ABSTRACT

External validation is a prerequisite in order for a prediction model to be introduced into clinical practice. Nonetheless, methodologically intact external validation studies are a scarce finding. Utilization of big datasets can help overcome several causes of methodological failure. However, transparent reporting is needed to standardize the methods, assess the risk of bias and synthesize multiple validation studies in order to infer model generalizability. We describe the methodological challenges faced when using multiple big datasets to perform the first retrospective external validation study of the Prospective Comparison of Methods for thromboembolic risk assessment with clinical Perceptions and AwareneSS in real life patients-Cancer Associated Thrombosis (COMPASS-CAT) Risk Assessment Model for predicting venous thromboembolism in patients with cancer. The challenges included choosing the starting point, defining time sensitive variables that serve both as risk factors and outcome variables and using non-research oriented databases to form validated definitions from administrative codes. We also present the structured plan we used so as to overcome those obstacles and reduce bias with the target of producing an external validation study that successfully complies with prediction model reporting guidelines.

PMID:32564180 | DOI:10.1007/s11239-020-02191-8

04:18

PubMed articles on: Cardio-Oncology

Successful Heart Transplant in a Childhood Cancer Survivor With Chemoradiotherapy-Induced Cardiomyopathy

Sipahi NF, et al. Exp Clin Transplant 2020.

ABSTRACT

Cancer therapy-related cardiotoxicity has been presenting a major problem in cancer survivors, who constitute a growing population caused by a significant improvement in cancer therapy during the past decades. Although some listing criteria have been defined for these patients, it is still a compelling decision to list patients with a complex cancer anamnesis. We describe herein a childhood cancer survivor after a cancer anamnesis with 2 different malignancies and an end-stage heart failure following chemoradiotherapy who was successfully treated with orthotopic heart transplant.

PMID:32552629 | DOI:10.6002/ect.2020.0062

04:18

PubMed articles on: Cardio-Oncology

Cardiac effects and toxicity of chloroquine: a short update

Mubagwa K. Int J Antimicrob Agents 2020 - Review.

ABSTRACT

There is currently increased interest in the use of the antimalarial drugs chloroquine and hydroxychloroquine for the treatment of other diseases, including cancer and viral infections such as coronavirus disease 2019 (COVID-19). However, the risk of cardiotoxic effects tends to limit their use. In this review, the effects of these drugs on the electrical and mechanical activities of the heart as well as on remodelling of cardiac tissue are presented and the underlying molecular and cellular mechanisms are discussed. The drugs can have proarrhythmic as well as antiarrhythmic actions resulting from their inhibition of ion channels, including voltage-dependent Na+ and Ca2+ channels, background and voltage-dependent K+ channels, and pacemaker channels. The drugs also exert a vagolytic effect due at least in part to a muscarinic receptor antagonist action. They also interfere with normal autophagy flux, an effect that could aggravate ischaemia/reperfusion injury or post-infarct remodelling. Most of the toxic effects occur at high concentrations, following prolonged drug administration or in the context of drug associations.

PMID:32565195 | PMC:PMC7303034 | DOI:10.1016/j.ijantimicag.2020.106057

04:18

PubMed articles on: Cancer & VTE/PE

Venous thromboembolism after adult thymus or thymic tumor resection: A single-center experience

Yang X, et al. Thorac Cancer 2020.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a common postoperative complication. Previous studies have shown that the VTE incidence after major thoracic surgery is high. However, there have been no exclusive data after thymectomy thus far. To investigate the incidence of postoperative VTE, we conducted a single-center, prospective cohort study.

METHODS: Patients who underwent thymectomy between December 2017 and January 2020 were enrolled. None of the patients received any prophylaxis perioperatively. Subjects were risk stratified into groups of low risk (0-4), moderate risk (5-8), and high risk (≥9). Occurrence of VTE events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), were identified by imaging.

RESULTS: There were 192 patients who underwent thymectomy enrolled into the study. The overall VTE incidence was 8.9%. All the patients were diagnosed with DVT, and none were diagnosed with PE. The VTE incidence was 4.6% in patients with benign thymic diseases and 14.5% with malignant diseases. The VTE incidence was 4.7% in patients undergoing thoracoscopic surgery and 22.7% undergoing median sternotomy. The VTE incidence increased with Caprini score. Scores in the low, moderate, and high risk groups were associated with a VTE incidence of 0%, 10.3% and 37.5%, respectively. In patients with thymic malignancy, the VTE incidence in the moderate and high risk groups were 8.8% and 31.8%, respectively.

CONCLUSIONS: VTE occurred frequently in patients after thymectomy without VTE prophylaxis. The median sternotomy procedure and malignant tumor may be the major risk factors for the development of VTE. Aggressive VTE screening/treatment protocols should be implemented in patents after thymectomy.

PMID:32558357 | DOI:10.1111/1759-7714.13543

04:18

PubMed articles on: Cancer & VTE/PE

Prevention and treatment of venous thromboembolism in cancer patients

Spehlmann ME, et al. Herz 2020 - Review.

ABSTRACT

Deep vein thrombosis and pulmonary artery embolism are common and serious concomitant diseases in patients with cancer. The prophylaxis and therapy of such venous thromboembolic events (VTE) in oncology have so far been achieved with low-molecular-weight heparins. An increasing number of studies show evidence of the use of direct oral anticoagulants. However, since none of the possible options were shown to have a clear advantage in all patients, the individual decision to use a drug should be made depending on its effectiveness in preventing VTE, the risk of bleeding, the nature of the cancer, the interactions with other medications, the route of administration, and finally the cost of treatment.

