkell E, Judy R, Lynch J, Levin M, Haessler J, Aragam K, Chaffin M, Haas M, Lindström S, Assimes TL, Huang J, Min Lee K, Shao Q, Huffman JE, Kabrhel C, Huang Y, Sun YV, Vujkovic M, Saleheen D, Miller DR, Reaven P, DuVall S, Boden WE, Pyarajan S, Reiner AP, Trégouët DA, Henke P, Kooperberg C, Gaziano JM, Concato J, Rader DJ, Cho K, Chang KM, Wilson PWF, Smith NL, O'Donnell CJ, Tsao PS, Kathiresan S, Obi A, Damrauer SM, Natarajan P, INVENT Consortium, Veterans Affairs’ Million Veteran Program

Atherosclerosis is driven by multifaceted contributions of the immune system within the circulation and at vascular focal sites. However

Abstract

Atherosclerosis is driven by multifaceted contributions of the immune system within the circulation and at vascular focal sites. However, specific characteristics of dysregulated immune cells within atherosclerotic lesions that lead to clinical events such as ischemic stroke or myocardial infarction are poorly understood. Here, using single-cell proteomic and transcriptomic analyses, we uncovered distinct features of both T cells and macrophages in carotid artery plaques of patients with clinically symptomatic disease (recent stroke or transient ischemic attack) compared to asymptomatic disease (no recent stroke). Plaques from symptomatic patients were characterized by a distinct subset of CD4+ T cells and by T cells that were activated and differentiated. Moreover, some T cell subsets in these plaques presented markers of T cell exhaustion. Additionally, macrophages from these plaques contained alternatively activated phenotypes, including subsets associated with plaque vulnerability. In plaques from asymptomatic patients, T cells and macrophages were activated and displayed evidence of interleukin-1β signaling. The identification of specific features of innate and adaptive immune cells in plaques that are associated with cerebrovascular events may enable the design of more precisely tailored cardiovascular immunotherapies.

PMID: 31591603 [PubMed - indexed for MEDLINE]

23 January 2020

13:07

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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A NSQIP analysis of trends in surgical outcomes for rectal cancer: What can we improve upon?

Am J Surg. 2020 Jan 10;:

Authors: Sharp SP, Malizia R, Skancke M, Arsoniadis EG, Ata A, Stain SC, Valerian BT, Lee EC, Wexner SD

Abstract

Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

PMID: 31959335 [PubMed - in process]

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Changes in Cardiovascular Biomarkers With Breast Cancer Therapy and Associations With Cardiac Dysfunction.

J Am Heart Assoc. 2020 Jan 21;9(2):e014708

Authors: Demissei BG, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, Narayan V, Domchek SM, DeMichele A, Shah P, Clark AS, Fox K, Matro J, Bradbury AR, Knollman H, Getz KD, Armenian SH, Januzzi JL, Tang WHW, Liu P, Ky B

Abstract

Background We examined the longitudinal associations between changes in cardiovascular biomarkers and cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer treated with cardotoxic cancer therapy. Methods and Results Repeated measures of high-sensitivity cardiac troponin T (hs-cTnT), NT-proBNP (N-terminal pro-B-type natriuretic peptide), myeloperoxidase, placental growth factor, and growth differentiation factor 15 were assessed longitudinally in a prospective cohort of 323 patients treated with anthracyclines and/or trastuzumab followed over a maximum of 3.7 years with serial echocardiograms. CTRCD was defined as a ≥10% decline in left ventricular ejection fraction to a value <50%.14 ng/L at anthracycline completion were associated with a 2-fold increased CTRCD risk (hazard ratio, 2.01; 95% CI, 1.00-4.06). There was a modest association between changes in NT-proBNP and left ventricular ejection fraction in the overall cohort; this was most pronounced with sequential anthracycline and trastuzumab (1.1% left ventricular ejection fraction decline [95% CI, -1.8 to -0.4] with each NT-proBNP doubling). Increases in NT-proBNP were also associated with CTRCD (hazard ratio per doubling, 1.56; 95% CI, 1.32-1.84). Increases in myeloperoxidase were associated with CTRCD in patients who received sequential anthracycline and trastuzumab (hazard ratio per doubling, 1.28; 95% CI, 1.04-1.58). Conclusions Cardiovascular biomarkers may play an important role in CTRCD risk prediction in patients with breast cancer who receive cardiotoxic cancer therapy, particularly in those treated with sequential anthracycline and trastuzumab therapy. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01173341.

PMID: 31959034 [PubMed - in process]

13:30

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Simultaneous Left Ventricular Volume and Strain Changes During Chemotherapy Associate With 2-Year Postchemotherapy Measures of Left Ventricular Ejection Fraction.

J Am Heart Assoc. 2020 Jan 21;9(2):e015400

Authors: Suerken CK, D'Agostino RB, Jordan JH, Meléndez GC, Vasu S, Lamar ZS, Hundley WG

Abstract

Background Although changes in left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume, and global circumferential strain occur during cancer treatment, the relationship of these changes to the 2-year post-cancer-treatment measures of left ventricular ejection fraction (LVEF) are unknown. Methods and Results In a prospective, continuously recruited cohort of 95 patients scheduled to receive potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or soft tissue sarcoma, measures of left ventricular end-diastolic volume, LVESV, global circumferential strain, and LVEF were acquired via cardiac magnetic resonance imaging before and then 3 and 24 months after initiating treatment by individuals blinded to all patient identifiers. Participants had an average age of 54±15 years; 68% were women, and 82% were of white race. LVEF declined from 62±7% to 58±9% over the 24 months (P<0.0001),5% decline in LVEF at 24 months. Predictors of a 24-month >5% decline in LVEF included the following factors from baseline to 3 months into treatment: (1) >3-mL increases in LVESV (P=0.033), (2) >3-mL increases in LVESV or 10-mL declines in left ventricular end-diastolic volume with little change in LVESV (P=0.001), or (3) ≥10% deteriorations in global circumferential strain with little change in LVESV (P=0.036). Conclusion During receipt of potentially cardiotoxic chemotherapy, increases in LVESV, the absence of its deterioration during decreases of left ventricular end-diastolic volume, or the deterioration of global circumferential strain without a marked decrease in LVESV help identify those who will develop more permanent 2-year declines in LVEF.

PMID: 31959033 [PubMed - in process]

13:30

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Cardio-Oncology at the Beginning of a New Decade.

J Am Heart Assoc. 2020 Jan 21;9(2):e015890

Authors: Grumbach IM

PMID: 31959029 [PubMed - in process]

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Single-cell immune landscape of human atherosclerotic plaques.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--www.nature.com-images-lo_nm.gif Related Articles

Single-cell immune landscape of human atherosclerotic plaques.

Nat Med. 2019 10;25(10):1576-1588

Authors: Fernandez DM, Rahman AH, Fernandez NF, Chudnovskiy A, Amir ED, Amadori L, Khan NS, Wong CK, Shamailova R, Hill CA, Wang Z, Remark R, Li JR, Pina C, Faries C, Awad AJ, Moss N, Bjorkegren JLM, Kim-Schulze S, Gnjatic S, Ma'ayan A, Mocco J, Faries P, Merad M, Giannarelli C

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