Presence Of Hypertrophic Cardiomyopathy Research Articles

Phenotypic spectrum of the first Belgian MYBPC3 founder: a large multi-exon deletion with a varying phenotype.

Variants in the MYBPC3 gene are a frequent cause of hypertrophic cardiomyopathy (HCM) but display a large phenotypic heterogeneity. Founder mutations are often believed to be more benign as they prevailed despite potential negative selection pressure. We detected a pathogenic variant in MYBPC3 (del exon 23-26) in several probands. We aimed to assess the presence of a common haplotype and to describe the cardiac characteristics, disease severity and long-term outcome of mutation carriers. Probands with HCM caused by a pathogenic deletion of exon 23-26 of MYBPC3 were identified through genetic screening using a gene panel encompassing 59 genes associated with cardiomyopathies in a single genetic center in Belgium. Cascade screening of first-degree relatives was performed, and genotype positive relatives were further phenotyped. Clinical characteristics were collected from probands and relatives. Cardiac outcomes included death, heart transplantation, life-threatening arrhythmia, heart failure hospitalization or septal reduction therapy. Haplotype analysis, using microsatellite markers surrounding MYBPC3, was performed in all index patients to identify a common haplotype. The age of the founder variant was estimated based on the size of the shared haplotype using a linkage-disequilibrium based approach. We identified 24 probands with HCM harbouring the MYBPC3 exon 23-26 deletion. Probands were on average 51 ± 16years old at time of clinical HCM diagnosis and 62 ± 10 years old at time of genetic diagnosis. A common haplotype of 1.19Mb was identified in all 24 probands, with 19 of the probands sharing a 13.8Mb haplotype. The founder event was estimated to have happened five generations, or 175-200years ago, around the year 1830 in central Flanders. Through cascade screening, 59 first-degree relatives were genetically tested, of whom 37 (62.7%) were genotype positive (G+) and 22 (37.3%) genotype negative (G-). They were on average 38 ± 19years old at time of genetic testing. Subsequent clinical assessment revealed a HCM phenotype in 19 (51.4%) G+ relatives. Probands were older (63 ± 10 vs. 42 ± 21years; p < 0.001) and had more severe phenotypes than G+ family members, presenting with more symptoms (50% vs. 13.5%; p = 0.002), arrhythmia (41.7% vs. 12.9%, p = 0.014), more overt hypertrophy and left ventricular outflow tract obstruction (43.5% vs. 3.0%; p < 0.001). Male G+ relatives more often had a HCM phenotype (78.6% vs. 34.8%; p = 0.010) and were more severely affected than females. At the age of 50, a penetrance of 78.6% was observed, defined as the presence of HCM in 11 of 14 G+ relatives with age ≥50years. Overall, 20.3% of all variant carriers developed one of the predefined cardiac outcomes after a median follow-up of 5.5years with an average age of 50 (±21) years. A Belgian founder variant, an exon 23-26 deletion in MYBPC3, was identified in 24 probands and 37 family members. The variant is characterized by a high penetrance of 78.6% at the age of 50years but has variable phenotypic expression. Adverse outcomes were observed in 20.3% of patients during follow-up.

Validation of the PRAETORIAN score in a large subcutaneous implantable cardioverter-defibrillator collective: Usefulness in clinical routine

BackgroundTo assess the risk of unsuccessful conversion of ventricular fibrillation during defibrillation testing (DFT) with the subcutaneous implantable cardioverter-defibrillator (S-ICD), the PRAETORIAN score has been proposed. ObjectiveThe purpose of this study was to validate the PRAETORIAN score in a large S-ICD collective. MethodsA retrospective single-center analysis of S-ICD patients receiving intraoperative DFT was performed. DFT was performed using a stepwise protocol with 65-J standard polarity, change of polarity, increase to 80 J, and repositioning if necessary. If all DFTs failed, we switched to a transvenous ICD. ResultsOverall, 398 patients were analyzed (268 male [67.3%]; mean age 42.4 ± 15.9 years; mean body mass index [BMI] 25.9 ± 4.8 kg/m2). Successful DFT with the first ICD shock was observed in 264 patients (66.3%). One hundred fourteen patients were defibrillated with the second (n = 104) or third (n = 10) DFT after changing shock polarity and/or shock energy. Overall, 20 patients needed at least 3 DFT (ie, 80 J and/or re-positioning). The majority (n = 88 [65.7%]) of DFT failures occurred before 2015 with the first-generation S-ICD. PRAETORIAN score was an independent predictor of DFT failure (odds ratio [OR] 1.007; 95% confidence interval [CI] 1.003–1.011 P ≤.001), while whereas BMI alone was not (P = .31). Presence of hypertrophic cardiomyopathy (HCM) (OR 2.6; 95% CI 1.3–4.4; P = .004) was predictive for at least 1 unsuccessful DFT in our multivariate regression analysis. ConclusionPRAETORIAN score proved to be a useful and valid predictive tool for successful DFT, whereas BMI only had a limited role. Patients with HCM were at increased risk for DFT failure or needed higher DFT energy.

