Expert opinion on mexiletine treatment in adult patients with myotonic dystrophy.

In France, mexiletine - a class I antiarrhythmic drug - can be prescribed for the symptomatic treatment of myotonia of the skeletal muscles in adult patients with myotonic dystrophy under a compassionate use programme. Mexiletine is used according to its summary of product characteristics, which describes its use for myotonia treatment in adult patients with non-dystrophic myotonia, a different neuromuscular condition without cardiac involvement. A cardiac assessment is required prior to initiation and throughout treatment due to potential proarrhythmic effects. The presence of conduction system disease, the most common cardiac manifestation of myotonic dystrophy, mandates repeated cardiac evaluations in patients with this condition, and becomes even more important when they are given mexiletine. A group of experts, including three neurologists and five cardiologists from French neuromuscular reference centres, were involved in a task force to develop a treatment algorithm to guide mexiletine use in myotonic dystrophy. The recommendations are based on data from a literature review of the safety of mexiletine-treated patients with myotonic dystrophy, the compassionate use protocol for mexiletine and the personal clinical experience of the experts. The main conclusion of the expert group is that, although existing safety data in mexiletine-treated patients with myotonic dystrophy are reassuring, cardiac assessments should be reinforced in such patients compared with mexiletine-treated patients with non-dystrophic myotonia. This expert opinion to guide mexiletine treatment in patients with myotonic dystrophy should help to reduce the risk of severe adverse events and facilitate interactions between specialists involved in the routine care of patients with myotonic dystrophy.

Mass cytometry reveals atypical immune profile notably impaired maturation of memory CD4 T with Gb3-related CD27 expression in CD4 T cells in Fabry disease.

Fabry disease (FD) is an X-linked disease characterized by an accumulation of glycosphingolipids, notably of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lysoGb3) leading to renal failure, cardiomyopathy, and cerebral strokes. Inflammatory processes are involved in the pathophysiology. We investigated the immunological phenotype of peripheral blood mononuclear cells in Fabry patients depending on the clinical phenotype, treatment, Gb3, and lysoGb3 levels and the presence of anti-drug antibodies (ADA). Leucocytes from 41 male patients and 20 controls were analyzed with mass cytometry using both unsupervised and supervised algorithms. FD patients had an increased expression of CD27 and CD28 in memory CD45- and CD45 + CCR7-CD4 T cells (respectively p < 0.014 and p < 0.02). Percentage of CD45RA-CCR7-CD27 + CD28+ cells in CD4 T cells was correlated with plasma lysoGb3 (r = 0.60; p = 0.0036) and phenotype (p < 0.003). The correlation between Gb3 and CD27 in CD4 T cells almost reached significance (r = 0.33; p = 0.058). There was no immune profile associated with the presence of ADA. Treatment with agalsidase beta was associated with an increased proportion of Natural Killer cells. These findings provide valuable insights for understanding FD, linking Gb3 accumulation to inflammation, and proposing new prognostic biomarkers.

Revealing the true nature of a parachute mitral valve during an ultra-trail race.

Pre-participation screening and management of congenital cardiac valvulopathy in competitive athletes can be challenging, particularly within the context of ultra-endurance disciplines. A 55-year-old female athlete without a reported history of cardiac disease exhibited clinical signs of cardiogenic pulmonary edema during a 156 km ultra-trail race. The echocardiographic assessment revealed the presence of a parachute mitral valve, with no evidence of mitral stenosis or regurgitation at rest, but it demonstrated severe dynamic mitral stenosis during exercise. In competitive athletes, the detection of rare valvulopathy should prompt a comprehensive cardiac evaluation aimed at assessing the potential for dynamic valvular dysfunction.

External Validation of a Risk Score Model for Predicting Major Clinical Events in Adults After Atrial Switch.

