Multidisciplinary recommendations for essential baseline functional and laboratory tests to facilitate early diagnosis and management of immune-related adverse events among cancer patients.

Immune checkpoint inhibitors (ICIs) have fundamentally changed the treatment landscape of various cancers. While ICI treatments result in improved survival, quality of life and are cost-effective, the majority of patients experience at least one immune-related adverse event (irAE). Many of these side effects cause little discomfort or are asymptomatic; however, irAEs can affect any organ and are potentially life-threatening. Consequently, early diagnosis and appropriate treatment of irAEs are critical for optimizing long-term outcomes and quality of life in affected patients. Some irAEs are diagnosed according to typical symptoms, others by abnormal findings from diagnostic tests. While there are various guidelines addressing the management of irAEs, recommendations for the early recognition of irAEs as well as the optimal extent and frequency of laboratory tests are mostly lacking. In clinical practice, blood sampling is usually performed before each ICI administration (i.e., every 2-3 weeks), often for several months, representing a burden for patients as well as health care systems. In this report, we propose essential laboratory and functional tests to improve the early detection and management of irAEs and in cancer patients treated with ICIs. These multidisciplinary expert recommendations regarding essential laboratory and functional tests can be used to identify possible irAEs at an early time point, initiate appropriate interventions to improve patient outcomes, and reduce the burden of blood sampling during ICI treatment.

Additional value of cardiac magnetic resonance feature tracking parameters for the evaluation of the arrhythmic risk in patients with mitral valve prolapse.

OBJECTIVES: The identification of patients with mitral valve prolapse (MVP) presenting high arrhythmic risk remains challenging. Cardiovascular Magnetic Resonance (CMR) feature tracking (FT) may improve risk stratification. We analyzed the role of CMR-FT parameters in relation to the incidence of complex ventricular arrhythmias (cVA) in patients with MVP and mitral annular disjunction (MAD). METHODS: 42 patients with MVP and MAD who underwent 1.5 T CMR were classified as MAD-cVA (n = 23, 55%) in case of cVA diagnosed on a 24-h Holter monitoring and as MAD-noVA in the absence of cVA (n = 19, 45%). MAD length, late gadolinium enhancement (LGE), basal segments myocardial extracellular volume (ECV) and CMR-FT were assessed. RESULTS: LGE was more frequent in the MAD-cVA group in comparison with the MAD-noVA group (78% vs 42%, p = 0.002) while no difference was observed in terms of basal ECV. Global longitudinal strain (GLS) was reduced in MAD-cVA compared to MAD-noVA (- 18.2% ± 4.6% vs - 25.1% ± 3.1%, p = 0.004) as well as global circumferential strain (GCS) at the mid-ventricular level (- 17.5% ± 4.7% vs - 21.6% ± 3.1%, p = 0.041). Univariate analysis identified as predictors of the incidence of cVA: GCS, circumferential strain (CS) in the basal and mid infero-lateral wall, GLS, regional longitudinal strain (LS) in the basal and mid-ventricular inferolateral wall. Reduced GLS [Odd ratio (OR):1.56 (confidence interval (CI) 95%: 1.45-2.47; p < 0.001)] and regional LS in the basal inferolateral wall [OR: 1.62 (CI 95%: 1.22-2.13; p < 0.001)] remained independent prognostic factors in multivariate analysis. CONCLUSION: In patients with MVP and MAD, CMR-FT parameters are correlated with the incidence of cVA and may be of interest in arrhythmic risk stratification.

Feasibility of adenosine stress cardiovascular magnetic resonance perfusion imaging in patients with MR-conditional transvenous permanent pacemakers and defibrillators.

