ABSTRACT

Introduction Acute pancreatitis (AP) is a common inflammatory disorder with acute onset and rapid progression. Studies have reported cardiac injury in patients with AP. It is often thought that stress cardiomyopathy can induce these changes leading to type 2 myocardial infarction (type 2 MI) in AP. Our study aims to assess the prevalence as well as the impact of type 2 MI on outcomes in patients with AP. Methods National Inpatient Sample (NIS) 2016-2020 was used to identify adult patients (age>18) with acute pancreatitis. We excluded patients with STEMI, NSTEMI, pancreatic cancer, or chronic pancreatitis. Patients with missing demographics and mortality were also excluded. Patients were stratified into two groups, based on the presence of type 2 MI. Multivariate logistic regression analysis was performed to assess the impact of concomitant type 2 MI on mortality, sepsis, acute kidney injury (AKI), ICU admission, deep venous thrombosis (DVT), and pulmonary embolism (PE) after adjusting for patient demographics, hospital characteristics, etiology of AP and the Elixhauser comorbidities. Results Of the 1.1 million patients in the study population, only 2315 patients had type 2 MI. The majority of the patients in the type 2 MI group were aged >65 years (49.2%, p<0.001),<0.001),<0.001),<0.001),<0.001),<0.001)<0.001).<0.001).<0.001)<0.001).

PMID:37750110 | PMC:PMC10518190 | DOI:10.7759/cureus.44113

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PubMed articles on: Cardio-Oncology

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PubMed articles on: Cardio-Oncology

Altered Peripheral Blood Gene Expression in Childhood Cancer Survivors With Anthracycline-Induced Cardiomyopathy - A COG-ALTE03N1 Report

J Am Heart Assoc. 2023 Sep 26:e029954. doi: 10.1161/JAHA.123.029954. Online ahead of print.

ABSTRACT

Background Anthracycline-induced cardiomyopathy is a leading cause of premature death in childhood cancer survivors, presenting a need to understand the underlying pathogenesis. We sought to examine differential blood-based mRNA expression profiles in anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Methods and Results We designed a matched case-control study (Children's Oncology Group-ALTE03N1) with mRNA sequencing on total RNA from peripheral blood in 40 anthracycline-exposed survivors with cardiomyopathy (cases) and 64 matched survivors without (controls). DESeq2 identified differentially expressed genes. Ingenuity Pathway Analyses (IPA) and Gene Set Enrichment Analyses determined the potential roles of altered genes in biological pathways. Functional validation was performed by gene knockout in human-induced pluripotent stem cell-derived cardiomyocytes using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) technology. Median age at primary cancer diagnosis for cases and controls was 8.2 and 9.7 years, respectively. Thirty-six differentially expressed genes with fold change ≥±2 were identified; 35 were upregulated. IPA identified "hepatic fibrosis" and "iron homeostasis" pathways to be significantly modulated by differentially expressed genes, including toxicology functions of myocardial infarction, cardiac damage, and cardiac dilation. Leading edge analysis from Gene Set Enrichment Analyses identified lactate dehydrogenase A (LDHA) and cluster of differentiation 36 (CD36) genes to be significantly upregulated in cases. Interleukin 1 receptor type 1, 2 (IL1R1, IL1R2), and matrix metalloproteinase 8, 9 (MMP8, MMP9) appeared in multiple canonical pathways. LDHA-knockout human-induced pluripotent stem cell-derived cardiomyocytes showed increased sensitivity to doxorubicin. Conclusions We identified differential mRNA expression profiles in peripheral blood of anthracycline-exposed childhood cancer survivors with and without cardiomyopathy. Upregulation of LDHA and CD36 genes suggests metabolic perturbations in a failing heart. Dysregulation of proinflammatory cytokine receptors IL1R1 and IL1R2 and matrix metalloproteinases, MMP8 and MMP9 indicates structural remodeling that accompanies the clinical manifestation of symptomatic cardiotoxicity.

PMID:37750583 | DOI:10.1161/JAHA.123.029954

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PubMed articles on: Cancer & VTE/PE

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PubMed articles on: Cardio-Oncology

Development and Phenotype of Heart Failure in Long-Term Survivors of Childhood Cancer: The CVSS Study

J Am Heart Assoc. 2023 Sep 26:e030020. doi: 10.1161/JAHA.123.030020. Online ahead of print.