BACKGROUND: A risk model has been proposed to provide a patient individualized estimation of risk for major clinical events (heart failure events, ventricular arrhythmia, all-cause mortality) in patients with transposition of the great arteries and atrial switch surgery. We aimed to externally validate the model. METHODS AND RESULTS: A retrospective, multicentric, longitudinal cohort of 417 patients with transposition of the great arteries (median age, 24 years at baseline [interquartile range, 18-30]; 63% men) independent of the model development and internal validation cohort was studied. The performance of the prediction model in predicting risk at 5 years was assessed, and additional predictors of major clinical events were evaluated separately in our cohort. Twenty-five patients (5.9%) met the major clinical events end point within 5 years. Model validation showed good discrimination between high and low 5-year risk patients (Harrell C index of 0.73 [95% CI, 0.65-0.81]) but tended to overestimate this risk (calibration slope of 0.20 [95% CI, 0.03-0.36]). In our population, the strongest independent predictors of major clinical events were a history of heart failure and at least mild impairment of the subpulmonary left ventricle function. CONCLUSIONS: We reported the first external validation of a major clinical events risk model in a large cohort of adults with transposition of the great arteries. The model allows for distinguishing patients at low risk from those at intermediate to high risk. Previous episode of heart failure and subpulmonary left ventricle dysfunction appear to be key markers in the prognosis of patients. Further optimizing risk models are needed to individualize risk predictions in patients with transposition of the great arteries.

Subcutaneous Implantable Cardioverter-Defibrillators in Patients With Congenital Heart Disease.

BACKGROUND: Very few data have been published on the use of subcutaneous implantable cardioverter-defibrillators (S-ICDs) in patients with congenital heart disease (CHD). OBJECTIVES: The aim of this study was to analyze outcomes associated with S-ICDs in patients with CHD. METHODS: This nationwide French cohort including all patients with an S-ICD was initiated in 2020 by the French Institute of Health and Medical Research. Characteristics at implantation and outcomes were analyzed in patients with CHD. RESULTS: From October 12, 2012, to December 31, 2019, among 4,924 patients receiving an S-ICD implant in 150 centers, 101 (2.1%) had CHD. Tetralogy of Fallot, univentricular heart, and dextro-transposition of the great arteries represented almost one-half of the population. Patients with CHD were significantly younger (age 37.1 ± 15.4 years vs 50.1 ± 14.9 years; P < 0.001), more frequently female (37.6% vs 23.0%; P < 0.001), more likely to receive an S-ICD for secondary prevention (72.3% vs 35.9%; P < 0.001), and less likely to have severe systolic dysfunction of the systemic ventricle (28.1% vs 53.1%; P < 0.001). Over a mean follow-up period of 1.9 years, 16 (15.8%) patients with CHD received at least 1 appropriate shock, with all shocks successfully terminating the ventricular arrhythmia. The crude risk of appropriate S-ICD shock was twice as high in patients with CHD compared with non-CHD patients (annual incidences of 9.0% vs 4.4%; HR: 2.1; 95% CI: 1.3-3.4); however, this association was no longer significant after propensity matching (especially considering S-ICD indication, P = 0.12). The burden of all complications (HR: 1.2; 95% CI: 0.7-2.1; P = 0.4) and inappropriate shocks (HR: 0.9; 95% CI: 0.4-2.0; P = 0.9) was comparable in both groups. CONCLUSIONS: In this nationwide study, patients with CHD represented 2% of all S-ICD implantations. Our findings emphasize the effectiveness and safety of S-ICD in this particularly high-risk population. (S-ICD French Cohort Study [HONEST]; NCT05302115).

Abnormal left atrial compliance is associated with a history of life-threatening arrhythmia in corrected Tetralogy of Fallot.

Objectives: The objectives of this study were to examine left atrial (LA) function and compliance using two-dimensional (2D) strain analysis in adult patients with corrected Tetralogy of Fallot (c-ToF) and to investigate the relationships between LA function and patient characteristics, especially history of life-threatening arrhythmia (h-LTA). Methods: Fifty-one c-ToF patients (34 males; age, 39 ± 15 years; h-LTA, n = 13) were included in this retrospective monocenter study. In addition to a 2D standard echocardiography examination, 2D strain analysis was performed to assess left ventricular (LV) and LA functions, including peak-positive LA strain (LAS-reservoir function) and LA compliance [defined as the ratio LAS/(E/Ea)]. Results: Patients with h-LTA were older and exhibited a longer QRS duration. LV ejection fraction, LAS and LA compliance were significantly lower in the group of patients with h-LTA. Indexed LA and RA volumes, RV end-diastolic area was significantly higher and RV fractional area change significantly lower in the h-LTA group. LA compliance was the best echocardiographic predictor for h-LTA (AUC: 0.839; p < 0.001). Moderate inverted correlations were found between LA compliance and age and QRS duration. Among the echocardiographic parameters, LA compliance was moderately inversely correlated with RV end-diastolic area (r = -0.40, p = 0.01). Conclusion: We documented abnormal LAS and LA compliance values in adult c-ToF patients. Further study is needed to determine how best to incorporate LA strain, particularly LA compliance, into multiparametric predictive models for LTA in c-ToF patients.

