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Mario Cazzola,1 Luigino Calzetta,2 Paola Rogliani,1 Maria Gabriella Matera3 1Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome ‘tor Vergata’, Rome, Italy; 2Unit of Respiratory Disease and Lung Function, Department of Medicine and Surgery, University of Parma, Parma, Italy; 3Unit of Pharmacology, Department of Experimental Medicine, University of Campania ‘luigi Vanvitelli’, Naples, ItalyCorrespondence: Mario Cazzola, Department of Experimental Medicine, University of Rome “tor Vergata”, Rome, Italy, Email mario.cazzola@uniroma2.itAbstract: Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory condition often complicated by cardiovascular disease (CVD) due to shared inflammatory pathways. This review explores the cardiovascular impacts of emerging anti-inflammatory therapies in COPD. Phosphodiesterase (PDE) inhibitors may offer anti-inflammatory effects with improved lung function but pose potential risks for arrhythmias when PDE3 is inhibited although PDE4 inhibitors reduce cardiovascular events by improving endothelial function and reducing thrombosis. Similarly, p38 mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) inhibitors target COPD-related inflammation and may benefit COPD patients with CVD. p38 MAPK inhibitors reduce cardiac fibrosis, enhance contractility and lower the risk of arrhythmia. PI3K inhibitors target the PI3K/Akt pathway, which drives atherosclerosis and cardiac fibrosis, and thus potentially mitigate both plaque instability and fibrosis. Biologic therapies, including monoclonal antibodies that inhibit IL-5, IL-13/IL-4, thymic stromal lymphopoietin, IL-33, and IL-17A, show promise in reducing exacerbations but require close cardiovascular monitoring due to their immunomodulatory effects. Single-target inhibitors of neutrophil elastase or matrix metalloproteinases show limited efficacy in COPD but may aid cardiovascular patients by stabilizing atherosclerotic plaques through promoting vascular smooth muscle cell proliferation. However, their tendency to degrade the extracellular matrix and attract immune cells may heighten plaque rupture risk, contraindicating use in CVD. Alpha-1 antitrypsin replacement therapy holds promise, potentially reducing COPD exacerbations and providing cardiovascular protection, especially in myocardial injury. Understanding the influence of these innovative therapies on CVD is vital, making it imperative to examine these molecules in COPD patients with CVD at an early stage.Keywords: chronic obstructive pulmonary disease, cardiovascular disease, inflammation, anti-inflammatory treatments, cardiac adverse events

Background We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with coronavirus disease 2019 (COVID-19) who received remdesivir plus standard of care (SoC) compared with SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. Methods This post hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19. Any first AE that occurred between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves, and Kaplan-Meier estimates were calculated for event rates. Results Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (hazard ratio [HR], 1.0; 95% confidence interval [CI],.7–1.5; P =.98), even when serious and nonserious cardiac AEs were evaluated separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between the two groups in the occurrence of cardiac AE subclasses, including arrhythmic events (HR, 1.1; 95% CI,.7–1.7; P =.68). Conclusions Remdesivir treatment was not associated with an increased risk of cardiac AEs compared with control in patients hospitalized with moderate or severe COVID-19. These results are consistent with other randomized, controlled trials and meta-analyses. Clinical Trials Registration. NCT 04315948; EudraCT 2020-000936-23. [ABSTRACT FROM AUTHOR]

Abstract Lacosamide was the first approved third-generation antiepileptic drug. However, real-world data regarding its adverse cardiac reactions in large samples still need to be completed. We evaluated the cardiac safety profile of lacosamide using the Food and Drug Administration Adverse Event Reporting System (FAERS). We performed disproportionality analysis computing reporting odds ratio (ROR) as a quantitative metric to assess the signal of lacosamide-related cardiac adverse events (AEs) from 2013 Q1 to 2022 Q4. The signal was considered significant when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1, and ≥ 5 AEs were reported. Serious and nonserious cases were compared by statistical analysis, and signals were further prioritized using a rating scale. A total of 812 cardiac AEs associated with lacosamide were identified, and 92 signals were detected, of which 17 AEs were significantly associated signals. The median time-to-onset (TTO) for moderate priority signals was 10 days, whereas for weak priority signals, it was 54 days. Notably, all cardiac AEs exhibited an early failing pattern, indicating the risk gradually decreasing. Based on the comprehensive analysis of the FAERS database and prioritization of cardiac AE signals, our research enhances the awareness among healthcare professionals regarding cardiac AEs associated with lacosamide.

ObjectiveTo evaluate the risk of cardiac adverse events in patients with malignant tumors after chemotherapy by using a combination of acoustic cardiography and blood indices. MethodsA total of 171 patients with malignant tumor who received chemotherapy were included. They were divided into cardiac adverse event group and non-cardiac adverse event group in accordance with whether cardiac adverse events occurred after chemotherapy. The general data, blood indices before chemotherapy, and acoustic cardiography-related indices in the early stage (1-3 cycles) of chemotherapy of the two groups were analyzed. The possible influencing factors were determined by binary logistic regression analysis, and the nomogram was drawn. The receiver operating characteristic (ROC) curve was used to evaluate the prediction ability of the nomogram. ResultsCardiac adverse events occurred in 44 of 171 patients with malignant tumors after chemotherapy, and the incidence of cardiac adverse events was 25.73%. Binary logistic regression results showed that age, red blood cell distribution width (RDW) before chemotherapy, activated partial thromboplastin time (APTT), and electromechanical activation time (EMAT) at the early stage of chemotherapy were independent predictors of cardiac adverse events in chemotherapy patients. The area under the ROC curve of the nomogram was 0.768 (95%CI: 0.693-0.843, P

