Myocardial Crypts Research Articles

Morphological, electrophysiological, and molecular alterations in foetal noncompacted cardiomyopathy induced by disruption of ROCK signalling.

Left ventricular noncompaction cardiomyopathy is associated with heart failure, arrhythmia, and sudden cardiac death. The developmental mechanism underpinning noncompaction in the adult heart is still not fully understood, with lack of trabeculae compaction, hypertrabeculation, and loss of proliferation cited as possible causes. To study this, we utilised a mouse model of aberrant Rho kinase (ROCK) signalling in cardiomyocytes, which led to a noncompaction phenotype during embryogenesis, and monitored how this progressed after birth and into adulthood. The cause of the early noncompaction at E15.5 was attributed to a decrease in proliferation in the developing ventricular wall. By E18.5, the phenotype became patchy, with regions of noncompaction interspersed with thick compacted areas of ventricular wall. To study how this altered myoarchitecture of the heart influenced impulse propagation in the developing and adult heart, we used histology with immunohistochemistry for gap junction protein expression, optical mapping, and electrocardiography. At the prenatal stages, a clear reduction in left ventricular wall thickness, accompanied by abnormal conduction of the ectopically paced beat in that area, was observed in mutant hearts. This correlated with increased expression of connexin-40 and connexin-43 in noncompacted trabeculae. In postnatal stages, left ventricular noncompaction was resolved, but the right ventricular wall remained structurally abnormal through to adulthood with cardiomyocyte hypertrophy and retention of myocardial crypts. Thus, this is a novel model of self-correcting embryonic hypertrabeculation cardiomyopathy, but it highlights that remodelling potential differs between the left and right ventricles. We conclude that disruption of ROCK signalling induces both morphological and electrophysiological changes that evolve over time, highlighting the link between myocyte proliferation and noncompaction phenotypes and electrophysiological differentiation.

Cardiovascular magnetic resonance insights into anomalies of the mitral valve apparatus in Fabry cardiomyopathy and hypertrophic cardiomyopathy.

Despite different etiopathogenesis, Fabry Disease cardiomyopathy (FDc) and sarcomeric hypertrophic cardiomyopathy (HCM) share a similar hypertrophic phenotype, including anomalies of the mitral valve apparatus (AMVA). Some of these anomalies have also been described in the pre-hypertrophic stage of both diseases. This cardiovascular magnetic resonance (CMR) study aimed to: (i) compare AMVA between FDc and HCM with a similar degree of left ventricular hypertrophy (LVH), to add new insights into differential diagnosis; (ii) assess whether AMVA represent an early and progressive alteration in FDc; (iii) propose simple and potentially reproducible measurements of AMVA. This observational, retrospective study enrolled: (i) 80 Fabry patients, divided into three groups with increasing severity of cardiac phenotype (20 patients LVH-/normal T1, 20 patients LVH-/low T1 and 40 patients LVH+), and (ii) 40 patients with HCM. All patients underwent CMR. The LVH + FDc and the HCM groups were matched for age, sex, body surface area and left ventricular (LV) mass. The following AMVA were measured on cine images: papillary muscles (PMs) hypertrophy (maximal diameter (Dmax) of anterolateral (Al) and posteromedial (Pm) PM), apical displacement, anteriorization of Al PM and anterior mitral valve leaflet (AMVL) elongation. Reference values for defining AMVA were derived from a matched healthy control group (n = 40). Both HCM and FDc LVH + patients showed PMs hypertrophy, with a greater degree in the FDc LVH + group [Dmax Al PM 16 ± 3.4 vs. 15 ± 3.1 mm, p 0.017; Dmax Pm PM 14 ± 4.0 vs.12 mm (10.0-14.0), p 0.039] As compared to controls, both HCM and FDc LVH + patients showed PMs apical displacement (HCM 83% vs. healthy volunteers 8%, p < 0.001; FDc LVH + 65% vs. healthy volunteers 8%, p < 0.001), with a greater prevalence in HCM. Anteriorization of Al PM was only evident in HCM (15 ± 6.2 vs. healthy controls 21 ± 5.3 mm, p < 0.001). Elongation of AMVL was detected both in HCM and FDc with LVH + (HCM 29 ± 4.0 vs. healthy volunteers 24 ± 2.9 mm, p < 0.001; FDc LVH + 27 ± 4.0 vs. healthy volunteers 24 ± 2.9 mm, p < 0.001) without significant differences between the two phenocopies. The prevalence of myocardial crypts was higher among HCM patients than in FDc LVH + patients (75% vs. 48%, p 0.012). we report greater PMs hypertrophy in FDc and a higher prevalence of PMs positional alterations (anterior and apical displacement) and myocardial crypts in HCM. All these AMVA became more pronounced with the progression of the FDc phenotype. We suggest the systematic inclusion of the analysis of AMVA by simple linear measurements on cine images in the CMR assessment of hypertrophic cardiomyopathies, to help in the differential diagnosis between HCM and FDc and to facilitate early detection of cardiac involvement in FDc.

Prevalence of Left Ventricular Myocardial Crypts in Japanese Patients.