Sport resumption and quality of life after surgical correction of anomalous origin of a coronary artery from the opposite sinus.

Objectives: We sought to assess the resumption of sport, exercise performances, and quality of life (QoL) in adults and children after surgical repair of anomalous coronary arteries originating from the opposite sinus (ACAOS). Materials and methods: Patients who underwent surgical repair for ACAOS between 2002 and 2022 were retrospectively identified. Information about sports activity and exercise performance based on metabolic equivalents of task (METs) calculated at the last exercise stress test, were collected. QoL was assessed using age-appropriate questionnaires (Paediatric QoL Inventory, cardiac module version 3.0 for patients <18 years; SF-36 QoL Inventory for adults). Patients' METS and patients' QoL-scores were compared to reference population using the Wilcoxon test. Results: 45 patients were enrolled (males 71%, adults 49%, anomalous right coronary 84%). Median age at surgery was 15 years; median follow-up after surgery was 2.3 years [4 months-12 years]. All post-operative exercise stress tests were normal, METs and VO2 max patients' values did not differ from healthy children or adults (Exercise intensity: 12.5 ± 4.7 vs. 13.4 ± 2 METS, p = 0.3; VO2 max: 43.6 ± 16.6 vs. 46.9 ± 7 ml/kg/min, p = 0.37). For adults, QoL-scores were similar between ACAOS patients and controls. For children, there was no significant difference between the study patients' scores and those of the reference population, except for physical appearance proxy-report (p = 0.02). Conclusion: In our study, the practice of sports, exercise stress testing and QoL were not adversely affected after ACAOS repair.

Abnormal Cellular Phenotypes Induced by Three TMPO/LAP2 Variants Identified in Men with Cardiomyopathies.

A single missense variant of the TMPO/LAP2α gene, encoding LAP2 proteins, has been associated with cardiomyopathy in two brothers. To further evaluate its role in cardiac muscle, we included TMPO in our cardiomyopathy diagnostic gene panel. A screening of ~5000 patients revealed three novel rare TMPO heterozygous variants in six males diagnosed with hypertrophic or dilated cardiomypathy. We identified in different cellular models that (1) the frameshift variant LAP2α p.(Gly395Glufs*11) induced haploinsufficiency, impeding cell proliferation and/or producing a truncated protein mislocalized in the cytoplasm; (2) the C-ter missense variant LAP2α p.(Ala240Thr) led to a reduced proximity events between LAP2α and the nucleosome binding protein HMGN5; and (3) the LEM-domain missense variant p.(Leu124Phe) decreased both associations of LAP2α/ß with the chromatin-associated protein BAF and inhibition of the E2F1 transcription factor activity which is known to be dependent on Rb, partner of LAP2α. Additionally, the LAP2α expression was lower in the left ventricles of male mice compared to females. In conclusion, our study reveals distinct altered properties of LAP2 induced by these TMPO/LAP2 variants, leading to altered cell proliferation, chromatin structure or gene expression-regulation pathways, and suggests a potential sex-dependent role of LAP2 in myocardial function and disease.

Rapid ventricular tachycardia in patients with tetralogy of Fallot and implantable cardioverter-defibrillator: Insights from the DAI-T4F nationwide registry.