Lacosamide was the first approved third-generation antiepileptic drug. However, real-world data regarding its adverse cardiac reactions in large samples still need to be completed. We evaluated the cardiac safety profile of lacosamide using the Food and Drug Administration Adverse Event Reporting System (FAERS). We performed disproportionality analysis computing reporting odds ratio (ROR) as a quantitative metric to assess the signal of lacosamide-related cardiac adverse events (AEs) from 2013 Q1 to 2022 Q4. The signal was considered significant when the lower limit of the 95% confidence interval (CI) of the ROR exceeded 1, and ≥ 5 AEs were reported. Serious and nonserious cases were compared by statistical analysis, and signals were further prioritized using a rating scale. A total of 812 cardiac AEs associated with lacosamide were identified, and 92 signals were detected, of which 17 AEs were significantly associated signals. The median time-to-onset (TTO) for moderate priority signals was 10 days, whereas for weak priority signals, it was 54 days. Notably, all cardiac AEs exhibited an early failing pattern, indicating the risk gradually decreasing. Based on the comprehensive analysis of the FAERS database and prioritization of cardiac AE signals, our research enhances the awareness among healthcare professionals regarding cardiac AEs associated with lacosamide. [ABSTRACT FROM AUTHOR]

Objective To evaluate the risk of cardiac adverse events in patients with malignant tumors after chemotherapy by using a combination of acoustic cardiography and blood indices. Methods A total of 171 patients with malignant tumor who received chemotherapy were included. They were divided into cardiac adverse event group and non-cardiac adverse event group in accordance with whether cardiac adverse events occurred after chemotherapy. The general data, blood indices before chemotherapy, and acoustic cardiography-related indices in the early stage (1-3 cycles) of chemotherapy of the two groups were analyzed. The possible influencing factors were determined by binary logistic regression analysis, and the nomogram was drawn. The receiver operating characteristic (ROC) curve was used to evaluate the prediction ability of the nomogram. Results Cardiac adverse events occurred in 44 of 171 patients with malignant tumors after chemotherapy, and the incidence of cardiac adverse events was 25.73%. Binary logistic regression results showed that age, red blood cell distribution width (RDW) before chemotherapy, activated partial throm- boplastin time (APTT), and electromechanical activation time (EMAT) at the early stage of chemother- apy were independent predictors of cardiac adverse events in chemotherapy patients. The area under the ROC curve of the nomogram was 0.768 (95%CI: 0.693-0.843, P<0.001). Conclusion A nomogram based on age, pre-chemotherapy RDW, APTT, and EMAT at the early stage of chemotherapy is useful for early assessment of the risk of cardiac adverse events in chemotherapy patients. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the potential of PARP inhibitors to prevent cardiotoxicity. Methods: First, a re-analysis and update of a previously published study was conducted. Additional searches were conducted of the PubMed and Cochrane Central Register of Controlled Trials databases on 2 June 2023. After the selection process, the pooled odds ratio (OR) for cardiac adverse events (AEs) was calculated. Second, the FAERS database was examined for 10 frequently co-administered anticancer agents. The reporting odds ratio (ROR) was calculated based on the occurrence of cardiac AEs depending on the co-administration of PARP inhibitors. Results: Seven studies were selected for the meta-analysis. Although not statistically significant, co-administration of PARP inhibitors with chemotherapy/bevacizumab decreased the risk of cardiac AEs (Peto OR = 0.61; p = 0.36), while co-administration with antiandrogens increased the risk of cardiac AEs (Peto OR = 1.83; p = 0.18). A total of 19 cases of cardiac AEs were reported with co-administration of PARP inhibitors in the FAERS database. Co-administration of PARP inhibitors with chemotherapy/bevacizumab significantly decreased the risk of cardiac AEs (ROR = 0.352; 95% confidence interval (CI), 0.194–0.637). On the other hand, for antiandrogens co-administered with PARP inhibitors, the ROR was 3.496 (95% CI, 1.539–7.942). The ROR for immune checkpoint inhibitors co-administered with PARP inhibitors was 0.606 (95% CI, 0.151–2.432), indicating a non-significant effect on cardiac AEs. Conclusion: This study reports that PARP inhibitors show cardioprotective effects when used with conventional anticancer agents. [ABSTRACT FROM AUTHOR]

Cardiac adverse events (AEs) are common in tyrosine kinase inhibitors(TKIs). This study explored the cardiac AEs of TKIs through the Food and Drug Administration's Adverse Event Reporting System (FAERS). Disproportionality analysis and Bayesian analysis were utilized for data mining of the suspected cardiac AEs of TKIs, based on FAERS data from January 2004 to December 2021. A total of 4708 cardiac AEs reports of sorafenib, regorafenib, lenvatinib, and cabozantinib were identified. Hypertension accounts for the most reported cardiac AE. Lenvatinib appears to induce cardiac failure with the highest signals strength [ROR = 7.7 (3.46,17.17)]. Acute myocardial infarction was detected in lenvatinib [ROR = 7.91 (5.64,11.09)] and sorafenib [ROR = 2.22 (1.74, 2.84)]. Acute coronary syndrome was detected in lenvatinib [ROR = 11.57 (6.84, 19.58)] and sorafenib [ROR = 2.81 (1.87,4.24)]. Atrial fibrillation was detected in sorafenib [ROR = 1.82 (1.55,2.14)] and regorafenib [ROR = 1.36 (1.03,1.81)]. Meanwhile, aortic dissections were detected in sorafenib [ROR = 5.08 (3.31,7.8)] and regorafenib [ROR = 3.39 (1.52,7.56)]. Most patients developed hypertension and cardiac failure within 30 days of initiating TKI treatments. Patients taking lenvatinib had an increased incidence of developing acute coronary syndrome after 180 days of treatment. Analysis of FAERS data provides a precise profile on the characteristics of cardiac AEs associated with different TKI regimens. Distinct monitoring and appropriate management are needed in the care of TKI recipients. [ABSTRACT FROM AUTHOR]

