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.

Monitoring of Hemodynamics With Right Heart Catheterization in Children With Pulmonary Arterial Hypertension.

Background Right heart catheterization (RHC) is a high-risk procedure in children with pulmonary arterial hypertension without clear guidelines for the indications and targets of invasive reassessment. Our objectives are to define the aims of repeated RHC and evaluate the correlation between noninvasive criteria and hemodynamic parameters. Methods and Results Clinical and hemodynamic characteristics from 71 incident treatment-naïve children (median age 6.2 years) with pulmonary arterial hypertension who had a baseline and reevaluation RHC were analyzed. Correlations between noninvasive predictors and hemodynamic parameters were tested. Adverse outcomes were defined as death, lung transplantation, or Potts shunt. At baseline, pulmonary vascular resistance index (hazard ratio [HR] 1.07 per 1 WU·m2 increase [95% CI, 1.02-1.12], P=0.002), stroke volume index (HR 0.95 per 1 L·min-1·m-2 increase [95% CI, 0.91-0.99], P=0.012), pulmonary artery compliance index (HR 0.16 per 1 mL·mm Hg-1·m-2 increase [95% CI, 0.051-0.52], P=0.002), and right atrial pressure (HR, 1.31 per 1 mm Hg increase [95% CI, 1.01-1.71], P=0.043) were associated with adverse outcomes. Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure were still associated with a worse outcome at second RHC. Noninvasive criteria accurately predicted hemodynamic evolution; however, 70% of the patients who had improved based on noninvasive criteria still presented at least 1 "at risk" hemodynamics at second RHC. Conclusions Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure are solid predictors of adverse outcomes in pediatric pulmonary arterial hypertension and potential therapeutic targets. Noninvasive criteria accurately predict the evolution of hemodynamic parameters, but insufficiently. Repeated RHC are helpful to identify children with persistent higher risk after treatment introduction.

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.

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.

Cardiovascular events in perimembranous ventricular septal defect with left ventricular volume overload: a French prospective cohort study (FRANCISCO).

The long-term prospective multi-centre nationwide (French) observational study FRANCISCO will provide new information on perimembranous ventricular septal defect with left ventricular overload but no pulmonary hypertension in children older than 1 year. Outcomes will be compared according to treatment strategy (watchful waiting, surgical closure, or percutaneous closure) and anatomic features of the defect. The results are expected to provide additional guidance about the optimal treatment of this specific population, which is unclear at present. BACKGROUND: The management of paediatric isolated perimembranous ventricular septal defect (pmVSD) with left ventricle (LV) volume overload but no pulmonary arterial hypertension (PAH) remains controversial. Three therapeutic approaches are considered: watchful waiting, surgical closure, and percutaneous closure. We aim to investigate the long-term outcomes of these patients according to anatomic pmVSD characteristics and treatment strategy. METHODS: The Filiale de Cardiologie Pediatrique et Congénitale (FCPC) designed the FRANCISCO registry, a long-term prospective nationwide multi-centre observational cohort study sponsored by the French Society of Cardiology, which enrolled, over 2 years (2018­2020), patients older than 1 year who had isolated pmVSD with LV volume overload. Prevalent complications related to pmVSD at baseline were exclusion criteria. Clinical, echocardiographic, and functional data will be collected at inclusion then after 1, 5, and 10 years. A core lab will analyse all baseline echocardiographic data to depict anatomical pmVSD features. The primary outcome is the 5-year incidence of cardiovascular events (infective endocarditis, sub-aortic stenosis, aortic regurgitation, right ventricular outflow tract stenosis, tricuspid regurgitation, PAH, arrhythmia, stroke, haemolysis, heart failure, or death from a cardiovascular event). We plan to enrol 200 patients, given the 10% estimated 5-year incidence of cardiovascular events with a 95% confidence interval of ±5%. Associations linking anatomical pmVSD features and treatment strategy to the incidence of complications will be assessed. CONCLUSIONS: The FRANSCICO study will provide the long-term incidence of complications in patients older than 1 year with pmVSD and LV volume overload. The results are expected to improve guidance for treatment decisions.

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.

Impaired left atrial stiffness in patients with corrected congenital left ventricular outflow obstructions.