BACKGROUND: The use of stress perfusion-cardiovascular magnetic resonance (CMR) imaging remains limited in patients with implantable devices. The primary goal of the study was to assess the safety, image quality, and the diagnostic value of stress perfusion-CMR in patients with MR-conditional transvenous permanent pacemakers (PPM) or implantable cardioverter-defibrillators (ICD). METHODS: Consecutive patients with a transvenous PPM or ICD referred for adenosine stress-CMR were enrolled in this single-center longitudinal study. The CMR protocol was performed using a 1.5 T system according to current guidelines while all devices were put in MR-mode. Quality of cine, late-gadolinium-enhancement (LGE), and stress perfusion sequences were assessed. An ischemia burden of ≥ 1.5 segments was considered significant. We assessed the safety, image quality and the occurrence of interference of the magnetic field with the implantable device. In case of ischemia, we also assessed the correlation with the presence of significant coronary lesions on coronary angiography. RESULTS: Among 3743 perfusion-CMR examinations, 66 patients had implantable devices (1.7%). Image quality proved diagnostic in 98% of cases. No device damage or malfunction was reported immediately and at 1 year. Fifty patients were continuously paced during CMR. Heart rate and systolic blood pressure remained unchanged during adenosine stress, while diastolic blood pressure decreased (p = 0.007). Six patients (9%) had an ischemia-positive stress CMR and significant coronary stenoses were confirmed by coronary angiography in all cases. CONCLUSION: Stress perfusion-CMR is safe, allows reliable ischemia detection, and provides good diagnostic value.

Myocardial extracellular volume by T1 mapping: a new marker of arrhythmia in mitral valve prolapse.

OBJECTIVES: We aimed to evaluate the relationship between mitral annular disjunction (MAD) severity and myocardial interstitial fibrosis at the left ventricular (LV) base in patients with mitral valve prolapse (MVP), and to assess the association between severity of interstitial fibrosis and the occurrence of ventricular arrhythmic events. BACKGROUND: In MVP, MAD has been associated with myocardial replacement fibrosis and arrhythmia, but the importance of interstitial fibrosis remains unknown. METHODS: In this retrospective study, 30 patients with MVP and MAD (MVP-MAD) underwent cardiovascular magnetic resonance (CMR) with assessment of MAD length, late gadolinium enhancement (LGE), and basal segments myocardial extracellular volume (ECVsyn). The control group included 14 patients with mitral regurgitation (MR) but no MAD (MR-NoMAD) and 10 patients with normal CMR (NoMR-NoMAD). Fifteen MVP-MAD patients underwent 24 h-Holter monitoring. RESULTS: LGE was observed in 47% of MVP-MAD patients and was absent in all controls. ECVsyn was higher in MVP-MAD (30 ± 3% vs 24 ± 3% MR-NoMAD, p < 0.001 and vs 24 ± 2% NoMR-NoMAD, p < 0.001), even in MVP-MAD patients without LGE (29 ± 3% vs 24 ± 3%, p < 0.001 and vs 24 ± 2%, p < 0.001, respectively). MAD length correlated with ECVsyn (rho = 0.61, p < 0.001), but not with LGE extent. Four patients had history of out-of-hospital cardiac arrest; LGE and ECVsyn were equally performant to identify those high-risk patients, area under the receiver operating characteristic (ROC) curve 0.81 vs 0.83, p = 0.84). Among patients with Holter, 87% had complex ventricular arrhythmia. ECVsyn was above the cut-off value in all while only 53% had LGE. CONCLUSION: Increase in ECVsyn, a marker of interstitial fibrosis, occurs in MVP-MAD even in the absence of LGE, and was correlated with MAD length and increased risk of out-of-hospital cardiac arrest. ECV should be includedin the CMR examination of MVP patients in an effort to better assess fibrous remodelling as it may provide additional value beyond the assessment of LGE in the arrhythmic risk stratification.

[Cardiotoxicity of immune checkpoint inhibitors used in cancer treatment]. / Cardiotoxicité des inhibiteurs de points de contrôle immunitaire utilisés dans le traitement des cancers.

Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, by reshaping the prognosis of many cancers and are progressively becoming the standard of care. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), of which cardiovascular irAEs are particularly feared. ICI-induced myocarditis is often a diagnostic challenge because of the vast heterogeneity of clinical presentations, and it is associated with a high mortality rate of around 50%. The present article summarizes the cardiac manifestations, the diagnostic strategy and the therapeutic management of patients with ICI-induced myocarditis used in the treatment of cancer.