Objective Myocardial crypts are congenital abnormalities associated with hypertrophic cardiomyopathy (HCM) and other conditions. This study assessed the prevalence of myocardial crypts in Japanese patients. Methods Myocardial crypts were evaluated in a consecutive series of 300 patients (13-92 years old) who underwent computed tomography angiography (CTA) because of clinical suspicion of ischemic heart disease. Results We found a myocardial crypt incidence of 9.7% (29 patients) in our study population, with multiple crypts observed in 2.3% (7 patients). Among these, myocardial crypts were found in 2 out of 8 (25%) patients with hypertrophic cardiomyopathy (HCM), 1 of which was apical-type HCM. In patients with a single crypt (22 patients), the most common location of the crypt was at the left ventricular apex (16/22 patients, 72.7%), followed by the inferior wall (5/22 patients, 22.7%) and the interventricular septum (1/22 patients, 4.6%). Conclusion The incidence of myocardial crypts observed in our study aligns with that reported in previous studies, although the most common location among the Japanese population was the left ventricular apex.

C76 FINDING OF MYOCARDIAL CRYPTS IN SUDDEN CARDIAC ARREST PATIENTS: TWO CASE REPORT

Abstract Left ventricular myocardial crypts are definined as deep blood–filled invaginations trasversing &amp;gt; 50% of the myocardial wall and are located predominantly at the mid–basal segment of inferoseptal wall or at the apical segment. To date the incidence of crypts is 9.1% of patients undergoing cardiac CT and are not associated with intermediate–term major adverse cardiovascular events. However several studies have suggested that the presence of crypts is a marker of myocardial disease that should warrant clinical follow–up prior to the potential development of left ventricular hypertrophy and occurrence of serious cardiovascular events, such as heart failure or death. A lot of publications demonstrate that ventricular crypts could be a pre–phenotypic marker of hypertrophic cardiomyopathy (HCM). HCM is a genetic ereditary cardiomyopathy which is associated with fatal ventricular arrhytmias. We present the case of two patients who had a sudden cardiac arrest resuscitated with cardiac defibrillation. These are two males, 59 and 53 years old respectively, without cardiovascular risk factor and with familiarity for HCM. The first patient had a sudden cardiac arrest during exercise and was resuscitated with early cardiac defibrillation. The second patient had ventricular fibrillation after otolaryngology surgery treated with single defibrillator shock. Coronary arteries were free from atherosclerotic lesions at the angiografy study and no other reversible causes of cardiac arrest were identified. CMR showed normal biventricular funtion and ruled out signs of myocardial oedema or fibrosis. The only morphological finding was the detection of single left ventricular myocardial crypt at the CMR study in both patients: in one patient the crypt was located at the inferior wall while in the other at the level of the septum in the mid–apical segment. Ultimately both patients underwent genetic testing for cardiomyopathy. These findings may be a pre–phenotypic markers of HCM in patients who don’t present a clear expression of the pathology but may be a correlation with sudden cardiac arrest. The rarity of their finding in patient who have had sudden cardiac arrest can be explained by the small survival rate in patients with sudden cardiac arrest. Future studies and the increasingly simple access to advanced imaging methods like CMR and CT will allow us to clarify the role of these myocardial anomalies in the risk of developing fatal arrhythmic events.

Ventricular Septal Crypts: Remnants of Spontaneous Interventricular Defect Closure?

Background: Ventricular crypts are quite a common finding during cardiac imaging, but their etiology is unclear. A possible final result of a spontaneous ventricular septal defect closure has been supposed but never investigated in earlier studies. Method: From January 1997 to December 2020, all newborns diagnosed to have a ventricular septal defect were prospectively entered in our database and those with an isolated defect were included in the study. Ventricular septal defects were classified into four types: perimembranous, trabecular muscular, inlet and outlet. A long-term follow up was performed in order to visualize the possible residual formation of a septal myocardial crypt. Results: A total of 376 isolated ventricular septal defects (314 muscular and 54 perimembranous, 4 inlet, 4 outlet) were detected. Follow up ranged from 1 to 23 years and showed that, among muscular type, a spontaneous closure occurred in 284 (91%), 26 did not close (8,28%), 2 required surgical intervention (0,63%), 3 were lost at follow up (0,95%). During this period, after spontaneous defect closure closure, 20 crypts were found (6,4%). Conclusion: This study shows that a muscular ventricular septal defect may evolve in the 6.4% of cases in a residual septal crypt. Although septal crypts occur more frequently in patients affected by hypertrophic and hypertensive cardiomyopathy, they may also represent the evolution of a spontaneous closure of a muscular interventricular defect.

