Chronobiological Variation in Takotsubo Syndrome: an Updated Systematic Review and Meta-analysis.

Takotsubo syndrome (TTS) might exhibit particular chronobiological patterns in its onset, characterized by variations according to time of the day, day of the week, and month of the year. The aim of this study was to fully explore the temporal patterns (circadian, weekly and seasonal) in the onset of TTS. A systematic review and meta-analysis of literature were conducted for studies (2006-2024) reporting the temporal patterns (circadian, weekly and/or seasonal) in the onset of TTS. Among the 4257 studies retrieved, 20 (including 64,567 subjects) fulfilled all eligibility criteria. Data were aggregated used random effects model as pooled risk ratio and the attributable risk (AR). The proportion analysis (including 8 studies; n=853) showed a decreasing pattern of the pooled rates of TTS shifting from the morning to the night (pooled TTS rates: 34.0%; 32.1%; 21.7%; 12.7% in the morning, afternoon, evening and night, respectively). The same pattern was observed stratifying by type of preceding stressful factor or event, considering physical stressors (pooled rates in the morning and night: 37.6% and 9.8%, respectively), and also in case no event could be identified. The pooled rates of TTS onset peaked on Monday and Tuesday (17.3% and 18.4% respectively), then declined during the week, reaching the lowest rates on Friday and Saturday (10.6% and 10.8%, respectively), with no sex differences. TTS onset reached the highest values on summer, and the lowest in winter (27.9% versus 21.7% in summer and winter, respectively). The TTS morning peak based analyses (∼33% of all the registered events) account for a RR of 1.46 (95% CI: 1.38-1.54), the week-based for a RR of 1.26 (1.16-1.35), the season-based for a RR of 1.04 (1.04-1.05). TTS onset exhibits specific chronobiological patterns, characterized by a peak during the morning hours, and on Monday and Tuesday. Differing from other cardiovascular emergencies TTS was more frequent during summer. Further studies are needed to fully understand the underlying pathophysiological mechanisms in order to tailor relative management and preventive strategies.

Exercise Pulmonary Hypertension in Heart Valve Disease.

The optimal management of heart valve disease (HVD) is still debated and many studies are underway to identify the best time to refer patients for the most appropriate treatment strategy (either conservative, surgical or transcatheter interventions). Exercise pulmonary hypertension (PH) can be detected during exercise stress echocardiography (ESE) and has been demonstrated to have an important prognostic role in HVD, by predicting symptoms and mortality. This review article aims to provide an overview on the prognostic role of exercise PH in valvulopathies, and its possible role in the diagnostic-therapeutic algorithm for the management of HVD.

Bicuspid Aortic Valve Disease With Early Onset Complications: Characteristics And Aortic Outcomes.

Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults but can also cause childhood-onset complications. In multicenter study, we found that adults who experience significant complications of BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early onset BAV complications.

Aortopathy and aortic valve surgery in patients with bicuspid aortic valve with and without raphe.

AIM: To evaluate the association between raphe in bicuspid aortic valve (BAV) patients and valve dysfunction, aortopathy and aortic valve surgery in the REBECCA registry [REgistro della valvola aortica Bicuspide della Società Italiana di ECocardiografia e CArdiovascular Imaging (SIECVI)]. METHODS: Prevalence of aortic valve dysfunction and aortopathy was investigated in BAV patients with and without raphe. Aortic valve dysfunction (regurgitation or stenosis) was categorized as mild, moderate and severe. Aortopathy was defined as annulus ≥14 mm/m2; root ≥20 mm/m2; sinotubular junction ≥16 mm/m2; ascending aorta ≥17 mm/m2, and classified in Type A, isolated ascending aorta dilatation; Type B, aortic root and ascending aorta dilatation; and Type C, isolated aortic root dilatation. RESULTS: Overall, 695 patients with BAV were enrolled; 520 (74.8%) with raphe and 175 (25.2%) without raphe. BAV patients with raphe presented more frequently with moderate or severe aortic stenosis than BAV patients without raphe (183 [35.2%] vs 34 [19.4%], p < 0.001). A higher prevalence of aortopathy, particularly Type B, was observed in patients with vs without raphe. At multivariable analysis, raphe was a predictor of aortic valve surgery at three-year follow-up (odds ratio 2.19, 95% confidence interval 1.08-4.44, p < 0.001). CONCLUSIONS: Patients with BAV and raphe have a higher prevalence of significant aortic stenosis, aortopathy, especially Type B, and a higher risk of undergoing aortic valve surgery at three-year follow-up.

