Gender differences in the development of heart failure after acute coronary syndrome: Insight from the CORALYS registry.

BACKGROUND: Impact of gender on heart remodeling after acute coronary syndrome (ACS) and consequently on development of heart failure (HF) remains to be elucidated. METHODS: CORALYS is a multicenter, retrospective, observational registry enrolling consecutive patients admitted for ACS and treated with percutaneous coronary intervention. HF hospitalization was the primary endpoint while all-cause mortality and the composite endpoint of incidence of first HF hospitalization and cardiovascular mortality were the secondary ones. RESULTS: Among 14,699 patients enrolled in CORALYS registry, 4578 (31%) were women and 10,121 (69%) males. Women were older, had more frequently hypertension and diabetes and less frequently smoking habit. History of myocardial infarction (MI), STEMI at admission and multivessel disease were less common in women. After median follow up of 2.9 ± 1.8 years, women had higher incidence of primary and secondary endpoints and female sex was an independent predictor of HF hospitalization (HR 1.26;1.05-1.50; p = 0.011) and cardiovascular death/HF hospitalization (HR 1.18;1.02-1.37; p = 0.022). At multivariable analysis women and men share as predictors of HF diabetes, history of cancer, chronic kidney disease, atrial fibrillation, complete revascularization and left ventricular ejection fraction. Chronic obstructive pulmonary disease (HR 2.34;1.70-3.22, p < 0.001) and diuretics treatment (HR 1.61;1.27-2.04, p < 0.001) were predictor of HF in men, while history of previous MI (HR 1.46;1.08-1.97, p = 0.015) and treatment with inhibitors of renin-angiotensin system (HR 0.69;0,49-0.96 all 95% CI, p = 0.030) in women. CONCLUSIONS: Women are at increased risk of HF after ACS and gender seems to be an outcome-modifier of the relationship between a variable and primary outcome.

Multicentric Carpo-Tarsal Osteolysis Syndrome (MCTO) and "Function Profile": a rehabilitative approach.

BACKGROUND: Multicentric Carpo-Tarsal Osteolysis Syndrome (MCTO) is an autosomal dominant disease with increased bone reabsorption in the carpus and tarsus and the elbows, knees and spine. The disease is extremely heterogeneous and secondary and tertiary injuries vary widely and can lead to progressive disability and severe functional limitations. In addition to the available and upcoming drug therapies, physical medicine and rehabilitation are important treatment options. Currently, the indication and plan are overlooked, nonspecific and reported only for one patient. METHODS: We describe a case series of MCTO patients diagnosed and followed by a centre to identify functional deficit as a potential clinical marker of disease progression for future etiological therapies. In addition, we define a symptomatic treatment approach and specific clinical management, including a patient-centred rehabilitation approach. Functional assessments are performed independently by a multidisciplinary group to establish the functional abilities of patients and the relationship between residual motor skills and their degree of autonomy and participation. We suggest a way to identify a rehabilitation plan based on a specific disease using the International Classification of Functioning, Disability and Health Children and Youth (ICF-CY). RESULTS: To define a reliable and reproducible "Function Profile", through age and over time, we used to value the disease status according to the ICF-CY domains. It could be used to determine the complexity of the illness, its overall impact on the complexity of the person and the burden on the caregiver, and an eventual short- and long-term rehabilitation plan for MCTO and other ultra-rare diseases. CONCLUSION: Based on the MCTO experience, we suggest a way to determine a rehabilitation plan based on a specific disease and patient needs, keeping in mind that often the final point is not recovering the full function but improving or maintaining the starting point. In all cases, each patient at the time of diagnosis requires a functional assessment that must be repeated over time to adjust the course of rehabilitation. The evaluations revealed the importance of early rehabilitation management in enhancing independence, participation and control of stress deconditioning, shrinking of muscle tendons and loss of movement to immobility.

Atrial septal pouches and ridges: Morphological features and potential implications in clinical practice.