BACKGROUND: In repaired tetralogy of Fallot (TOF), little is known about characteristics of patients with rapid ventricular tachycardia (VT). Also, whether patients with a first episode of nonrapid VT may subsequently develop rapid VT or ventricular fibrillation (VF) has not been addressed. OBJECTIVES: The objectives of this study were to compare patients with rapid VT/VF with those with nonrapid VT and to assess the evolution of VT cycle lengths (VTCLs) overtime. METHODS: Data were analyzed from a nationwide registry including all patients with TOF and implantable cardioverter-defibrillator (ICD) since 2000. Patients with ≥1 VT episode with VTCL ≤250 ms (240 beats/min) formed the rapid VT/VF group. RESULTS: Of 144 patients (mean age 42.0 ± 12.7 years; 104 [72%] men), 61 (42%) had at least 1 VT/VF episode, including 28 patients with rapid VT/VF (46%), during a median follow-up of 6.3 years (interquartile range 2.2-10.3 years). Compared with patients in the nonrapid VT group, those in the rapid VT/VF group were significantly younger at ICD implantation (35.2 ± 12.6 years vs 41.5 ± 11.2 years; P = .04), had more frequently a history of cardiac arrest (8 [29%] vs 2 [6%]; P = .02), less frequently a history of atrial arrhythmia (11 [42%] vs 22 [69%]; P = .004), and higher right ventricular ejection fraction (43.3% ± 10.3% vs 36.6% ± 11.2%; P = .04). The median VTCL of VT/VF episodes was 325 ms (interquartile range 235-429 ms). None of the patients with a first documented nonrapid VT episode had rapid VT/VF during follow-up. CONCLUSION: Patients with TOF and rapid VT/VF had distinct clinical characteristics. The relatively low variation of VTCL over time suggests a room for catheter ablation without a backup ICD in selected patients with well-tolerated VT.

Recurrent acute myocarditis: An under-recognized clinical entity associated with the later diagnosis of a genetic arrhythmogenic cardiomyopathy.

Background: Myocardial inflammation has been consistently associated with genetic arrhythmogenic cardiomyopathy (ACM) and it has been hypothesized that episodes mimicking acute myocarditis (AM) could represent early inflammatory phases of the disease. Objective: We evaluated the temporal association between recurrent acute myocarditis (RAM) episodes and the later diagnosis of a genetic ACM. Materials and methods: Between January 2012 and December 2021, patients with RAM and no previous cardiomyopathy were included (Recurrent Acute Myocarditis Registry, NCT04589156). A follow-up visit including clinical evaluation, resting and stress electrocardiogram, cardiac magnetic resonance imaging, and genetic testing was carried out. Endpoints of the study was the incidence of both ACM diagnosis criteria and ACM genetic mutation at the end of follow-up. Results: Twenty-one patients with RAM were included and follow-up was completed in 19/21 patients (90%). At the end of follow-up, 3.3 ± 2.9 years after the last AM episode, 14/21 (67%) patients with an ACM phenotype (biventricular: 10/14, 71%; left ventricular: 4/14, 29%) underwent genetic testing. A pathogenic or likely pathogenic mutation was found in 8/14 patients (57%), 5/8 in the Desmoplakin gene, 2/8 in the Plakophillin-2 gene, and 1/8 in the Titin gene. Family history of cardiomyopathy or early sudden cardiac death had a positive predictive value of 88% for the presence of an underlying genetic mutation in patients with RAM. Conclusion: RAM is a rare entity associated with the latter diagnosis of an ACM genetic mutation in more than a third of the cases. In those patients, RAM episodes represent early inflammatory phases of the disease. Including RAM episodes in ACM diagnosis criteria might allow early diagnosis and potential therapeutic interventions.

Preventive effect of beta-blockers in the development of aortic dilation in giant cell arteritis-related aortitis.