Lung cancer is the second most common cancer worldwide and the leading cause of cancer-related death. While survival rates have improved with advancements in cancer therapeutics, additional health challenges have surfaced. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in patients with lung cancer. CVD and lung cancer share many risk factors, such as smoking, hypertension, diabetes, advanced age, and obesity. Optimal management of this patient population requires a full understanding of the potential cardiovascular (CV) complications of lung cancer treatment. This review outlines the common shared risk factors, the spectrum of cardiotoxicities associated with lung cancer therapeutics, and prevention and management of short- and long-term CVD in patients with non-small cell (NSCLC) and small cell (SCLC) lung cancer. Due to the medical complexity of these patients, multidisciplinary collaborative care among oncologists, cardiologists, primary care physicians, and other providers is essential. [ABSTRACT FROM AUTHOR]

Introduction: Reduced left ventricular ejection fraction (LVEF) is a well-known predictor of adverse events after cardiac surgery. We aimed to assess the outcomes in patients with low LVEF undergoing coronary artery bypass graft. Methods: In this retrospective cohort, we included all patients with left ventricular ejection fraction ≤ 40 who underwent coronary artery bypass grafting between March 2007 and March 2016 (with a median follow-up of nine years) at Tehran Heart Center. Demographics and clinical characteristics were extracted from the data registry. Akaike information criterion (AIC) was used. The univariate Cox regression was performed. We investigated the predictors of mortality and major adverse cardiac and cerebrovascular events (MACCE) using Cox multivariable regression. Results: In total, 5,532 cases (79 % male) with a mean age of 65.58 were included in the study. The nine-year overall survival was calculated at 68 %, and more than half of the patients had MACCE (55 %). In adjusted multivariable Cox regression analysis, moderate to severe mitral valve regurgitation, glomerular filtration rate ≤ 60, mild right ventricular dysfunction, and valvular heart disease independently predicted higher mortality. The abovementioned predictors and peripheral vascular disease significantly increased MACCE. Conclusion: Our study indicates the clinical significance of mitral regurgitation, valvular heart disease, and renal function in patients with low ejection fraction treated by coronary artery bypass grafting surgery. Identifying predictors of adverse events can help with clinical decision-making and risk stratification, ultimately improving patient outcomes.

Lung cancer is the second most common cancer worldwide and the leading cause of cancer-related death. While survival rates have improved with advancements in cancer therapeutics, additional health challenges have surfaced. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in patients with lung cancer. CVD and lung cancer share many risk factors, such as smoking, hypertension, diabetes, advanced age, and obesity. Optimal management of this patient population requires a full understanding of the potential cardiovascular (CV) complications of lung cancer treatment. This review outlines the common shared risk factors, the spectrum of cardiotoxicities associated with lung cancer therapeutics, and prevention and management of short- and long-term CVD in patients with non-small cell (NSCLC) and small cell (SCLC) lung cancer. Due to the medical complexity of these patients, multidisciplinary collaborative care among oncologists, cardiologists, primary care physicians, and other providers is essential.

Immune checkpoint inhibitors (ICI) are approved as first-line therapy for multiple cancers and significantly improve patients' prognoses. However, they can also cause immune-related adverse events, among which cardiac adverse events are rare but highly lethal. Therefore, it is important to understand the spectrum of cardiac manifestations, because early detection and treatment are crucial to reduce the mortality. While myocarditis is the most common cardiac adverse event, other manifestations include takotsubo and dilated cardiomyopathy, pericarditis, pericardial effusion, cardiac tamponade, arrhythmia, giant cell arteritis, and atherosclerosis. Incidence ranges from 3.1% with monotherapy to 5.8% with combination therapy. Mortality reaches up to 50% in myocarditis and 26% in arrhythmia. Risk factors include older age, male gender, black race, and cardiovascular disease, but combination therapy is the most established predictor of cardiac adverse events. This article aims to present the spectrum of ICI cardiac adverse events and epidemiological data regarding those therapy complications. [ABSTRACT FROM AUTHOR]

Objective: Quetiapine, an atypical second‐generation antipsychotic drug, is approved for treatment of schizophrenia, bipolar disorder, and depression. Due to the limitations of clinical trials, the association between quetiapine and rare cardiac adverse events (AEs) is still unclear. This study is to evaluate quetiapine‐associated cardiac AEs through data mining of FDA Adverse Event Reporting System (FAERS). Methods: Reporting odds ratio (ROR) was used to quantify the signals of quetiapine‐related cardiac AEs from the first quarter (Q1) of 2018–2022 Q1. Serious and nonserious cases were compared, and signals were prioritized using a rating scale. Results: A total of 1004 cases of quetiapine‐associated cardiac AEs were identified, with 31 signals being detected, among which 13 AEs were identified as new and unexpected signals. Besides, nine and 22 cardiac AEs were identified as moderate and weak clinical priority. The median TTO for moderate and weak clinical priority signals were 0 and 4 days, respectively. All of the cardiac AEs had early failure type characteristics, suggesting that most of the patients developed cardiac AEs in a few days after quetiapine treatment, and that the risk of cardiac AEs occurrence would be gradually decreased over time. Conclusion: Our study provided valuable evidence for health‐care professionals to mitigate the risk of quetiapine‐associated cardiac AEs based on an extensive analysis of a real‐world, large‐sample FAERS database, and prioritize cardiac AE signals. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy of ponatinib was demonstrated in patients resistant or intolerant to prior BCR-ABL tyrosine kinase inhibitors. However, cardiac adverse events (CAEs) have become a concern as a serious side effect of ponatinib administration. No reports have described the incidence of CAEs associated with ponatinib in Japanese patients. Thus, this study aimed to determine the risk of ponatinib-induced CAEs, time to onset, and post hoc outcomes using the Japanese Adverse Drug Event Report database. Methods: We analyzed data for the period between April 2004 and March 2021. Data on CAEs were extracted, and relative risk of AEs was estimated using the reporting odds ratio. Results: We analyzed 1,772,494 reports and identified 1,152 reports of AEs caused by ponatinib. Of these, 163 CAEs were reportedly associated with ponatinib. Signals were detected for thirteen CAEs: hypertension, cardiac failure, acute cardiac failure, atrial fibrillation, increased blood pressure, coronary artery stenosis, myocardial infarction, angina pectoris, pulmonary hypertension, prolonged QT on electrocardiography, cardiomyopathy, cardiac dysfunction, and acute myocardial infarction. Among these, hypertension was the most frequently reported AE (27.6%). A histogram of times to onset showed occurrence from 4.5 to 150.5 days. Discussion/Conclusion: Hypertension, cardiac failure, coronary artery stenosis, and myocardial infarction could potentially result in serious outcomes and some cases occurred earlier or even more than 1 year after starting administration. Patients should be monitored for signs of the onset of these AEs not only at the start of ponatinib administration but also over the longer term. [ABSTRACT FROM AUTHOR]

