Changes in echocardiographic parameters over time in paradoxical low-flow low-gradient aortic stenosis.

AIMS: To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe low-flow low-gradient (LFLG) AS compared to other severe AS subtypes. METHODS AND RESULTS: Longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (aortic valve area, AVA < 1.0 cm²) and normal left ventricle ejection fraction (LVEF ≥ 50%). Patients were classified according to baseline echocardiography into: HG (high gradient; mean gradient ≥ 40 mmHg), NFLG (normal-flow low-gradient; mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35mL/m2), or LFLG (mean gradient < 40 mmHg, SVi ≤ 35 mL/m²). AS progression was analyzed by comparing patients' baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, P = 0.005) and NFLG vs. HG (regression coefficient 0.068, P = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, P = 0.195). However, AVA reduction was slower in the LFLG group compared to the NFLG (P < 0.001). During follow-up, in conservatively-managed patients, 19.1% (n = 9) of LFLG patients evolved to having NFLG AS and 44.7% (n = 21) to having HG AS. In patients undergoing AVR, 58.0% (n = 29) of LFLG baseline patients received AVR with a HG AS. CONCLUSION: LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with a HG AS.

Imaging in atrial fibrillation: A way to assess atrial fibrosis and remodeling to assist decision-making.

The 2020 ESC atrial fibrillation (AF) guidelines suggest the novel 4S-AF scheme for the characterization of AF. Imaging techniques could be helpful for this objective in everyday clinical practice, and information derived from these techniques reflects basic aspects of the pathophysiology of AF, which may facilitate treatment decision-making, and optimal management of AF patients. The aim of this review is to provide an overview of the mechanisms associated with atrial fibrosis and to describe imaging techniques that may help the management of AF patients in clinical practice. Transthoracic echocardiography is the most common procedure given its versatility, safety, and simplicity. Transesophageal echocardiography provides higher resolution exploration, and speckle tracking echocardiography can provide incremental functional and prognostic information over conventional echocardiographic parameters. In addition, LA deformation imaging, including LA strain and strain rate, are related to the extent of fibrosis. On the other hand, multidetector-row computed tomography and cardiac magnetic resonance provide higher resolution data and more accurate assessment of the dimensions, structure, and spatial relationships of the LA. Imaging is central when deciding on catheter ablation or cardioversion, and helps in selecting those patients who will really benefit from these procedures. Moreover, imaging enhances the understanding of the underlying mechanisms of atrial remodeling and might assists in refining the risk of stroke, which help to select the best medical therapies/interventions. In summary, evaluation of LA enlargement, LA remodeling and fibrosis with imaging techniques adds clinical and prognostic information and should be assessed as a part of routine comprehensive AF evaluation.

Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits.

Objectives: To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS). Methods: A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] < 1.0 cm2) and normal left ventricular ejection fraction (LVEF). Patients were classified as: high-gradient (HG, mean gradient ≥ 40 mmHg), normal-flow low-gradient (NFLG, mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2). Results: Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3-30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12-0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13-0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20-0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively. Conclusions: Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.

Global longitudinal strain assessment of cardiac function and extravascular lung water formation after diving using semi-closed circuit rebreather.

PURPOSE: The aim of the present investigation is to study the relationship of ventricular global longitudinal strain (GLS) and ultrasound lung comets (ULC) formation to establish a link between extravascular pulmonary water formation and cardiac contractile dysfunction. METHODS: This is a prospective observational study including 14 active military divers. The subjects performed two sea dives of 120 min each with a semi-closed SCUBA circuit at 10 m depth. Divers were examined at baseline, 15 min (D1) and 60 min (D2) after diving. The evaluation included pulmonary and cardiac echography (including speckle tracking techniques). Blood samples were drawn at baseline and after diving, assessing hs-TnT and Endothelin-1. RESULTS: ULC were detected in 9 (64.2%) and 8 (57.1%) of the subjects after D1 and D2 respectively. No differences were found in right and left ventricular GLS after both immersions (RV: Baseline: - 17.9 4.9 vs. D1: - 17.2 6.5 and D2: - 16.7 5.8 s-1; p = 0.757 and p = 0.529; LV: Baseline: - 17.0 2.3 vs. D1: - 17.4 2.1 and D2: - 16.9 2.2 s-1; p = 0.546 and p = 0.783). However, a decrease in atrial longitudinal strain parameters have been detected after diving (RA: Baseline: 35.5 9.2 vs. D1: 30.3 12.8 and D2: 30.7 13.0 s-1; p = 0.088 and p = 0.063; LA: Baseline: 39.0 10.0 vs. D1: 31.6 6.1 and D2: 32.4 10.6 s-1; p = 0.019 and p = 0.054). CONCLUSION: In the present study, no ventricular contractile dysfunction was observed. However, increase pulmonary vasoconstriction markers were present after diving.

