Septal Morphology Research Articles

Atrial septal defect morphology and stenting in hypoplastic left heart syndrome after hybrid palliation.

Complex morphologies were more frequently related to restrictiveness. Stenting technique has a crucial role, as the procedure carries a significant risk for stent migration. Effective treatment of restrictive atrial septal defect is related to a better outcome, as it leads to equalisation of survival between patients with and those without restrictive atrial septal defect.

Nonfamilial Hypertrophic Cardiomyopathy: Prevalence, Natural History, and Clinical Implications.

Yield of causative variants in hypertrophic cardiomyopathy (HCM) is increased in some probands, suggesting different clinical subgroups of disease occur. We hypothesized that a negative family history and no sarcomere mutations represent a nonfamilial subgroup of HCM. We sought to determine the prevalence, natural history, and potential clinical implications of this nonfamilial subgroup of HCM. Four hundred and thirteen unrelated probands with HCM seen in a specialized HCM center between 2002 and 2015 and genetic testing performed were included in this retrospective cohort study. There were 251 (61%) probands with no reported family history of HCM, including 166 (40% of total) probands with no sarcomere mutation, that is, nonfamilial HCM. Quantified family pedigree data revealed no difference in mean number of first-degree relatives screened between nonfamilial and sarcomere-positive groups. Adjusted predictors of nonfamilial status were older age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P=0.0001), male sex (odds ratio, 1.96; 95% confidence interval, 1.11-3.45; P=0.02), hypertension (odds ratio, 2.80; 95% confidence interval, 1.57-5.00; P=0.0005), and nonasymmetric septal morphology (odds ratio, 3.41; 95% confidence interval, 1.64-7.08; P=0.001). They had a less severe clinical course with greater event-free survival from major cardiac events (P=0.04) compared with sarcomere-positive HCM probands. Genotype prediction scores showed good performance in identifying genotype-positive patients (area under the curve, 0.71-0.75) and, in combination with pedigree characteristics, were further improved. Approximately 40% of HCM probands have a nonfamilial subtype, with later onset and less severe clinical course. We propose a revised clinical pathway for management, highlighting the role of genetic testing, a detailed pedigree, and refined clinical surveillance recommendations for family members.

Prevalence and Impact of Coexistent Bicuspid Aortic Valve in Hypertrophic Cardiomyopathy

The association between bicuspid aortic valve (BAV) and hypertrophic cardiomyopathy (HCM) has been reported but its true prevalence is unknown. This study investigated the prevalence and clinical impact of coexistent BAV in a large referral HCM population. Retrospective analysis of 3765 echocardiograms between 2004 and 2014 in 2640 consecutive patients with HCM was performed to assess for BAV. Patients with coexistent conditions were studied. Twenty-three patients (0.9%) were identified with coexisting BAV and HCM. Mean age was 52±16years, 18 males (78%), 16 with NYHA functional class I/II at initial evaluation (70%). A family history of HCM was present in five patients (22%); none had a family history of BAV or aortopathy. Maximal left ventricular wall thickness was 24±6mm; the majority had either reverse curve or sigmoid septal morphology. Moderate or greater aortic valve dysfunction was present in seven patients (30%), BAV-related aortopathy in 18 patients (78%) and dynamic left ventricular outflow tract (LVOT) obstruction in nine patients (39%). Three patients had combined LVOT obstruction and aortic stenosis. Median time from diagnosis of BAV or HCM to last follow-up was 11±12.5years. At last follow-up, 22% had undergone BAV-related surgeries, 30% had septal reduction therapy (SRT), and 17% had combined SRT and BAV-related surgeries. Overall survival was 95% at 10 years. This study reported a 0.9% prevalence of BAV among HCM population, similar to the general population. Aortopathy and LVOT obstruction were common, necessitating cardiac interventions in over one-third of cases. Long-term survival appeared favourable.