PMID:32564097 | DOI:10.1007/s00059-020-04961-9

04:18

PubMed articles on: Cardio-Oncology

Pluripotent Stem Cell Modeling of Anticancer Therapy-Induced Cardiotoxicity

Lyra-Leite DM and Burridge PW. Curr Cardiol Rep 2020 - Review.

ABSTRACT

PURPOSE OF REVIEW: In this article, we review the different model systems based on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and how they have been applied to identify the cardiotoxic effects of anticancer therapies.

RECENT FINDINGS: Developments on 2D and 3D culture systems enabled the use of hiPSC-CMs as screening platforms for cardiotoxic effects of anticancer therapies such as anthracyclines, monoclonal antibodies, and tyrosine kinase inhibitors. Combined with computational approaches and higher throughput screening technologies, they have also enabled mechanistic studies and the search for cardioprotective strategies. As the population ages and cancer treatments become more effective, the cardiotoxic effects of anticancer drugs become a bigger problem leading to an increased role of cardio-oncology. In the past decade, human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have become an important platform for preclinical drug tests, elucidating mechanisms of action for drugs, and identifying cardioprotective pathways that could be further explored in the development of combined treatments. In this article, we highlight 2D and 3D model systems based on hiPSC-CMs that have been used to study the cardiotoxic effects of anticancer drugs, investigating their mechanisms of action and the potential for patient-specific prediction. We also present some of the important challenges and opportunities in the field, indicating possible future developments and how they could impact the landscape of cardio-oncology.

PMID:32562096 | DOI:10.1007/s11886-020-01325-x

04:18

PubMed articles on: Cardio-Oncology

High molecular weight kininogen contributes to early mortality and kidney dysfunction in a mouse model of sickle cell disease

Sparkenbaugh EM, et al. J Thromb Haemost 2020.

ABSTRACT

BACKGROUND: Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, vaso-occlusive crises, chronic inflammation, and activation of coagulation. The clinical complications such as painful crisis, stroke, pulmonary hypertension, nephropathy and venous thromboembolism lead to cumulative organ damage and premature death. High molecular weight kininogen (HK) is a central cofactor for the kallikrein-kinin and intrinsic coagulation pathways, which contributes to both coagulation and inflammation.

OBJECTIVE: We hypothesize that HK contributes to the hypercoagulable and pro-inflammatory state that causes end-organ damage and early mortality in sickle mice.

METHODS: We evaluated the role of HK in the Townes mouse model of SCD.

RESULTS/CONCLUSIONS: We found elevated plasma levels of cleaved HK in sickle patients compared to healthy controls, suggesting ongoing HK activation in SCD. We used bone marrow transplantation to generate wild type and sickle cell mice on a HK-deficient background. We found that short-term HK deficiency attenuated thrombin generation and inflammation in sickle mice at steady state, which was independent of bradykinin signaling. Moreover, long-term HK deficiency attenuates kidney injury, reduces chronic inflammation, and ultimately improves of sickle mice.

PMID:32573897 | DOI:10.1111/jth.14972

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PubMed articles on: Cancer & VTE/PE

Effectiveness and Safety of Apixaban and Rivaroxaban for Acute Venous Thromboembolism Therapy in Patients with Extremes in Body Weight (ClinicalTrials.gov: NCT03504007)

Wysokinski WE, et al. Eur J Haematol 2020.

ABSTRACT

OBJECTIVES: To investigate the association of extremes in body weight EBW and outcomes in patients with acute venous thromboembolism (VTE), recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with body weight <60120 kg.

METHODS: Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview.

RESULTS: Amongst 2577 patients with the weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 - 120 kg, 223 (8.7%) bodyweight <60120 kg. Patients with bodyweight <60kg120kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (p=0.01).

CONCLUSIONS: Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60kg.120kg on rivaroxaban.

PMID:32557773 | DOI:10.1111/ejh.13471

04:18

PubMed articles on: Cardio-Oncology

Cardioprotective Strategies to Prevent Cancer Treatment-Related Cardiovascular Toxicity: a Review

Upshaw JN. Curr Oncol Rep 2020 - Review.

ABSTRACT

PURPOSE OF REVIEW: Patients with cancer have an elevated risk of cardiovascular disease. This review describes the cardiovascular risks of different cancer therapies and the evidence for cardioprotective strategies.

RECENT FINDINGS: Recent studies have provided additional support for the safety and efficacy of dexrazoxane and liposomal anthracycline formulations in certain high-risk patients receiving anthracyclines and for neurohormonal antagonist therapy in patients with breast cancer receiving sequential anthracyclines and trastuzumab. Ongoing studies are exploring the benefit of: (1) statins for anthracycline cardioprotection; (2) strict blood pressure control during vascular endothelial growth factor inhibitor treatment and; (3) dexrazoxane on long-term cardiac outcomes in pediatric populations. To date, there are no evidence-based cardioprotective strategies specifically for radiation-related heart and vascular disease, immunotherapy myocarditis, fluoropyrimidine cardiotoxicity, vascular endothelial growth factor inhibitor-related hypertension, BCR-Abl multikinase inhibitor vascular disease, and other established and emerging cancer therapeutics with cardiovascular effects. Current evidence supports specific cardioprotective strategies for high risk patients receiving anthracyclines or sequential anthracycline-trastuzumab therapy; however, major evidence gaps exist.

PMID:32564220 | DOI:10.1007/s11912-020-00923-w

04:18

PubMed articles on: Cardio-Oncology

Establishing an oncocardiology service

Lehmann LH and Totzeck M. Herz 2020 - Review.