Cardiac Multislice Computed Tomography in the Detection of Phenotypic Polymorphism of Hypertrophic Cardiomyopathy

Background. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease with a prevalence of 1 case per 500 people and is the most common cause of sudden cardiac death in young patients. As clinical manifestations and electrocardiographic data are nonspecific and diverse, noninvasive imaging techniques play a key role in the detection of HCM and the understanding of its pathophysiology.&#x0D; The aim. To evaluate the possibilities of ECG-synchronized cardiac multislice computed tomography (MSCT) as a highly informative diagnostic tool for assessing the morpho-functional state of the heart in patients with HCM.&#x0D; Materials and methods. This was a retrospective analysis conducted at the National Amosov Institute of Cardiovascular Surgery from January 2020 to December 2021. We examined 221 cardiac MSCT scans of patients who underwent the examination to assess the spread of myocardial hypertrophy. Particular attention was paid to the presence of crypts at different levels of the left ventricle (LV), anatomical features of the mitral valve and subvalvular apparatus. The presence of systolic pulling of the anterior mitral valve to the interventricular septum, myocardial mass, LV end-diastolic, LV end-systolic volumes and the corresponding indices of body surface area, ejection fraction were determined and calculated during the functional analysis. Additionally, the anatomy and patency of the coronary arte­ ries were assessed. The studies were performed on a 640-slice Canon Aquilion One CT scanner with retrospective ECG gating and subsequent image processing. The studies were transferred to a workstation for review and evaluation by a team of radiologists.&#x0D; Results. The mean patient age was 46 ± 23 years, 48% were male. Mean maximal LV wall thickness was 19 mm (range 16–34). In 159 patients (71.9%), there was an asymmetric form of HCM with a predominant thickening of the anterior and anteroseptal segments of the left ventricle at the basal and midventricular levels. Fifty-four (24.4%) patients had symmetric form of HCM. The midventricular form of HCM was detected in 4 patients (1.8%). Apical form of HCM was detected in 3 patients (1.3%). One patient was diagnosed with a tumor-like variant of HCM (0.5%). In 198 patients (89.6%), systolic anterior motion of the mitral valve to the interventricular septum was found. In 95 cases (42.9%), morphological abnormality, abnormality of the number or attachment of the papillary muscles were detected. Forty-eight myocardial crypts were detected in 44 patients (21.7%). In 194 patients (87.7%), patent coronary arteries without signs of stenosis were found, 68 patients (30.7%) had 74 myocardial bridges (33.4%).&#x0D; Conclusions. HCM is a genetic heart disease with enormous phenotypic diversity. Due to its high spatial resolution, cardiac MSCT is an accurate diagnostic tool, which allows to assess the morphofunctional state of the LV, mitral valve, subvalvular apparatus, as well as to analyze the anatomy and narrowing of coronary arteries in patients with HCM.

High take off left main coronary artery accompanied by multicryptic left ventricle myocardium detected by cardiac computerized tomography in a young male: case report

BackgroundMyocardial crypts are discrete, narrow, blood filled invaginations within the left ventricular myocardium and high-take-off coronary artery are rare manifestations where coronary arteries originate above the sinotubuler junction.Case presentationA 41-year-old man with multiple coronary artery disease risk factors admitted to our outpatient department with progressive dyspnea and atypical chest pain. Physical examination revealed no pathological findings. His blood examination revealed only mild to moderately high IgE and LDL levels. Transthoracic echocardiography (TTE) was normal. His treadmill test was normal, yet in the 3rd stage of the test he had an atypically located chest pain which was relieved in the resting period. As he had multiple cardiovascular risk factors, we performed a coronary CT angiography to exclude coronary artery disease. Coronary CT angiography(CCTA) demonstrated multiple myocardial crypts, a muscular VSD like defect which were not detectable with TTE and a high take off left main coronary artery (LMCA). After CCTA, we repeated the TTE to investigate the crypts and VSD-like defect which were clear on CCTA, yet a precise TTE hardly showed crypts and didn’t confirm a shunt between the left and right ventricle. We defined the defect as ‘spontaneously closed muscular VSD’. None of these pathologies were clinically relevant with the patient’s symptoms, thus pneumonology started a montelukast therapy for 1 year and we decided to follow up the patient, as multiple crypts may indicate an early phase hypertrophic cardiomyopathy.ConclusionsConsidering that a high take-off LMCA is a congenital anomaly, encountering multiple crypts which are also congenital pathologies, is plausible, as congenital anomalies may accompany eachother. Echocardiography is a very useful, practical imaging tool but regrettably may be suboptimal due to various patient and method related reasons. Target combination of different cardiovascular imaging tools like echocardiography, cardiac CT(CCT), may be utilized in order to ensure a comprehensive diagnosis particularly.

Novel Morphological Features on CMR for the Prediction of Pathogenic Sarcomere Gene Variants in Subjects Without Hypertrophic Cardiomyopathy.

