Positron emission tomography (PET) imaging is useful in cardiovascular disease across several areas, from assessment of myocardial

 

ABSTRACT

Positron emission tomography (PET) imaging is useful in cardiovascular disease across several areas, from assessment of myocardial perfusion and viability, to highlighting atherosclerotic plaque activity and measuring the extent of cardiac innervation in heart failure. Other important roles of PET have emerged in prosthetic valve endocarditis, implanted device infection, infiltrative cardiomyopathies, aortic stenosis and cardio-oncology. Advances in scanner technology, including hybrid PET/MRI and total body PET imaging, as well as the development of novel PET tracers and cardiac-specific postprocessing techniques using artificial intelligence will undoubtedly continue to progress the field.

PMID:32571959 | DOI:10.1136/heartjnl-2019-315183

01:32

PubMed articles on: Cancer & VTE/PE

Using big data to retrospectively validate the COMPASS-CAT risk assessment model: considerations on methodology

Nikolakopoulos I, et al. J Thromb Thrombolysis 2020.

Oncocardiology is an emerging field in cardiovascular healthcare. Besides establishing surveillance and follow-up strategies for

 

ABSTRACT

Oncocardiology is an emerging field in cardiovascular healthcare. Besides establishing surveillance and follow-up strategies for cancer patients, it will be essential to set up specialized oncocardiology services. However, there is a lack of clinical studies to give evidence-based recommendations regarding cardiological diagnostic and therapeutic approaches for cancer patients. An oncocardiology service is a patient-centered structure that aims to integrate research and interdisciplinary patient care to bridge this gap. We discuss the current challenges in developing an oncocardiology service and review the literature on this topic. We further provide an overview of the essential diagnostic tools and upcoming ethical issues to be considered in the management of oncology patients.

PMID:32572500 | PMC:PMC7306932 | DOI:10.1007/s00059-020-04952-w

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PubMed articles on: Cardio-Oncology

Positron emission tomography imaging in cardiovascular disease

Tarkin JM, et al. Heart 2020 - Review.

BACKGROUND: PIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM).

 

ABSTRACT

BACKGROUND: PIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM). We aimed to evaluate survival and postoperative outcome of patients with unresectable PM from gastric origin treated with chemotherapy and PIPAC.

METHODS: A retrospective analysis of a prospective maintained PIPAC database was queried for all patients diagnosed with unresectable PM from gastric cancer who underwent PIPAC before 2018. PIPAC with Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 6-week intervals. Outcome criteria were overall survival and adverse events according to (CTCAE) version4.0.

RESULTS: One hundred Sixty-three PIPAC were done in 42 consecutive patients. Twenty-two (52%) of the patients were female. Signet-ring cells were observed in 33/42 patients (78.6%). At the first PIPAC, median age was 51.5 years (32-74). Median PCI was 17 (1-39). Twenty (47.6%) patients underwent more than 2 lines of pre-PIPAC chemotherapy. All patients had systemic chemotherapy alternating with PIPAC. Median consecutive PIPAC procedures were 3 (1-12). Overall and major complications (CTCAE - III, IV) occurred in 10 (6.1%) and 5 procedures (3.1%), respectively. Two patients (4.7%) died within 30 days of a PIPAC procedure, one related to small bowel obstruction and a pulmonary embolism for the other. Overall Survival was 19.1 months. Six (14.3%) patients became resectable during treatment and underwent curative intent CRS and HIPEC.

CONCLUSIONS: PIPAC with low-dose cisplatin and doxorubicin is safe and feasible in association with systemic chemotherapy for gastric PM. Survival data are encouraging and justify further clinical studies in this indication.

PMID:32561204 | DOI:10.1016/j.ejso.2020.05.021

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PubMed articles on: Cardio-Oncology

Establishing an oncocardiology service

Lehmann LH and Totzeck M. Herz 2020 - Review.