Les inhibiteurs de points de contrôle immunitaire (ICI), ou immune checkpoint inhibitors (ICI), ont révolutionné la prise en charge de nombreux cancers en améliorant significativement la survie des patients et en devenant progressivement la norme de soins. Cette efficacité a néanmoins pour prix un taux élevé d'effets indésirables immunomédiés avec un large spectre d'organes touchés. Les toxicités cardiaques, dominées par la myocardite induite par les ICI, sont particulièrement redoutées du fait des difficultés diagnostiques et du risque d'évolution rapidement défavorable associée à une mortalité élevée, de l'ordre de 50 %. Le présent article s'intéresse aux manifestations cardiaques, à la stratégie diagnostique ainsi qu'à la prise en charge des patients présentant une myocardite induite par les ICI utilisés dans le traitement du cancer.

Implementation of a large-scale simulation-based cardiovascular clinical examination course for undergraduate medical students - a pilot study.

BACKGROUND: We report the implementation of a large-scale simulation-based cardiovascular diagnostics course for undergraduate medical students. METHODS: A simulation-based course was integrated into the curriculum of second-year medical students (> 400 students/year). The first session aimed at teaching cardiac auscultation skills on mannequins and the second at teaching blood pressure measurement, peripheral arterial examination, and the clinical examination of heart failure in a technical skill-based manner and in a scenario. RESULTS: A total of 414 (99.8%) and 402 (98.5%) students, as well as 102 and 104 educators, participated during the 2016-2017 and 2017-2018 academic years across both types of sessions. The number of positive appreciations by students was high and improved from the first to the second year (session 1: 77% vs. 98%, session 2: 89% vs. 98%; p < 0.0001). Similar results were observed for educators (session 1: 84% vs. 98%, p = 0.007; session 2: 82% vs. 98%, p = 0.01). Feedbacks by students were positive regarding the usefulness of the course, fulfillment of pedagogical objectives, quality of the teaching method, time management, and educator-student interactivity. In contrast, 95% of students criticized the quality of the mannequins during the first year leading to the replacement of the simulation material the following year. Students most appreciated the auscultation workshop (25%), the practical aspect of the course (22%), and the availability of educators (21%). CONCLUSIONS: Despite the need to commit significant human and material resources, the implementation of this large-scale program involving > 400 students/year was feasible, and students and educators reacted favorably.

Hepatic T1 Mapping as a Novel Cardio-Hepatic Axis Imaging Biomarker Early after STEMI.

BACKGROUND: The hepatic response after ST-elevation myocardial infarction (STEMI) may be associated with mortality and morbidity. We aimed to assess the cardio-hepatic axis post-STEMI using cardiovascular magnetic resonance (CMR). METHODS: This prospective, observational, single-centre study included consecutive STEMI patients who underwent CMR after primary angioplasty from January 2015 to January 2019. Standard infarct characteristics were analysed, and hepatic T1 and hepatic extracellular volume (ECV) were assessed using pre- and post-contrast T1-mapping sequences. The primary endpoint was the relationship between native hepatic T1-values and ischemic right ventricular (RV) involvement, determined by RV ejection fraction (EF) dysfunction and/or the presence of RV acute myocardial infarction (AMI). The diagnostic performance of hepatic T1 values for detecting RV involvement was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Of 177 consecutive STEMI patients undergoing CMR, 142 were included. Patients with RV ischemic involvement, compared to those without, had significantly higher native hepatic T1 (p < 0.001) and hepatic ECV (p = 0.016). Hepatic T1 values demonstrated a good diagnostic performance in detecting RV involvement (AUC 0.826, p < 0.001) and correlated positively with NT-proBNP values (r = 0.754, p < 0.001). Patients with high hepatic T1 values (>605 ms) had significantly higher NT-proBNP levels (<0.001), larger RV end-diastolic volume (p < 0.001), lower RV-EF (p < 0.001), and a higher prevalence of RV AMI (p = 0.022) compared to those with hepatic T1 ≤ 605 ms, while left ventricular EF and infarct size were similar. Multivariable logistic regression analysis identified RV-EF (p = 0.010) and NT-proBNP values (p < 0.001) as independent predictors of increased hepatic T1 values. Patients with increased hepatic T1 values had a higher rate of re-hospitalization for heart failure at 17-month follow-up (12.1% vs 2.0%, p = 0.046). CONCLUSIONS: Hepatic T1 mapping has emerged as a possible novel imaging biomarker of the cardio-hepatic axis in STEMI, being associated with RV involvement and increased NT-proBNP values.