OBJECTIVE: We examined the left atrial stiffness index (LA Stiff) on echocardiography and its determinants in adults and adolescents with repaired congenital left ventricular outflow obstructions (c-LVOOs), including isolated subaortic stenosis (SAS), stenotic bicuspid aortic valve (BAV), and aortic coarctation (CoA). METHODS: Seventy-two patients (43 males, age: 31 ± 15 years) with repaired c-LVOOs (SAS: n = 12; BAV: n = 27; CoA: n = 33) were compared to 72 age- and sex-matched controls. 2D strain imaging was performed to assess left ventricular (LV) and LA function, including peak positive longitudinal LA strain (LAS), late diastolic LA strain (LDS), and LV global longitudinal strain (GLS). The (E/Ea)/LAS ratio was used to calculate LA Stiff. RESULTS: LA Stiff was significantly higher in the c-LVOO group than in the control group. Among the c-LVOO patients, the CoA group had the lowest GLS and the highest LA Stiff; no significant differences were found with respect to sex, hypertension history, smoking status, or repeated repair among c-LVOO subtypes. Multivariable regression analysis with the variables "BMI" and "c-LVOO subtype" revealed that BMI and c-LVOO subtypes were independently associated with LA Stiff (b = 0.290, P = .009 and b = 0.353, P = .002, respectively). CONCLUSIONS: We documented abnormal LA Stiff values in adults and adolescents after c-LVOO repair. Patients with CoA demonstrated the most impaired LA Stiff values. Overweight may contribute to worse LA Stiff values. Further studies are required to determine the prognostic implications of LA Stiff in patients with repaired c-LVOOs.

Reversal of Cardiac Hypertrophy With a Ketogenic Diet in a Child With Mitochondrial Disease and Hypertrophic Cardiomyopathy.

Mitochondrial diseases are rare metabolic disorders that can cause hypertrophic cardiomyopathy. Herein we describe the case of a 3-year-old girl diagnosed with mitochondrial disease (mutation m.5559A>G in the mitochondrial-tRNATrp gene). Echocardiography showed left ventricular hypertrophy with an enlarged septum (9 mm, z score = 3.26). Antioxidant supplementation associated with a high-fat ketogenic diet was introduced and, as expected, improved neurologic status. In addition, heart parameters improved with normalisation of interventricular septum thickness at 6 years of age (6 mm, z score = 1.05). In this case report, we suggest that a ketogenic diet may improve hypertrophic cardiomyopathy in the context of mitochondrial disease.

Right Ventricular Strain Impairment in Adults and Adolescents with Repaired Aortic Coarctation.

This study examines the function of the right ventricle (RV) using two-dimensional (2D) strain analysis after aortic coarctation (CoA) repair, as well as relationships between potential RV strain abnormalities and patient characteristics. The study examined 39 patients (61% male, age 32 ± 16 years) with CoA repair (33 post end-to-end anastomosis/sub-clavian flap, 6 post stenting/bypass/Teflon patch) and 42 controls. The structure and function of the left ventricle (LV), left atrium (LA), and RV were assessed using 2D standard echocardiography, tissue Doppler imaging, and 2D strain imaging. The characteristics examined included global RV longitudinal strain (RV-GLS), global LV longitudinal strain (LV-GLS), and LA longitudinal strain (LA strain). RV dysfunction was defined by RV-GLS lower than the mean minus 2 standard deviations (SDs) of the control group value. LV mass and mitral E/Ea were significantly higher in the CoA group. Septal Ea, LV-GLS, and LA strain were significantly lower in the CoA group. RV dysfunction (RV-GLS > - 16%) was present in 10 (25.6%) CoA patients. RV-GLS was correlated with lateral Ea, LV-GLS, and LA strain (r = - 0.35, p = 0.02; r = - 0.54, p < 0.001; and r = - 0.44, p = 0.005, respectively). Patients who had a stenting/bypass/Teflon patch as the first initial repair exhibited significantly lower RV-GLS. RV systolic strain abnormalities may occur in patients late after CoA repair. RV strain was correlated with parameters of LV dysfunction. Further large-scale studies are required to confirm these findings and to determine the mechanisms and prognostic implications of RV strain in such patients.

Decreased regional left ventricular myocardial strain in type 1 diabetic children: a first sign of diabetic cardiomyopathy?

BACKGROUND AND OBJECTIVES: Type 1 diabetes is a major cardiovascular risk factor associated with an excess of mortality in young adults due to premature cardiovascular events, which includes heart failure. The relation between type 1 diabetes and cardiac structure and function in children was poorly documented. Our study investigates (1) whether type 1 diabetic children have echocardiographic signs of subclinical cardiac dysfunction assessed by tissue Doppler strain and (2) whether state of metabolic control and diabetes duration have any influence on the cardiac event. METHODS: Standard echocardiography and tissue Doppler imaging were prospectively performed in type 1 diabetic children. Left ventricular dimensions, standard indices of systolic and diastolic function, and septal longitudinal strain were investigated. RESULTS: Thirty consecutive asymptomatic diabetic children (age: 12.4 [5-17] years; males: 53%) were compared to 30 age and sex-matched healthy control subjects. Left ventricular mass index and diastolic septal thickness were significantly increased in diabetic children. There was no difference between two groups as regards the left ventricular ejection fraction and conventional mitral Doppler parameters (E, A, Ea). The global longitudinal systolic strain and strain rate were found to be decreased in children with diabetes. The global longitudinal early diastolic strain rate (Esr) was negatively correlated with metabolic control. Longitudinal strain was not correlated with diabetes duration. CONCLUSION: Children with Type 1 diabetes had subclinical alterations in left ventricular size and longitudinal myocardial deformation.