Thymic carcinoma typically exhibits more clinically aggressive behavior and portends a worse prognosis as compar

 

ABSTRACT

Thymic carcinoma typically exhibits more clinically aggressive behavior and portends a worse prognosis as compared to thymoma. Venous thromboembolism is a significant cause of morbidity and mortality in oncologic patients. Traditionally, the standard-of-care management of cancer-associated venous thromboembolism has been therapeutic anticoagulation with low molecular weight heparins; however, with the advent of direct oral anticoagulants, there is an ongoing paradigm shift to transition to these novel agents in an attempt to attenuate cancer-associated venous thromboembolism events. We describe an exceedingly rare case of metastatic thymic carcinoma-associated right atrial thrombus with high-risk embolic features, which subsequently underwent near-complete dissolution with rivaroxaban after 3 months.

PMID:32551115 | PMC:PMC7278298 | DOI:10.1177/2050313X20927596

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PubMed articles on: Cancer & VTE/PE

An International Survey on the Use of Thromboprophylaxis in Urological Surgery

Violette PD, et al. Eur Urol Focus 2020.

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).

 

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

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PubMed articles on: Cancer & VTE/PE

Dissolution of metastatic thymic carcinoma-associated right atrial thrombus with rivaroxaban

Nimblette C, et al. SAGE Open Med Case Rep 2020.

AIMS: To examine the efficacy and safety of direct oral anticoagulants (DOAC) versus low molecular weight heparin (LMWH)

 

ABSTRACT

AIMS: To examine the efficacy and safety of direct oral anticoagulants (DOAC) versus low molecular weight heparin (LMWH) in patients with cancer-related venous thrombo-embolism (VTE).

METHODS AND RESULTS: An electronic search of MEDLINE, SCOPUS and COCHRANE without language restrictions was performed through April 2020 for randomized controlled trials that compared the effects of DOACs versus LMWH on patients with cancer-related VTE. Summary estimates were reported using random effects model. The main efficacy outcome was VTE recurrence while the main safety outcome was major bleeding events. The final analysis included 4 randomized trials with a total of 2,907 patients. The weighted mean follow-up was 6.1 months. Compared with LMWH, DOACs were associated with lower risk of VTE recurrence (5.7% vs. 9.1%, risk ratio [RR] 0.62; 95% confidence interval [CI] 0.44 to 0.87; P = 0.01), driven by lower deep venous thrombosis (P = 0.02). There was no difference between DOACs and LMWH in major bleeding events (4.8% vs. 3.6%, RR 1.33; 95% CI 0.84 to 2.11; P = 0.23). The incidence of all-cause mortality was similar (RR 0.99; 95% CI 0.84 to 1.16; P = 0.91). Subgroup analysis suggested no differences according to the type of DOAC in recurrent VTE or major bleeding (Pinteraction= 0.53 and Pinteraction= 0.11, respectively).

CONCLUSION: Among patients with cancer-related VTE, DOACs were associated with lower risk of VTE recurrence and similar risk of major bleeding compared with LMWH. Future studies examining the subset of cancer patients who drive the most benefit are encouraged.

PMID:32556105 | DOI:10.1093/ehjcvp/pvaa067

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PubMed articles on: Cardio-Oncology

Cardiac effects and toxicity of chloroquine: a short update

Mubagwa K. Int J Antimicrob Agents 2020 - Review.

Venous thromboembolism (VTE) is common in cancer patients and is an important cause of morbidity and mortality. The Glo

 