Acute Response of the Noninfarcted Myocardium and Surrounding Tissue Assessed by T2 Mapping After STEMI.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is associated with a systemic and local inflammatory response with edema. However, their role at the tissue level is poorly characterized. OBJECTIVES: This study aims to characterize T2 values of the noninfarcted myocardium (NIM) and surrounding tissue and to investigate prognostic relevance of higher NIM T2 values after STEMI. METHODS: A total of 171 consecutive patients with STEMI without prior cardiovascular events who underwent cardiac magnetic resonance after primary percutaneous coronary intervention were analyzed in terms of standard infarct characteristics. Edema of the NIM, liver, spleen, and pectoralis muscle was assessed based on T2 mapping. Follow-up was available for 130 patients. The primary endpoint was major adverse cardiac events (MACE), defined as cardiovascular death, myocardial infarction, unplanned coronary revascularization or rehospitalization for heart failure. The median time from primary percutaneous coronary intervention to cardiac magnetic resonance was 3 days (IQR: 2-5 days). RESULTS: Higher (above the median value of 45 ms) T2 values in the NIM area were associated with larger infarct size, microvascular obstruction, and left ventricular dysfunction and did not correlate with C-reactive protein, white blood cells, or T2 values of the pectoralis muscle, liver, and spleen. At a median follow-up of 17 months, patients with higher (>45 ms) NIM T2 values had increased risk of MACE (P < 0.001) compared with subjects with NIM T2 values ≤45 ms, mainly caused by a higher rate of myocardial reinfarction (26.3% vs 1.4%; P < 0.001). At multivariable analysis, higher NIM T2 values independently predicted MACE (HR: 2.824 [95% CI: 1.254-6.361]; P = 0.012). CONCLUSIONS: Higher NIM T2 values after STEMI are independently associated with worse cardiovascular outcomes, mainly because of higher risk of myocardial infarction.

Metaverse-based cardiac magnetic resonance imaging simulation application for overcoming claustrophobia: a preliminary feasibility trial.

Introduction: Cardiac magnetic resonance imaging (CMR) is vital, but claustrophobia affects 10% of patients. The metaverse, an immersive virtual and augmented reality environment, has healthcare potential. We present a metaverse-based CMR simulation for claustrophobic patients. Methods: Three cardiomyopathy patients, initially CMR-refusing due to claustrophobia, received training via a virtual reality headset in a metaverse-based virtual hospital. Training efficacy was assessed through questionnaires and anxiety scales. Results: The patients successfully completed metaverse-based training, adapting to the CMR simulation. On CMR day, all entered the machine without issues and with reduced anxiety. Patients found the training useful, suggesting platform familiarization. Discussion: Our study demonstrates the metaverse's potential in alleviating CMR-related claustrophobia. The immersive nature enhances patient preparation, although usability improvements are needed. Further research should compare this approach with alternatives.

Cardiac magnetic resonance imaging (CMR) is a vital tool for diagnosing heart problems, but some patients cannot undergo it due to claustrophobia. To address this, researchers are exploring new methods like hypnosis and simulations. One emerging technology, the metaverse, a 3D virtual reality (VR) environment, is being tested in healthcare. This study created a metaverse-based simulation to help claustrophobic patients prepare for CMR.Three patients with heart issues were given VR headsets to access a virtual hospital in the metaverse. Inside, they were trained for CMR step by step, experiencing the process and sounds realistically. Training was done 1 week, 3 days, and 1 day before the real CMR. Anxiety levels were measured.All patients completed the virtual training without issues. During the first simulations, some could not complete entering the virtual CMR machine due to anxiety. However, by the final simulation, all succeeded. On CMR day, all completed the scan without problems, and their anxiety levels decreased significantly from the initial training.Patients found the training helpful, but the platform's usability needed improvement. The study demonstrates that metaverse-based simulations can help patients overcome claustrophobia to successfully undergo CMR. This technology holds promise for simulating medical situations, easing patient fears, and improving preparation. However, further work is needed to make it user-friendly and accessible without assistance. This study encourages more research to assess the usefulness of the metaverse for broader patient groups, comparing it with other methods like hypnosis or sedation.

