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Objective: To assess the link between systemic immune-inflammation index (SII) and risk of major adverse cardiovascular events (MACE), contrast-induced nephropathy (CIN), and overall mortality in patients with acute myocardial infarction (AMI). Patients and Methods: Electronic search of PubMed, EMBASE, Web of Science, and Scopus databases was done for observational studies with the data on the association of SII and outcomes, such as MACE, and CIN in adult (≥18 y) patients with AMI. A random-effects model was used, and the pooled effect sizes were expressed as relative risk (RR) with corresponding 95% confidence intervals (CI). Subgroup analysis was conducted on the basis of the type of AMI (ST elevation myocardial infarction and non-ST elevation myocardial infarction), sample size (≥500 and <500), and study design. GRADE assessment was used to evaluate the certainty of the evidence. Results: The analysis included 23 studies. Most studies were conducted in China (n = 13), followed by Turkey (n = 10). Majority of the studies (n = 20) had a retrospective cohort design. Patients with high SII had increased risk of MACE (RR 2.95, 95% CI: 1.25, 6.99; n = 5, I 2 = 97.5%), overall mortality (RR 2.59, 95% CI: 1.64, 4.07; n = 6, I 2 = 58.0%), and CIN (RR 4.58, 95% CI: 3.44, 6.10; n = 4, I 2 = 0.0%), compared with patients with lower SII. Egger's test detected publication bias for MACE (p = 0.047) and overall mortality (p = 0.012) but not for CIN. These associations remained valid in subgroup analysis. Conclusion: Findings suggest that higher SII in patients with AMI is associated with increased risks of MACE, CIN, and overall mortality. This underscores SII's potential as a prognostic marker in AMI.

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., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Cazzola et al.)

Background: 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., Methods: 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)., Results: 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., Conclusions: The prediction and grading model of ircAEs based on two-stage ensemble learning established in this study has good performance and potential clinical application., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

This case report describes a 27-year-old healthy female patient undergoing bilateral salpingectomy for sterilization who experienced sudden bradycardia following induction with propofol (2, 6 diisopropylphenol) and succinylcholine. Despite lacking prior cardiac issues, the patient's heart rate dropped precipitously, necessitating intervention with glycopyrrolate. This case report highlights the importance of premedication with anticholinergics to prevent bradycardia in similar scenarios, underscoring the need for vigilance and preparedness to manage adverse cardiac events during anesthesia induction, even in patients without evident risk factors., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Solanki et al.)

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. NCT04315948; EudraCT 2020-000936-23., Competing Interests: Potential conflicts of interest. D. C. reports an human immunodeficiency virus grant from Janssen and lecture fees from Pfizer, outside the submitted work. F. M. reports grants and consulting fees from Pharmatheus, grants from Sanofi, and consulting fees from Ipsen, outside the submitted work. M. H. reports grants from the Belgian Center for Knowledge, the Fonds Erasme-COVID-Université Libre de Bruxelles, and the EU-Horizon programme, for the submitted work; support for attending meetings from Pfizer, MSD and Gilead, Pharmamar; support for participation on an advisory board for therapeutics on COVID-19 (DisCoVeRy trial); support for leadership for the Belgian guidelines on therapeutics for COVID-19; acting as president for the Belgian Society of Clinical Microbiology and Infectious Diseases; and payment for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Pfizer, Gilead, GKS, INSMED, and Shionogi. J. P. reports lecture fees from Gilead and MSD; support for attending meetings from Gilead, Eumedica, and Merck Sharp & Dohme, outside the submitted work. C. B. reports participation on a DSMB for 4Living Biotech and consulting fees from Da Volterra and Mylan Pharmaceuticals, outside the submitted work. R. G. reports consulting fees from Celgene, Novartis, Roche, Bristol Myers Squibb, Takeda, AbbVie, AstraZeneca, Janssen, Merck Sharp & Dohme, Merck, Gilead, and Daiichi Sankvo; lecture fees from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Sandoz, AbbVie, Gilead, and Daiichi Sankvo; support for attending meetings from Roche, Amgen, Janssen, AstraZeneca, Novartis, Merck Sharp & Dohme, Celgene, Gilead, Bristol Myers Squibb, AbbVie, and Daiichi Sankvo; participation on a DSMB for Celgene, Novartis, Roche, Bristol Myers Squibb, Takeda, AbbVie, AstraZeneca, Janssen, Merck Sharp & Dohme, Merck, Gilead, and Daiichi Sankyo; research grants from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Sandoz, AbbVie, Gilead, and Daiichi Sankyo; and stock or stock options from Novo Nordisk, Lilly. J.-A. P. reports consulting fees from Pfizer, Merck Sharp & Dohme, Janssen-Cilag, and AOP Orphan Pharmaceuticals; lecture fees from Cepheid, Pfizer, and Gilead; and support for attending meetings from Pfizer and Gilead. C. A. reports lecture fees from Insmed, GSK, Moderna, AstraZeneca, and Chiesi; grants or contracts from FEDER funding; support for attending meetings from Home perf; a leadership or fiduciary role as president of the Scientific Council of the French Respiratory Society; and serving as a member of the French ANRS-MIE for COVID and member of the COVID Group of the French Public Health High Council. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: 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., Methods: 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., Results: 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., Conclusions: Oral and intravenous lansoprazole may increase the risk of ventricular arrhythmia and cardiac arrest in patients who are receiving ceftriaxone., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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., (© 2024. The Author(s).)