Background: Carriers of pathogenic DNA variants (G+) causing hypertrophic cardiomyopathy (HCM) can be identified by genetic testing. Several abnormalities have been brought forth as pre-clinical expressions of HCM, some of which can be identified by cardiovascular magnetic resonance (CMR). In this study, we assessed morphological differences between G+/left ventricular hypertrophy-negative (LVH-) subjects and healthy controls and examined whether CMR-derived variables are useful for the prediction of sarcomere gene variants.Methods: We studied 57 G+ subjects with a maximal wall thickness (MWT) < 13 mm, and compared them to 40 healthy controls matched for age and sex on a group level. Subjects underwent CMR including morphological, volumetric and function assessment. Logistic regression analysis was performed for the determination of predictive CMR characteristics, by which a scoring system for G+ status was constructed.Results: G+/LVH- subjects were subject to alterations in the myocardial architecture, resulting in a thinner posterior wall thickness (PWT), higher interventricular septal wall/PWT ratio and MWT/PWT ratio. Prominent hook-shaped configurations of the anterobasal segment were only observed in this group. A model consisting of the anterobasal hook, multiple myocardial crypts, right ventricular/left ventricular ratio, MWT/PWT ratio, and MWT/left ventricular mass ratio predicted G+ status with an area under the curve of 0.92 [0.87–0.97]. A score of ≥3 was present only in G+ subjects, identifying 56% of the G+/LVH- population.Conclusion: A score system incorporating CMR-derived variables correctly identified 56% of G+ subjects. Our results provide further insights into the wide phenotypic spectrum of G+/LVH- subjects and demonstrate the utility of several novel morphological features. If genetic testing for some reason cannot be performed, CMR and our purposed score system can be used to detect possible G+ carriers and to aid planning of the control intervals.

Differences in left ventricular mass and morphology and right ventricular function differentiate phenotype-negative sarcomere gene mutation carriers from healthy volunteers

Abstract Funding Acknowledgements Type of funding sources: None. Carriers of pathogenic DNA variants (G+) causing hypertrophic cardiomyopathy (HCM) can be identified by genetic testing, before manifestation of left ventricular hypertrophy (LVH). These G+/LVH- subjects are routinely monitored for phenotypic expression, which, alongside LVH, can include other HCM-related abnormalities, including crypts and myocardial fibrosis. Cardiovascular magnetic resonance (CMR) imaging has emerged as a valuable technique in diagnosing and follow-up of HCM. In this study, we identified clinical features of subclinical HCM in a G+/LVH- population compared to healthy subjects. We studied 33 G+ subjects with CMR and a maximal wall thickness (MWT) &amp;lt;13mm, and compared them to an age- and gender-matched group of 35 healthy controls (44 ± 14 vs 48 ± 10 y, p = 0.17; 11 (33%) vs 12 (34%) men, p = 0.93). The CMR imaging protocol consisted of 1) steady state free procession cine imaging, 2) 2-dimensional late gadolinium enhancement (LGE) images in the G+ patients and 3) pre-contrast T1 mapping using a modified look-locker inverse recovery sequence. We assessed CMR examinations for features of HCM. Forward logistic regression analysis was performed to determine which of the CMR characteristics were predictive of G+ status. G+ subjects had a higher MWT (10.9 ± 1.6 vs 10.2 ± 1.3 mm, p = 0.04), a similar interventricular septal wall (IVS) thickness (8.8 ± 1.6 vs 8.7 ± 1.6 mm, p = 0.85), a smaller posterior wall (PW) and a higher IVS/PW ratio (6.6 ± 1.2 vs 7.7 ± 1.3mm, p &amp;lt; 0.001; 1.4 ± 0.3 vs 1.1 ± 0.2, p = 0.001). Indexed left ventricular (LV) mass was significantly lower in the G+ group (Table). LV function was similar (63 ± 6 vs. 61 ± 5%, p = 0.12), but right ventricular (RV) function was higher in the G+ group. They often had a characteristic hook-shaped thickening of the basal anterior wall (7 (21%) vs 0, p &amp;lt; 0.004; Figure) and more frequently exhibited myocardial crypts. Midwall LGE was present in 3 (9%) G+ subjects. Native septal T1 values were elevated in G+ patients compared to controls, although mostly within the normal range (986 ± 31 vs 963 ± 28 ms, p &amp;lt; 0.01). Crypts, indexed LV mass and RV ejection fraction were significant predictors of G+ status in logistic regression analysis (Table). CMR demonstrates significant morphological differences between the G+/LVH- population and healthy controls. Further studies are needed to assess the prognostic significance of these morphological features. Predictors of genotype-positive status Variables G+ subjects (n = 33) Controls (n = 35) P value OR for G+ status P value Left ventricular mass/BSA (g/m&amp;sup2;) 45 ± 7.4 53 ± 7.9 &amp;lt;0.001 0.86 [0.78-0.95] 0.003 Right ventricular ejection fraction (%) 58 ± 6 53 ± 4 &amp;lt;0.001 1.15 [1.00-1.32] 0.047 Crypts 17 (55%) 4 (11%) &amp;lt;0.001 9.62 [1.93-48.00] 0.006 G+: genotype-positive, OR: odds ratio Abstract Figure. CMR findings

Diagnostic opportunities of magnetic resonant imagingmri of heart in differential diagnosis of phenotypical forms of hypertrophic cardiomyopathy