ABSTRACT

Venous thromboembolism (VTE) is common in cancer patients and is an important cause of morbidity and mortality. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE (ClinicalTrials.gov: NCT02155491) is a prospective, observational study of 10,684 patients with objectively diagnosed VTE from 415 sites in 28 countries. We compared baseline characteristics, VTE treatment patterns, and 1-year outcomes (mortality, recurrent VTE and major bleeding) in 1075 patients with active cancer, 674 patients with a history of cancer, and 8935 patients without cancer. Patients with active cancer and history of cancer were older than cancer-free patients, with median ages of 64.8, 68.9, and 58.4 years, respectively. The most common sites of active cancer were lung (14.5%),  colorectal (11.0%), breast (10.6%), and gynaecological (10.3%). Active cancer patients had a higher incidence of upper limb and vena cava thrombosis than cancer-free patients (9.0% vs 4.8% and 5.1% vs 1.4%, respectively), and were more likely to receive parenteral anticoagulation as monotherapy than cancer-free patients (57.8% vs 12.1%), and less likely to receive DOACs (14.2% vs 50.6%). Rates of death, recurrent VTE, and major bleeding were higher in active cancer patients than in cancer-free patients, with hazard ratios (95% confidence intervals) of 14.2 (12.1-16.6), 1.6 (1.2-2.0) and 3.8 (2.9-5.0), respectively. VTE was the second most common cause of death in patients with active cancer or history of cancer. In patients with VTE, those with active cancer are at higher risk of death, recurrence, and major bleeding than those without cancer.

PMID:32583306 | DOI:10.1007/s11239-020-02180-x

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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

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PubMed articles on: Cancer & VTE/PE

Efficacy and safety of direct oral anticoagulants versus low molecular weight heparin for cancer related venous thromboembolism: A meta-analysis of randomized trials

Elbadawi A, et al. Eur Heart J Cardiovasc Pharmacother 2020.

Purpose:Adult survivors of childhood cancer (ASCCs) are at high risk for cardiovascular disease from chemotherapy

 

ABSTRACT

Purpose:Adult survivors of childhood cancer (ASCCs) are at high risk for cardiovascular disease from chemotherapy- and radiation therapy-related cardiotoxicity. Physical activity (PA) can reduce this risk, but the majority of ASCCs do not engage in sufficient PA. The purpose of this study was to identify barriers, facilitators, and resources for PA among ASCCs using the ecological model of physical activity (EMPA) as a theoretical framework. Methods:A concept elicitation survey was distributed independently to ASCCs (diagnosed with cancer before the age of 18, and currently 18-39 years old) and parents/legal guardians of an ASCC. The survey consisted of open-ended questions asking about barriers, facilitators, and resources for PA. Content analysis of open-ended questions categorized responses into levels of the EMPA and identified key themes. Results:Seventeen ASCCs and eight parents of ASCCs completed the survey. The majority of barriers, facilitators, and resources reported were at the individual and microsystem level of the EMPA. Six themes emerged, suggesting that ASCC's PA was related to proximity/access, social support, equipment, time/schedule, finances, and health-related barriers. Conclusion:This is the first study to examine barriers, facilitators, and resources of PA among ASCCs using the EMPA. Findings from this study provide a multilevel perspective on the influences of PA among ASCCs, and can be used for future, in-depth qualitative studies and quantitative survey development, and as a foundational step toward supportive efforts in increasing PA among ASCCs.

PMID:32598196 | DOI:10.1089/jayao.2019.0169

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PubMed articles on: Cancer & VTE/PE

Cancer associated thrombosis in everyday practice: perspectives from GARFIELD-VTE

Weitz JI, et al. J Thromb Thrombolysis 2020.

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory

 

ABSTRACT

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003-2012). Epoetin and darbepoetin use were primary outcomes. Segmented linear regression was used to estimate changes in ESA use levels and trends, clinical appropriateness, and adverse events (VTEs) among chemotherapy-treated cancer patients. To estimate changes in level of drug prescription rate after policy actions, model-specific indicator variables as covariates based on specific actions were included. ESA use fell by 95% and 90% from 2005, for epoetin and darbepoetin, from 22% and 11%, respectively, to 1% and 1%, respectively, among cancer patients with CIA, respectively (p<0.01).<0.01).

PMID:32584835 | PMC:PMC7316310 | DOI:10.1371/journal.pone.0234541

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PubMed articles on: Cardio-Oncology

Exploring Social Ecological Determinants of Physical Activity Among Adult Survivors of Childhood Cancer

Dugan KF, et al. J Adolesc Young Adult Oncol 2020.