Intramyocardial calcification in apical hypertrophic cardiomyopathy assessed using multimodality imaging: a case series.

Apical hypertrophic cardiomyopathy (ApHCM) is an HCM variant, affecting frequently males in midlife. It is characterized by apical obliteration and persistent diastolic contraction, often resulting in microvascular ischaemia. We report five cases of ApHCM, with evidence of intramyocardial calcification on echocardiogram. On cardiac magnetic imaging (MRI), a hypointense component at early gadolinium enhancement (EGE) sequences, compatible with calcium, and a deep layer, with hyperintensity at late gadolinium enhancement (LGE) sequences, referable to fibrosis, suggest an endomyocardial fibrosis (EMF) diagnosis. EMF pathologic hallmark is endocardium and myocardium scarring, evolving to dystrophic calcification. It is found only in few ApHCM patients. Our series is the largest one described until now. Analysing patients' history, coexistent inflammatory triggers were evident in all of them, so their co-morbidities could represent a further cause of small vessel disease, in the context of ischaemic microvascular stress due to hypertrophy, leading to fibrosis and dystrophic calcification. This series could demonstrate the relation between apical fibrosis/calcification and microvascular ischaemia due to hypertrophy and inflammatory triggers.

Whole Exome Sequencing Uncovers the Genetic Complexity of Bicuspid Aortic Valve in Families with Early Onset Complications.

Bicuspid Aortic Valve (BAV) is the most common adult congenital heart lesion with an estimated population prevalence of 1%. We hypothesize that early onset complications of BAV (EBAV) are driven by specific impactful genetic variants. We analyzed whole exome sequences (WES) to identify rare coding variants that contribute to BAV disease in 215 EBAV families. Predicted pathogenic variants of causal genes were present in 111 EBAV families (51% of total), including genes that cause BAV (8%) or heritable thoracic aortic disease (HTAD, 17%). After appropriate filtration, we also identified 93 variants in 26 novel genes that are associated with autosomal dominant congenital heart phenotypes, including recurrent deleterious variation of FBN2, MYH6, channelopathy genes, and type 1 and 5 collagen genes. These findings confirm our hypothesis that unique rare genetic variants contribute to early onset complications of BAV disease.

Characteristics and prognosis of isolated aortic valve infective endocarditis in patients with bicuspid aortic valves: a propensity matched study.

Introduction: Bicuspid aortic valve (BAV) is the most common congenital heart disease with an increased risk of infective endocarditis (IE). Few data are available on isolated native BAV-IE. The aim of this study was to compare patients with tricuspid aortic valve (TAV) IE and BAV-IE in terms of characteristics, management and prognosis. Material and methods: We included 728 consecutive patients with IE on isolated native aortic valve in 3 centres: Amiens and Marseille Hospitals in France and Salerno Hospital in Italy. We studied in hospital and long-term mortality before and after matching for age, sex and comorbidity index. Median follow-up was 67.2 [IQR: 19-120] months. Results: Of the 728 patients, 123 (16.9%) had BAV. Compared with patients with TAV-IE, patients with BAV-IE were younger, had fewer co-morbidities and were more likely to be male. They presented more major neurological events and perivalvular complications (both p < 0.05). Early surgery (<30 days) was performed in 52% of BAV-IE cases vs. 42.8% for TAV-IE (p = 0.061). The 10-year survival rate was 74 ± 5% in BAV-IE patients compared with 66 ± 2% in TAV-IE patients (p = 0.047). After propensity score matching (for age, gender and comorbidities), there was no difference in mortality between the two groups, with an estimated 10-year survival of 73 ± 5% vs. 76 ± 4% respectively (p = 0.91). Conclusion: BAV is a frequent finding in patients with isolated aortic valve IE and is associated with more perivalvular complications and neurological events. The differences in survival with TAV-IE are probably related to the age and comorbidity differences between these two populations.

Clinical Outcomes in Patients With Bicuspid Aortic Valves and Ascending Aorta ≥50 mm Under Surveillance.

