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Background: Immune checkpoint inhibitor (ICI)-induced myocarditis is a life-threatening adverse drug reaction. Abatacept (a CTLA-4-immunoglobulin fusion protein) has been proposed as a compassionate-use treatment for ICI myocarditis (in combination with corticosteroids and ruxolitinib) but no clinical trial has yet been performed. The abatacept dose can be adjusted using real-time assessment of its target, the CD86 receptor occupancy on circulating monocytes (CD86RO)., Methods: The ACHLYS trial is an ongoing dose-finding, Phase II, randomized, double-blind trial in which three different abatacept doses are being tested, aiming to reach CD86RO≥80% after the first dose and sustainably during the first 3 weeks of ICI myocarditis treatment (primary outcome). Adult patients with cancer presenting severe or corticosteroid-resistant ICI myocarditis have been included. ICI are withheld after inclusion and for the study duration. Abatacept is administered by intravenous injection on Days 1, 5±2 and 14±2 at 10, 20 or 25mg/kg depending on the randomization arm (n=7 per arm) with concomitant ruxolitinib and corticosteroids. After evaluation of the primary outcome on Day 21, complementary injections of abatacept (for≤3 months) and a ruxolitinib/corticosteroids weaning strategy are standardized depending on criteria evaluating resolution of ICI myocarditis severity (troponin T level and clinical assessment). Secondary objectives compare immunological, myocardial and muscular proxies of treatment response between randomization arms, and cancer progression-free and overall survivals up to 1 year., Conclusion: The ACHLYS trial will define the most appropriate starting dose of abatacept to treat life-threatening ICI myocarditis, in combination with ruxolitinib and corticosteroids., Clinicaltrials: GOV: NCT05195645., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Immune-checkpoint inhibitor-associated myocarditis (ICI-myocarditis) often presents with arrhythmias, but the prognostic value of early electrocardiogram findings is unclear. Although ICI-myocarditis and acute cellular rejection (ACR) following cardiac transplantation use similar treatment strategies, differences in arrhythmia burden are unknown., Objective: To evaluate the association of electrocardiogram findings in ICI-myocarditis with myocarditis-related mortality and life-threatening arrhythmia., Methods: A total of 125 cases of ICI-myocarditis were identified retrospectively across 49 hospitals worldwide; 50 cases of grade 2R or 3R ACR were included as comparators. Two cardiologists blinded to clinical data interpreted electrocardiograms. Associations between electrocardiogram features, myocarditis-related mortality and the composite of myocarditis-related mortality and life-threatening arrhythmias were examined. Adjusted hazard ratios (aHRs) were calculated., Results: The cohort had 78 (62.4%) men; median (interquartile range) age was 67 (58-76) years. At 30 days, myocarditis-related mortality was 20/124 (16.1%), and 28/124 (22.6%) met the composite endpoint. Patients who developed complete heart block (aHR by subdistribution hazards model [aHR(sh)] 3.29, 95% confidence interval [CI] 1.24-8.68; P=0.02) or life-threatening cardiac arrhythmias (aHR(sh) 6.82, 95% CI: 2.87-16.21; P<0.001) had a higher risk of myocarditis-related mortality. Pathological Q waves (aHR(sh) 3.40, 95% CI: 1.38-8.33; P=0.008), low QRS voltage (aHR(sh) 6.05, 95% CI: 2.10-17.39; P<0.001) and Sokolow-Lyon index (aHR(sh)/mV 0.54, 95% CI: 0.30-0.97; P=0.04) on admission electrocardiogram were also associated with increased risk of myocarditis-related mortality. These associations were mirrored in the composite outcome analysis. Compared with ACR, ICI-myocarditis had a higher incidence of life-threatening cardiac arrhythmias (15/125 [12.0%] vs 1/50 [2%]; P=0.04) and third-degree heart block (19/125 [15.2%] vs 0/50 [0%]; P=0.004)., Conclusions: Electrocardiograms in ICI-myocarditis with ventricular tachycardias, heart block, low-voltage and pathological Q waves were associated with myocarditis-related mortality and life-threating arrhythmia. Arrhythmia burden in ICI-myocarditis exceeds that of ACR after heart transplant., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