BACKGROUND: Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, vaso-occlusive crises

 

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

01:32

PubMed articles on: Cancer & VTE/PE

End of an era of administering erythropoiesis stimulating agents among Veterans Administration cancer patients with chemotherapy-induced anemia

Hoque S, et al. PLoS One 2020.

OBJECTIVES: Patients with gynecologic malignancies have high rates of post-operative venous thromboembolism. Currently

 

ABSTRACT

OBJECTIVES: Patients with gynecologic malignancies have high rates of post-operative venous thromboembolism. Currently, there is no consensus for peri-operative thromboprophylaxis specific to gynecologic oncology. We aimed to compare rates of symptomatic pulmonary embolus within 30 days post-operatively, and to identify risk factors for pulmonary embolus.

METHODS: The Division of Gynecologic Oncology at Sunnybrook Health Sciences Centre implemented dual thromboprophylaxis for laparotomies in December 2017. We conducted a prospective study of laparotomies for gynecologic malignancies from December 2017 to October 2018, with comparison to historical cohort from January 2016 to November 2017 using the institutional National Surgical Quality Improvement Program database (NSQIP). Pre-intervention, patients received low molecular weight heparin during admission and extended 28-day prophylaxis was continued at the surgeon's discretion. Post-intervention, all patients received both mechanical thromboprophylaxis with sequential compression devices during admission and 28-day prophylaxis with low molecular weight heparin.

RESULTS: There were 371 and 163 laparotomies pre- and post-intervention, respectively. Patient characteristics (age, body mass index, diabetes, smoking, tumor stage), rate of malignant cases, operative blood loss and duration, and length of stay were similar between groups. After implementation, pulmonary emboli rates decreased from 5.1% to 0% (p=0.001). There were more cytoreductive procedures pre-intervention (p≤0.0001) but surgical complexity scores were similar (p=0.82). Univariate analysis revealed that surgery pre-intervention (OR 4.25, 95% CI 1.04 to 17.43, p=0.04), length of stay ≥5 days (OR 11.94, 95% CI 2.65 to 53.92, p=0.002), and operative blood loss ≥500 mL (OR 2.85, 95% CI 1.05 to 7.8, p=0.04) increased risk of pulmonary embolus. On multivariable analysis, surgery pre-intervention remained associated with more pulmonary emboli (OR 4.16, 95% CI 1.03 to 16.79, p=0.045), when adjusting for operative blood loss.

CONCLUSION: Dual thromboprophylaxis after laparotomy significantly reduced rates of pulmonary embolus in this high-risk patient population.

PMID:32571889 | DOI:10.1136/ijgc-2020-001205

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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.

Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are a new type of glucose-lowering drug that can reduce blood glucose b

 

ABSTRACT

Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are a new type of glucose-lowering drug that can reduce blood glucose by inhibiting its reabsorption in proximal tubules and by promoting urinary glucose excretion. SGLT2i are widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). In recent studies, SGLT2i were found to not only reduce blood glucose but also protect the heart and kidney, which can significantly reduce cardiovascular events, delay the progression of renal failure, greatly improve the quality of life of patients, and reduce medical expenses for families and society. As adverse cardiac and renal events are the most common and serious complications of T2DM, it is very important to understand the cardio- and renoprotective mechanisms of SGLT2i. This article reviews the historical development, pharmacological mechanism, heart and kidney protection and safety of SGLT2i. The information presented provides a theoretical basis for the clinical prevention and treatment of diabetes and its complications and for the development of new glucose-lowering drugs.

PMID:32590982 | PMC:PMC7320582 | DOI:10.1186/s12933-020-01071-y

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PubMed articles on: Cancer & VTE/PE

Dual mechanical and pharmacological thromboprophylaxis decreases risk of pulmonary embolus after laparotomy for gynecologic malignancies

Nguyen JMV, et al. Int J Gynecol Cancer 2020.