Background: Proteasome inhibitors (PIs) are standard treatments for multiple myeloma (MM). The risk of cardiac adverse events (CAEs) with PIs has been documented with bortezomib and carfilzomib; however, only a few studies have been reported on ixazomib. Furthermore, the effects of concomitant medications including dexamethasone and lenalidomide remain unclear. Objectives: This study aimed to determine the safety signals of adverse events related to CAEs, the effect of concomitant medications, the time to the occurrence of CAEs, and the incidence of fatal clinical outcomes after the occurrence of CAEs for three PIs using the US Pharmacovigilance database. Methods: We examined 1,567,240 cases of 231 drugs registered as anticancer drugs in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from January 1997 to March 2021. We compared the odds of developing CAEs between patients who received PIs and those who received non-PI anticancer drugs. Results: Bortezomib treatment resulted in significantly higher reporting odds ratios (RORs) for cardiac failure, cardiac failure congestive, and atrial fibrillation. Carfilzomib treatment resulted in significantly higher RORs for cardiac failure, congestive cardiac failure, atrial fibrillation, and QT prolonged. However, no adverse event CAE signals were observed with ixazomib treatment. A signal was detected for the safety of cardiac failure with bortezomib or carfilzomib, regardless of the presence or absence of concomitant medications. Safety signals for cardiac failure congestive with bortezomib and for cardiac failure congestive, atrial fibrillation, and QT prolonged with carfilzomib were observed only with dexamethasone combination therapy. Co-administration of lenalidomide and its derivatives did not affect the safety of bortezomib and carfilzomib. Conclusion: We identified CAE safety signals for bortezomib and carfilzomib exposure when compared with 231 other anticancer agents. The safety signal for developing cardiac failure for both the drugs did not differ between patients with and without concomitantly administered medications. [ABSTRACT FROM AUTHOR]

Treatment of malignant lymphoma has for years been represented by many cardiotoxic agents especially anthracyclines, cyclophosphamide, and thoracic irradiation. Although they are in clinical practice for decades, the precise mechanism of cardiotoxicity and effective prevention is still part of the research. At this article we discuss most routinely used anti-cancer drugs in chemotherapeutic regiments for malignant lymphoma with the focus on novel insight on molecular mechanisms of cardiotoxicity. Understanding toxicity at molecular levels may unveil possible targets of cardioprotective supportive therapy or optimization of current therapeutic protocols. Additionally, we review novel specific targeted therapy and its challenges in cardio-oncology.

• The performance of existing prediction models for immune-related cardiac adverse reactions is relatively low, and there is no graded prediction model for these reactions. • This study presents a novel two-stage ensemble machine-learning strategy for predicting and grading immune-related cardiac adverse reactions. The proposed method demonstrates good performance. • The two-stage ensemble learning model for predicting and grading immune-related cardiac adverse reactions holds potential clinical application value in preventing and treating patients. Immune-related cardiac adverse events (ircAEs) caused by programmed cell death protein-1 (PD-1) and programmed death-ligand-1 (PD-L1) inhibitors can lead to fulminant and even fatal consequences. This study aims to develop a prediction and grading model for ircAEs, enabling graded management of patients. This study utilized medical record systems from two medical institutions to develop a prediction and grading model for ircAEs using ten machine learning algorithms and two variable screening methods. The model was developed based on a two-stage ensemble learning framework. In the first stage, the ircAEs and non-ircAEs cases were classified. In the second stage, ircAEs cases were grouped into grades 1–2 and 3–5. The experiments were evaluated using five-fold cross-validation. The model's prediction performance was assessed using accuracy, precision, recall, F1 value, Brier score, receiver operating characteristic curve area (AUC), and area under the precision-recall curve (AUPR). 615 patients were included in the study. 147 experienced ircAEs, and 44 experienced grade 3–5 ircAEs. The soft voting classifier trained using the variables screened by feature importance ranking performed better than other classifiers in both stages. The average AUC for the first and second stages is 84.18 % and 85.13 %, respectively. In the first stage, the three most important variables are N-terminal B-type natriuretic peptide (NT-proBNP), interleukin-2 (IL-2), and C-reactive protein (CRP). In the second stage, the patient's age, NT-proBNP, and left ventricular ejection fraction (LVEF) are the three most critical variables. The prediction and grading model of ircAEs based on two-stage ensemble learning established in this study has good performance and potential clinical application. [ABSTRACT FROM AUTHOR]