An increasing number of studies of left ventricular myocardial deformation have been published. Layer-specific strain using speckle tracking echocardiography to evaluate left ventricular function is not recommended in clinical practice. However, evaluation of myocardial mechanics using longitudinal and circumferential layer-specific strain enables the detection of subclinical impairment of myocardial deformation in various diseases. Unfortunately, normal values for longitudinal and circumferential strain have not been clearly defined. In normal subjects, layer-specific strain decreases from the endocardial to the epicardial layer, and from the apex to the base of the left ventricle. Although various studies have tried to define normal values for each layer in healthy subjects, studies with more subjects are needed. This tool has good reproducibility in terms of intraobserver and interobserver variability, but, as with monolayer strain, it has poor intervendor variability. Efforts that aim for standardization between vendors will be required before widespread use of this technique can be advocated., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) can be used to detect the presence of left atrial thrombus and left atrial spontaneous echocardiographic contrast (LASEC)., Aim: To evaluate the prognostic value of TTE and TOE in predicting stroke and all-cause death at 5-year follow-up in patients with non-valvular atrial fibrillation (NVAF)., Methods: This study included patients hospitalised with electrocardiography-diagnosed NVAF in Saint-Antoine University Hospital, Paris, between July 1998 and December 2011, who underwent TTE and TOE evaluation within 24hours of admission. Cox proportional-hazards models were used to identify predictors of the composite outcome (stroke or all-cause death)., Results: During 5 years of follow-up, stroke/death occurred in 185/903 patients (20.5%). By multivariable analysis, independent predictors of stroke/death were CHA 2 DS 2 -VASc score (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.25-1.47; P<0.001), left atrial area>20 cm 2 (HR 1.59, 95% CI 1.08-2.35; P=0.018), moderate LASEC (HR 1.72, 95% CI 1.13-2.62; P=0.012) and severe LASEC (HR 2.04, 95% CI 1.16-3.58; P=0.013). Independent protective predictors were dyslipidaemia (HR 0.60, 95% CI 0.43-0.83; P=0.002) and discharge prescription of anti-arrhythmics (HR 0.59, 95% CI 0.40-0.87; P=0.008). Adding LASEC to the CHA 2 DS 2 -VASc score modestly improved predictive accuracy and risk classification, with a C index of 0.71 vs. 0.69 (P=0.004)., Conclusions: In this retrospective monocentric study, the presence of moderate/severe LASEC was an independent predictor of stroke/death at 5-year follow-up in patients with NVAF. The inclusion of LASEC in stroke risk scores could modestly improve risk stratification., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Cancer and acute myocardial infarction (AMI) have important prognostic consequences. Treatment of some cancers may affect coronary artery disease, myocardial function and/or AMI management. Whether the early and long-term mortality of patients with AMI differ according to their history of cancer remains questionable., Aims: To determine in-hospital outcomes and 5-year mortality following AMI according to patient history of cancer., Methods: The FAST-MI registry is a nationwide French survey collecting data on characteristics, management and outcomes of 3670 consecutive patients admitted for AMI during October 2005., Results: Overall, 246/3664 patients (6.7%) admitted for an AMI (47.6% with ST-segment elevation myocardial infarction [STEMI]; 52.4% with non-STEMI [NSTEMI]) had a history of cancer. In-hospital mortality was not significantly different for patients with versus without a history of cancer, overall (adjusted odds ratio [OR]: 1.15, 95% confidence interval [CI]: 0.68-1.94; P=0.61) and in patients with STEMI (adjusted OR: 1.37, 95% CI: 0.69-2.71; P=0.37) or NSTEMI (adjusted OR: 0.97, 95% CI: 0.41-2.28; P=0.95). All-cause mortality at 5 years was higher among patients with a history of cancer (adjusted hazard ratio [HR]: 1.36, 95% CI: 