ABSTRACT

Background The CVSS (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer) study aimed to investigate the prevalence of different stages of heart failure (HF) in childhood cancer survivors (CCSs) compared with the general population. Methods and Results A total of 1002 CCSs (age range, 23-48 years) diagnosed with neoplasia before an age of 15 years underwent a comprehensive cardiovascular screening. An age- and sex-matched sample from the population-based GHS (Gutenberg Health Study) served as a comparison group. Although prevalence of HF was significantly higher in CCSs, prevalence of different HF stages varied strongly by specific tumor history. Compared with the population, the prevalence ratio was 2.6 (95% CI, 2.4-2.8) for HF stage A and 4.6 (95% CI, 4.1-5.1) for the composite of HF stage B to D in an age- and sex-adjusted Poisson regression model. Multivariable linear regression, adjusting for tumor entities, age, sex, and cardiovascular risk factors, revealed a lower left ventricular ejection fraction in patients with history of bone tumors (β, -4.30 [95% CI, -5.70 to -2.80]), soft tissue sarcoma (β, -1.60 [95% CI, -2.90 to -0.30]), and renal tumors (β, -1.60 [95% CI, -2.80 to -0.29]) compared with the population. The same model for the diastolic marker, ratio of the peak early diastolic filling velocity/lateral mitral annular early diastolic velocity, showed an association only with cardiovascular risk factors but not with tumor entities. Conclusions The prevalence of HF stage A to D was significantly higher among long-term CCSs compared with the population and varied strongly by tumor entity. Systolic dysfunction was primarily associated with tumor entities, whereas diastolic dysfunction was associated with a higher burden of cardiovascular risk factors in CCSs.

PMID:37750584 | DOI:10.1161/JAHA.123.030020

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PubMed articles on: Cancer & VTE/PE

Risk of thromboembolic events associated with different multiple myeloma regimens in Taiwan: a nested case-control study

J Thromb Thrombolysis. 2023 Sep 22. doi: 10.1007/s11239-023-02887-7. Online ahead of print.

ABSTRACT

Although novel agents for multiple myeloma (MM) have a better response rate and survival in both newly diagnosed and relapsed/refractory MM patients, concerns regarding the association between MM treatments and thromboembolic events have been raised. The aim of this population-based study was to examine the association between different combinations of MM treatments and the risk of thromboembolic events. We conducted a nested case-control study using the Taiwan Cancer Registry (TCR) and National Health Insurance Research Database (NHIRD). Adult patients newly diagnosed with MM and treated with at least one of the immunomodulatory agents between 2008 and 2016 were identified. Among them, we further identified patients who developed thromboembolic events as cases and selected controls matched by age, sex and duration of MM diagnosis at a ratio of 1:5. The index date was defined as the day one year before the diagnosis date of thromboembolic events in the case group and the corresponding date in the control group. Conditional logistic regression was used to examine the association between different MM treatment regimens and the risk of thromboembolic events. A total of 4,180 newly diagnosed MM patients treated with at least one of the immunomodulatory agents were identified (mean age: 67.2 years; male: 55.7%). In this MM cohort, we further identified 388 cases and 1,940 matched controls (mean age: 71 years; male: 64.2%). The use of a thalidomide/bortezomib/steroid combination (odds ratio (OR) 2.95 [95% confidence interval (CI) 1.47-5.95]), thalidomide monotherapy (OR 3.33; 95% CI, 1.59-6.94), and a thalidomide/steroid combination (OR 4.24; 95% CI, 2.00-8.98) were associated with an increased risk of thromboembolic events. Other risk factors, particularly a history of thromboembolic events, including ischemic heart disease and pulmonary embolism, were significantly associated with increased risk of thromboembolic events. We found that the use of thalidomide alone and in specific combinations was associated with an increased risk of thromboembolic events.

PMID:37737970 | DOI:10.1007/s11239-023-02887-7

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PubMed articles on: Cancer & VTE/PE

A Rare Incidence of Hepatocellular Carcinoma With Tumor Thrombus Extending to the Right Heart

Cureus. 2023 Aug 23;15(8):e43965. doi: 10.7759/cureus.43965. eCollection 2023 Aug.