NON-FAMILIAL HYPERTROPHIC CARDIOMYOPATHY: PREVALENCE, NATURAL HISTORY AND CLINICAL IMPLICATIONS

Background: The yield of positive sarcomere mutations in hypertrophic cardiomyopathy (HCM) is increased in probands with a family history of disease, younger age and asymmetric septal morphology, suggesting different clinical subgroups of disease occur. We hypothesized probands with no family

Influence of nasal septum deformity on nasal obstruction, disease severity, and medical treatment response among children and adolescents with persistent allergic rhinitis

ObjectiveTo evaluate the impact of different types of nasal septum deformity (NSD) on nasal obstruction, rhinitis severity and response to medical treatment among pediatric persistent allergic rhinitis (PER) patients. MethodsIn a prospective, real-life study, 150 children and adolescents (mean age 13 ± 2.8 years, females 32.6%) diagnosed with PER according to ARIA guidelines were assessed by nasal endoscopy for NSD according to Mladina's classification, their response to medical treatment (intranasal steroids and antihistamines or antileucotriens), the presence of comorbidities, rhinitis severity (modified-ARIA criterion) and nasal obstruction visual analog scale score (VAS). ResultsMost patients (87%) had 1 of the 7 types of septal deformities. There was a high prevalence of bilateral (types 4 and 6; 46%) and anterior unilateral (types 1 and 2; 25%) NSD in patients not responding to medical treatment. Type 4 (OR = 6.4; p = 0.005) or type 6 (OR = 4.4; p = 0.03) NSD increased the risk of lack of improvement with medical treatment. Coexistence of anterior unilateral or bilateral NSD with severe turbinate enlargement increased >20-fold the risk of lack of improvement. Patients with bilateral NSD presented greater rhinitis severity. Non-responder adolescents displayed higher prevalence of bilateral NSD than children (53% vs. 23%; p = 0.02). Nasal obstruction VAS was higher for patients with anterior than posterior NSD, and greater for patients with bilateral NSD than any other type of septal morphology. ConclusionNasal endoscopy shows that bilateral and unilateral anterior nasal septum deformities are strongly associated with a poor response to medical treatment, greater rhinitis severity and higher nasal obstruction VAS. Consequently, nasal endoscopy is necessary in the PER patients to understand the disease severity as well as to plan a specific surgical treatment in order to improve nasal obstruction, disease severity, and patient's quality of life.

Comparative cephalopod shell strength and the role of septum morphology on stress distribution.

The evolution of complexly folded septa in ammonoids has long been a controversial topic. Explanations of the function of these folded septa can be divided into physiological and mechanical hypotheses with the mechanical functions tending to find widespread support. The complexity of the cephalopod shell has made it difficult to directly test the mechanical properties of these structures without oversimplification of the septal morphology or extraction of a small sub-domain. However, the power of modern finite element analysis now permits direct testing of mechanical hypothesis on complete, empirical models of the shells taken from computed tomographic data. Here we compare, for the first time using empirical models, the capability of the shells of extant Nautilus pompilius, Spirula spirula, and the extinct ammonite Cadoceras sp. to withstand hydrostatic pressure and point loads. Results show hydrostatic pressure imparts highest stress on the final septum with the rest of the shell showing minimal compression. S. spirula shows the lowest stress under hydrostatic pressure while N. pompilius shows the highest stress. Cadoceras sp. shows the development of high stress along the attachment of the septal saddles with the shell wall. Stress due to point loads decreases when the point force is directed along the suture as opposed to the unsupported chamber wall. Cadoceras sp. shows the greatest decrease in stress between the point loads compared to all other models. Greater amplitude of septal flutes corresponds with greater stress due to hydrostatic pressure; however, greater amplitude decreases the stress magnitude of point loads directed along the suture. In our models, sutural complexity does not predict greater resistance to hydrostatic pressure but it does seem to increase resistance to point loads, such as would be from predators. This result permits discussion of palaeoecological reconstructions on the basis of septal morphology. We further suggest that the ratio used to characterize septal morphology in the septal strength index and in calculations of tensile strength of nacre are likely insufficient. A better understanding of the material properties of cephalopod nacre may allow the estimation of maximum depth limits of shelled cephalopods through finite element analysis.

Percutaneous Intervention to Treat Platypnea-Orthodeoxia Syndrome: TheToronto Experience.