Background & Aims: 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)., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Background: 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)., Methods: 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., Results: 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., Conclusion: 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.

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 de Jesus, Chanda, Grabauskas, Kumar and Kim.)

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., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Rihackova, Rihacek, Vyskocilova Valik and Elbl.)

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., Competing Interests: Declaration of Competing Interest RB was supported by a Swedish Research Council Grant 2016–02,362. JS reports stock ownership in companies providing services to Itrim, Amgen, Janssen, Novo Nordisk, Pfizer, Takeda, AstraZeneca, and Vifor Pharma, outside the submitted work. JR, EC, LB, and ML are affiliated with/employed at the center for Pharmacoepidemiology, Karolinska Institutet, which receives grants from several entities (pharmaceutical companies, regulatory authorities, contract research organizations) for the performance of drug safety and drug utilization studies., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., (© 2023 S. Karger AG, Basel.)

Background: The increased frequency of liposuction has resulted in more complications being reported. Adding epinephrine to the wetting solution could induce some cardiac adverse effects, some of which may be fatal. For instance, magnesium sulfate (MgSO 4 ) is known for its cardioprotective effects., Objectives: This study aimed to evaluate the efficacy of intravenous (IV) versus wetting solution containing MgSO 4 in decreasing such cardiac adverse events during abdominal liposuction., Methods: This randomized controlled study included 129 adult cases undergoing abdominal liposuction under general anesthesia. The participants were divided into 3 groups: Group I (control group) was only subjected to the injection of the wetting fluid (1 mL 1/1000 epinephrine added to every 1000 mL of normal saline), group II was subjected to IV MgSO 4 (40 mg/kg over 1 minute) at the same time of installing the wetting solution, and group III was subjected to MgSO 4 (40 mg/kg) added to the wetting solution., Results: Intraoperative isoflurane consumption, intraoperative heart rate (HR), mean arterial pressure (MAP), and postoperative pain scores were significantly lower in the MgSO 4 groups (groups II and III) than group I. Cardiac adverse events (sinus tachycardia and premature ventricular contractions (PVCs)) were also significantly less frequent in groups II and III compared to group I., Conclusions: Adding MgSO 4 , either through IV or subcutaneous routes, is associated with lower intraoperative HR, MAP, and postoperative pain scores and a remarkable decrease in epinephrine-induced cardiac adverse events during liposuction., Competing Interests: Conflict of Interests: There is none to be declared., (Copyright © 2022, Author(s).)

Introduction: Fingolimod was the first oral disease-modifying treatment approved for relapsing-remitting multiple sclerosis (MS) that serves as a sphingosine-1-phosphate receptor (S1PR) agonist. The efficacy is primarily mediated by S1PR subtype 1 activation, leading to agonist-induced down-modulation of receptor expression and further functional antagonism, blocking the egression of auto-aggressive lymphocytes from the lymph nodes in the peripheral compartment. The role of S1P signaling in the regulation of other pathways in human organisms through different S1PR subtypes has received much attention due to its immune-modulatory function and its significance for the regeneration of the central nervous system. The more selective second-generation S1PR modulators have improved safety and tolerability profiles., Areas Covered: This review has been carried out based on current data on S1PR modulators, emphasizing the benefits of recent advances in this emergent class of immunomodulatory treatment for MS., Expert Opinion: Ongoing clinical research suggests that S1PR modulators represent an alternative to first-line therapies in selected cases of MS. A better understanding of the relevance of selective S1PR pathways and the ambition to optimize selective modulation has improved the safety and tolerability of S1PR modulators in MS therapy and opened new perspectives for the treatment of other diseases.