Venous thromboembolism (VTE) and major bleeding in primary central nervous system lymphoma (PCNSL) patients

 

ABSTRACT

Venous thromboembolism (VTE) and major bleeding in primary central nervous system lymphoma (PCNSL) patients are not well described. We identified 992 PCNSL patients using the California Cancer Registry (2005-2014). The cumulative incidence of VTE and major bleeding was determined using California hospitalization data. The 12-month cumulative incidence of VTE was 13.6% (95% confidence interval (CI) 11.5-15.8%); chemotherapy and radiation therapy were associated with increased risk of VTE (hazard ratio (HR) 2.41, CI 1.31-4.46 and HR 1.56, CI 1.08-2.25, respectively). The 12-month cumulative incidence of major bleeding was 12.4% (CI 10.1-14.6%). Pulmonary embolism (PE) and proximal deep vein thrombosis were associated with increased risk of major bleeding, likely due to anticoagulation. PE (HR 1.61, CI 1.11-2.33, p=.011) and major bleeding (HR 2.36, CI 1.82-3.06, p<.0001)

PMID:32573292 | DOI:10.1080/10428194.2020.1780584

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PubMed articles on: Cardio-Oncology

SGLT2i: beyond the glucose-lowering effect

Ni L, et al. Cardiovasc Diabetol 2020 - Review.

The senescence of vascular smooth muscle cells (VSMCs), characterized by the acquisition of senescence-associated secretory

 

ABSTRACT

The senescence of vascular smooth muscle cells (VSMCs), characterized by the acquisition of senescence-associated secretory phenotype (SASP), is relevant for VSMCs osteoblastic differentiation and vascular calcification (VC). MicroRNA-34a (miR-34a) is a driver of such phenomena and could play a role in vascular inflammaging. Herein, we analyzed the relationship between miR-34a and the prototypical SASP component IL6 in in vitro and in vivo models. miR-34a and IL6 levels increased and positively correlated in aortas of 21 months-old male C57BL/6J mice and in human aortic smooth muscle cells (HASMCs) isolated from donors of different age and undergone senescence. Lentiviral overexpression of miR-34a in HASMCs enhanced IL6 secretion. HASMCs senescence and calcification accelerated after exposure to conditioned medium of miR-34a-overexpressing cells. Analysis of miR-34a-induced secretome revealed enhancement of several pro-inflammatory cytokines and chemokines, including IL6, pro-senescent growth factors and matrix-degrading molecules. Moreover, induction of aortas medial calcification and concomitant IL6 expression, with an overdose of vitamin D, was reduced in male C57BL/6J Mir34a-/-mice. Finally, a positive correlation was observed between circulating miR-34a and IL6 in healthy subjects of 20-90 years. Hence, the vascular age-associated miR-34a promotes VSMCs SASP activation and contributes to arterial inflammation and dysfunctions such as VC.

PMID:32585876 | DOI:10.3390/ijms21124454

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PubMed articles on: Cancer & VTE/PE

High incidence of venous thromboembolism and major bleeding in patients with primary CNS lymphoma

Mahajan A, et al. Leuk Lymphoma 2020.

Patients with multiple myeloma are at elevated risk of venous thromboembolism (VTE), the second leading cause of death in pat

 

ABSTRACT

Patients with multiple myeloma are at elevated risk of venous thromboembolism (VTE), the second leading cause of death in patients with cancer, but physician adherence to VTE prevention guidelines is low. Several organizations partnered in designing and implementing a 2-year quality improvement (QI) program in a tertiary care/academic cancer center, to increase awareness of VTE prophylaxis for patients with multiple myeloma and thus improve adherence to prophylaxis guidelines and protocols. The QI arm included 2 chart audits, conducted 2 years apart, of unmatched cohorts of 100 patients with multiple myeloma. An Education arm included 2 grand rounds presentations, 3 web-based case discussions, and a patient education module. Twenty providers took part in the continuous QI arm. More than 1100 learners participated in the online cases; the patient education curriculum reached 112 multiple myeloma patients. The initiative proved helpful in defining barriers to guideline adherence and identifying data-driven practice improvement strategies for VTE prophylaxis. It also increased learner awareness of VTE guidelines, patient risk stratification, and optimal thromboprophylaxis strategies. There was a reduction in VTE events (primary clinical outcome) from 10% at baseline to 4% in the follow-up cohort, although this was not statistically significant. Higher rates of guideline-based prophylaxis were observed in low-risk patients, and a lower incidence of VTE was observed in multiple myeloma patients with a prior history of VTE. Additional research is needed to refine prophylaxis guidelines. With appropriate institutional support, this type of QI program can be readily adopted by other organizations to address practice improvement needs.