This study reviewed a series of patients treated with transcatheter closure of septal defect to treat platypnea-orthodeoxia syndrome, with specific attention to septal characteristics and device choice. Platypnea-orthodeoxia syndrome is an uncommon condition characterized by positional dyspnea and hypoxemia due to intracardiac right-to-left shunting through a patent foramen ovale (PFO), an atrial septal defect, or pulmonary arteriovenous malformations. Percutaneous closure of such defects is the treatment of choice. In this single-center series, 52 patients were treated with percutaneous closure of an interatrial communication after presentation between January 1997 and July 2015. Septal morphology, clinical, procedural, and outcomesdata were analyzed. All patients had a PFO; however, nearly one-quarter required a non-PFO device (11 Amplatzer Septal Occluder and 1 post-infarct muscular VSD), as opposed to a dedicated PFO device to achieve shunt occlusion. These patients werecharacterized by an aneurysmal septum, shorter primum septum overlap with the secundum septum, and greaterseptal angulation from the midline. After closure, all demonstrated acute improvements in oxygen saturation (pre-procedure: 81 ± 8%; post-procedure: 95.1 ± 0.5% on room air). Each patient was treated with a single device and no one required re-intervention. Patients presenting with platypnea-orthodeoxia syndrome can be treated successfully with a percutaneous intervention often requiring a variety of devices. Those requiring a non-PFO-type device had a greater prevalence of an aneurysmal septum, shorter primum septal overlap with the secundum septum, and greater septal angulation with the midline.

Overexpression of SepJ alters septal morphology and heterocyst pattern regulated by diffusible signals in Anabaena.

Filamentous, N2 -fixing, heterocyst-forming cyanobacteria grow as chains of cells that are connected by septal junctions. In the model organism Anabaena sp. strain PCC 7120, the septal protein SepJ is required for filament integrity, normal intercellular molecular exchange, heterocyst differentiation, and diazotrophic growth. An Anabaena strain overexpressing SepJ made wider septa between vegetative cells than the wild type, which correlated with a more spread location of SepJ in the septa as observed with a SepJ-GFP fusion, and contained an increased number of nanopores, the septal peptidoglycan perforations that likely accommodate septal junctions. The septa between heterocysts and vegetative cells, which are narrow in wild-type Anabaena, were notably enlarged in the SepJ-overexpressing mutant. Intercellular molecular exchange tested with fluorescent tracers was increased for the SepJ-overexpressing strain specifically in the case of calcein transfer between vegetative cells and heterocysts. These results support an association between calcein transfer, SepJ-related septal junctions, and septal peptidoglycan nanopores. Under nitrogen deprivation, the SepJ-overexpressing strain produced an increased number of contiguous heterocysts but a decreased percentage of total heterocysts. These effects were lost or altered in patS and hetN mutant backgrounds, supporting a role of SepJ in the intercellular transfer of regulatory signals for heterocyst differentiation.

The Impact of Middle Turbinate Concha Bullosa on the Severity of Inferior Turbinate Hypertrophy in Patients with a Deviated Nasal Septum.

Inferior turbinate hypertrophy and concha bullosa often occur opposite the direction of nasal septal deviation. The objective of this retrospective study was to determine whether a concha bullosa impacts inferior turbinate hypertrophy in patients who have nasal septal deviation. The electronic medical record was used to identify sinus CT scans exhibiting nasal septal deviation for 100 adult subjects without and 100 subjects with unilateral middle turbinate concha bullosa. Exclusion criteria included previous sinonasal surgery, tumor, sinusitis, septal perforation, and craniofacial trauma. Nasal septal deviation was characterized in the coronal plane by distance from the midline (severity) and height from the nasal floor. Measurement differences between sides for inferior turbinate width (overall and bone), medial mucosa, and distance to the lateral nasal wall were calculated as inferior turbinate hypertrophy indicators. The cohorts with and without concha bullosa were similarly matched for age, sex, and nasal septal deviation severity, though nasal septal deviation height was greater in the cohort with concha bullosa than in the cohort without concha bullosa (19.1 ± 4.3 mm versus 13.5 ± 4.1 mm, P < .001). Compensatory inferior turbinate hypertrophy was significantly greater in the cohort without concha bullosa than in the cohort with it as measured by side-to-side differences in turbinate overall width, bone width, and distance to the lateral nasal wall (P < .01), but not the medial mucosa. Multiple linear regression analyses found nasal septal deviation severity and height to be significant predictors of inferior turbinate hypertrophy with positive and negative relationships, respectively (P < .001). Inferior turbinate hypertrophy is directly proportional to nasal septal deviation severity and inversely proportional to nasal septal deviation height. The effect of a concha bullosa on inferior turbinate hypertrophy is primarily mediated through influence on septal morphology, because the nasal septal deviation apex tends to be positioned more superior from the nasal floor in these patients.