OBJECTIVES: To analyze whether beta-blockers (BBs), in addition to conventional care, can decrease the risk of aortic dilation in giant-cell arteritis (GCA)-related aortitis. METHODS: We conducted in a single medical center retrospective study including 65 consecutive patients with GCA-related aortitis who all underwent aortic morphology control during follow-up. The impact of previous cardiovascular (CV) risk factors and/or events on BB prescription and on the risk for new aortic dilation was analyzed using a weighted (8-point maximum) score between 0 (i.e., 0/8 CV risk factors and events) and 1 (i.e., 8/8). RESULTS: Among the 65 patients with GCA-related aortitis, 15 (23%) were taking BBs before GCA diagnosis and continued them thereafter. The vascular score was significantly higher in patients who received BBs (0.25 [0.125-0.625] vs. 0.125 [0-0.625] in patients without BBs, p < 0.0001). The median follow-up was 91 [25-163] months in GCA patients taking BBs and 61 [14-248] months in patients not taking BBs (p = 0.13). None of the patients taking BBs developed a new aortic dilation, whereas 15 (15/50; 30%) patients not taking BBs did (p = 0.01), as detected at a median time of 38 [6-120] months after the first imaging. Rates of other CV events during follow-up did not differ between the groups (p = 1). CONCLUSIONS: This study is the first to suggest that BBs in addition to conventional care in patients with GCA-related aortitis may help to prevent the risk of aortic dilation during follow-up. Larger-sized studies are required to confirm these results.

Sex Differences in Outcomes of Tetralogy of Fallot Patients With Implantable Cardioverter-Defibrillators.

BACKGROUND: Women with congenital heart disease at high risk for sudden cardiac death have been poorly studied thus far. OBJECTIVES: The aim of this study was to assess sex-related differences in patients with tetralogy of Fallot (TOF) and implantable cardioverter-defibrillators (ICDs). METHODS: Data were analyzed from the DAI-T4F (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator) cohort study, which has prospectively enrolled all patients with TOF with ICDs in France since 2010. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age 42.2 ± 13.3 years) were enrolled from 40 centers, including 49 women (29.7%). Among the 9,692 patients with TOF recorded in the national database, the proportion of women with ICDs was estimated to be 1.1% (95% CI: 0.8%-1.5%) vs 2.2% (95% CI: 1.8%-2.6%) in men (P < 0.001). The clinical profiles of patients at implantation, including the number of risk factors for ventricular arrhythmias, were similar between women and men. During a median follow-up period of 6.8 years (IQR: 2.5-11.4 years), 78 patients (47.3%) received at least 1 appropriate ICD therapy, without significant difference in annual incidences between women (12.1%) and men (9.9%) (HR: 1.22; 95% CI: 0.76-1.97; P = 0.40). The risk for overall ICD-related complications was similar in women and men (HR: 1.33; 95% CI: 0.81-2.19; P = 0.30), with 24 women (49.0%) experiencing at least 1 complication. CONCLUSIONS: Our findings suggest that women with TOF at high risk for sudden cardiac death have similar benefit/risk balance from ICD therapy compared with men. Whether ICD therapy is equally offered to at-risk women vs men warrants further evaluation in TOF as well as in other congenital heart disease populations. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574).

A new score for life-threatening ventricular arrhythmias and sudden cardiac death in adults with transposition of the great arteries and a systemic right ventricle.

AIMS: To investigate the incidence of major adverse ventricular arrhythmias and related events (MAREs) and to develop a stratification tool predicting MAREs in adults with a systemic right ventricle (sRV). METHODS AND RESULTS: In a multicentre approach, all adults (≥16 years old) with a sRV undergoing follow-up between 2000 and 2018 were identified. The incidence of MAREs, defined as sudden cardiac death, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator (ICD) therapy, was analysed. The association of MAREs with clinical, electrical, and echocardiographic parameters was evaluated. A total of 1184 patients (median age 27.1 years; interquartile range 19.9-34.9 years; 59% male; 70% with atrial switch repair for D-transposition of the great arteries) were included. The incidence of MAREs was 6.3 per 1000 patient-years. On multivariate analysis, age, history of heart failure, syncope, QRS duration, severe sRV dysfunction and at least moderate left ventricular outflow tract obstruction were retained in the final model with a C-index of 0.78 [95% confidence interval (CI) 0.72-0.83] and a calibration slope of 0.93 (95% CI 0.64-1.21). For every five ICDs implanted in patients with a 5-year MARE risk >10%, one patient may potentially be spared from a MARE. CONCLUSION: Sudden cardiac death remains a devastating cause of death in a contemporary adult cohort with a sRV. A prediction model based on clinical, electrocardiographic, and echocardiographic parameters was devised to estimate MARE risk and to identify high-risk patients who may benefit from primary prevention ICD implantation.