Introduction. Phenotype variants of left ventricular (LV) remodeling in patients with hypertrophic cardiomyopathy (HCM) are often associated with abnormalities of the mitral valve (MV), myocardiumstructure, contributing to the development of medium and/or subaortic obstruction. Itcauses the detail visualization of morphological obstruction substrates, tissue characteristics.Aim. To evaluate the possibilities of magnetic resonance imaging (MRI) in the diagnosis of various forms of HCM and combined abnormalities.Materials and methods. 75 patients with suspected HCM were examined. For verification, all patients underwentMRI using protocol: short-pulse T1w-TSE/ T2w-TSE (STIR), gradient echo in cine (CINE), T1-weighted post-contrast images (Inversion Recovery IR-MDE). Results. Patients classified into 4 types according to the anatomical principle (Wiggle E.D. et al., 1985). In addition to the most frequent forms affecting the interventricular septum (IVS) — 64 patients, unusual forms covering the apical zones and papillary muscles — 11 patients. The majority of patients were diagnosed with abnormalities of MV, divided into abnormalities of the number and position of papillary muscles, as well as the ratio of chords and muscles. Myocardial crypts were diagnosed in 12 patients, some combined with areas of non-compact myocardium. Post-contrast visualization using the delayed contrast technique allowed differentiating HCM with accumulation diseases, excluding cavity thrombosis, and evaluating the severity of myocardial fibrosis.Conclusions. MRI allows to estimate in details anatomic picture of LV remodeling, to diagnose features of the mitral valve, tissue characteristics that allows to stratify risk of sudden death, classify the HCM phenotype form and to determine the volume of surgical intervention.

The diagnostic value of cardiac magnetic resonance in athletes with suspected structural myocardial diseases

Abstract Introduction Sudden cardiac death (SCD) is the leading cause of death in athletes occurring usually during intensive training. Cardiac magnetic resonance (CMR) is a reliable technique to assess ventricular volumes and function. Furthermore, it provides tissue-specific information and has a crucial role in detecting structural myocardial diseases. Aim We aimed to investigate the prevalence of myocardial structural heart diseases and the etiology of sudden cardiac death in highly trained athletes and their outcome during follow-up. Method We examined athletes (training ≥6 hours/week) who underwent CMR due to suspected structural myocardial disease at Semmelweis University Heart and Vascular Center between 2009 and 2019. Cine movie images and late gadolinium enhanced (LGE) images were performed. Athletes with structural myocardial alterations were followed for the endpoint of all-cause-mortality. Results CMR was performed on a total of 338 athletes (280 male, 24±11 age). The indications for CMR were as follows: aborted sudden cardiac death/sustained ventricular tachycardia (SVT) (4%), ECG alterations (36%), echocardiographic alterations (32%), positive family history of SCD or cardiomyopathies (CMP) (3%), and patients' complaints, e.g. palpitation, syncope, dyspnoea, chest complaints (25%). CMR confirmed structural myocardial disease in 82 athletes with the following distribution: 20 hypertrophic (HCM), 10 arrhythmogenic (AC), 8 dilated (DCM), and 7 non-compact (NCCMP) CMP. The CMR images of three patients indicated Fabry disease. We found post-myocardial infarction scars in 7 cases, and atypical non-ischemic scars in 28 athletes. Besides pathological conditions, we identified minor alterations in 58 patients (51 male, 25±12 age) such as: increased trabeculation, nonspecific LGE in left ventricular insertion point and myocardial crypts. Among athletes examined after aborted sudden cardiac death or SVT we found structural heart disease in 11 males and one female: AC (n=7), HCM (n=1), NCCMP (n=1) and atypical non-ischemic scars (n=3, in two patients the localisation was lateral subepicardial) were diagnosed. During the median follow up of five years one patient died in whom CMR showed lateral scar formation and only mildly reduced left ventricular ejection fraction (50%). Conclusions The most common structural alteration was non-ischaemic scar, the most common CMP was HCM, and the leading cause of sudden cardiac death or SVT in our competitive athletes was AC and lateral subepicardial scar formation. LGE pattern in various cardiomyopathies Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Project no. NVKP_16-1-2016-0017 has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the NVKP_16 funding scheme. This project was supported by a grant from the National Research, Development and Innovation Office (NKFIH) of Hungary (K 120277).

Congenital diverticulum of the left ventricle – diagnosis with echocardiography, ventriculography and magnetic resonance imaging: clinical case

Myocardial diverticula are rare and incidental fi ndings. They are most probably congenital anomalies of the cardiac wall, mainly of the left ventricle (LV), which in the majority of the cases are associated with other anomalies – cardiac, vascular or thoraco-abdominal. The lack of specifi c clinical symptoms and electrocardiographic changes in the presence of cardiac diverticulum, make them most commonly an incidental fi nding during a diagnostic imaging examination. The diagnosis of LV diverticulum can be made with echocardiography, left ventriculography, computed tomography or magnetic-resonance imaging (MRI). Among all, MRI gives the best morphologic assessment of the ventricular wall, the location and the relation of the diverticulum to surrounding structures and its dynamic behaviour during systole and diastole. MRI can rule out infl ammatory, traumatic and ischemic cardiac pathology, and cardiomyopathy, and thus differentiate the diverticulum from another entity – myocardial crypts, pathologically formed focal aneurysm or pseudoaneurysm of the LV. Therefore, MRI is the preferred non-invasive method for evaluating the cardiac wall in detail and helps to differentiate and defi nitively diagnose congenital cardiac diverticulum, which in most cases does not require therapeutic intervention.