Background: Clinical outcomes of bicuspid aortic valve (BAV) patients with ascending aortic diameters ≥50 mm who are under surveillance are poorly defined. Objectives: The purpose of this study was to assess clinical outcomes in BAV patients with ascending aorta ≥50 mm. Methods: Multicenter retrospective cohort study of BAV adults with ascending aorta diameters ≥50 mm by transthoracic echocardiography (TTE). Patients were categorized into 50 to 54 mm and ≥55 mm groups. Clinical outcomes were aortic dissection (AoD), aorta surgery, surgical mortality, and all-cause death. Results: Of 875 consecutive BAV patients (age 60 ± 13 years, 86% men, aortic diameter 51 mm [interquartile range (IQR): 50-53 mm]), 328 (37%) underwent early surgery ≤3 months from index TTE. Of the remaining 547 patients under surveillance, 496 had diameters 50 to 54 mm and 51 had diameters ≥55 mm and were collectively followed for 7.51 (IQR: 3.98-12.20) years. Of 496 patients with diameters 50 to 54 mm under surveillance, 266 (54%) underwent surgery 2.0 (IQR: 0.77-4.16) years from index TTE. AoD occurred in 9/496 (1.8%) patients for an incidence of 0.4 cases per 100 person-years, surgical mortality was 5/266 (1.9%); and ≥moderate aortic stenosis (but not aorta size) was associated with all-cause death, hazard ratio: 2.05 (95% CI: 1.32-3.20), P = 0.001. Conversely, in 547 total patients under surveillance (including 50-54 mm and ≥55 mm), both aorta size and ≥moderate aortic stenosis were associated with all-cause death (both P ≤ 0.027). AoD rate in patients ≥55 mm under surveillance was 5.9%. Conclusions: In BAV patients with ascending aorta 50 to 54 mm under surveillance, AoD incidence is low and the overall rates of AoD and surgical mortality are similar, suggesting clinical equivalence between surgical and surveillance strategies. Conversely, patients with aortas ≥55 mm should undergo surgery. Aortic stenosis is associated with all-cause death in these patients.

Software integral de eco estrés para protocolo ABCDE de última generación / Stress Echo Comprehensive Software (SECS) for State-of-the-art ABCDE Protocol

RESUMEN Introducción: Existen diversos softwares especializados en el mercado para el almacenamiento electivo de datos de eco estrés (EE). El EE de última generación incorpora nuevos parámetros además de la motilidad parietal. Objetivo: Desarrollar un nuevo software para el almacenamiento de datos e informe de EE. Métodos: Desarrollamos el prototipo de Software Integral de EE (SIEE) con un conjunto mínimo de datos que permite la eventual recolección estandarizada de datos. El software corre en computadoras con capacidad de trabajo mediana-baja y con los sistemas operativos más usados (Windows, MAC OS y Linux). Las funciones de exportación hacia formatos altamente aceptados permiten compartir los datos fácilmente. El software es capaz de generar un informe personalizado que se puede expandir en PDF y en formatos de valores separados por comas. Resultados: El ingreso de datos en el programa prototipo requiere menos de 2 minutos por estudio. Las páginas principales se concentran en las 5 fases ABCDE del EE: fase A (motilidad parietal regional); fase B (líneas B con escaneo simplificado de 4 sitios); fase C (reserva contráctil con fuerza derivada de la presión arterial sistólica y volumen de fin de sístole; fase D (Doppler de reserva coronaria de la arteria descendente anterior); y fase E (reserva cronotrópica derivada del electrocardiograma medida como la razón de frecuencia cardíaca pico/reposo). La última página resume la información ABCDE en un modelo de predicción de riesgo (tasa de muerte cardiovascular anual, abarcando desde riesgo bajo <1% hasta riego alto >3%. Conclusión: El SIEE puede proporcionar una infraestructura adecuada para una aplicación clínica y de investigación avanzada, con un formato gráfico simple y opción de informe satisfactoria. Puede representar una solución intermedia entre la información exhaustiva requerida por los estándares científicos y la prioridad de un flujo de trabajo fluido de actividades relacionadas a la clínica con gran volumen de pacientes. Su validación en gran escala y la adaptación de acuerdo a la opinión de los usuarios es necesaria antes de su difusión a demanda.

ABSTRACT Background: Several specialized softwares are commercially available for the elective storage of stress echo (SE) data. State-of-the-art SE is based upon novel parameters in addition to regional wall motion. Objective: To develop a novel software for SE data storage and reporting. Methods: We developed the prototype of a SE Comprehensive Software (SECS) with a minimum data set eventually allowing standardized collection of data. The software runs with medium-low performance computers as well as with the most popular operating systems (Windows, MAC OS and Linux). The export functions towards widely accepted formats allow easy data sharing. The software is able to generate a customized report which can be expanded in PDF and comma-separated value formats. Results: The program prototype data entry requires <2 min per study. The main pages focus on the 5 steps of ABCDE-SE: step A (regional wall motion); step B (B-lines with 4-site simplified scan); step C (contractile reserve with force derived from systolic blood pressure and end-systolic volume); step D (Doppler-based coronary flow velocity reserve in left anterior descending coronary artery); step E (EKG-based chronotropic reserve measured as peak/rest heart rate). The final page graphically summarizes the ABCDE information in a risk prediction model (cardiac death rate per year, from low risk <1% to high risk >3 %). Conclusion: SECS may provide a suitable infrastructure for an advanced clinical and research application, with simple graphic format and convenient reporting option. It may represent a trade-off between exhaustive information required by scientific standards and smooth workflow priority of busy, high volume, clinically-driven activities. Large scale validation and adaptation from users' feedback is necessary prior to dissemination on demand.