To determine whether concomitant use of ceftriaxone and oral or intravenous lansoprazole increases the risk of ventricular arrhythmia and cardiac arrest in the real-world setting in Japan. The data analyzed were obtained from the JMDC hospital-based administrative claims database for the period April 2014 to August 2022. Patients who received a proton pump inhibitor (PPI) while receiving ceftriaxone or sulbactam/ampicillin were identified. The frequency of ventricular arrhythmia and cardiac arrest was analyzed according to whether oral or intravenous PPI was concomitant with ceftriaxone or sulbactam/ampicillin. Estimates of the incidence of ventricular arrhythmia and cardiac arrest were then compared among the groups, using the Fine–Gray competing risk regression model. The results showed that the risk of ventricular arrhythmia and cardiac arrest was significantly higher with concomitant ceftriaxone and oral lansoprazole (hazard ratio 2.92, 95% confidence interval 1.99–4.29, P < 0.01) or intravenous lansoprazole (hazard ratio 4.57, 95% confidence interval 1.24–16.80, P = 0.02) than with concomitant sulbactam/ampicillin and oral or intravenous lansoprazole. Oral and intravenous lansoprazole may increase the risk of ventricular arrhythmia and cardiac arrest in patients who are receiving ceftriaxone. • Ceftriaxone and PPIs are often unintentionally co-administered in clinical practice. • Concomitant ceftriaxone and lansoprazole may lead to cardiac events. • The risk of cardiac events was much higher with oral and intravenous lansoprazole. • The selection of PPI or antibiotics could affect outcomes. [ABSTRACT FROM AUTHOR]

Background: Past studies have shown the sex-related difference in the efficacy of cardiac resynchronization therapy (CRT). However, the data for cardiac sarcoidosis (CS) are limited.Objective: The purpose of this study was to assess the sex-related prognostic differences in CS patients with CRT.Methods: This multicenter CS survey included 430 patients (295 females) who met the diagnostic criteria for CS. Patients were divided into those treated with primary CRT or upgraded CRT from the pacemaker (CRT group; n = 73) and others (control group; n = 357). Sex differences in the incidence of all-cause death, heart failure (HF) death including heart transplantation, ventricular arrhythmia events (VAEs) (sudden death, appropriate device therapy), cardiac adverse events (CAEs) (HF death, VAEs), changes in serum brain natriuretic peptide (BNP) levels, and left ventricular ejection fraction (LVEF) over the follow-up period were analyzed.Results: During median follow-up of 5.2 years, males, but not females, in the CRT group had significantly worse all-cause mortality than patients in the control group (P <.001). In the CRT group, there was no significant sex-related difference in the incidence of HF death; however, females had significantly better VAE- and CAE-free survival than males (P = .033 and P = .008, respectively). Multivariate analysis of the CRT group showed that female sex (hazard ratio 0.37; 95% confidence interval 0.15-0.89; P = .02 and P = .6) independently predicted freedom from CAEs. During follow-up, BNP levels were significantly improved in all groups. LVEF was maintained in females with CRT.Conclusions: In CS patients with CRT, HF death-free survival was similar between sexes. However, females exhibited better VAE- and CAE-free survival than males. [ABSTRACT FROM AUTHOR]

Background: Despite harboring a high burden of cancer patients who are at high risk of potential drug-drug interactions (pDDIs), there is scarcity of published information about pDDIs in cancer patients from Pakistan. Objective: To evaluate frequency, pattern, mechanism and factors associated with pDDIs in cancer patients treated at a tertiary care hospital in Pakistan. Methods: In this cross-sectional analytical study, a total of 253 eligible ambulatory cancer patients treated at Center for Nuclear Medicine and Radiotherapy Hospital Quetta were evaluated for pDDIs using IBM Micromedex® Drug Interactions. SPSS (version 26) was used for conducting multivariate analysis to find factors associated with the presence pDDIs. A p-value <0.05 was considered statistically significant. Results: A total of 141/253 (55.7%) patients were exposed to at-least one pDDI. A total of 251 pDDIs were noted with a median of one pDDI/per patient (interquartile range:1–2) Majority interactions were of major severity (72.9%), pharmacodynamic (49.8%) and had fair documentation level (64.1%). Anti-cancer drugs were involved in 73.0% pDDIs with doxorubicin as the most commonly involved (40.0%) anti-cancer followed by cyclophosphamide (27.6%) and cisplatin (13.5%). Potential cardiac adverse events made the bulk (33.8%) of predicted events. Receiving >2 anti-cancer (OR = 5.19, p-value = 0.001) and >6 ancillary drugs (OR = 4.16, p-value = 0.033) emerged as the risk factors of pDDIs. Conclusions: The prevalence of pDDIs was within the range reported in published literature. Solid medication review, availability of DDI detecting tools and clinical pharmacist, and paying special attention to the high-risk patients may reduce the frequency of pDDIs at the study site. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to assess osimertinib-associated cardiac adverse events (AEs) in a real-world setting, using a retrospective single-center cohort study in Japan. Background: Cases of osimertinib-associated cardiac AEs have been reported but remain poorly understood. Methods: A total of 123 cases of advanced non–small cell lung cancer (NSCLC) with confirmed EGFR mutations who received osimertinib monotherapy from 2014 to 2019 at the Osaka International Cancer Institute (Osaka, Japan) were evaluated. Cardiac AEs were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Changes in left ventricular ejection fraction (LVEF) and rates of cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a ≥10 % absolute decline in LVEF from baseline to a value of

