ABSTRACT

PURPOSE: Therapy for cancer-associated venous thromboembolism (VTE) includes long-term anticoagulation, which may have substantial impact on the health-related quality of life (HRQL) of patients. We assessed patient-reported outcomes to characterize the HRQL associated with VTE treatment and to begin to examine those HRQL elements impacting anticoagulation adherence (AA).

METHODS: Participants were adult cancer patients with confirmed symptomatic acute lower extremity deep venous thrombosis. Patients were excluded if there was an indication for anticoagulation other than VTE, ECOG performance status >3, or life expectancy < 3 months. Participants were assessed with a self-reported adherence tool. HRQL was measured with a 6-domain questionnaire using a seven-point Likert scale. Evaluations were performed at 30 days and 3 months after enrollment. For the primary objective, an overall adherence rate was calculated at each time point of evaluation. For the HRQL domains, non-parametric testing was used to compare results between subgroups.

RESULTS: Seventy-four patients were enrolled. AA and HRQL at 30 days and 3 months were assessed in 50 and 36 participants, respectively. At 30 days the AA rate was 90%, and at 3 months it was 83%. In regard to HRQL, patients suffered frequent and moderate-severe distress in the domains of emotional and physical symptoms, sleep disturbance, and limitations to physical activity. An association between emotional or physical distress and AA was observed.

CONCLUSION: Patients with VTE suffer a substantial impairment of their HRQL. Increased emotional distress correlated with better long-term AA. These results can be used to inform additional research aimed at developing novel strategies to improve AA.

PMID:37801086 | DOI:10.1007/s00520-023-08073-y

21:52

PubMed articles on: Cardio-Oncology

Aortic Valve Stenosis and Cancer: Problems of Management

J Clin Med. 2023 Sep 6;12(18):5804. doi: 10.3390/jcm12185804.

ABSTRACT

Aortic valve stenosis and malignancy frequently coexist and share the same risk factors as atherosclerotic disease. Data reporting the prognosis of patients with severe aortic stenosis and cancer are limited. Tailoring the correct and optimal care for cancer patients with severe aortic stenosis is complex. Cancer patients may be further disadvantaged by aortic stenosis if it interferes with their treatment by increasing the risk associated with oncologic surgery and compounding the risks associated with cardiotoxicity and heart failure (HF). Surgical valve replacement, transcatheter valve implantation, balloon valvuloplasty, and medical therapy are possible treatments for aortic valve stenosis, but when malignancy is present, the choice between these options must take into account the stage of cancer and associated treatment, expected outcome, and comorbidities. Physical examination and Doppler echocardiography are critical in the diagnosis and evaluation of aortic stenosis. The current review considers the available data on the association between aortic stenosis and cancer and the therapeutic options.

PMID:37762745 | PMC:PMC10532214 | DOI:10.3390/jcm12185804

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PubMed articles on: Cardio-Oncology

When helping hurts: restricting cardiotoxicity of cancer therapeutics with accurate cardiovascular risk assessment works!

Eur J Prev Cardiol. 2023 Sep 25:zwad273. doi: 10.1093/eurjpc/zwad273. Online ahead of print.

NO ABSTRACT

PMID:37747453 | DOI:10.1093/eurjpc/zwad273

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PubMed articles on: Cardio-Oncology

The Impact of Drug-Drug Interactions on the Toxicity Profile of Combined Treatment with BRAF and MEK Inhibitors in Patients with BRAF-Mutated Metastatic Melanoma

Cancers (Basel). 2023 Sep 15;15(18):4587. doi: 10.3390/cancers15184587.

ABSTRACT

BACKGROUND: BRAF and MEK inhibition is a successful strategy in managing BRAF-mutant melanoma, even if the treatment-related toxicity is substantial. We analyzed the role of drug-drug interactions (DDI) on the toxicity profile of anti-BRAF/anti-MEK therapy.

METHODS: In this multicenter, observational, and retrospective study, DDIs were assessed using Drug-PIN software (V 2/23). The association between the Drug-PIN continuous score or the Drug-PIN traffic light and the occurrence of treatment-related toxicities and oncological outcomes was evaluated.