Major congenital coronary artery anomalies in a paediatric and adult population: a prospective echocardiographic study.

AIMS: We sought to describe our experience with major coronary anomalies (MCAs) diagnosed in transthoracic echocardiography (TTE) in a large adult and paediatric population. MCAs may have serious clinical consequences. No echocardiographic studies have prospectively screened MCA in a general adult and paediatric population. METHODS AND RESULTS: From June 2008 to January 2012, a systematic search for MCA was prospectively conducted in children and adult patients, coming for a TTE. Three thousand five hundred and two patients (84% adults and 16% children) underwent a TTE. Fourteen coronary anomalies (0.39%) were diagnosed: nine anomalous origins of coronary artery from the opposite sinus with inter-arterial course, one abnormal left coronary artery from the pulmonary artery, three single coronary ostia, and one coronary fistula. Cardiac symptoms initiated investigation in seven patients. Five patients underwent specific surgery: two coronary reimplantations and three coronary bypass grafting. Ten patients had already undergone at least one TTE with the anomalous coronary artery being neither diagnosed nor suspected. CONCLUSIONS: MCA is a rare condition. TTE appears to be a potentially useful modality for the initial screening of MCA in adults and children, provided special attention is paid to coronary artery analysis.

Alterations of left ventricular myocardial strain in obese children.

AIMS: Obesity may have implications in the myocardial structural change, which may contribute to mechanical consequences. Using 2D speckle echocardiography, we looked for myocardial changes and investigated their relation to obesity, inflammation, insulin resistance and physical capacity in children with isolated obesity. METHODS AND RESULTS: Standard echocardiography and 2D strain were prospectively performed in obese children and compared them with age- and sex-matched controls. Z-score body mass index (BMI Z-score), ultra-sensitive C reactive protein, indices of insulin resistance (HOMA-IR) and metabolic stress test were assessed in obese children. Thirty-two consecutive obese patients [age: 12.8 (8-17) years; 15 males; BMI Z-score: 5.8 [2.05-8.6)] were compared with 32 controls. Longitudinal strain and circumferential strain were significantly lower in the obese group (respectively -18.0 ± 2.4% vs. -20.6 ± 2.5%; P = 0.0001 and -18.2 ± 3.5% vs. -20.1 ± 2.3%; P = 0.013), while radial strain did not differ. Longitudinal strain was correlated with HOMA-IR (Pearson's rho = -0.39) and with the exercise capacity (Pearson's rho = 0.62). In the multivariate analysis, after adjusting for age, the mean arterial pressure and left ventricular (LV) mass, the BMI Z-score remained independently related to the longitudinal and circumferential strain. CONCLUSION: Childhood obesity may be associated with an early alteration of the longitudinal and circumferential LV strain. These findings have potentially significant clinical implications for the outcomes and follow-up of obese children meriting further studies.

Muerte súbita debida a miocardiopatía histiocitoide / Sudden death due to histiocytoid cardiomyopathy

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Origen anómalo de la coronaria derecha con un trayecto interarterial / Anomalous origin of the right coronary artery with an interarterial course

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Characteristics and prospective 2-year follow-up of children with pulmonary arterial hypertension in France.

BACKGROUND: Limited data are available describing paediatric pulmonary arterial hypertension. AIMS: To characterize the epidemiology, management and impact on quality of life and outcome of paediatric pulmonary arterial hypertension, excluding persistent pulmonary hypertension of the newborn and pulmonary arterial hypertension caused by congenital heart disease. METHODS: In this multicentre study, children with pulmonary arterial hypertension were included and followed prospectively for two years at 21 referral centres in France. WHO functional class, 6-minute walk distance and quality of life (CHQ-PF50 questionnaire) were evaluated. RESULTS: Fifty children were included with a mean age of 8.9 +/- 5.4 years from May 2005 until June 2006. The estimated prevalence for pulmonary arterial hypertension was 3.7 cases/million. Patients had idiopathic pulmonary arterial hypertension (60%), familial pulmonary arterial hypertension (10%), pulmonary arterial hypertension associated with, but not caused by, congenital heart disease (24%), pulmonary arterial hypertension associated with connective tissue disease (4%) or portal hypertension (2%). During follow-up, the combination of pulmonary arterial hypertension-specific therapies was increasingly prescribed (44% patients versus 22% at inclusion). Patients remained stable regarding clinical status, 6-minute walk distance and quality of life. Survival estimates after one and two years were 86% (95% CI 76, 96) and 82% (95% CI 71, 93), respectively. CONCLUSIONS: In children, idiopathic/familial pulmonary arterial hypertension accounts for the majority of cases. A specific pulmonary arterial hypertension group in conjunction with congenital heart disease can be identified that resembles patients with idiopathic pulmonary arterial hypertension. Combined pulmonary arterial hypertension-specific therapies may have contributed to disease stability and favourable survival.