1.08-1.69; P=0.008), whereas 5-year cardiovascular mortality did not differ (adjusted HR: 1.17, 95% CI: 0.89-1.53; P=0.25), regardless of whether the patients had STEMI or NSTEMI. Similar results were found in populations matched on a propensity score including baseline characteristics and early management., Conclusion: A history of cancer, per se, does not appear to be a risk factor for increased in-hospital mortality or long-term cardiovascular mortality in patients admitted for AMI., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: Atrial remodelling has been poorly investigated in atrial fibrillation (AF), and few studies have focused on biatrial remodelling., Aim: To evaluate right atrial (RA) and left atrial (LA) remodelling in AF using global atrial reservoir strain and three-dimensional (3D) atrial volumes, according to rhythm outcome at mid-term follow-up., Methods: Two-dimensional and 3D transthoracic echocardiography (TTE) were performed within 24hours after admission (M0) and at 6-month follow-up (M6) in patients admitted for AF. RA and LA variables were assessed: body surface area-indexed maximum 3D volume (Max 3D RA Vol i , Max 3D LA Vol i ) and minimum 3D volume (Min 3D RA Vol i , Min 3D LA Vol i ); atrial emptying fraction (3D RAEF, 3D LAEF); atrial expansion index (3D RAEI, 3D LAEI); and global RA and LA reservoir strain., Results: Forty-eight consecutive patients were included prospectively. Three groups were identified depending on rhythm at M0 and M6: AF at M0 and sinus rhythm (SR) at M6 (AF-SR) in 25 (52.1%) patients; AF at M0 and AF at M6 (AF-AF) in 13 (27.1%) patients; and SR at M0 (spontaneous cardioversion before first TTE) and SR at M6 (SR-SR) in 10 (20.8%) patients. Between M0 and M6 in the AF-SR group, we found: significant decreases in Max 3D RA Vol i (P=0.020), Min 3D RA Vol i (P=0.0008), Max 3D LA Vol i (P=0.001) and Min 3D LA Vol i (P=0.0021); significant increases in 3D RAEF (P=0.037) and 3D RAEI (P=0.034); no significant differences in 3D LAEF and 3D LAEI; and significant increases in global RA and LA reservoir strain (both P<0.0001). There was no significant difference with regard to these variables in the AF-AF and SR-SR groups., Conclusion: 3D volume and strain analyses were useful in the evaluation of RA and LA reverse remodelling in successfully cardioverted patients with AF., (Copyright © 2019. Published by Elsevier Masson SAS.)

Background: Global longitudinal strain (GLS) has several sources of variation. Strain multilayer tracking is a new tool that has not yet been validated in clinical practice., Aim: The purpose of this study was to investigate intervendor variability when measuring multilayer strain in patients receiving chemotherapy for cancer., Methods: Patients receiving chemotherapy for cancer, who were referred for echocardiography, were included prospectively. First, the same operator performed two-dimensional echocardiography on each patient using the Vivid E9™ (General Electric, Fairfield, CT, USA) and the ACUSON SC2000™ (Siemens, Munich, Germany) ultrasound systems. Second, we assessed myocardial deformation by using their respective speckle-tracking software. Third, we compared absolute values of GLS for the two vendors in each apical view (four-, three- and two-chamber) and for each layer (endocardial, mid-myocardial and epicardial)., Results: Eighty patients with cancer were included prospectively between February and June 2015. For a given vendor, GLS values decreased from the endocardial layer to the epicardial layer. For a given view, GLS values obtained with the ACUSON SC2000 platform were systematically lower than those obtained with the Vivid E9 platform (P<0.0001). We observed a significant difference between the two platforms, irrespective of the layer, interlayer gradient or chamber view considered (P<0.0001)., Conclusions: There was poor agreement for layer-specific strain evaluation between the Vivid E9 and ACUSON SC2000 platforms, using their dedicated software for strain multilayer assessment. These results suggest that, in clinical practice, the same system and software from the same vendor should be used for longitudinal follow-up., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)