Case Report: Late Presentation of Hypertrophic Cardiomyopathy in a 65- Year- Old Sudanese Man at Royal Care International Hospital

Background: HCM Syndrome is a left ventricle hypertrophic in the absence of another cardiac or other systemic condition. An epidemiologic study reported that the prevalence of HCM is 0.02in the general population. Case Presentation: We report a case report of a 65- year- old man who was referred to the clinic after presenting with a typical symptom. Past medical history and family history were insignificant. Echocardiography showed asymmetrical basal septal hypertrophy with a preserved ejection fraction of 65%. The patient was asymptomatic with no functional limitation but later developed atrial fibrillation with mild diastolic heart failure, which was treated by pharmacological medication and cardio version. Conclusion: In conclusion, the earlier the diagnosis, better the prognosis. HCM has a lot of complications including atrial fibrillation. Therefore, awareness of how often AF and other arrhythmias are associated with HCM patients will lead to lower mortality as a follow-up ECG and echocardiography can be performed to prevent subsequent complications.

Identifying Obstructive Hypertrophic Cardiomyopathy from Nonobstructive Hypertrophic Cardiomyopathy: Development and Validation of a Model Based on Electrocardiogram Features.

The clinical presentation and prognosis of hypertrophic cardiomyopathy (HCM) are heterogeneous between nonobstructive HCM (HNCM) and obstructive HCM (HOCM). Electrocardiography (ECG) has been used as a screening tool for HCM. However, it is still unclear whether the features presented on ECG could be used for the initial classification of HOCM and HNCM. We aimed to develop a pragmatic model based on common 12-lead ECG features for the initial identification of HOCM/HNCM. Between April 1st and September 30th, 2020, 172 consecutive HCM patients from the International Cooperation Center for Hypertrophic Cardiomyopathy of Xijing Hospital were prospectively included in the training cohort. Between January 4th and February 30th, 2021, an additional 62 HCM patients were prospectively included in the temporal internal validation cohort. External validation was performed using retrospectively collected ECG data with definite classification (390 HOCM and 499 HNCM ECG samples) from January 1st, 2010 to March 31st, 2020. Multivariable backward logistic regression (LR) was used to develop the prediction model. The discrimination performance, calibration and clinical utility of the model were evaluated. Of all 30 acquired ECG parameters, 10 variables were significantly different between HOCM and HNCM (all P < 0.05). The P wave interval and SV1 were selected to construct the model, which had a clearly useful C-statistic of 0.805 (0.697, 0.914) in the temporal validation cohort and 0.776 (0.746, 0.806) in the external validation cohort for differentiating HOCM from HNCM. The calibration plot, decision curve analysis, and clinical impact curve indicated that the model had good fitness and clinical utility. The pragmatic model constructed by the P wave interval and SV1 had a clearly useful ability to discriminate HOCM from HNCM. The model might potentially serve as an initial classification of HCM before referring patients to dedicated centers and specialists. What are the novel findings of this work? Evident differences exist in the ECG presentations between HOCM and HNCM.To the best of our knowledge, this study is the first piece of evidence to quantify the difference in the ECG presentations between HOCM and HNCM.Based on routine 12-lead ECG data, a probabilistic model was generated that might assist in the initial classification of HCM patients.

An Atypical Non-Cardiac Presentation of Hypertrophic Cardiomyopathy.

An Atypical Non-Cardiac Presentation of Hypertrophic Cardiomyopathy.

Long term mortality in patients with hypertrophic cardiomyopathy – A Danish nationwide study

BackgroundPatients with hypertrophic cardiomyopathy (HCM) are generally regarded as having increased risk of arrhythmia, stroke, heart failure, and sudden cardiac death, but reported mortality rates vary considerably and originate from selected populations. Study objectiveWe aimed to investigate the long-term mortality rate in a nationwide cohort of patients with HCM compared to a matched cohort from the general Danish population. MethodsAll patients with a first-time HCM diagnosis in Denmark between January 1, 2007 and December 31, 2018 were identified through nationwide registries. In the main analysis, two visits in an outpatient clinic were required in order to increase specificity. Patients were matched to controls from the background population in a 1:3 ratio based on age, sex, selected comorbidities and date of HCM. Mortalities were compared using Kaplan Meier estimator and multivariable Cox regression models. ResultsWe identified 3126 patients with a first-time diagnosis of HCM. 1197 patients had at least two visits in the outpatient clinic (43 % female, median age 63.1 [25th–75th percentile 52.1–72.1] years). All-cause mortality was significantly higher in HCM patients than in matched controls: 10-year probabilities of death were 36.4 % (95 % CI 30.2–43.5 %) for HCM patients and 19.4 % (95 % CI 16.8–22.5 %) for controls. After adjusting for additional comorbidities and medications, a diagnosis with HCM was associated with an increased mortality rate (HR 1.48 (95 % CI 1.18–1.84, p = 0.001)). ConclusionCompared to matched controls from the background population, presence of HCM was associated with a significant increase in mortality rate.