Genotype-phenotype Correlations of Hypertrophic Cardiomyopathy When Diagnosed in Children, Adolescents, and Young Adults.

Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiovascular disease and a leading cause of identifiable sudden cardiac death (SCD) in the young. Herein, we sought to determine the genotype-phenotype correlations in a cohort of unrelated, genotyped patients diagnosed with HCM at a young age, as well as to characterize the differences between HCM diagnosed in adulthood and HCM diagnosed at a young age. From 1999 to 2011, 1053 unrelated patients diagnosed with HCM were enrolled in research-based genetic testing. The electronic medical record was reviewed to identify those with HCM diagnosed at ≤21 years (N = 137, mean age at diagnosis 13.2 ± 6 years, 64% male). From this cohort of patients recruited from a tertiary care referral center, the genetic test was positive in 71 (52%), which was significantly higher than patients diagnosed >21 years (31%; P < .001). Genotype-positive patients had increased maximum left ventricular wall thickness (24.9 ± 8.0 vs. 21.6 ± 7.4 mm, P = .01) and higher incidence of reverse-curve ventricular septal morphology (71% vs. 40%, P < .001). Unrelated to genotype status, 26/137 patients (19%) experienced significant HCM-related morbidity/mortality including progressive heart failure symptoms in 12, transplantation in 4, and death in 10. Among patients diagnosed with HCM during the first two decades of life, the yield of genetic testing is significantly higher than when diagnosed at later age. While the phenotype of young HCM patients is worse than patients whose HCM is diagnosed at later age, the phenotypes of genotype-positive and genotype-negative young patients were similar. Independent of genotype, nearly 30% of the patients with follow-up in this study had symptom progression, transplant, or death.

Predictive Value of Computed Tomography in Acute Pulmonary Embolism: Systematic Review and Meta-analysis

BackgroundMany computed tomography (CT) parameters have been proposed as potential predictors of outcome in acute pulmonary embolism. We sought to summarize available evidence on the predictive value of CT severity parameters for short-term clinical outcome in pulmonary embolism. MethodsWe searched PubMed and EMBASE through February 2014 for studies that reported on the association between CT parameters of acute pulmonary embolism severity and short-term (≤6 months) clinical outcome. Risk estimates for quantitative parameters of right ventricular (RV) dysfunction (abnormally increased RV/left ventricular [LV] diameter ratio on transverse sections and 4-chamber views), qualitative parameters of RV dysfunction (abnormal septal morphology and contrast reflux), thrombus load, and central thrombus location were derived using random effect regression analysis. Meta-regression analysis was performed to quantify and explain study heterogeneity. ResultsA total of 49 studies with 13,162 patients with acute pulmonary embolism (median age of 61 years, 55.1% were women) who underwent diagnostic CT imaging were included in the analysis. An abnormally increased RV/LV diameter ratio measured on transverse sections was associated with an approximately 2.5-fold risk for all-cause mortality (pooled odds ratio [OR], 2.5; 95% confidence interval [CI], 1.8-3.5) and adverse outcome (OR, 2.3; 95% CI, 1.6-3.4) and a 5-fold risk for pulmonary embolism-related mortality (OR, 5.0; 95% CI, 2.7-9.2). Thrombus load (OR, 1.6, 95% CI, 0.7-3.9; P = .2896) and central location (OR, 1.7; 95% CI, 0.7-4.2; P = .2609) were not predictive for all-cause mortality, although both were associated with adverse clinical outcome. ConclusionsAcross all end points, the RV/LV diameter ratio on transverse CT sections has the strongest predictive value and most robust evidence base for adverse clinical outcomes in patients with acute pulmonary embolism.