BackgroundSeveral anti-cancer drugs have been linked to new onset atrial fibrillation (AF) but the true association of these drugs with AF is unknown. The FDA Adverse Event Reporting System (FAERS), a publicly available pharmacovigilance mechanism provided by the FDA, collects adverse event reports from the United States and other countries, thus providing real-world data.ObjectivesTo identify anti-cancer drugs associated with AF using the FAERS database.MethodsThe FAERS database was searched for all drugs reporting AF as an adverse event (AE). The top 30 anti-cancer drugs reporting AF cases were shortlisted and analyzed. Proportional reporting ratio (PRR) was used to measure disproportionality in reporting of adverse events for these drugs.ResultsWhen analyzed for AF as a percentage of all reported AE for a particular drug, Ibrutinib had the highest percentage (5.3%) followed distantly by venetoclax (1.6%), bortezomib (1.6%), carfilzomib (1.5%), and nilotinib (1.4%). The percentage of cardiac AE attributable to AF was also highest for ibrutinib (41.5%), followed by venetoclax (28.4%), pomalidomide (23.9%), bortezomib (18.2%), and lenalidomide (18.2%). Drugs with the highest PRR for AF included ibrutinib (5.96, 95% CI= 5.70–6.23), bortezomib (1.65, 95% CI = 1.52–1.79), venetoclax (1.65, 95% CI = 1.46–1.85), carfilzomib (1.53, 95% CI = 1.33–1.77), and nilotinib (1.46, 95% CI = 1.31–1.63).ConclusionsWhile newer anti-cancer drugs have improved the prognosis in cancer patients, it is important to identify any arrhythmias they may cause early on to prevent increased morbidity and mortality. Prospective studies are needed to better understand the true incidence of new onset AF associated with anti-cancer drugs.

IntroductionOver one-half of patients with multiple myeloma (MM) die of heart failure or arrhythmia. Left ventricular ejection fraction (LVEF) is used to describe left ventricular systolic function. However, depressed LVEF means advanced stage of left ventricular dysfunction in patients with MM. Left ventricular pressure-strain-derived myocardial work (LVMW) is a novel and noninvasive method for evaluating LV function related to LV dynamic pressure load. MW is assessed by LV MW index (LVMWI), constructive work, wasted work, and LV MW efficiency (LVMWE). In this study, we aimed to investigate the value of LVMW in cardiac function assessment and clinical prognosis of MM patients with preserved LVEF.MethodsA total of 72 subjects, including 40 untreated MM patients with preserved EF (including the thick wall and normal wall groups) and 32 non-MM patients, were enrolled in this study. Laboratory data and clinical history of all the patients were collected. All the patients underwent comprehensive echocardiographic examinations and then LVMWI and LVMWE were calculated. Moreover, cardiac adverse events (CAEs) were observed in MM patients treated with bortezomib-based therapy after 6 months and the prognostic value of MW was assessed.Results(1) LV myocardial global work index (GWI), myocardial global work efficiency (GWE), and global longitudinal strain (GLS) were lower in the thick wall group of patients with MM compared with the normal wall group and controls. Cardiac segmental analysis of LVMWI in patients with MM showed an apical sparing pattern; (2) The area under the curve (AUC) of GWE for judging the disease severity based on the Revised International Staging System (R-ISS) was 0.835 (95% CI: 0.684–0.933, p < 0.05); (3) GWE, LgdFLC, and arrhythmia were independent risk factors of CAEs. The AUC of GWE for predicting CAEs in MM patients treated with bortezomib-based therapy for 6 months follow-up was 0.896 (95% CI: 0.758–0.970, p < 0.05).ConclusionMM Patients with preserved EF had subclinical LV systolic dysfunction, which was worse in the thick wall group. LVMWI was presented as “apical sparing” in patients with MM. A lower LVGWE may have a predictive value for CAEs in patients with MM after 6 months of follow-up.

Background: Carfilzomib is a proteasome inhibitor widely used for the treatment of multiple myeloma. However, cardiac adverse events (CAEs) are a serious side effect of carfilzomib administration. Observational studies based on systematic reviews and real-world data have revealed that the risk of CAEs tends to be high. However, there have been no reports on the incidence of CAEs associated with carfilzomib in Japanese patients. Furthermore, there have been no reports on the timing and post-event outcomes of CAEs. Objectives: The purpose of this study was to identify the trends in carfilzomib-associated adverse events, the time to onset of CAEs, and the clinical outcomes after the occurrence of CAEs using the Japanese Adverse Drug Event Report (JADER) database. Method: We analyzed data from the JADER database, which contains reports of spontaneous adverse events submitted to the Pharmaceutical and Medical Device Agency, between April 2004 and December 2020. The relative risk of adverse events was estimated using the reporting odds ratio. The time to onset and post-event outcomes were evaluated for adverse cardiotoxic events with >10 reports. Results: The reporting rate was significantly higher for all 6 detected CAEs. A time-to-onset histogram of the 6 CAEs showed that they all occurred early after carfilzomib administration. The median time of onset of heart failure, congestive heart failure, and acute heart failure was approximately 2 weeks after treatment. The adverse events with the largest proportion of fatal clinical outcomes were acute heart failure (26%) and heart failure (9.5%). Conclusions: This study suggests that the early signs and symptoms of potential fatal heart failure should be monitored during carfilzomib treatment. [ABSTRACT FROM AUTHOR]