Cardiac magnetic resonance imaging-derived right ventricular volume and function, and association with outcomes in isolated tricuspid regurgitation.

BACKGROUND: In patients with significant tricuspid regurgitation, cardiac magnetic resonance imaging (CMR) is the preferred method for the evaluation of right ventricular function and volumes. However validated thresholds are lacking. AIM: The aim of this study was to evaluate CMR assessment of right ventricular volumes in patients with significant (moderate or severe) tricuspid regurgitation, and to define its association with outcomes. METHODS: The PRONOVAL study is a retrospective multicentre study using the clinical data warehouse of Greater Paris University Hospitals (AP-HP). Patients were screened for CMR in the PMSI (Programme de médicalisation des systèmes d'information). Hospitalization reports were analysed by natural language processing to include patients with tricuspid regurgitation. Exclusion criteria were left heart valvular disease, heart transplantation and cardiac amyloidosis. Primary outcome was a combined criterion of death or tricuspid surgery. RESULTS: Between September 2017 and September 2021, 151 patients with isolated tricuspid regurgitation were screened. Right ventricular function and volumes were available in 86 (57.0%) CMR reports (the complete CMR group). In the complete CMR group, tricuspid regurgitation was severe in 62 patients (72.1%). Median age was 67.0 years (interquartile range 58.0-75.8). Median right ventricular indexed end-diastolic volume was 98.0 mL/m2 (interquartile range 66.8-118.5). At 2-year follow-up, six patients (9.2%) had undergone tricuspid valve surgery, and 12 patients (18.5%) had died. Right ventricular indexed end-diastolic volume was associated with death or surgery at 2years, with an area under the receiver operating characteristic curve of 0.76 (95% confidence interval 0.75-0.77) for a threshold of 119mL/m2. CONCLUSION: Right ventricular indexed end-diastolic volume >119mL/m2 was found to be an independent indicator of death or surgery in patients with significant tricuspid regurgitation.

Extracorporeal membrane oxygenation (ECMO) during aplasia: A bridge towards myopericarditis recovery after autologous hematopoietic stem cell transplant for systemic sclerosis and recent Coronarovirus disease (COVID-19) vaccination.

Systemic sclerosis (SSc) is a rare autoimmune disease (AD), characterised by early diffuse vasculopathy, activation of the immune response and progressive skin and internal organ fibrosis. In severe progressive diffuse SSc (dSSc), autologous hematopoietic stem cell transplantation (aHSCT) improves survival, despite its own risk of complications and transplant related mortality (TRM). We present herein the case of a dSSc patient undergoing aHSCT with low dose cyclophosphamide conditioning and sudden acute myopericarditis and cardiogenic shock, four weeks after a second mRNA SARS-CoV-2 vaccine (Pfizer) injection. Four days of extracorporeal membrane oxygenation (ECMO) support during the aplasia period, allowed to observe full cardiac function recovery and progressive SSc rehabilitation with sustained disease response at 30 months follow-up. This report illustrates, for the first time to our knowledge, that ECMO can be indicated despite aplasia during aHSCT and successfully used as a bridge towards heart function recovery in highly selected and fragile AD patients. We review the factors that may contribute to endothelial and myocardial stunning and acute reversible cardiac failure in SSc and aggravate intrinsic endothelial injury during the aHSCT procedure. These classically include: cyclophosphamide drug toxicity, viral infections and autoimmune activation with disease flair per se. In the COVID-19 pandemic times, acute myocarditis due to recent viral infection or mRNA vaccine per se, must also be considered.

Outcomes and Safety of Transcaval Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-analysis.