Usefulness of a New Transthoracic Echocardiography Score to Assess Right Ventricular Volumes in Patients with Repaired Tetralogy of Fallot.

Quantification of right ventricular (RV) volumes is essential in the follow-up of patients with a repaired tetralogy of Fallot (TOF). Cardiac magnetic resonance imaging (MRI) is the gold standard for RV assessment. However, given its cost and availability, the systematic use of MRI for serial longitudinal follow-up is limited. Herein, we examined the utility of a new two-dimensional (2D) transthoracic echocardiography (TTE) score (the RVDi score), which includes a compilation of 2D RV dimensions indexed to the body surface area, for predicting MRI-derived RV end-diastolic volume (RVEDV) in patients with a repaired TOF. Using our congenital heart clinic database, we retrospectively included 29 adult patients with a repaired TOF between February 2015 and July 2019. The 2D TTE RVDi score was compared with the MRI-derived RVEDV. Sensitivity and specificity values for predicting an RVEDVi > 150 ml/m2 were calculated. The TTE RVDi score was highly correlated (r = 0.944) with MRI RVEDVi. A cut-off RVDi score set at 120 mm/m2 predicted an RVEDVi > 150 ml/m2 with a sensitivity of 83% and specificity of 94%. Use of a simple echocardiographic score based on indexed RV dimensions from 2D standard TTE imaging may complement the assessment of RV volumes in TOF patients.

Hypertrophic cardiomyopathies requiring more monitoring for less atrial fibrillation-related complications: a clustering analysis based on the French registry on hypertrophic cardiomyopathy (REMY).

AIMS: Defining the risk of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients is an important clinical and prognostic challenge. The aim of this study is to determine HCM phenogroups with different risk of AF occurrence at 5 years. METHODS AND RESULTS: We applied retrospectively the Bayesian method, which can analyze a large number of variables, to differentiate phenogroups of patients with different risks of AF and prognoses across a French prospective on-going hospital-based registry of adult HCM patients (REMY). Clinical and imaging data were prospectively recorded, and patients were followed for 5 years. A total of 1431 HCM patients were recruited, including 1275 analyzed in the present study after exclusion criteria. The population included 412 women, 369 patients with obstructive HCM, and 252 implanted with an ICD. AF occurred in 167 (11.6%) patients during the 5 year follow-up. Three phenogroups were defined according to their common clinical and echocardiographic characteristics. Patients at the highest risk were oldest, more often female, with more frequent comorbidities, anteroposterior diameter of the left atrium was significantly greater, with diastolic dysfunction, outflow-tract obstruction, and mitral valve abnormality, and presented higher pulmonary artery pressure and/or right-ventricular dysfunction. These also had a higher risk of all-cause hospitalizations and death. CONCLUSION: Based on a clustering analysis, three phenogroups of HCM according to the risk of AF occurrence can be identified. It can indicate which patients should be more monitored and/or treated, particular to prevent the risk of stroke.

Definition of left ventricular remodelling following ST-elevation myocardial infarction: a systematic review of cardiac magnetic resonance studies in the past decade.

An increase in left ventricular volumes between baseline and follow-up imaging is the main criteria for the quantification of left ventricular remodelling (LVR) after ST-elevation myocardial infarction (STEMI), but without consensual definition. We aimed to review the criteria used for the definition of LVR based on cardiac magnetic resonance imaging (CMR) in STEMI patients. A systematic literature search was conducted using MEDLINE and the Cochrane Library from January 2010 to August 2019. Thirty-seven studies involving 4209 patients were included. Among these studies, 30 (81%) used a cut-off value for defining LVR, with a pooled LVR prevalence estimate of 22.8%, 95% CI [19.4-26.7%] and a major between-study heterogeneity (I2 = 82%). The seven remaining studies (19%) defined LVR as a continuous variable. The definition of LVR using CMR following STEMI is highly variable, among studies including highly selected patients. A 20% increase or a 15% increase in left ventricular volumes between a baseline and a follow-up CMR imaging were the two most common criterion (13 [35%] and 9 [24%] studies, respectively). The most frequent LVR criterion was a 20% increase in end-diastolic volumes or a 15% increase in end-systolic volumes. A composite cut-off value of a 12 to 15% increase in end-systolic volume and a 12 to 20% increase in end-diastolic volume using a follow-up CMR imaging 3 months after STEMI might be proposed as a consensual cut-off for defining adverse LVR for future large-sized, prospective studies with serial CMR imaging and long-term follow-up in unselected patients.