RESULTS: In total, 177 patients with advanced BRAF-mutated melanoma undergoing BRAF/MEK targeted therapy were included. All grade toxicity was registered in 79% of patients. Cardiovascular toxicities occurred in 31 patients (17.5%). Further, 94 (55.9%) patients had comorbidities requiring specific pharmacological treatments. The median Drug-PIN score significantly increased when the target combination was added to the patient's home therapy (p-value < 0.0001). Cardiovascular toxicity was significantly associated with the Drug-PIN score (p-value = 0.048). The Drug-PIN traffic light (p = 0.00821) and the Drug-PIN score (p = 0.0291) were seen to be significant predictors of cardiotoxicity. Patients with low-grade vs. high-grade interactions showed a better prognosis regarding overall survival (OS) (p = 0.0045) and progression-free survival (PFS) (p = 0.012). The survival analysis of the subgroup of patients with cardiological toxicity demonstrated that patients with low-grade vs. high-grade DDIs had better outcomes in terms of OS (p = 0.0012) and a trend toward significance in PFS (p = 0.068).

CONCLUSIONS: DDIs emerged as a critical issue for the risk of treatment-related cardiovascular toxicity. Our findings support the utility of DDI assessment in melanoma patients treated with BRAF/MEK inhibitors.

PMID:37760556 | PMC:PMC10526382 | DOI:10.3390/cancers15184587

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PubMed articles on: Cardio-Oncology

Droplet Digital PCR Is a Novel Screening Method Identifying Potential Cardiac G-Protein-Coupled Receptors as Candidate Pharmacological Targets in a Rat Model of Pressure-Overload-Induced Cardiac Dysfunction

Int J Mol Sci. 2023 Sep 7;24(18):13826. doi: 10.3390/ijms241813826.

ABSTRACT

The identification of novel drug targets is needed to improve the outcomes of heart failure (HF). G-protein-coupled receptors (GPCRs) represent the largest family of targets for already approved drugs, thus providing an opportunity for drug repurposing. Here, we aimed (i) to investigate the differential expressions of 288 cardiac GPCRs via droplet digital PCR (ddPCR) and bulk RNA sequencing (RNAseq) in a rat model of left ventricular pressure-overload; (ii) to compare RNAseq findings with those of ddPCR; and (iii) to screen and test for novel, translatable GPCR drug targets in HF. Male Wistar rats subjected to transverse aortic constriction (TAC, n = 5) showed significant systolic dysfunction vs. sham operated animals (SHAM, n = 5) via echocardiography. In TAC vs. SHAM hearts, RNAseq identified 69, and ddPCR identified 27 significantly differentially expressed GPCR mRNAs, 8 of which were identified using both methods, thus showing a correlation between the two methods. Of these, Prostaglandin-F2α-receptor (Ptgfr) was further investigated and localized on cardiomyocytes and fibroblasts in murine hearts via RNA-Scope. Antagonizing Ptgfr via AL-8810 reverted angiotensin-II-induced cardiomyocyte hypertrophy in vitro. In conclusion, using ddPCR as a novel screening method, we were able to identify GPCR targets in HF. We also show that the antagonism of Ptgfr could be a novel target in HF by alleviating cardiomyocyte hypertrophy.

PMID:37762130 | PMC:PMC10531061 | DOI:10.3390/ijms241813826

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PubMed articles on: Cardio-Oncology

Evaluation of Expression Level of miR-3135b-5p in Blood Samples of Breast Cancer Patients Experiencing Chemotherapy-Induced Cardiotoxicity

Indian J Clin Biochem. 2023 Oct;38(4):536-540. doi: 10.1007/s12291-022-01075-3. Epub 2022 Sep 6.