Left ventricular non-compaction cardiomyopathy automatic diagnosis using a deep learning approach.

BACKGROUND AND OBJECTIVE: Left ventricular non-compaction (LVNC) is an uncommon cardiomyopathy characterised by a thick and spongy left ventricle wall caused by the high presence of trabeculae (hyper-trabeculation). Recently, the percentage of the trabecular volume to the total volume of the external wall of the left ventricle (VT%) has been proposed to diagnose this illness. METHODS: This paper presents the use of a deep learning-based method to measure the (VT%) value and diagnose this rare cardiomyopathy. The population used in this research was composed of 277 patients suffering from hypertrophic cardiomyopathy. 134 patients only suffered hypertrophic cardiomyopathy, and 143 also suffered left ventricular non-compaction. Our deep learning solution is based on a 2D U-Net. This artificial neural network (ANN) was trained on short-axis magnetic resonance imaging to segment the left ventricle's internal cavity, external wall, and trabecular tissue. 5-fold cross-validation was performed to ensure the robustness of the results. The Dice coefficient of the three classes was computed as a measure of the precision of the segmentation. Based on this segmentation, the percentage of the trabecular volume (VT%) was computed. Two specialist cardiologists rated the segmentation produced by the neural network for 25 patients to evaluate the clinical validity of the outputs. The computed VT% was used to automatically diagnose the 277 patients depending on whether or not a given threshold was exceeded. A receiver operating characteristic analysis was also performed. RESULTS: According to the cross-validation results, the average and standard deviation of the Dice coefficient for the internal cavity, external wall, and trabeculae were 0.96±0.00, 0.89±0.00, and 0.84±0.00, respectively. The cardiologists rated 99.5% of the evaluated segmentations as clinically valid for diagnosis, outperforming existing automatic traditional tools. The area under the ROC curve was 0.94 (95% confidence interval, 0.91-0.96). The accuracy, sensitivity, and specificity values of diagnosis using a threshold of 25% were 0.87, 0.93, and 0.80, respectively. CONCLUSIONS: The U-Net neural network can achieve excellent results in the delineation of different cardiac structures of short-axis cardiac MRI. The high-quality segmentation allows for the correct measurement of left ventricular hyper-trabeculation and a definitive diagnosis of LVNC illness. Using this kind of solution could lead to more objective and faster analysis, reducing human error and time spent by cardiologists.

Caracterización de la tipología circadiana en estudiantes universitarios en relación con el tipo de carrera / Characterization of the circadian typology in university students in relation to the type of career

RESUMEN Fundamento: El cronotipo es un atributo de los seres humanos, que refleja su fase circadiana individual, y repercute en las funciones biológicas y psicológicas, tanto en la salud como en la enfermedad. Su estudio es particularmente valioso en escenarios educacionales. Objetivo: caracterizar el cronotipo de estudiantes universitarios en relación con el tipo de carrera que estudian. Métodos: e realizó un estudio analítico trasversal, en una serie de 273 estudiantes universitarios, seleccionados por muestreo aleatorio simple, estructurados en tres grupos bajo criterio de procedencia: 88 de Ciencias Técnicas, 88 de Ciencias Sociales y Humanísticas y 97 de Ciencias Médicas. Se exploró el cronotipo de cada sujeto por medio del Cuestionario de Matutinidad- Vespertinidad. Para cada grupo fueron calculadas las puntuaciones medias resultantes del cuestionario y las proporciones de individuos matutinos, intermedios y vespertinos. Resultados: las puntuaciones medias de los tres grupos estuvieron enmarcadas en el rango de cronotipo intermedio, y no se constaron diferencias estadísticamente significativas. El 67 % de los sujetos fueron clasificados como intermedios, el 23,8 % como matutinos y el 9,2 % como vespertinos; las proporciones de los cronotipos por grupos tampoco mostraron diferencias significativas. Conclusión: existió un claro predominio del cronotipo intermedio, seguido en frecuencia por el matutino y el vespertino. No se demostró que el tipo de carrera influyera en las puntuaciones, ni en las proporciones de las tipologías circadianas por grupos.