"Chronic fatigue, quality of life and long-term side-effects of chemotherapy in patients treated for non-epithelial ovarian cancer: national case-control protocol study of the GINECO-Vivrovaire rare tumors INCa French network for rare malignant ovarian tumors".

BACKGROUND: Germ cell tumors and sex cord stromal tumors are rare cancers of the ovary. They mainly affect young women and are associated with a high survival rate. The standard treatment mainly involves conservative surgery combined with chemotherapy [bleomycin, etoposide and cisplatin (BEP)] depending on the stage and the prognostic factors, as for testicular cancers. As reported in testicular cancer survivors, chemotherapy may induce sequelae impacting quality of life, which has not yet been evaluated in survivors of germ cell tumors and sex cord stromal tumors. The GINECO-VIVROVAIRE-Rare tumor study is a two-step investigation aiming to assess i) chronic fatigue and quality of life and ii) long-term side-effects of chemotherapy with a focus on cardiovascular and pulmonary disorders. METHODS: Using self-reported questionnaires, chronic fatigue and quality of life are compared between 134 ovarian cancer survivors (cancer-free ≥2 years after treatment) treated with surgery and chemotherapy and 2 control groups (67 ovarian cancer survivors treated with surgery alone and 67 age-matched healthy women). Medical data are collected from patient records. In the second step evaluating the long-term side-effects of chemotherapy, a subgroup of 90 patients treated with chemotherapy and 45 controls undergo the following work-up: cardiovascular evaluation (clinical examination, non-invasive cardiovascular tests to explore heart disease, blood tests), pulmonary function testing, audiogram, metabolic and hormonal blood tests. Costs of sequelae will be also assessed. Patients are selected from the registry of the INCa French Network for Rare Malignant Ovarian Tumors, and healthy women by the 'Seintinelles' connected network (collaborative research platform). DISCUSSION: This study will provide important data on the potential long-term physical side-effects of chemotherapy in survivors of Germ Cell Tumors (GCT) and Sex Cord Stromal Tumors (SCST), especially cardiovascular and pulmonary disorders, and neurotoxicity. The identification of long-term side-effects can contribute to adjusting the treatment of ovarian GCT or SCST patients and to managing follow-up with adapted recommendations regarding practices and chemotherapy regimens, in order to reduce toxicity while maintaining efficacy. Based on the results, intervention strategies could be proposed to improve the management of these patients during their treatment and in the long term. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov : 03418844 , on 1 February 2018. This trial was registered on 25 October 2017 under the unique European identification number (ID-RCB): 2017-A03028-45. Recruitment Status: Recruiting. PROTOCOL VERSION: Version n° 4.2 dated from Feb 19, 2021. TRIAL SPONSOR: Centre François Baclesse, 3 avenue du Général Harris, F-14076 Caen cedex 05, France.

Impact of Pulmonary Valve Replacement on Ventricular Arrhythmias in Patients With Tetralogy of Fallot and Implantable Cardioverter-Defibrillator.