Incomplete or irregular fusion of the interatrial septum may result in several anatomic variants, including atrial septal pouches and ridges, whose knowledge and recognition are still poorly widespread in clinical practice. An educational review focused on the definition, clinical significance and diagnostic work-up of these anatomic findings was performed using PubMed, MEDLINE, Embase and Cochrane Central databases up to June 2023. Atrial septal pouches and ridges have been associated with an increased difficulty of catheter-based interventions requiring a transseptal approach, due to procedural challenges for transseptal puncture and the restricted motion of guidewires and catheters through the transseptal access. Additionally, left atrial septal pouch may serve as a thrombogenic nidus and a source of systemic embolism, mostly in the presence of factors leading to higher left atrial pressure and/or atrial blood stasis, which increase the risk of thrombus formation and embolic events, rather than for the only presence of left atrial septal pouch itself. Further investigations are needed in order to better elucidate the implications of such anatomic findings in daily clinical practice, and to provide the most appropriate decision-making strategies.

Asymptomatic Patients With Brugada ECG Pattern: Long-Term Prognosis From a Large Prospective Study.

BACKGROUND: Brugada syndrome poses significant challenges in terms of risk stratification and management, particularly for asymptomatic patients who comprise the majority of individuals exhibiting Brugada ECG pattern (BrECG). The aim of this study was to evaluate the long-term prognosis of a large cohort of asymptomatic patients with BrECG. METHODS: Asymptomatic patients with BrECG (1149) were consecutively collected from 2 Italian centers and followed-up at least annually for 2 to 22 years. For the 539 asymptomatic patients (men, 433 [80%]; mean age, 46±13 years) with spontaneous type 1 documented on baseline ECG (87%) or 12-lead 24-hour Holter monitoring (13%), an electrophysiologic study (EPS) was proposed; for the 610 patients with drug-induced-only type 1 (men, 420 [69%]; mean age, 44±14 years), multiple ECGs and 12-lead Holter were advised in order to detect the occurrence of a spontaneous type-1 BrECG. Arrhythmic events were defined as sudden death or documented ventricular fibrillation or tachycardia. RESULTS: Median follow-up was 6 (4-9) years. Seventeen (1.5%) arrhythmic events occurred in the overall asymptomatic population (corresponding to an event-rate of 0.2% per year), including 16 of 539 (0.4% per year) in patients with spontaneous type-1 BrECG and 1 of 610 in those with drug-induced type-1 BrECG (0.03% per year; P<0.001). EPS was performed in 339 (63%) patients with spontaneous type-1 BrECG. Patients with spontaneous type-1 BrECG and positive EPS had significantly higher event rates than patients with negative EPS (7 of 103 [0.7% per year] versus 4 of 236 [0.2% per year]; P=0.025). Among 200 patients who declined EPS, 5 events (0.4% per year) occurred. There was 1 device-related death. CONCLUSIONS: The entire population of asymptomatic patients with BrECG exhibits a relatively low event rate per year, which is important in view of the long life expectancy of these young patients. The presence of spontaneous type-1 BrECG associated with positive EPS identifies a subgroup at higher risk. Asymptomatic patients with drug-induced-only BrECG have a minimal arrhythmic risk, but ongoing follow-up with 12-lead Holter monitoring is recommended to detect the appearance of spontaneous type-1 BrECG pattern.

Forecasting the Risk of Heart Failure Hospitalization After Acute Coronary Syndromes: the CORALYS HF Score.

The present study aimed to identify patients at a higher risk of hospitalization for heart failure (HF) in a population of patients with acute coronary syndrome (ACS) treated with percutaneous coronary revascularization without a history of HF or reduced left ventricular (LV) ejection fraction before the index admission. We performed a Cox regression multivariable analysis with competitive risk and machine learning models on the incideNce and predictOrs of heaRt fAiLure After Acute coronarY Syndrome (CORALYS) registry (NCT04895176), an international and multicenter study including consecutive patients admitted for ACS in 16 European Centers from 2015 to 2020. Of 14,699 patients, 593 (4.0%) were admitted for the development of HF up to 1 year after the index ACS presentation. A total of 2 different data sets were randomly created, 1 for the derivative cohort including 11,626 patients (80%) and 1 for the validation cohort including 3,073 patients (20%). On the Cox regression multivariable analysis, several variables were associated with the risk of HF hospitalization, with reduced renal function, complete revascularization, and LV ejection fraction as the most relevant ones. The area under the curve at 1 year was 0.75 (0.72 to 0.78) in the derivative cohort, whereas on validation, it was 0.72 (0.67 to 0.77). The machine learning analysis showed a slightly inferior performance. In conclusion, in a large cohort of patients with ACS without a history of HF or LV dysfunction before the index event, the CORALYS HF score identified patients at a higher risk of hospitalization for HF using variables easily accessible at discharge. Further approaches to tackle HF development in this high-risk subset of patients are needed.