ABSTRACT Foundation: Chronotype is an attribute of human beings, which reflects its individual circadian phase, and affects biological and psychological functions, both in health and disease. Its study is particularly valuable in educational settings. Objective: to characterize the chronotype of university students in relation to the type of career they study. Methods: a cross-sectional analytical study was conducted in a series of 273 university students, selected by simple random sampling, structured in three groups based on provenance criteria: 88 from Technical Sciences, 88 from Social and Humanistic Sciences and 97 from Medical Sciences. The chronotype of each subject was explored through the Morningness and Eveningness Questionnaire. For each group the mean scores of the questionnaire and the proportions of morning, intermediate and evening individuals were calculated. Results: the mean scores of the three groups were framed in the intermediate chronotype range, and there were no statistically significant differences. Subjects were classified as 67% of as intermediate, 23.8% as morning and 9.2 % as evening; chronotype proportions by groups also showed no significant differences. Conclusion: there was a clear predominance of intermediate chronotype, followed in frequency by morning and evening. It was not demonstrated that the type of career influenced scores, nor in proportions of the circadian typologies by groups.

Familial clustering of bicuspid aortic valve and its relationship with aortic dilation in first-degree relatives.

OBJECTIVE: Bicuspid aortic valve (BAV) is the most common congenital heart disease. This study aimed to determine the prevalence rate of BAV in first-degree relatives (FDR) and the inheritance pattern according to different morphotypes and aortic dilation. METHODS: BAV probands were consecutively studied at eight tertiary referral centres. After sequential screening, FDR were included in the study. The BAV morphotype, aortic dilation and aortic phenotype were assessed by transthoracic echocardiography. RESULTS: Seven hundred and twenty-four FDR of 256 BAV probands agreed to undergo family screening. The prevalence of BAV was 6.4% in FDR (9.2% in men, 3.5% in women, p=0.002). Aortic dilation was diagnosed in 9.6% of FRD with tricuspid aortic valves (TAV), with a root phenotype in 2.7% and tubular in 6.9% and more frequently in the presence of arterial hypertension (OR 4.48; CI 95% 2.51 to 7.99; p=0.0001) and valvular regurgitation (OR 5.87, CI 95% 1.37 to 25.16; p=0.025). The heritability (h2 ) of BAV was highly significant (0.47; p=0.002); however, no concordance was observed among valve morphotypes. Aortic dilation heritability was not significant. CONCLUSIONS: The BAV prevalence rate in FDR was low (6.4%) but aortic dilation was observed in 9.6% of FDR with TAV. The heritability of BAV was high without concordance in valve morphotypes, and aortic dilation heritability was not observed. Patients with BAV should be made aware of its familial pattern.

Selección de lo mejor del año 2017 en imagen cardiovascular en las cardiopatías familiares / Selection of the best of the year 2017 in cardiovascular imaging in familial cardiopathies

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Anatomical and clinical predictors of valve dysfunction and aortic dilation in bicuspid aortic valve disease.