OBJECTIVES: This study aimed to assess the impact of pulmonary valve replacement (PVR) on ventricular arrhythmias burden in a population of tetralogy of Fallot (TOF) patients with continuous cardiac monitoring by implantable cardioverter-defibrillators (ICDs). BACKGROUND: Sudden cardiac death is a major cause of death in TOF, and right ventricular overload is commonly considered to be a potential trigger for ventricular arrhythmias. METHODS: Data were analyzed from a nationwide French ongoing study (DAI-T4F) including all TOF patients with an ICD since 2000. Survival data with recurrent events were used to compare the burden of appropriate ICD therapies before and after PVR in patients who underwent PVR over the study period. RESULTS: A total of 165 patients (mean age 42.2 ± 13.3 years, 70.1% male) were included from 40 centers. Over a median follow-up period of 6.8 (interquartile range: 2.5 to 11.4) years, 26 patients (15.8%) underwent PVR. Among those patients, 18 (69.2%) experienced at least 1 appropriate ICD therapy. When considering all ICD therapies delivered before (n = 62) and after (n = 16) PVR, the burden of appropriate ICD therapies was significantly lower after PVR (HR: 0.21; 95% confidence interval [CI]: 0.08 to 0.56; p = 0.002). Respective appropriate ICD therapies rates per 100 person-years were 44.0 (95% CI: 35.7 to 52.5) before and 13.2 (95% CI: 7.7 to 20.5) after PVR (p < 0.001). In the overall cohort, PVR before ICD implantation was also independently associated with a lower risk of appropriate ICD therapy in primary prevention patients (HR: 0.29 [95% CI: 0.10 to 0.89]; p = 0.031). CONCLUSIONS: In this cohort of high-risk TOF patients implanted with an ICD, the burden of appropriate ICD therapies was significantly reduced after PVR. While optimal indications and timing for PVR are debated, these findings suggest the importance of considering ventricular arrhythmias in the overall decision-making process. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574).

Evaluation of Transthoracic Echocardiography in the Assessment of Atherosclerosis of the Left Main Coronary Artery: Comparison with Optical Frequency Domain Imaging (a Pilot Study).

BACKGROUND: Risk stratification using non-invasive imaging of the coronary vessels is emerging as an optimal standard of care for patients with dyslipidemias. Of particular interest is the evaluation of the left main coronary artery (LMCA), where calcium deposition appears to be a predictor of cardiovascular events. METHODS: In coronary patients, we evaluated wall thickness and internal diameter of the LMCA examined by transthoracic echocardiography (TTE) and compared these with findings obtained by optical frequency domain imaging (OFDI), this latter also used to evaluate calcium deposition. RESULTS: A significant positive correlation between TTE and OFDI for the anterior wall thickness (r = 0.41, p = 0.043) and internal diameter (r = 0.36, p = 0.048) of the LMCA was detected. Echocardiographic wall measurements were higher in patients with fibro-calcific plaques. The receiver operating characteristic (ROC) curve showed that an anterior wall thickness of LMCA ≥ 1.4 mm was predictive of fibro-calcific plaque (area under the curve = 0.815 and p = 0.006), sensitivity and specificity being 76.9% and 80%, respectively (Youden's Index = 0.56). CONCLUSIONS: Measurement of anterior wall thickness of the LMCA by TTE and OFDI appears to be closely correlated and may predict the presence of coronary calcification.

Impaired left atrial function in adults and adolescents with corrected aortic coarctation.

This study examined the left atrial (LA) function using two-dimensional (2D) strain analysis after aortic coarctation (CoA) repair, as well as relationships between LA function and patient characteristics, especially aortic arch anatomy. 56 patients (34 males, age: 31 ± 16 years) with CoA repair (46 post 'end-to-end anastomosis/subclavian flap') and 56 controls were studied. 2D strain imaging was performed to assess left ventricular (LV) and LA functions including peak-positive LA strain, early and late diastolic LA strains, and global longitudinal (LV-GLS) and circumferential (LV-GCS) strains. LA dysfunction (LAD) was defined as a peak-positive LA strain value lower than the mean value of the control group minus 2 SDs. Peak-positive LA strain, early and late diastolic LA strains, and LV-GLS were significantly lower in the CoA group while LV-GCS did not differ. No significant correlation was found between LA strain and either current age, age at initial repair, or blood pressure; Ea and LV-GLS were moderately correlated to peak-positive LA strain (r = 0.49, p < 0.001 and r = - 0.55, p < 0.001, respectively). 23 CoA patients (41%) presented LAD (abnormal peak-positive LA strain < 25%). Among patients who underwent end-to-end anastomosis/subclavian flap, those with a non-romanesque aortic arch anatomy exhibited a significantly lower peak-positive LA strain. Ischemic stroke and atrial arrhythmia were more frequent in CoA patients with LAD. Our findings suggest that LAD may be prevalent late after CoA repair. Postoperative aortic arch anatomy may impact peak-positive LA strain.