The year in cardiology 2014: imaging.

Non-invasive cardiac imaging is pivotal for the diagnosis and decision making of patients with cardiovascular diseases. Recent innovations in echocardiography, nuclear imaging, computed tomography, and cardiac magnetic resonance have provided novel pathophysiological insights that may impact on the clinical management of patients. The current review provides a summary of selected articles on technological innovations in imaging and emerging clinical applications. In 2014, many articles were published on the use of non-invasive cardiovascular imaging, including echocardiography, nuclear imaging, computed tomography (CT), and cardiac magnetic resonance (CMR) imaging. A selection of these articles is presented here. The focus is on technical innovations and emerging applications in clinical cardiology. Accumulating data have demonstrated the role of speckle tracking echocardiography (STE) in characterization left ventricular (LV) mechanics and risk stratification of patients with various cardiac diseases. Geske et al .1 demonstrated that LV septal morphology rather than genetic basis is the main determinant of regional LV strain abnormalities in patients with hypertrophic cardiomyopathy (HCM). Genotype-positive HCM patients ( n = 51) were more likely to have reverse curve morphology of the interventricular septum (59%) whereas genotype-negative patients ( n = 80) had more frequently sigmoidal septal curvature (49%). Interestingly, while global LV strain (GLS) was not significantly different between groups, regional strain analysis revealed that genotype-positive HCM patients had significantly more impaired longitudinal strain in the mid inferoseptal, basal inferoseptal, and basal anteroseptal regions compared with genotype-negative patients. When patients were divided according to genotype and LV septal morphology, LV GLS was significantly more impaired among genotype-positive HCM patients with a reverse septal curvature than in genotype-negative HCM patients with a sigmoid septal morphology ( Figure 1 ). Figure 1 Speckle tracking echocardiography …

Genotype-Phenotype Correlations in Apical Variant Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy is underscored by profound phenotypic and genotypic heterogeneity. Echocardiographically, hypertrophic cardiomyopathy can be categorized into four morphological subtypes: reverse curve, sigmoidal, neutral contour, and apical variant. Previous studies indicate that reverse curve hypertrophic cardiomyopathy is the strongest predictor of a positive genetic test. Little is known about the spectrum and prevalence of mutations and genotype-phenotype correlations in apical hypertrophic cardiomyopathy. Between 1999 and 2007, 1053 patients with the diagnosis of hypertrophic cardiomyopathy (60% male, age at diagnosis 44.4 ± 19 years) underwent sarcomeric genetic testing. Blinded to the genetic test results, each echocardiogram was scored for septal morphology and phenotyping was performed using the patient's medical record. Subset analysis was performed to elucidate the genotype, phenotype, and outcome of apical hypertrophic cardiomyopathy. Overall, 71 patients (7%) had apical hypertrophic cardiomyopathy on echocardiography (63% male, mean age 47.8 ± 15 years, mean left ventricular wall thickness 19.8 ± 6 mm). Left ventricular outflow tract obstruction was uncommon (seven patients; 10%). Eighteen patients (25%) had a positive genetic test, with the majority of mutations found in MYBPC3 (six; 35%) and MYH7 (six; 35%). Follow-up was available on 68 patients (96%) with a median age of 57.3 years (range 19.3-82 years). Mean follow-up was 5.5 years (range 0.1-18.2 years). There was no statistical difference between the occurrence rates of adverse events between genotype-positive and genotype-negative groups. In this largest cohort of patients with genetic testing for hypertrophic cardiomyopathy, <10% exhibited apical disease. This least common subtype was associated with a negative genetic test result 75% of the time. In contrast to prior publications suggesting a predilection for ACTC1/TPM1 mutations in patients with apical hypertrophic cardiomyopathy, the two most common genotypes (MYBPC3-HCM and MYH7-HCM) remained most common among patients who had a positive genetic test.