OBJECTIVE: Bicuspid aortic valve (BAV) is associated with early valvular dysfunction and proximal aorta dilation with high heterogeneity. This study aimed to assess the determinants of these complications. METHODS: Eight hundred and fifty-two consecutive adults diagnosed of BAV referred from cardiac outpatient clinics to eight echocardiographic laboratories of tertiary hospitals were prospectively recruited. Exclusion criteria were aortic coarctation, other congenital disorders or intervention. BAV morphotype, significant valve dysfunction and aorta dilation (≥2 Z-score) at sinuses and ascending aorta were established. RESULTS: Three BAV morphotypes were identified: right-left coronary cusp fusion (RL) in 72.9%, right-non-coronary (RN) in 24.1% and left-non-coronary (LN) in 3.0%. BAV without raphe was observed in 18.3%. Multivariate analysis showed aortic regurgitation (23%) to be related to male sex (OR: 2.80, p<0.0001) and valve prolapse (OR: 5.16, p<0.0001), and aortic stenosis (22%) to BAV-RN (OR: 2.09, p<0.001), the presence of raphe (OR: 2.75, p<0.001), age (OR: 1.03; p<0.001), dyslipidaemia (OR: 1.77, p<0.01) and smoking (OR: 1.63, p<0.05). Ascending aorta was dilated in 76% without differences among morphotypes and associated with significant valvular dysfunction. By contrast, aortic root was dilated in 34% and related to male sex and aortic regurgitation but was less frequent in aortic stenosis and BAV-RN. CONCLUSIONS: Normofunctional valves are more prevalent in BAV without raphe. Aortic stenosis is more frequent in BAV-RN and associated with some cardiovascular risk factors, whereas aortic regurgitation (AR) is associated with male sex and sigmoid prolapse. Although ascending aorta is the most commonly dilated segment, aortic root dilation is present in one-third of patients and associated with AR. Remarkably, BAV-RL increases the risk for dilation of the proximal aorta, whereas BAV-RN spares this area.

Selección de lo mejor del año 2016 en ecocardiografía para la valoración de las valvulopatías / Selection of the best of 2016 in echocardiography in heart valve disease

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Selección de lo mejor del año 2016 en imagen cardiaca: Novedades en cardiorresonancia magnética de estrés / Selection of the best of 2016 in cardiac imaging: Advances in stress cardiac magnetic resonance

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Nueva mutación fundadora en MYBPC3: comparación fenotípica con la mutación de MYBPC3 más frecuente en España / A novel founder mutation in MYBPC3: Phenotypic comparison with the most prevalent MYBPC3 mutation in Spain

Introducción y objetivos: Las mutaciones en MYBPC3 son causa de miocardiopatía hipertrófica (MCH). A pesar de que la mayoría de ellas producen una proteína truncada, la gravedad del fenotipo es diversa. Se describe el fenotipo clínico de una nueva mutación en MYBPC3, p.Pro108Alafs*9, presente en 13 familias del sur de España, y se compara con la mutación de MYBPC3 con mayor prevalencia en dicha región (c.2308 + 1 G > A). Métodos: Se estudió a 107 familiares de 13 casos índice que tenían diagnóstico de MCH y portaban la mutación p.Pro108Alafs*9. Se realizó un análisis del árbol genealógico, junto con una evaluación clínica y determinación del genotipo. Resultados: Se identificó en total a 54 portadores de la mutación p.Pro108Alafs*9, de los que 39 tenían MCH. Hubo 5 casos de muerte súbita en las 13 familias. La penetrancia de la enfermedad aumentaba a medida que se incrementaba la edad, y los pacientes con MCH fueron con más frecuencia varones, y estos contrajeron la enfermedad más precozmente que las mujeres. El fenotipo fue similar en la p.Pro108Alafs*9 y la c.2308 + 1 G > A, pero se observaron diferencias en varios factores de riesgo y en la supervivencia. Hubo tendencia a mayor masa ventricular izquierda en la p.Pro108Alafs*9 que en la c.2308 + 1G > A. La resonancia magnética cardiaca reveló una extensión y un patrón de fibrosis similares en ambas. Conclusiones: La mutación p.Pro108Alafs*9 se asoció a MCH, alta penetrancia y aparición de la enfermedad a mediana edad (AU)

Introduction and objectives: Mutations in MYBPC3 are the cause of hypertrophic cardiomyopathy (HCM). Although most lead to a truncating protein, the severity of the phenotype differs. We describe the clinical phenotype of a novel MYBPC3 mutation, p.Pro108Alafs*9, present in 13 families from southern Spain and compare it with the most prevalent MYBPC3 mutation in this region (c.2308 + 1 G > A). Methods: We studied 107 relatives of 13 index cases diagnosed as HCM carriers of the p.Pro108Alafs*9 mutation. Pedigree analysis, clinical evaluation, and genotyping were performed. Results: A total of 54 carriers of p.Pro108Alafs*9 were identified, of whom 39 had HCM. There were 5 cases of sudden death in the 13 families. Disease penetrance was greater as age increased and HCM patients were more frequently male and developed disease earlier than female patients. The phenotype was similar in p.Pro108Alafs*9 and in c.2308 + 1 G > A, but differences were found in several risk factors and in survival. There was a trend toward a higher left ventricular mass in p.Pro108Alafs*9 vs c.2308 + 1G > A. Cardiac magnetic resonance revealed a similar extent and pattern of fibrosis. Conclusions: The p.Pro108Alafs*9 mutation is associated with HCM, high penetrance, and disease onset in middle age (AU)