Left ventricular myocardial crypts: morphological patterns and prognostic implications.

Left ventricular (LV) myocardial crypts are considered a subtle marker of hypertrophic cardiomyopathy. However, crypts have also been observed in seemingly healthy individuals and it is unknown whether myocardial crypts are associated with adverse outcome. Myocardial crypts were defined as invaginations traversing >50% of the myocardial wall and assessed using contrast-enhanced cardiac computed tomography in 10 097 individuals from the Copenhagen General Population Study. Number of crypts, location, shape, penetrance, and volume were assessed. The endpoint was a composite of major adverse cardiovascular events and defined as death, myocardial infarction, heart failure, or stroke. Cox regression models were adjusted for clinical variables, medical history, electrocardiographic parameters, and cardiac chamber sizes. A total of 1199 LV myocardial crypts were identified in 915 (9.1%) individuals. Seven hundred (6.9%) had one crypt and 215 (2.1%) had multiple crypts. During a median follow-up of 4.0 years (interquartile range 1.5-6.7), major adverse cardiovascular events occurred in 619 individuals. Individuals with one or multiple crypts had a hazard ratio for major adverse cardiovascular events of 1.00 [95% confidence interval (CI): 0.72-1.40; P = 0.98] and 0.90 (95% CI: 0.47-1.75; P = 0.76), respectively, compared with those with no crypts. No specific pattern of crypt location, shape, penetrance, or volume was associated to an increased hazard ratio for major adverse cardiovascular events. LV myocardial crypts are frequent in the general population and are not associated with intermediate-term major adverse cardiovascular events.

P645 Familial restrictive cardiomyopathy and Noonan"s syndrome: a rare association

Abstract Background Noonan syndrome is a rare genetic disorder. Typical cardiac involvement include pulmonary stenosis and hypertrophic cardiomyopathy. We present the association of Noonan syndrome with familial non-hypertrophic cardiomyopathy with haemodynamic features of restrictive physiology. Case description. A 30-year old male patient presented to the outpatient clinic with clinical symptoms of heart failure which was slowly progressive since age 20. He was found to have features of restrictive cardiomyopathy aged 12 years at the time when his mother was diagnosed with Noonan syndrome and restrictive cardiomyopathy. On examination, his 1st and 2nd heart sounds were normal, however 3rd heart sound was present. Pulse was regular, 75 per minute, BP 110/70 mmHg. Chest was clear and saturation 98%. Echocardiography showed small left ventricle (LV) with preserved ejection fraction (EF), borderline LV wall thickness (10-11 mm), restrictive filling pattern with mitral valve E/A ratio 4.2 and deceleration time 68 ms; dilated both atria; and pulmonary artery systolic pressure of 37 mmHg (Figure, panels A-C; F). Prominent late diastolic reversal flow was noted in hepatic veins (Panel D). LV longitudinal strain was borderline in absolute value (-18%) however demonstrated ‘apical sparing’ pattern (Panel E). The right ventricle was small in size with mild hypertrophy and dynamic function, but normal flow through pulmonary valve. Prominent diastolic reversal flow was also noted in superior vena cava. Cardiac magnetic resonance confirmed echocardiographic findings and additionally demonstrated prominent trabeculations and myocardial crypts in the LV, small pericardial effusion; no signs of amyloidosis, myocardial infarction, infiltration or fibrosis. Right heart catheterisation showed borderline pulmonary hypertension with a mean pressure of 25 mmHg, raised pulmonary artery wedge pressure 18 mmHg, normal pulmonary vascular resistance 1.9 WU, and a ‘square root sign’ (Panel G). Patient underwent cardiopulmonary exercise testing, he stopped after 9 mins of Bruce protocol due to fatigue, reaching the Peak VO2 of 21.1ml/kg/min (49% of predicted value). No ST changes or arrhythmic events were noted. Patient was diagnosed with primary (non-infiltrative) familial restrictive cardiomyopathy and discussed at multidisciplinary team meeting with recommendation of close follow-up for timing for heart transplantation. Meanwhile he was encouraged to continue treatment with ramipril and start regular physical activity. Discussion There are only few reports describing familial non-hypertrophic cardiomyopathy in patients with Noonan syndrome and none in their family members. We review typical clinical and diagnostic features of restrictive cardiomyopathy involving both ventricles and raise awareness of clinicians of primary familial restrictive cardiomyopathy as a possible cardiac manifestation in patients with Noonan syndrome and their immediate family members. Abstract P645 Figure.

Structural abnormalities in hypertrophic cardiomyopathy beyond left ventricular hypertrophy by multimodality imaging evaluation.