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Evaluating cardiovascular safety of sphingosine 1-phosphate (S1P) receptor modulators is warranted due to S1P receptor expression on cardiomyocytes and vascular endothelial cells. This analysis reports the cardiovascular safety of ozanimod, an S1P receptor modulator, in patients with moderately to severely active ulcerative colitis from the phase 3 True North (TN) and open-label extension (OLE). All patients who received ozanimod in TN (n = 796) and all eligible TN patients who entered the OLE (n = 823) were included. Cardiovascular-related adverse events were evaluated in patients with up to 146 weeks of ozanimod exposure (2219 patient-years), which included 52 weeks during TN. On TN day 1, first-dose ozanimod resulted in a 0.2 beats per minute mean decrease in heart rate from pretreatment to hour 6; 2 patients experienced bradycardia, which resolved without treatment modification. Mean systolic and diastolic blood pressure increases of 5.1 and 2.2 mm Hg, respectively, were observed at TN week 52. No second-degree Mobitz type II atrioventricular block events were reported; 1 third-degree atrioventricular block unrelated to ozanimod occurred in the OLE. Cardiac and vascular treatment-emergent adverse events were infrequent (3.8% [31 of 823] and 8.5% [70 of 823]); no ozanimod-related cardiovascular deaths occurred. The incidences of deep-vein thrombosis (0.2%; 2 of 823), pulmonary embolism (0.2%; 2 of 823), and ischemic stroke (0.4%; 3 of 823) in the OLE were low. No new cardiovascular safety signals were identified, consistent with findings from previous ozanimod studies. There were few major adverse cardiovascular events or thromboembolic events, which were unrelated or unlikely related to ozanimod. Ozanimod has a well-tolerated cardiovascular safety profile when prescribed in accordance with the label. Clinical trial registry website and trial numbers: ClinicalTrials.gov numbers: NCT02435992 and NCT02531126. [Display omitted] [ABSTRACT FROM AUTHOR]

We assessed the prognostic meaning of very early (

Objective To the investigate the safety and efficacy of reverse use tirofiban and contrast agent through thrombus suction catheter after occlusion artery route in hyperthrombotic load patients with acute myocardial infarction. Methods From July 2018 to October 2019, 376 acute STEMI patients treated by emergency percutaus coronary intervention were admitted to the hospital successively. According to the different treatment methods，the 376 acute STEMI patients were divided into the study group (n = 54) and the control group (n = 322). The effects of two different routes of administration on postoperative myocardial perfusion (TIMI flow grades) and the incidence of severe hemorrhage，stroke and serious cardiac adverse events during hospitalization were compared. Results The preoperative thrombotic load of the study group was significantly higher than that of the control group (3.23±0.95 vs 2.14±0.66，P < 0.05). There was no significant difference in the incidence of intraoperative complications (P > 0.05)，and there was no significant difference in the postoperative rate of TIMI 3 between the two groups （95.3% vs 96.3，P > 0.05). There was no significant infference to the incidence of severe hemorrhage，stroke during PCI and serious cardiac adverse events during the hospitalization between the two groups（P > 0.05). Conclusion With the use of tirofiban and contrast agent through thrombus suction catheter after the occlude artery route，it can effectively improve the myocardial perfusion and reduce the perioperative risk of acute STEMI patients with hyperthrombotic load and it is worthy of further study. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical characteristics of ST segment elevation in elderly patients with acute myocarditis and provide reference for clinical diagnosis and treatment. Methods A retrospective analysis was performed on 87 elderly patients with acute myocarditis treated in our hospital. Patients with ST segment elevation were included in group A,while patients with non-ST segment elevation were included in group B. The clinical characteristics of ST segment elevation,including treatment,outcome,laboratory and auxiliary examinations were analyzed. The incidence of cardiac events such as cardiogenic shock,ventricular fibrillation and death were counted. Results The rate of ventilator application in group A was significantly higher than that in group B(P <0. 05). The incidence of temporary pacemaker,CRRT,IABP and ECMO treatment in group A were slightly higher than that in group B,and there was no statistical difference(all P > 0. 05). The levels of myocardial injury markers such as CK peak value,CKMB peak value,and Tn I peak value in group A were significantly higher than that in group B(all P < 0. 05). Cardiac adverse events in group A occurred. The rate was 20. 8%,which was significantly higher than 2. 5% in group B,and the difference was statistically significant(P < 0. 05). Conclusion ST-segment elevation in elderly patients with acute myocarditis is characterized by acute onset,severe illness,and rapid progress,and the risk of cardiac adverse events such as ventricular fibrillation is greater. Therefore,clinicians should attach great importance to ST-segment elevation in elderly patients with acute myocarditis and provide timely targeted treatment. [ABSTRACT FROM AUTHOR]

Purpose: Cardiac dysfunction risk associated with intravenous trastuzumab (H IV) treatment may differ in real-world practice versus randomized trials. We investigated cardiac events in patients with HER2-positive early breast cancer (EBC) treated with H IV as adjuvant therapy in routine practice.Methods: The observational study of cardiac events in patients with HER2-positive EBC treated with Herceptin (OHERA; NCT01152606) enrolled patients with stage I-IIIb disease eligible for H IV in the adjuvant setting per the European Summary of Product Characteristics (SmPC). Primary outcomes were symptomatic congestive heart failure incidence (CHF; New York Heart Association class II-IV) and cardiac death. Patient visits/assessments were per local practice.Results: 3733 Patients received ≥ 1 H IV dose per local practice; 88.9% received H IV for > 300 days (median follow-up: ~ 5 years). Prior to disease recurrence (if any), symptomatic CHF occurred in 106 patients (2.8%); 6 (0.2%) cardiac deaths occurred (5 in patients with cardiac disease history). Median time to symptomatic CHF onset was 5.7 months (95% CI 5.3-6.5); 77/106 (72.6%) patients with symptomatic CHF achieved resolution. CHF incidence was higher in patients ≥ 65 years, and those with pre-existing cardiac conditions, hypertension, or left ventricular ejection fraction ≤ 55% at baseline.Conclusions: OHERA is the largest prospective observational study to investigate the cardiac safety of H IV as adjuvant EBC therapy in a real-world setting. Symptomatic CHF and cardiac event incidences were consistent with randomized trials in this setting and baseline risk factors identified in the H IV European SmPC. [ABSTRACT FROM AUTHOR]