Two-dimensional transthoracic echocardiographic normal reference ranges for proximal aorta dimensions: results from the EACVI NORRE study.

AIMS: To report normal reference ranges for echocardiographic dimensions of the proximal aorta obtained in a large group of healthy volunteers recruited using state-of-the-art cardiac ultrasound equipment, considering different measurement conventions, and taking into account gender, age, and body size of individuals. METHODS AND RESULTS: A total of 704 (mean age: 46.0 ± 13.5 years) healthy volunteers (310 men and 394 women) were prospectively recruited from the collaborating institutions of the Normal Reference Ranges for Echocardiography (NORRE) study. A comprehensive echocardiographic examination was obtained in all subjects following pre-defined protocols. Aortic dimensions were obtained in systole and diastole, following both the leading-edge to leading-edge and the inner-edge to inner-edge conventions. Diameters were measured at four levels: ventricular-arterial junction, sinuses of Valsalva, sino-tubular junction, and proximal tubular ascending aorta. Measures of aortic root in the short-axis view following the orientation of each of the three sinuses were also performed. Men had significantly larger body sizes when compared with women, and showed larger aortic dimensions independently of the measurement method used. Dimensions indexed by height and body surface area are provided, and stratification by age ranges is also displayed. In multivariable analysis, the independent predictors of aortic dimensions were age, gender, and height or body surface area. CONCLUSION: The NORRE study provides normal values of proximal aorta dimensions as assessed by echocardiography. Reference ranges for different anatomical levels using different (i) measurement conventions and (ii) at different times of the cardiac cycle (i.e. mid-systole and end-diastole) are provided. Age, gender, and body size were significant determinants of aortic dimensions.

Adult echocardiographic nomograms: overview, critical review and creation of a software for automatic, fast and easy calculation of normal values.

There is a crescent interest on normal adult echocardiographic values and the introduction of new deformation imaging and 3D parameters pose the issue of normative data. A multitude of nomograms has been recently published, however data are often fragmentary, difficult to find, and their strengths/limitations have been never evaluated. AIMS: (I) to provide a review of current echocardiographic nomograms; (II) to generate a tool for easy and fast access to these data. A literature search was conducted accessing the National Library of Medicine using the keywords: 2D/3D echocardiography, strain, left/right ventricle, atrial, mitral/tricuspid valve, aorta, reference values/nomograms/normal values. Adding the following keywords, the results were further refined: range/intervals, myocardial velocity, strain rate and speckle tracking. Forty one published studies were included. Our study reveals that for several of 2D/3D parameters sufficient normative data exist, however, a few limitations still persist. For some basic parameters (i.e., mitral/tricuspid/pulmonary valves, great vessels) and for 3D valves data are scarce. There is a lack of studies evaluating ethnic differences. Data have been generally expressed as mean values normalised for gender and age instead of computing models incorporating different variables (age/gender/body sizes) to calculate z scores. To summarize results a software (Echocardio-Normal Values) who automatically calculate range of normality for a broad range of echocardiographic measurements according to age/gender/weight/height, has been generated. We provide an up-to-date and critical review of strengths/limitation of current adult echocardiographic nomograms. Furthermore we generated a software for automatic, easy and fast access to multiple echocardiographic normative data.

The genetic component of bicuspid aortic valve and aortic dilation. An exome-wide association study.