Echocardiography- and cardiovascular magnetic resonance (CMR)-based studies have revealed a wide range of phenotypic manifestations in hypertrophic cardiomyopathy (HCM) apart from hypertrophy. This study sought to comprehensively describe a number of structural abnormalities in HCM beyond hypertrophy, by multimodality imaging. A total of 100 HCM patients were prospectively enrolled, undergoing standard and contrast echocardiography, and CMR. Morphological characteristics involving mitral valve leaflets (MVL), subvalvular apparatus, and left ventricular cavity and wall were investigated. Seventy healthy volunteers served as control population. As assessed by echo, MVLs were longer in HCM patients than in controls (anterior method 1: 24[22,28] vs 19[18,20] mm, P<0.01; anterior method 2: 27[24, 29] vs 21[19, 23] mm, P<0.01; posterior: 15[12,19] vs 14[13,15] mm, P<0.01). Abnormal chordal attachment to anterior MVL, anterior papillary muscle displacement, and accessory apical-basal muscle bundle were present in 42 (42%), 61 (61%), and 35 (35%) patients, respectively (P values vs controls <0.01); direct papillary muscle insertion into MVL and hypertrabeculation were found in two and five patients, respectively. Contrast echocardiography (n=94) detected myocardial crypts in 15 patients (16%). Overall, 83% of HCM subjects had at least one of these phenotypic manifestations. Echocardiography and CMR agreement for MVL length was poor, while for structural characteristics was moderate to substantial (Cohen's Kappa: 0.53-1.00). Except for posterior MVL length and hypertrabeculation, the phenotypic characteristics studied had acceptable reproducibility by echocardiography and CMR. Structural abnormalities in HCM beyond hypertrophy are significantly common. Multimodality imaging approach to these HCM facets by echocardiography and CMR is feasible and desirable.

PREPHENOTYPIC MYOCARDIAL CRYPT MORPHOLOGY IN HYPERTROPHIC CARDIOMYOPATHY

SESSION TITLE: Cardiovascular Disease 2 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a genetic heart disease first described over 50 years ago. More recently, cardiovascular magnetic resonance imaging has advanced our understanding of the phenotypic heterogeneity of the disease. CASE PRESENTATION: A 21-year-old man presented after a syncopal episode while playing soccer. He reported two prior similar events that occurred ten years ago. Family history further revealed a father who was diagnosed with non-obstructive hypertrophic cardiomyopathy at a young age. Electrocardiogram showed normal sinus rhythm. Transthoracic echocardiogram identified mild concentric left ventricular hypertrophy with preserved left ventricular ejection fraction and an interventricular septal end diastolic diameter estimated at 11-millimeters. Cardiac magnetic resonance imaging (CMR) was done, which revealed a maximal wall thickness of 13-millimeters in the basal septum. There was no systolic motion of the mitral valve or evidence of flow acceleration of left ventricular outflow tract. However, myocardial crypts were noted in the basal inferior wall. These findings represent a distinctive, but unclear morphology of hypertrophic cardiomyopathy currently thought to be more prevalent in phenotype-negative patients. A four generation family pedigree of the patient was obtained. His paternal family history was notable for ischemic cardiac disease in several members but only his father had an established diagnosis of hypertrophic cardiomyopathy. Maternal family history was unremarkable for any cardiovascular disease. Father underwent genetic testing, which revealed that he was heterozygous for the p.R502W pathogenic mutation in the myosin binding protein gene (MYBPC3). Patient was then discharged home on a Life Vest with a plan for genetic testing as outpatient. Genetic testing was also offered to the other family members. DISCUSSION: HCM is an autosomal dominant genetic cardiomyopathy with most mutations having a high penetrance. In HCM, the common phenotypes encountered on Echo or Cardiac MRI are unexplained left ventricular hypertrophy, especially asymmetric, involving the septum/anterolateral wall, increased LV outflow tract gradient and systolic anterior motion of the mitral valve leaflets. Left ventricular myocardial crypts found on cardiac MRI can serve as a good ‘pre-phenotypic’ imaging marker of HCM that can help identify family members of HCM affected families to undergo genetic testing. They occur with variable frequency, but represent a distinctive morphological expression of HCM. CONCLUSIONS: Myocardial crypt identification by cardiac magnetic resonance is emerging as a potential marker for earlier recognition of genotype positive patients at risk of developing clinical hypertrophic cardiomyopathy. This case emphasizes this clinical implication and reinforces the importance of careful history taking in diagnostic decision making. Reference #1: Maron MS, Rowin EJ, Lin D et al. Prevalence and clinical profile of myocardial crypts in hypertrophic cardiomyopathy. Circ Cardiovasc Imaging 2012;5:441-7. Reference #2: Rowin EJ, Maron MS. Myocardial crypts in hypertrophic cardiomyopathy: the new gang in town. Eur Heart J Cardiovasc Imaging 2012;13:281-3. DISCLOSURES: no disclosure on file for Shantal Gupta; No relevant relationships by Sharana Hegde, source=Web Response No relevant relationships by Jae Kim, source=Web Response No relevant relationships by Anupama Rao, source=Web Response

First evidence of maternally inherited mosaicism in TGFBR1 and subtle primary myocardial changes in Loeys-Dietz syndrome: a case report