ABSTRACT

The efficacy of chemotherapeutics in the treatment of breast cancer is limited by cardiotoxicity, which could lead to irreversible heart failure. The evaluation of miRNA levels as a vital biomarker could predict cardiotoxicity induced by chemotherapy. According to our previous meta-analysis study on patients with heart failure, we found that miR-3135b had a significant increase in patients with heart failure. Therefore, the present study aimed to evaluate the expression level of miR-3135b in the blood sample of patients experiencing chemotherapy-induced cardiotoxicity. Blood samples were collected from breast cancer patients or breast cancer patients who had received chemotherapy and had not experienced any chemotherapy-induced cardiotoxicity (N = 37, control group) and breast cancer patients experiencing chemotherapy-induced cardiotoxicity after chemotherapy (N = 33). The expression level of miR-3135b was evaluated using real-time polymerase chain reaction (RT-PCR). The 2-ΔCt values of miR-3135b were compared between two groups. We observed a significant increase in the expression level of miR-3135b between patients experiencing chemotherapy-induced cardiotoxicity and the control group (P = 0.0001). Besides, the ejection fraction parameter was correlated with the expression level of miR-3135b (r = 0.5 and P = 0.0001). To sum up, miR-3135b might be useful as a promising circulating biomarker in predicting cardiotoxicity induced by chemotherapy. However, more studies are needed to validate miR-3135b as a biomarker for the diagnosis of chemotherapy-induced cardiotoxicity.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12291-022-01075-3.

PMID:37746544 | PMC:PMC10516830 | DOI:10.1007/s12291-022-01075-3

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PubMed articles on: Cardio-Oncology

Creatine and Resistance Training: A Combined Approach to Attenuate Doxorubicin-Induced Cardiotoxicity

Nutrients. 2023 Sep 19;15(18):4048. doi: 10.3390/nu15184048.

ABSTRACT

Doxorubicin (DOX), a potent chemotherapy agent, useful in the treatment of solid tumors, lymphomas, and leukemias, is limited by its potentially lethal cardiotoxicity. However, exercise has been consistently shown to mitigate the side effects of DOX, including cardiotoxicity. To date, most studies examining the relationship between exercise and DOX-induced cardiotoxicity have focused on aerobic exercise, with very few examining the role of anerobic activity. Therefore, this investigation explored the potential of creatine (CR) and resistance training (RT) in preserving cardiac health during DOX therapy. Male Sprague-Dawley rats were grouped into RT, RT + CR, sedentary (SED), and SED + CR, with each division further branching into saline (SAL) or DOX-treated subsets post-10 weeks of RT or SED activity. RT comprised progressive training utilizing specialized cages for bipedal stance feeding. CR-treated groups ingested water mixed with 1% CR monohydrate and 5% dextrose, while control animals received 5% dextrose. At week 10, DOX was administered (2 mg/kg/week) over 4-weeks to an 8 mg/kg cumulative dose. Cardiac function post-DOX treatment was assessed via transthoracic echocardiography. Left ventricular diameter during diastole was lower in DOX + CR, RT + DOX, and RT + CR + DOX compared to SED + DOX (p < 0.05). Additionally, cardiac mass was significantly greater in RT + CR + DOX SED + DOX animals (p < 0.05). These results suggest RT and CR supplementation, separately and in combination, could attenuate some measures of DOX-induced cardiotoxicity and may offer a cost-effective way to complement cancer treatments and enhance patient outcomes. More investigations are essential to better understand CR's prolonged effects during DOX therapy and its clinical implications.

PMID:37764831 | PMC:PMC10536171 | DOI:10.3390/nu15184048

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PubMed articles on: Cancer & VTE/PE

Development and validation of a new risk assessment model for immunomodulatory drug-associated venous thrombosis among Chinese patients with multiple myeloma

Thromb J. 2023 Oct 4;21(1):105. doi: 10.1186/s12959-023-00534-y.

ABSTRACT

BACKGROUND: Individuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients.

METHODS: We retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis.

RESULTS: The overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively.

CONCLUSIONS: The new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.

PMID:37794471 | PMC:PMC10552366 | DOI:10.1186/s12959-023-00534-y

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PubMed articles on: Cancer & VTE/PE

Ruptured Baker's cyst presenting with a palpable popliteal mass and crescent sign

BMJ Case Rep. 2023 Oct 4;16(10):e257869. doi: 10.1136/bcr-2023-257869.

NO ABSTRACT

PMID:37793850 | PMC:PMC10551967 | DOI:10.1136/bcr-2023-257869

21:53

PubMed articles on: Cancer & VTE/PE

Monocyte recruitment in venous pulmonary embolism at time of cancer diagnosis in upper gastrointestinal cancer patients

J Thromb Thrombolysis. 2023 Oct 4. doi: 10.1007/s11239-023-02897-5. Online ahead of print.