Entrenamiento por etapas basado en la web: el camino hacia el Eco Estrés 2020 / Multi-step Web-based Training: the Road to Stress Echo 2020

RESUMEN Introducción: Una plataforma de entrenamiento estandarizada ayuda a armonizar la lectura de la ecocardiografía de estrés (EE) más allá de las anormalidades en la motilidad parietal regional (AMPR) Objetivo: Armonizar los criterios de lectura del EE a través de diferentes laboratorios. Métodos: El laboratorio central preparó para los lectores de ecocardiografía un módulo obligatorio de 5 parámetros basado en la web de 2 horas de duración: AMPR; líneas B, reserva de la velocidad de flujo coronario (RVFC) evaluada mediante la velocidad pico del flujo diastólico en la arteria coronaria descendente anterior; reserva contráctil ventricular izquierda (RCVI, evaluada a partir de mediciones crudas del volumen de fin de sístole, VFS); y presión sistólica de la arteria pulmonar (basada en mediciones crudas de la velocidad del jet de regurgitación tricuspídea, VRT). La prueba de control de calidad consistió en 20 casos seleccionados por el centro coordinador. El umbral de aprobación determinado a priori fue de 18/20 (> 90%) con un coeficiente de correlación intraclase entre el laboratorio coordinador y el lector periférico > 0.90. Resultados: Ochenta y cuatro lectores completaron la certificación para las AMPR, 65 para las líneas B, 30 para la RVFC, 24 para el VFS y 20 para la VRT. El tiempo de lectura medio por intento fue más corto para la VRT (9 ± 4 min), la RVFC (13 ± 6 min) y las líneas B (17 ± 3 min), intermedio para el VFS (24 ± 7 min), y más prolongado para las AMPR (29 ± 12 min, p < 0.01). La tasa de acierto del primer intento fue más alta para la RVFC (85%), intermedia para la VRT (75%) y las líneas B (43%), menor para el VFS (35%) y más baja para las AMPR (28%, p < 0.01). Conclusiones: La plataforma de aprendizaje basada en la web mejora las habilidades de interpretación de imágenes sin necesidad de un equipamiento de imágenes costoso o de estudiar un paciente. El camino hacia la certificación es más largo para las AMPR, intermedio para el VFS y más corto para la VRT, la RVFC y las líneas B.

ABSTRACT Background: A standardized training platform helps to achieve reading harmonization in stress echocardiography (SE) beyond regional wall motion abnormalities (RWMA). Objective: To harmonize SE reading criteria across different laboratories. Methods: The core lab prepared for readers an obligatory 2-hour web-based learning module for 5 parameters: RWMA; B-lines; coronary flow velocity reserve (CFVR) based on peak diastolic flow velocity on the left anterior descending coronary artery; left ventricular contractile reserve (LVCR, from raw measurementis of end-systolic volume, ESV); systolic arterial pulmonary pressure (from raw measurementis of peak tricuspid regurgitant jet velocity, TRV). The quality control test consisted of 20 cases selected by the coordinating center. The a priori determined pass threshold was 18/20 (>90%) with intra-class correla-tion coefficient between the coordinating lab and the peripheral reader >0.90. Resultis: The certification was completed by 84 readers for RWMA, 65 for B-lines, 30 for CFVR, 24 for ESV and 20 for TRV The mean reading time per attempt was shorter for TRV (9±4 min), CFVR (13±6 min) and B-lines (17±3 min), intermedi-ate for ESV (24±7 min), and longer for RWMA (29±12 min, p <0.01). The success rate of the first attempt was higher for CFVR (85%), intermediate for TRV (75%) and B-lines (43 %), lower for ESV (35%) and lowest for RWMA (28 %, p <0.01). Conclusions: A web-based learning platform improves image interpretation skills without need for expensive imaging equip-ment or a patient to scan. The road to certification is longer for RWMA, intermediate for ESV, and shorter for TRV, CFVR and B-lines.