BackgroundLoeys-Dietz syndrome (LDS) is a rare multisystemic disorder characterized by vascular and skeletal abnormalities, with considerable intra- and interfamilial variability.Case presentationWe report the case of an 8-year-old male with clinical features of two distinct genetic disorders, namely LDS, manifesting in the first months by progressive aortic root dilatation, arterial tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA) manifesting by white hair and skin that does not tan, nystagmus, reduced iris pigment with iris translucency, and reduced retinal pigment). We identified previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and heterozygous, missense mutation of TGFBR1, c.1460G > A (p.Arg487Gln). Family history revealed that his mother underwent multiple surgical repairs for recurrent hemorrhage originating from the buccal artery. Molecular studies confirmed a maternally inherited low grade TGFBR1 mutation somatic mosaicism (18% in peripheral blood leukocytes, 18% in buccal cells and 10% in hair root cells). Maternal cardiac investigations revealed peculiar cardiovascular features: mild tortuosity at the aortic arch, dilatation of the proximal abdominal aorta, multiple deep left ventricular myocardial crypts, and dysplastic mitral valve. TGFBR2 germline mosaicism has been described in three fathers of children carrying TGFBR2 mutations but, to the best of our knowledge, no case of maternally inherited TGFBR1 mutation mosaicism has been reported so far.ConclusionsThis case report suggests that individuals with somatic mosaicism might be at risk for mild and unusual forms of LDS but germline mosaicism can lead to full blown picture of the disease in offspring.

P2753Prevalence of myocardial crypts in the hypertrophied heart: a computed tomography study

P2753Prevalence of myocardial crypts in the hypertrophied heart: a computed tomography study

High Spatial Resolution Cardiovascular Magnetic Resonance at 7.0 Tesla in Patients with Hypertrophic Cardiomyopathy - First Experiences: Lesson Learned from 7.0 Tesla.

BackgroundCardiovascular Magnetic Resonance (CMR) provides valuable information in patients with hypertrophic cardiomyopathy (HCM) based on myocardial tissue differentiation and the detection of small morphological details. CMR at 7.0T improves spatial resolution versus today’s clinical protocols. This capability is as yet untapped in HCM patients. We aimed to examine the feasibility of CMR at 7.0T in HCM patients and to demonstrate its capability for the visualization of subtle morphological details.MethodsWe screened 131 patients with HCM. 13 patients (9 males, 56 ±31 years) and 13 healthy age- and gender-matched subjects (9 males, 55 ±31years) underwent CMR at 7.0T and 3.0T (Siemens, Erlangen, Germany). For the assessment of cardiac function and morphology, 2D CINE imaging was performed (voxel size at 7.0T: (1.4x1.4x2.5) mm3 and (1.4x1.4x4.0) mm3; at 3.0T: (1.8x1.8x6.0) mm3). Late gadolinium enhancement (LGE) was performed at 3.0T for detection of fibrosis.ResultsAll scans were successful and evaluable. At 3.0T, quantification of the left ventricle (LV) showed similar results in short axis view vs. the biplane approach (LVEDV, LVESV, LVMASS, LVEF) (p = 0.286; p = 0.534; p = 0.155; p = 0.131). The LV-parameters obtained at 7.0T where in accordance with the 3.0T data (pLVEDV = 0.110; pLVESV = 0.091; pLVMASS = 0.131; pLVEF = 0.182). LGE was detectable in 12/13 (92%) of the HCM patients. High spatial resolution CINE imaging at 7.0T revealed hyperintense regions, identifying myocardial crypts in 7/13 (54%) of the HCM patients. All crypts were located in the LGE-positive regions. The crypts were not detectable at 3.0T using a clinical protocol.ConclusionsCMR at 7.0T is feasible in patients with HCM. High spatial resolution gradient echo 2D CINE imaging at 7.0T allowed the detection of subtle morphological details in regions of extended hypertrophy and LGE.

Feasibility and significance of preclinical diagnosis in hypertrophic cardiomyopathy.

Preclinical diagnosis in hypertrophic cardiomyopathy (HCM) refers to the detection of functional or histopathological abnormalities in subjects who carry any HCM-causing gene mutation, before or even without the development of left ventricular hypertrophy [genotype(+)/phenotype(-)subjects]. The concept that HCM pathology may exist in the absence of left ventricular hypertrophy is quite old but the ability to recognize the presence of early myocardial changes is quite new. Lessons from animal models have shown that in experimental human HCM, myocardial cell mechanical dysfunction precedes histopathological changes, such as myocyte disarray, fibrosis, and hypertrophy. Several clinical reports have demonstrated that the majority of HCM genotype(+)/phenotype(-) subjects display myocardial functional or histopathological changes, such as reduced tissue Doppler imaging-derived systolic and diastolic velocities, abnormal electrocardiogram, cardiac magnetic resonance-visualized myocardial crypts, mitral leaflet elongation, and evidence of a fibrotic state, such as increased type I procollagen synthesis, cardiac magnetic resonance-increased myocardial extracellular volume, and late gadolinium myocardial enhancement. All these signs have been proposed as preclinical markers of HCM. At present the separation of such a group of subjects in the early phase of their disease provides the opportunity to test new therapies to prevent the development of fibrosis, hypertrophy, and dysfunction.