PMID:32551873 | PMC:PMC7303783 | DOI:10.1177/1073274820930204

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PubMed articles on: Cardio-Oncology

The microRNA-34a-Induced Senescence-Associated Secretory Phenotype (SASP) Favors Vascular Smooth Muscle Cells Calcification

Zuccolo E, et al. Int J Mol Sci 2020.

Doxorubicin is a potent anticancer drug used to treat a variety of cancer types. However, its use is limited by doxorubicin-

ABSTRACT

Doxorubicin is a potent anticancer drug used to treat a variety of cancer types. However, its use is limited by doxorubicin-induced cardiotoxicity (DIC). A missense variant in the RARG gene (S427L; rs2229774) has been implicated in susceptibility to DIC in a genome wide association study. The goal of this study was to investigate the functional role of this RARG variant in DIC. We used induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) from patients treated with doxorubicin. iPSC-CMs from individuals who experienced DIC (cases) showed significantly greater sensitivity to doxorubicin compared to iPSC-CMs from doxorubicin-treated individuals who did not develop DIC (controls) in cell viability and optical mapping experiments. Using CRISPR/Cas9, we generated isogenic cell lines that differed only at the RARG locus. Genetic correction of RARG-S427L to wild type resulted in reduced doxorubicin-induced double stranded DNA breaks, reactive oxygen species production, and cell death. Conversely, introduction of RARG-S427L increased susceptibility to doxorubicin. Finally, genetic disruption of the RARG gene resulted in protection from cell death due to doxorubicin treatment. Our findings suggest that the presence of RARG-S427L increases sensitivity to DIC, establishing a direct, causal role for this variant in DIC.

PMID:32587261 | PMC:PMC7316788 | DOI:10.1038/s41598-020-65979-x

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PubMed articles on: Cancer & VTE/PE

Quality Improvement at an Academic Cancer Center: Venous Thromboembolism Prophylaxis in Patients With Multiple Myeloma

Baz R, et al. Cancer Control 2020.

Safety pharmacology is an essential part of drug development aiming to identify, evaluate and investigate

 

ABSTRACT

Safety pharmacology is an essential part of drug development aiming to identify, evaluate and investigate undesirable pharmacodynamic properties of a drug primarily prior to clinical trials. In particular, cardiovascular adverse drug reactions (ADR) have halted many drug development programs. Safety pharmacology has successfully implemented a screening strategy to detect cardiovascular liabilities, but there is room for further refinement. In this setting, we present the INSPIRE project, a European Training Network in safety pharmacology for Early Stage Researchers (ESRs), funded by the European Commission's H2020-MSCA-ITN programme. INSPIRE has recruited 15 ESR fellows that will conduct an individual PhD-research project for a period of 36 months. INSPIRE aims to be complementary to ongoing research initiatives. With this as a goal, an inventory of collaborative research initiatives in safety pharmacology was created and the ESR projects have been designed to be complementary to this roadmap. Overall, INSPIRE aims to improve cardiovascular safety evaluation, either by investigating technological innovations or by adding mechanistic insight in emerging safety concerns, as observed in the field of cardio-oncology. Finally, in addition to its hands-on research pillar, INSPIRE will organize a number of summer schools and workshops that will be open to the wider community as well. In summary, INSPIRE aims to foster both research and training in safety pharmacology and hopes to inspire the future generation of safety scientists.