Abnormalities of pubertal development and gonadal function in Noonan syndrome.

Background: Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males. Methods: In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS. Conclusions: According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.

Impact of Complete Revascularization on Development of Heart Failure in Patients With Acute Coronary Syndrome and Multivessel Disease: A Subanalysis of the CORALYS Registry.

Background The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy-three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow-up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]), first HF hospitalization (adjusted HR, 0.67 [95% CI, 0.49-0.90]) along with all-cause death and cardiovascular death alone (adjusted HR, 0.74 [95% CI, 0.56-0.97] and HR, 0.56 [95% CI, 0.38-0.84], respectively). The results were consistent in the propensity-score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 [95% CI, 0.39-0.89] for ST-segment elevation myocardial infarction and HR, 0.71 [95% CI, 0.50-0.99] for non-ST-elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 [95% CI, 0.37-0.72]), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 [95% CI, 0.37-1.10], P for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST-segment elevation myocardial infarction and non-ST-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04895176.

Insight into contact force local impedance technology for predicting effective pulmonary vein isolation.

Background: Highly localized impedance (LI) measurements during atrial fibrillation (AF) ablation have the potential to act as a reliable predictor of the durability of the lesions created. Objective: We aimed to collect data on the procedural parameters affecting LI-guided ablation in a large multicenter registry. Methods: A total of 212 consecutive patients enrolled in the CHARISMA registry and undergoing their first pulmonary vein (PV) isolation for paroxysmal and persistent AF were included. Results: In all, 13,891 radiofrequency (RF) applications of ≥3 s duration were assessed. The first-pass PV isolation rate was 93.3%. A total of 80 PV gaps were detected. At successful ablation spots, baseline LI and absolute LI drop were larger than at PV gap spots (161.4 ± 19â€…Ω vs. 153.0 ± 13 Ω, p < 0.0001 for baseline LI; 22.1 ± 9â€…Ω vs. 14.4 ± 5 Ω, p < 0.0001 for LI drop). On the basis of Receiver operating characteristic curve analysis, the ideal LI drop, which predicted successful ablation, was >21â€…Ω at anterior sites and >18â€…Ω at posterior sites. There was a non-linear association between the magnitude of LI drop and contact-force (CF) (r = 0.14, 95% CI: 0.13-0.16, p < 0.0001) whereas both CF and LI drop were inversely related with delivery time (DT) (-0.22, -0.23 to -0.20, p < 0.0001 for CF; -0.27, -0.29 to -0.26, p < 0.0001 for LI drop). Conclusion: An LI drop >21â€…Ω at anterior sites and >18â€…Ω at posterior sites predicts successful ablation. A higher CF was associated with an increased likelihood of ideal LI drop. The combination of good CF and adequate LI drop allows a significant reduction in RF DT. Clinical trial registration: http://clinicaltrials.gov/, identifier: NCT03793998.

Hyperthyroidism in a 15-year-old adolescent treated with Dupilumab for severe allergic asthma and atopic dermatitis.

Dupilumab is a biologic, acting on IL-4 and IL-13 pathways. Dupilumab has a pediatric indication for treating severe asthma and atopic dermatitis. We report a pediatric case concerning paucisymptomatic, transient, and self-resolving hyperthyroidism. The updated literature includes the case of an adult patient who reported with hyperthyroidism, which was transient and self-resolving. Despite that these cases were transient and self-resolving, we would suggest that thyroid function assessment could be included in the follow-up of patients treated with Dupilumab. Dupilumab discontinuation is not required pending endocrinological assessment, mainly if there is an optimal clinical response to the biologic.

Assisted Reproductive Techniques and Risk of Congenital Heart Diseases in Children: a Systematic Review and Meta-analysis.