BACKGROUND: The transcaval (TCv) vascular approach is increasingly used in transcatheter aortic valve replacement (TAVR) in patients unsuitable for the gold-standard transfemoral approach. We aimed to evaluate the efficacy, safety, and clinical outcomes associated with TCv-TAVR. METHODS: A systematic review and meta-analysis was conducted by searching PubMed/Medline, Embase, and the Cochrane Library for all articles assessing the TCv approach published through December 2023. Outcomes included 30-day and 1-year all-cause mortality (ACM), 30-day rehospitalisation, perioperative complications and postoperative complications at 30 days. The meta-analysis was registered on the PROSPERO database with the identifier CRD42024501921. RESULTS: A total of 8 studies with 467 patients were included. TCv-TAVR procedures achieved a success rate of 98.5%. TCv-TAVR was associated with a 30-day ACM rate of 6.1% (95% confidence interval [CI]: 3.9%-8.2%), a 1-year ACM rate of 14.9% (95% CI 2.3%-27.6%) and a 30-day rehospitalisation rate of 4.2% (95% CI -2.2% to 10.6%). Postoperative stroke or transient ischemic attack, major vascular complications, and major or life-threatening bleeding occurred in 3.3%, 8.7%, and 7.5% of cases, respectively. Cumulative meta-analyses showed a temporal trend of decreasing rates of vascular complications. CONCLUSIONS: The TCv approach in TAVR demonstrated a reassuring efficacy and safety profile, with mortality and postoperative complication rates similar to those reported for supra-aortic alternative TAVR access routes. The temporal decrease in vascular complications suggests potential improvements in procedural techniques and device technology. These findings further support the TCv approach as a viable option in patients ineligible for the transfemoral access. PROSPERO: CRD42024501921.

Predictors and Risk Score for Immune Checkpoint-Inhibitor-Associated Myocarditis Severity.

Background: Immune-checkpoint inhibitors (ICI) are associated with life-threatening myocarditis but milder presentations are increasingly recognized. The same autoimmune process that causes ICI-myocarditis can manifest concurrent generalized myositis, myasthenia-like syndrome, and respiratory muscle failure. Prognostic factors for this "cardiomyotoxicity" are lacking. Methods: A multicenter registry collected data retrospectively from 17 countries between 2014-2023. A multivariable cox regression model (hazard-ratio(HR), [95%confidence-interval]) was used to determine risk factors for the primary composite outcome: severe arrhythmia, heart failure, respiratory muscle failure, and/or cardiomyotoxicity-related death. Covariates included demographics, comorbidities, cardio-muscular symptoms, diagnostics, and treatments. Time-dependent covariates were used and missing data were imputed. A point-based prognostic risk score was derived and externally validated. Results: In 748 patients (67% male, age 23-94), 30-days incidence of the primary composite outcome, cardiomyotoxic death, and overall death were 33%, 13%, and 17% respectively. By multivariable analysis, the primary composite outcome was associated with active thymoma (HR=3.60[1.93-6.72]), presence of cardio-muscular symptoms (HR=2.60 [1.58-4.28]), low QRS-voltage on presenting electrocardiogram (HR for ≤0.5mV versus >1mV=2.08[1.31-3.30]), left ventricular ejection fraction (LVEF) <50% (HR=1.78[1.22-2.60]), and incremental troponin elevation (HR=1.86 [1.44-2.39], 2.99[1.91-4.65], 4.80[2.54-9.08], for 20, 200 and 2000-fold above upper reference limit, respectively). A prognostic risk score developed using these parameters showed good performance; 30-days primary outcome incidence increased gradually from 3.9%(risk-score=0) to 81.3%(risk-score≥4). This risk-score was externally validated in two independent French and US cohorts. This risk score was used prospectively in the external French cohort to identify low risk patients who were managed with no immunosuppression resulting in no cardio-myotoxic events. Conclusions: ICI-myocarditis can manifest with high morbidity and mortality. Myocarditis severity is associated with magnitude of troponin, thymoma, low-QRS voltage, depressed LVEF, and cardio-muscular symptoms. A risk-score incorporating these features performed well. Trial registration number: NCT04294771 and NCT05454527.