BACKGROUND: Bicuspid aortic valve is the most common cardiovascular congenital malformation affecting 2% of the general population. The incidence of life-threatening complications, the high heritability, and familial clustering rates support the interest in identifying risk or protective genetic factors. The main objective of the present study was to identify population-based genetic variation associated with bicuspid aortic valve and concomitant ascending aortic dilation. MATERIALS AND METHODS: A cross-sectional exome-wide association study was conducted in 565 Spanish cases and 484 controls. Single-marker and gene-based association analyses enriched for low frequency and rare genetic variants were performed on this discovery stage cohort and for the subsets of cases with and without ascending aortic dilation. Discovery-stage association signals and additional markers indirectly associated with bicuspid aortic valve, were genotyped in a replication cohort that comprised 895 Caucasian cases and 1483 controls. RESULTS: Although none of the association signals were consistent across series, the involvement of HMCN2 in calcium metabolism and valve degeneration caused by calcium deposit, and a nominal but not genome-wide significant association, supported it as an interesting gene for follow-up studies on the genetic susceptibility to bicuspid aortic valve. CONCLUSIONS: The absence of a genome-wide significant association signal shows this valvular malformation may be more genetically complex than previously believed. Exhaustive phenotypic characterization, even larger datasets, and collaborative efforts are needed to detect the combination of rare variants conferring risk which, along with specific environmental factors, could be causing the development of this disease.

Three-Dimensional Morphology of the Left Ventricular Outflow Tract: Impact on Grading Aortic Stenosis Severity.

BACKGROUND: Left ventricular outflow tract (LVOT) measurement is a critical step in the quantification of aortic valve area. The assumption of a circular morphology of the LVOT may induce some errors. The aim of this study was to assess the three-dimensional (3D) morphology of the LVOT and its impact on grading aortic stenosis severity. METHODS: Fifty-eight patients with aortic stenosis were studied retrospectively. LVOT dimensions were measured using 3D transesophageal echocardiography at three levels: at the hinge points (HP) of the aortic valve and at 4 and 8 mm proximal to the annular plane. Results were compared with standard two-dimensional echocardiographic measurements. RESULTS: Three-dimensional transesophageal echocardiography showed a funnel shape that was more circular at the HP and more elliptical at 4 and 8 mm proximal to the annular plane (circularity index = 0.92 vs 0.83 vs 0.76, P < .001). Cross-sectional area was smaller at the HP and larger at 4 and 8 mm from the annular plane (3.6 vs 3.9 vs 4.1 cm2, P = .001). The best correlation between two-dimensional and 3D transesophageal echocardiographic dimensions was at the HP (intraclass correlation coefficient = 0.75; 95% CI, 0.59-0.86). When the HP approach was selected, there was a reduction in the percentage of patients with low flow (from 41% to 29%). CONCLUSIONS: A large portion of patients with aortic stenosis have funnel-shaped and elliptical LVOTs, a morphology that is more pronounced in the region farther from the annular plane. Two-dimensional LVOT measurement closer to the annular plane has the best correlation with 3D measurements. Measurement of the LVOT closer to the annular plane should be encouraged to reduce measurement errors.

A Novel Founder Mutation in MYBPC3: Phenotypic Comparison With the Most Prevalent MYBPC3 Mutation in Spain.

INTRODUCTION AND OBJECTIVES: Mutations in MYBPC3 are the cause of hypertrophic cardiomyopathy (HCM). Although most lead to a truncating protein, the severity of the phenotype differs. We describe the clinical phenotype of a novel MYBPC3 mutation, p.Pro108Alafs*9, present in 13 families from southern Spain and compare it with the most prevalent MYBPC3 mutation in this region (c.2308+1 G>A). METHODS: We studied 107 relatives of 13 index cases diagnosed as HCM carriers of the p.Pro108Alafs*9 mutation. Pedigree analysis, clinical evaluation, and genotyping were performed. RESULTS: A total of 54 carriers of p.Pro108Alafs*9 were identified, of whom 39 had HCM. There were 5 cases of sudden death in the 13 families. Disease penetrance was greater as age increased and HCM patients were more frequently male and developed disease earlier than female patients. The phenotype was similar in p.Pro108Alafs*9 and in c.2308+1 G>A, but differences were found in several risk factors and in survival. There was a trend toward a higher left ventricular mass in p.Pro108Alafs*9 vs c.2308+1G>A. Cardiac magnetic resonance revealed a similar extent and pattern of fibrosis. CONCLUSIONS: The p.Pro108Alafs*9 mutation is associated with HCM, high penetrance, and disease onset in middle age.