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
08:31
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
08:31
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PubMed articles on: Cancer & VTE/PE
Thrombotic Risk in Cancer Patients: Diagnosis and Management of Venous Thromboembolism
Citro R, et al. J Cardiovasc Echogr 2020 - Review.
ABSTRACT
Venous thromboembolism (VTE) represents a major health problem, especially in cancer patients, who experience a significantly higher incidence of both deep vein thrombosis and pulmonary embolism compared to the general population. Indeed, patients with cancer have a prothrombotic state resulting in both increased expression of procoagulants and suppression of fibrinolytic activity. In addition, VTE increases the morbidity and mortality of these patients. For all these reasons, the prevention and treatment of VTE in cancer setting represent major challenges in daily practice. In general, low-molecular-weight heparin monotherapy is the standard of care for the management of cancer-associated VTE, as Vitamin K antagonists are less effective in this setting. Direct oral anticoagulants offer a potentially promising treatment option for cancer patients with VTE, since recent studies demonstrated their efficacy and safety also in this peculiar setting.
PMID:32566465 | PMC:PMC7293865 | DOI:10.4103/jcecho.jcecho_63_19
08:31
PubMed articles on: Cancer & VTE/PE
A Case of Trousseau's Syndrome Accompanying Ovarian Cancer with Widespread Thromboembolisms
Kobayashi H, et al. Case Rep Obstet Gynecol 2020.
ABSTRACT
The patient was a 41-year-old woman, gravida 0. She had no notable medical history. Laparoscopic right salpingo-oophorectomy and left cystectomy were performed for bilateral ovarian endometriomas, which were both pathologically diagnosed as benign. Six months later, she presented with left lower abdominal pain and expressive aphasia. Examination revealed multiple cerebral infarctions and pulmonary embolism. The patient was diagnosed with Trousseau's syndrome secondary to ovarian cancer, and anticoagulant therapy was initiated. Despite treatment, she developed visual field loss due to occlusion of the left retinal artery; dizziness due to cerebellar infarction and myocardial infarction; and right hemiplegia due to new cerebral infarction. She received chemotherapy (two courses of paclitaxel and carboplatin), which did not improve her condition, and died two months after onset. An autopsy revealed that her left ovary was enlarged to a size of 12 cm and an endometrioid carcinoma G2 was identified. Ovarian cancer had spread throughout the abdominal cavity, and a large amount of pleural and ascites fluid was present. Multiple thrombi were found in bilateral pulmonary arteries and bilateral common iliac veins. There was a 2.5 cm thrombus in the left ventricle apex, and the anterior descending branch was obstructed by thrombus with recanalization.
PMID:32566336 | PMC:PMC7293738 | DOI:10.1155/2020/3738618
12:35
Cardiotoxicity News
PubMed articles on: Cancer & VTE/PE
Adverse Events and Mortality in Anticoagulated Patients with Different Categories of Pulmonary Embolism
Cambron JC, et al. Mayo Clin Proc Innov Qual Outcomes 2020.
ABSTRACT
OBJECTIVE: To determine whether the pulmonary embolism (PE) categories of massive, submassive, PE with no right ventricle dysfunction (NRVD), and subsegmental only (SSO) adequately predict clinical outcome.
METHODS: Patients treated for acute PE (March 1, 2013, through July 31, 2019) were followed forward prospectively to compare venous thromboembolism (VTE) recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) across 4 PE categories.