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., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Several 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., Objectives: To identify anti-cancer drugs associated with AF using the FAERS database., Methods: The 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., Results: When 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)., Conclusions: While 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ahmad, Thurlapati, Thotamgari, Grewal, Sheth, Gupta, Beedupalli and Dominic.)

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.

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.

Introduction: Over 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., Methods: A 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, Lg dFLC , 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)., Conclusion: MM 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zhang, Liu, Wang, Xiong, Tang, Li, Lu, Liang, Niu and Huang.)

We assessed the prognostic meaning of very early (<6 h) troponin increase after noncardiac surgery in a population of patients admitted to the recovery room, for whom troponin measurements were taken because of a suspected cardiac event. Among a total of 296 patients, abnormal troponin was found in 24 (8.1%). Ten patients in this group (41.7%) and 27 among those with normal troponin (9.9%) experienced cardiovascular death, myocardial infarction, or decompensated heart failure at one month (p < 0.0001). Troponin was independently associated with a two-fold risk of events (p < 0.0001). In these patients, very early troponin measurement in the recovery room may help to identify patients at risk of cardiovascular events., Competing Interests: Declaration of Competing Interest All authors have none to declare., (Copyright © 2020. Published by Elsevier B.V.)

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 <53%, were further assessed in 36 patients in whom serial measurements of LVEF were obtained before and during osimertinib treatment., Results: Severe cardiac AEs (CTCAE grade 3 or higher) occurred in 6 patients (4.9%) after osimertinib administration. These AEs included acute myocardial infarction (n = 1), heart failure with reduced LVEF (n = 3), and valvular heart disease (n = 2). Five of the 6 patients had a history of cardiovascular risk factors or disease. Myocardial biopsies in 2 of the patients showed cardiomyocyte hypertrophy and lipofuscin deposition. In 36 patients assessed with serial LVEF, LVEF declined from 69.4 ± 4.2% to 63.4 ± 10.5% with osimertinib therapy (p < 0.001). CTRCD occurred in 4 patients with a nadir LVEF of 40.3 ± 9.1% with osimertinib., Conclusions: In this retrospective cohort analysis, the incidence of cardiac AEs in patients treated with osimertinib was 4.9%. Additional prospective data collected from patients with NSCLC treated with osimertinib will be important in understanding the incidence, pathophysiology, and management of cardiac AEs with osimertinib., (© 2020 The Authors.)

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.

Introduction: 5-Hydroxytryptamine3-receptor antagonists (5-HT3-RA) are the most widely used antiemetics in oncology, and although tolerability is high, QTC prolongation has been observed in some patients., Areas Covered: The purpose of this article is to outline the risk of cardiac adverse events (AEs) from 5-HT3-RAs, with focus on the three most commonly used, ondansetron, granisetron and palonosetron., Expert Opinion: Most of the studies analyze electrocardiogram (ECG) changes after 5-HT3-RA administrations in healthy, young adults, or in noncancer patients to treat postoperative nausea and vomiting (PONV). Only a few studies have addressed ECG changes in cancer patients treated for chemotherapy-induced nausea and vomiting (CINV). Investigations in cancer patients are essential, because these patients are older and have a higher incidence of comorbidity, than those usually included in clinical trials. Furthermore, polypharmacy is frequent and drug-drug interactions between chemotherapy and other QTc-prolonging drugs may influence the pharmacokinetics and pharmacodynamics of the 5-HT3-RAs. During the next 10 - 15 years a huge increase in the number of cancer patients is expected, primarily in the group of 65-plus-year old. Therefore it will be crucial to address the incidence of cardiac AEs in cancer patients with known heart disease receiving chemotherapy and a 5-HT3 RA for the prophylaxis of CINV.

Lacosamide (LCM) is a novel antiepileptic drug (AED) approved by the FDA for adjunctive treatment of partial epilepsy with and without secondary generalization. Lacosamide dose-dependent dysrhythmias (PR-interval prolongation, AV block, and atrial fibrillation/flutter) have been reported. This case represents the first instance of LCM-induced atrial fibrillation following a low loading dose (200 mg). Risk factors for atrial fibrillation are addressed and discussed in the context of this case. Full cardiac history is recommended prior to patients being initiated on LCM. Cardiac monitoring may be required for at-risk patients on LCM. Clinicians need to be cognizant of this potential adverse effect.