Infertility is a growing phenomenon and leads to an increased use of assisted reproductive techniques (ARTs). In recent years, concerns about the safety of these procedures emerged and ARTs were hypothesized to be a risk factor for developing congenital heart diseases (CHDs) in offspring. Our aim is to investigate the association between ART and CHD, specifying results according to various subtypes of defects. We performed a systematic review and random-effects meta-analysis following the PRISMA guidelines. MEDLINE and Google Scholar were searched from January 2011 to May 2022. Data about incidence of CHD in ART were tabulated and extracted from all the studies included. Twenty-four studies were included. Pooled incidence of CHDs after IVF pregnancies was 3% (95% CI 0.3-0.4; I2 = 99%), decreasing to 1% (95% CI 0.00-0.01; I2 = 93%) for major CHDs only. An increased risk of CHDs, especially minor (i.e., not requiring surgical correction), seems to occur in ART compared with non-ART pregnancies [RR 1.71 (95% CI 1.25-2.34; I2 = 99%)]. For major CHDs, not enough evidence is available to assess the real risk. Moreover, some confounding factors (i.e., maternal age and male infertility) seem to play a critical role to determine an increased risk of CHDs. Conflicting results emerged among the studies, setting the need for further research to validate the actual evidence and state the real risk of CHD following ART pregnancies.

Transplacental permeability of heavy metals in relation to newborn sex - evidence from the neurodevelopment project.

Introduction: Gender medicine is an innovative medical approach that studies how some biological variables are influenced by the male or female sex and gender. This issue is under debate because it characterizes the impact of tailored or individual medicine. In this scenario, the aim of this study is to study the correlation between heavy metal exposure and pathologies of neurodevelopment, according to the sex of newborns. In particular, this is an observational study under the name of the Neurosviluppo Project, involving 217 mother-child couples. Material and methods: The correlation with phenotype small for gestational age and congenital malformations were studied, but above all we focused on the pattern of placental permeability to heavy metals. Results: Our results are specifically related to foetal medicine and investigate the impact of foetal sex in transplacental metal exposure. Our results did not show any significant differences related to foetal sex in terms of congenital malformations or the other variables taken into consideration. However, because these conclusions are the first related to the gender medicine in transplacental foetal medicine, they could be a marked background for further studies. Conclusions: Considering the lack of data in literature regarding foetal sexual medicine and transplacental exposure, these study results are pioneering in terms of sexual foetal medicine. Possibly in the future, studies regarding the correlation between foetal sex and obstetrics outcomes will be performed.

Hyperthyroidism in a 15-year-old adolescent treated with Dupilumab for severe allergic asthma and atopic dermatitis

Dupilumab is a biologic, acting on IL-4 and IL-13 pathways. Dupilumab has a pediatric indication for treating severe asthma and atopic dermatitis. We report a pediatric case concerning paucisymptomatic, transient, and self-resolving hyperthyroidism. The updated literature includes the case of an adult patient who reported with hyperthyroidism, which was transient and self-resolving. Despite that these cases were transient and self-resolving, we would suggest that thyroid function assessment could be included in the follow-up of patients treated with Dupilumab. Dupilumab discontinuation is not required pending endocrinological assessment, mainly if there is an optimal clinical response to the biologic (AU)

Corrigendum: Pubertal timing in children with Silver Russell syndrome compared to those born small for gestational age.

[This corrects the article DOI: 10.3389/fendo.2022.975511.].

Ablation of CTI-dependent flutter using different ablation technologies: acute and long-term outcome from the LEONARDO study.

BACKGROUND: A novel ablation catheter has been released to map and ablate the cavo-tricuspid isthmus (CTI) in patients with atrial flutter (AFL), improving ablation efficiency. METHODS: We evaluated the acute and long-term outcome of CTI ablation aiming at bidirectional conduction block (BDB) in a prospective, multicenter cohort study enrolling 500 patients indicated for typical AFL ablation. Patients were grouped on the basis of the AFL ablation method (linear anatomical approach, Conv group n = 425, or maximum voltage guided, MVG group, n = 75) and ablation catheter (mini-electrodes technology, MiFi group, n = 254, or a standard 8-mm ablation catheter, BLZ group, n = 246). RESULTS: Complete BDB according to both validation criteria (sequential detailed activation mapping or mapping only the ablation site) was achieved in 443 patients (88.6%). The number of RF applications needed to achieve BDB was lower in the MiFi MVG group vs both the MiFi Conv group and the BLZ Conv group (3.2 ± 2 vs 5.2 ± 4 vs 9.3 ± 5, p < 0.0001 for all comparisons). Fluoroscopy time was similar among groups, whereas we observed a reduction in the procedure duration from the BLZ Conv group (61.9 ± 26min) to the MiFi MVG group (50.6 ± 17min, p = 0.048). During a mean follow-up of 548 ± 304 days, 32 (6.2%) patients suffered an AFL recurrence. No differences were found according to BDB achieved by both validation criteria. CONCLUSIONS: Ablation was highly effective in achieving acute CTI BDB and long-term arrhythmia freedom irrespective of the ablation strategy or the validation criteria for CTI chosen by the operator. The use of an ablation catheter equipped with mini-electrodes technology seems to improve ablation efficiency. CLINICAL TRIAL REGISTRATION: Atrial Flutter Ablation in a Real World Population. (LEONARDO). CLINICALTRIALS: gov Identifier: NCT02591875.