RESULTS: Of 2703 patients with VTE, 1188 (44%) had PE, of which 1021 (85.9%) completed at least 3 months of therapy or had clinical outcomes precluding further treatment (27 with massive, 217 submassive, 557 NRVD, and 220 SSO PE). One patient with massive, 8 with submassive, 23 with NRVD, and 5 with SSO PE had recurrent VTE (3.90, 5.33, 5.36, and 3.66 per 100 person-years, respectively; P=.84). There were 3 deaths in massive, 27 in submassive, 140 in NRVD, and 34 in SSO PE groups (11.59, 17.37, 31.74, and 24.74 per 100 person-years, respectively; P=.02); when adjusted for cancer, the relationship was no longer significant (P=.27). One patient with massive, 5 with submassive, 22 with NRVD, and 5 with SSO PE had major bleeding (3.90, 3.31, 5.24, and 3.75 per 100 person-years, respectively; P=.66). Similar cumulative rates for CRNMB were observed (P=.87). Three-month rates of VTE recurrence, death, major bleeding, and CRNMB did not differ by PE category.
CONCLUSION: In the setting of anticoagulation therapy with maximal standardization and evidence-based practice, there is no evidence of a difference between PE categories and outcomes.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03504007.
PMID:32542216 | PMC:PMC7283932 | DOI:10.1016/j.mayocpiqo.2020.02.002
12:35
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PubMed articles on: Cardio-Oncology
Resiliency and Our Cardio-Oncology Community
Ky B. JACC CardioOncol 2020.
NO ABSTRACT
PMID:32548596 | PMC:PMC7243765 | DOI:10.1016/j.jaccao.2020.05.003
12:35
PubMed articles on: Cancer & VTE/PE
Infantile hepatic hemangioendothelioma associated with pulmonary artery hypertension and cardiac insufficiency successfully treated with transcatheter arterial embolization and propranolol: A case report
Wang L, et al. Medicine (Baltimore) 2020.
ABSTRACT
INTRODUCTION: Infantile hepatic hemangioendothelioma is a type of benign hepatic tumor that occurs in infancy. Many hepatic tumors are diagnosed when screening is done for multiple cutaneous hemangiomas. Hepatic tumors are small multifocal lesions and are mostly asymptomatic. There have been many case reports of asymptomatic infantile hepatic hemangioendothelioma, but few of these have pointed out that hepatic hemangiomas can sometimes be life-threatening due to fatal hepatomegaly complications such as pulmonary artery hypertension or even congestive heart failure. At present, there are no standard protocols for treating infantile hepatic hemangioendothelioma, though most clinicians agree that treatment is unnecessary for multiple small hepatic hemangiomas in asymptomatic patients. Little is known about treatment for cases with life-threatening complications induced by infantile hepatic hemangioendothelioma as there are so few reported cases. Here, we report a special case with hepatomegaly, pulmonary artery hypertension, and cardiac insufficiency induced by infantile hepatic hemangioendothelioma.
PATIENT CONCERNS: We present a case with hepatomegaly, pulmonary artery hypertension, and cardiac insufficiency caused by infantile hepatic hemangioendothelioma.
DIAGNOSIS: Infantile hepatic hemangioendothelioma was diagnosed.
INTERVENTIONS: The patient underwent transcatheter arterial embolization and was given propranolol.
OUTCOMES: The patient responded well to treatment with transcatheter arterial embolization and propranolol. The patient gained weight steadily, liver volume, and mass size have decreased considerably, echocardiography showed normal pulmonary artery pressure and ejection fraction, and we discovered no serious complications after 1 year of follow-up.
CONCLUSION: Transcatheter arterial embolization combined with propranolol is an effective treatment for life-threatening infantile hepatic hemangioendothelioma.
PMID:32541524 | PMC:PMC7302649 | DOI:10.1097/MD.0000000000020728
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PubMed articles on: Cardio-Oncology
Cardio-Oncology in Brazil: The Dimensions of a New Era in the Care of Patients
Hajjar LA and Mathias C. JACC CardioOncol 2020.
NO ABSTRACT
PMID:32548595 | PMC:PMC7243784 | DOI:10.1016/j.jaccao.2020.05.004
12:35
PubMed articles on: Cancer & VTE/PE
Real world data regarding the management of cancer-associated thrombosis
Tsoukalas N, et al. Curr Opin Oncol 2020.
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