• In a population-based study, clozapine is associated with cardiac adverse events. • Clozapine is associated with a tripled risk of perimyocarditis. • Clozapine is associated with heart failure within three years. • Olanzapine and/or quetiapine not associated with studied cardiac adverse events. The risk of cardiac adverse events following clozapine use is debated and is unknown for the chemically related and widely used antipsychotics olanzapine and quetiapine. National Swedish registers were used to identify all patients 16–75 years old with antipsychotic dispensations between 2005 and 2018. The short-term outcome was a diagnosis of perimyocarditis (pericarditis and/or myocarditis) within two months of first dispensation, and the long-term outcome was heart failure (including cardiomyopathy) within three years. Cox regressions with time varying exposure were used to estimate hazard rates (HR) and their 95% confidence intervals (CI). A total of 201,045 individuals were included in the cohort. The risk of developing perimyocarditis during clozapine treatment tripled compared to no antipsychotic treatment (HR 3.4, CI 1.6–7.3), although the absolute rate remained comparably low. The long-term risk of heart failure during clozapine treatment was also elevated (HR 1.3, CI 1.1–1.7). Treatment with either or both olanzapine or quetiapine was not associated with an increased relative risk of perimyocarditis, or heart failure compared to no antipsychotic treatment. Clozapine use is therefore associated with a substantially elevated short-term risk of perimyocarditis and an increased risk of heart failure within three years. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective study.Objective: To report the incremental hospital resources consumed with treating adverse events experienced by Medicare beneficiaries undergoing a two or three vertebrae level cervical spinal fusion.Summary Of Background Data: Hospitals are increasingly at financial risk for patients experiencing adverse events due "pay for performance." Little is known about incremental resources consumed when treating patients who experienced an adverse event after cervical spinal fusions.Methods: Fiscal years 2013 and 2014 Medicare Provider Analysis and Review file was used to identify 86,265 beneficiaries who underwent 2 or 3 vertebrae level cervical spinal fusion. International Classification of Diseases 9th Clinical Modification diagnostic and procedure codes were used to identify 10 adverse events. This study estimated both the observed and risk-adjusted incremental hospital resources consumed (cost [2014 US $] and length-of-stay) in treating beneficiaries experiencing each adverse event.Results: Overall, 6.2% of beneficiaries undergoing cervical spinal fusion experienced at least one of the study's adverse events. Beneficiaries experiencing any complication consumed significantly more hospital resources (incremental cost of $28,638) and had longer length-of-stay (incremental stays of 9.1 days). After adjusting for patient demographics and comorbid conditions, incremental cost of treating adverse events ranged from $42,358 (infection) to $10,100 (dural tear).Conclusion: Adverse events frequently occur and add substantially to the hospital costs of patients undergoing cervical spinal fusion. Shared decision-making instruments should clearly provide these risk estimates to the patient before surgical consideration. Investment in activities that have been shown to reduce specific adverse events is warranted, and this study may allow health systems to prioritize performance improvement areas.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Depressive symptoms are common among post myocardial infarction (MI) patients and may cause negative impacts on cardiac prognosis. The studies supported that depression is an independent risk factor for poor prognosis in post MI patients. The various articles about the plausible mechanisms between post-MI depression and adverse outcomes were found and studied. The plausible pathways involved in this link were described.The study of the results of these articles showed that the different behavioral, neuroendocrinological, and immunological, arrhythmias mechanisms and increased thrombosis are likely the pathways by which depression may cause increased risk for adverse outcomes and mortality. It seems that particularly increased thrombosis and arrhythmias may cause increased risk for mortality in depressed patients with heart disease. This review showed important role of psychological and biological pathways for increasing risk of mortality and adverse consequences among patients with post MI depression.

Simple Summary: With nonspecific activation of the immune system, immune checkpoint inhibitors (ICIs) can lead to off-target immune-related adverse events (irAEs) to every organ system. Immune-related cardiotoxicity is rare but often fatal. Large population-based studies examining different ICI-associated cardiotoxicity across cancer types and agents are limited. Using data from a large network of health care organizations, this study aims to: (1) provide an estimate of the incidence of ICI-associated cardiotoxicity, (2) to determine patient and clinical characteristics associated with the risk of developing ICI-associated cardiotoxicity, and (3) to assess the overall survival of patients experiencing ICI-associated cardiotoxicity compared to patients who did not develop cardiotoxicity after ICI use. Large population-based studies examining differences in ICI-associated cardiotoxicity across cancer types and agents are limited. Data of 5518 cancer patients who received at least one cycle of ICIs were extracted from a large network of health care organizations. ICI treatment groups were classified by the first ICI agent(s) (ipilimumab, nivolumab, pembrolizumab, cemiplimab, avelumab, atezolizumab, or durvalumab) or its class (PD-1 inhibitors, PD-L1 inhibitors, CTLA4-inhibitors, or their combination (ipilimumab + nivolumab)). Time to first cardiac adverse event (CAE) (arrhythmia, acute myocardial infarction, myocarditis, cardiomyopathy, or pericarditis) developed within one year after ICI initiation was analyzed using a competing-risks regression model adjusting for ICI treatment groups, patient demographic and clinical characteristics, and cancer sites. By month 12, 12.5% developed cardiotoxicity. The most common cardiotoxicity was arrhythmia (9.3%) and 2.1% developed myocarditis. After adjusting for patient characteristics and cancer sites, patients who initiated on monotherapy with ipilimumab (adjusted Hazard Ratio (aHR): 2.00; 95% CI: 1.49–2.70; p < 0.001) or pembrolizumab (aHR: 1.21; 95% CI: 1.01–1.46; p = 0.040) had a higher risk of developing CAEs within one year compared to nivolumab monotherapy. Ipilimumab and pembrolizumab use may increase the risk of cardiotoxicity compared to other agents. Avelumab also estimated a highly elevated risk (aHR: 1.92; 95% CI: 0.85–4.34; p = 0.117) compared to nivolumab and other PD-L1 agents, although the estimate did not reach statistical significance, warranting future studies. [ABSTRACT FROM AUTHOR]