Matching Ablation Endpoints to Long-Term Outcome: The Prospective Multicenter Italian Ventricular Tachycardia Ablation Registry.

BACKGROUND: Multicenter ventricular tachycardia (VT) ablation studies have shown poorer outcomes compared with single-center experiences. This difference could be related to heterogeneous mapping and ablation strategies. OBJECTIVES: This study evaluated a homogenous simplified catheter ablation strategy for different substrates and compared the results with those of a single referral center. METHODS: This was a multicenter prospective VT ablation registry of patients with the following 4 causes of VT: previous myocardial infarction; previous myocarditis; arrhythmogenic right ventricular dysplasia; or idiopathic dilated cardiomyopathy. The procedural protocol included precise mapping and ablation steps with the combined endpoint of late potential (LP) abolition and noninducibility of VT. The long-term primary efficacy endpoint was freedom from VT. RESULTS: A total of 309 patients were enrolled. LPs were present in 70% of patients and were abolished in 83%. At the end of the procedure 74% of LPs were noninducible. The primary combined endpoint of LP abolition and noninducibility was achieved in 64% of patients with LPs at baseline. Freedom from VT at 12 months was observed in 67% of patients. In the overall study group, VT inducibility was the only predictor of freedom from VT (P = 0.013). In patients with LPs, the VT recurrence rate was lower both for patients with complete LP abolition (P = 0.040) and for patients meeting the composite endpoint (P = 0.035). CONCLUSIONS: A standardized VT mapping and ablation technique reproduced the procedural outcomes of a single referral center in a multicenter prospective study. LP abolition and noninducibility were effective in reducing VT recurrences in patients with 4 causes of cardiomyopathy. (Ventricular Tachycardia Ablation Registry; NCT03649022).

IncidenCe and predictOrs of heaRt fAiLure after acute coronarY Syndrome: The CORALYS registry.

BACKGROUND: Previous studies investigating predictors of Heart Failure (HF) after acute coronary syndrome (ACS) were mostly conducted during fibrinolytic era or restricted to baseline characteristics and diagnoses prior to admission. We assessed the incidence and predictors of HF hospitalizations among patients treated with percutaneous coronary intervention (PCI) for ACS. METHODS AND RESULTS: CORALYS is a multicenter, retrospective, observational registry including consecutive patients treated with PCI for ACS. Patients with known history of HF or reduced left ventricular ejection fraction (LVEF) were excluded. Incidence of HF hospitalizations was the primary endpoint. The composite of HF hospitalization or cardiovascular death, and cardiovascular and all-cause death were the secondary endpoints. Predictors of HF hospitalizations and the impact of HF hospitalization on cardiovascular and all-cause death were assessed by means of multivariable Cox proportional hazards model.14699 patients were included. After 2.9 ± 1.8 years, the incidence of HF hospitalizations was 12.7%. Multivariable analysis identified age, diabetes, chronic kidney disease, previous myocardial infarction, atrial fibrillation, pulmonary disease, GRACE risk-score ≥ 141, peripheral artery disease, cardiogenic shock at admission and LVEF ≤40% as independently associated with HF hospitalizations. Complete revascularization was associated with a lower risk of HF (HR 0.46,95%CI 0.39-0.55). HF hospitalization was associated with higher risk of CV and all-cause death (HR 1.89,95%CI 1.5-2.39 and HR 1.85,95%CI 1.6-2.14, respectively). CONCLUSIONS: Incidence of HF hospitalizations among patients treated with PCI for ACS is not negligible and is associated with detrimental impact on patients' prognosis. Several variables may help to assess the risk of HF after ACS.