Septum Primum Atrial Septal Defect in an Infant with Hypoplastic Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a form of congenital heart disease characterized by severe underdevelopment of the left heart, leading to inadequate systemic blood flow. Several different atrial septal morphologies are observed in HLHS, most commonly a secundum atrial septal defect, patent foramen ovale, intact septum, and leftward displacement of the superior attachment of the septum primum. It has been postulated that atrial septal development is associated with the development of the left heart. We present a case of a newborn infant with HLHS and the unusual finding of a primum ASD.

Use of a murine Advanced Intercross Line combined with whole genome sequencing and transcriptome analysis confirms previously discovered QTL and identifies candidate genetic loci for cardiac atrial septal morphology

truncating Titin (TTN) mutations are present in 25% of familial DCM cases; however, it is unclear whether they are sufficient to cause disease or modify disease susceptibility. The aim of this study was to investigate the prevalence of TTN mutations in an Australian DCM cohort. Targeted re-sequencing of 69 cardiomyopathy genes was conducted on DNA from 60 probands with familial DCM. Truncating TTN mutations were identified in 18 probands (30%) and detailed analysis of genotype-phenotype correlation was performed in six of these families. There was good correlation between truncating TTNmutations and disease in three families with TTN mutations present in all the affected and none of the unaffected family members tested. In the remaining three families, six individualswith TTNmutations but normal echocardiograms were identified. However, these individuals were all younger than 50 years of age at testing suggesting the possibility of age-dependent penetrance. Varying age of diagnosis and disease severity suggest the involvement of additional genetic or acquired factors in at least one family. Truncating TTN mutations are present in a significant proportion of our familial DCM cases. However, further work is required to classify the segregation of these mutations with disease in larger cohorts. Inclusion of TTN in genetic screening should improve the yield from genetic testing to greater than 50% and may potentially improve the management and treatment for these families.

Deformation patterns in genotyped patients with hypertrophic cardiomyopathy

Echocardiographic strain imaging with two-dimensional speckle tracking is an emerging tool for defining cardiac function and identifying preclinical hypertrophic cardiomyopathy (HCM). In HCM, a reverse septal contour is a strong predictor of mutation positive sarcomeric HCM. The objective of this study was to determine whether left ventricular (LV) deformation patterns can differentiate between genotype positive and negative patients within a large HCM cohort. One hundred and thirty one patients (89 males, age 55 ± 15 years) with clinically diagnosed HCM underwent comprehensive transthoracic echocardiography inclusive of LV strain imaging, LV dimensions and ejection fraction, septal contour and thickness, and identification of obstructive physiology. Longitudinal peak systolic strain was assessed from 17 LV myocardial segments blinded to the patient's genetic test results derived from comprehensive genotyping of nine myofilament HCM-associated genes. Genotyping revealed that 51 of 131 patients (39%) were mutation positive for sarcomeric/myofilament-HCM (genotype positive). Regional strain was lower in genotype-positive patients in mid inferoseptal (P = 0.004), basal anteroseptal (P = 0.04), and basal inferoseptal segments (P = 0.002) compared with HCM patients lacking a mutation (genotype negative). Strain patterns in reverse-curve, genotype-positive HCM differed significantly from genotype negative, sigmoidal HCM in multiple segments. However, when comparing genotype-negative and genotype-positive patients with the same septal morphology, there were no significant regional strain differences. Septal thickness positively correlated with global and basal anteroseptal longitudinal strain (r = 0.34 and r = 0.54, respectively, P < 0.0001). Significant regional strain differences in genotyped HCM patients are dependent upon septal morphology or thickness, not genotype. Phenotypic expression of deformation patterns appears heterogeneous.