PMID:32565326 | DOI:10.1016/j.vascn.2020.106889

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PubMed articles on: Cardio-Oncology

Variation in RARG increases susceptibility to doxorubicin-induced cardiotoxicity in patient specific induced pluripotent stem cell-derived cardiomyocytes

Christidi E, et al. Sci Rep 2020.

BACKGROUND: Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, vaso-occlusive crises, chroni

 

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

01:31

PubMed articles on: Cardio-Oncology

INSPIRE: A European training network to Foster research and training in cardiovascular safety pharmacology

Guns PD, et al. J Pharmacol Toxicol Methods 2020.

INTRODUCTION: Cerebral sinovenous thrombosis (CSVT) represents the second most common type of venous thromboembolism (VTE)

 

ABSTRACT

INTRODUCTION: Cerebral sinovenous thrombosis (CSVT) represents the second most common type of venous thromboembolism (VTE) in children. Current literature includes limited evidence on risk factors for CSVT, particularly in the pediatric population. We sought to determine risk factors for CSVT in pediatric patients through a single-institutional case-control study. In addition, we evaluated thrombophilias, treatments and outcomes in CSVT among cases.

METHODS: A case-control study was performed at Johns Hopkins All Children's Hospital on patients admitted from March 31, 2006 through April 1, 2018. Cases were identified using diagnostic codes and confirmed based on electronic health record (EHR) and neuroimaging review. Controls were matched in a 2:1 fashion accounting for the month and year of admission.

RESULTS: A total of 60 CSVT cases and 120 controls were identified. Median (range) age was 4.8 years (0-21.3 years) for cases and 5.6 years (0-20.0 years) for controls. Factors putatively associated with CSVT in unadjusted analyses were: corticosteroid use, presence of a central venous catheter, mechanical ventilation, systemic infection, head/neck infection, head/neck trauma, and chronic inflammatory disease. In the multivariable model, head/neck infection (OR: 13.8, 95% CI: 4.87-38.7; P < 0.01), head/neck trauma (OR: 12.7, 95% CI: 2.88-56.2; P < 0.01), and mechanical ventilation (OR: 9.32, 95% CI: 2.35-36.9; P = 0.01) remained independent, statistically-significant risk factors. 61% of patients were subacutely treated with anticoagulants and of those, only two developed relevant bleeding after initiation of therapy.

CONCLUSIONS: This single-institutional case-control study reveals that head/neck infection, head/neck trauma, and mechanical ventilation are independent risk factors for pediatric CSVT. These findings will be further investigated via a cooperative registry of pediatric hospital-acquired VTE, by which a risk model for pediatric CSVT will be developed and validated, in order to inform future preventive strategies in at-risk pediatric patients.

PMID:32554256 | DOI:10.1016/j.thromres.2020.06.013

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PubMed articles on: Cancer & VTE/PE

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.

Venous thromboembolism (VTE) is associated with significant mortality and morbidity in patients with cancer. Therefore

 

ABSTRACT

Venous thromboembolism (VTE) is associated with significant mortality and morbidity in patients with cancer. Therefore, tailoring anticoagulation is of utmost importance in order to decrease the risk of recurrent VTE while minimizing the risk of bleeding. Direct oral anticoagulants have been recently compared to low-molecular-weight heparin for the management of acute cancer-associated thrombosis. Although direct oral anticoagulants are a welcome addition, clinicians need to incorporate clinical characteristics, drug-drug interactions and patient preference in decision making.

PMID:32575112 | DOI:10.1182/blood.2019004177

01:31

PubMed articles on: Cardio-Oncology

Cardiac Imaging in Cardio-oncology: An Ongoing Challenging

Citro R and Monte IP. J Cardiovasc Echogr 2020.

NO ABSTRACT

PMID:32566459 | PMC:PMC7293867 | DOI:10.4103/jcecho.jcecho_1_19

01:31

PubMed articles on: Cancer & VTE/PE

Risk factors for pediatric cerebral sinovenous thrombosis: A case-control study with case validation

Sellers A, et al. Thromb Res 2020.