Abstract 9969: Genotype-phenotype Correlations According to Clinical and Echocardiographic Characteristics in Hypertrophic Cardiomyopathy

Background: Many mutations among genes encoding sarcomeric proteins have been identified in hypertrophic cardiomyopathy (HCM). Data on specific genotype-phenotype correlations are limited and highly variable. Methods: Identified mutations in genes TNNI3 (troponin I), TNNT2 (troponin T), MYBPC3 (myosin-binding protein C) and MYH7 (myosin heavy chain) were screened in 284 patients at the Cardiovascular Genetic Clinic of the Montreal Heart Institute. Mutations were identified in 113 patients (40%) and 84 patients (74%) were included for analysis. Five cardiac transplant recipients without previous echocardiographic images available were analysed according to clinical characteristics only. We excluded 16 patients without HCM phenotype and 13 patients with follow-up outside of our center. Results: MYH7 (40%) and MYBPC3 (40%) mutations were the most common. Only one patient was identified with a TNNI3 (1%) mutation and was excluded. Patients with MYH7 mutations were younger at diagnosis and presented more often with a familial history of sudden cardiac death (76%) and defibrillator implantation (59%). Patients with MYH7 mutations were also more likely to progress to “burn-out” HCM (27%) and cardiac transplantation (18%). Significant mitral insufficiency was more prevalent in patients with MYBPC3 mutations (33%). Patients with TNNT2 (18%) mutations showed an increased probability of having a significant resting and provocable left outflow tract obstruction (47%) with systolic anterior movement of the mitral valve (53%) leading to septal myomectomy (27%). Genotype did not affect septal morphology with an overall predominance of the midseptal form (73% overall). Conclusion: This retrospective study suggests that TNNT2 mutations are associated with obstructive HCM while MYH7 mutations are related with arrhythmic complications. Moreover, septal morphologies do not appear to be influenced by any specific gene mutation.

TCT-760 Mid-term Outcomes of Alcohol Septal Ablation for Obstructive Hypertrophic Cardiomyopathy in Patients with Sigmoid versus Neutral Ventricular Septum

The aim of this study was to determine whether the differences in the baseline septal morphology influenced outcomes of patients after alcohol septal ablation (ASA). A total of 100 consecutive, highly symptomatic patients with HOCM and a neutral or sigmoid septum (74 patients vs 26 patients)

772 Genotype-Phenotype Correlations According to Clinical and Echocardiographic Characteristics in Hypertrophic Cardiomyopathy

772 Genotype-Phenotype Correlations According to Clinical and Echocardiographic Characteristics in Hypertrophic Cardiomyopathy

Evolutionary morphology, cranial biomechanics and the origins of tarsiers and anthropoids

During the Time of Messel, the dominant groups of primates were the adapiform strepsirhines and the tarsiiform haplorhines, both important in discussions of anthropoid origins. Living tarsiers are at the centre of these ideas as one school of thought, representing the Tarsier-Anthropoid Hypothesis, holds they are the sister-group of Anthropoidea. The Tarsier-Tarsiiform Hypothesis, however, maintains that tarsiers are phyletically nested among the (paraphyletic) fossil tarsiiforms (∼omomyids). Orbital morphology is crucial to this debate: the possibility that the postorbital septa of tarsiers and anthropoids are synapomorphic and that it evolved in their last common ancestor to insulate the eyeballs from muscular interference. Our biomechanical model of forces acting on the enormous eyeballs and orbits of tarsiers especially during locomotion provides a strong counterargument to this proposition. The uniquely specialised orbita of Tarsius, which include prominent circumorbital flanges that are continuous with the postorbital septum, are designed to sustain enormous inertial loads transmitted by the eyeballs during the acceleration and deceleration phases of powerful leaping, for which Tarsius is also famous. The eyeballs are thus secured, and pressure absorbed by the retina during acceleration is minimised, by enlarging its surface area of contact with a “walled socket”, i.e., by the extra-fossa expansion of these flanges. The tarsier septum is, therefore, a form–function convergence on the small-eyed anthropoid condition. Several related Eocene tarsiiforms exhibit a precisely Tarsius-like morphology of the rostrum relating to eyeball hypertrophy, although they lack the exaggerated circumorbital and septal morphology and only rarely exhibit postcranial features indicative of super leaping abilities.