Abstract 11157: A Rare Case of Concomitant Dual Genetic Cardiomyopathies in a Patient Complicated by Stroke

Background: Very little evidence exists on the prevalence of co-existing cardiomyopathies. We report in this case a highly atypical presentation of concurrent arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) likely attributable to simultaneous separate somatic mutations, complicated by stroke. Case: A 60-year-old male with a history of rheumatoid arthritis, sleep apnoea and obesity with no significant coronary disease referred for review of asymptomatic ECG abnormalities was found to have severe asymmetrical left ventricular (LV) wall thickening with apical segment akinesis and an LV apex mass on echocardiogram. She had a family history of early sudden cardiac death, with an otherwise unremarkable history and physical examination. Clinical Course: Cardiac MRI (CMR) subsequently demonstrated aneurysmal dilatation of LV apical segments with a 17x13mm thrombus present. Systolic anterior mitral leaflet motion was seen, and a dilated right ventricle (RV) with 240ml end-diastolic volume and 27% ejection fraction. "Accordion" sign was present in the sub-tricuspid RV free wall with dyskinesia, and ECGs confirmed presence of epsilon waves. One week after CMR, she suffered a large left middle cerebral artery (MCA) stroke in the setting of warfarin cessation due to echocardiography-suggestive absence of thrombus. Discussion: Genetic analysis revealed a mutated Plakophillin 2 (PKP2) gene, and FHOD3 gene associated with HCM of uncertain significance. The diagnosis was concomitant genetic cardiomyopathies of ARVC and HCM complicated by large LV apical aneurysm and thrombus culminating in left MCA stroke. PKP2 mutations to date have not been associated with hypertrophic phenotypes. This case therefore demonstrates the unlikely 1 in 2,500 incidence of coexistence of two separate cardiomyopathies likely attributable to simultaneous separate somatic mutations, while also highlighting the central role of CMR in investigation and diagnosis of RV pathology. In addition to this case, prior studies have also shown echocardiography can only identify 50% of ARVC cases identified by CMR, suggesting that selective use of CMR may double the number of identified cases of this life-threatening disease.

Abstract 14068: Reduced Left Atrial Conduction Velocity in Patients With Hypertrophic Cardiomyopathy and Normal Left Atrial Voltage Presenting for Paroxysmal Atrial Fibrillation Ablation

Introduction: Patients with hypertrophic cardiomyopathy (HCM) exhibit abnormal cardiac tissue arrangement characterized as myocardial disarray. The incidence of atrial fibrillation (AF) is increased 4-fold in patient with HCM and confers a 4-fold increased risk of death. Catheter ablation is less effective in HCM, with a 2-fold increased risk of AF recurrence. The mechanisms of AF perpetuation and recurrence in HCM are poorly understood. We sought to investigate the left atrial conduction characteristics in patients with HCM, paroxysmal AF and normal left atrial bipolar voltage. Methods: We analyzed 24 consecutive patients with HCM and 24 consecutive controls, all presenting for radiofrequency (RF) ablation of paroxysmal atrial fibrillation. Only patients with normal left atrial voltage (mean voltage &gt;0.8 mV) were included in the study. Intracardiac electrograms were extracted from CARTO (Biosense Webster Inc.) mapping system and analyzed using custom Matlab/Python code interfacing with Core OpenEP software. Conduction velocity was calculated using local activation time gradients. Results: There was no difference in baseline demographic characteristics or atrial size measured by echocardiography between HCM and control patients. Patients with HCM had significantly reduced atrial conduction velocity and conduction velocity dispersion compared to controls (Fig A,C) [0.62±0.03 m/s vs 0.44±0.04 m/s, p=0.002], despite no differences in bipolar voltage (Fig B,D) or voltage dispersion. Patients with HCM had significantly less freedom from AF than controls after catheter ablation [OR for recurrence 3.3 (1.02-10.90), p&lt;0.05 vs control]. Conclusion: Atrial conduction velocity and dispersion is significantly reduced in patients with HCM and paroxysmal AF, possibly contributing to arrhythmia perpetuation and persistence after catheter ablation. This finding may be useful in characterizing left atrial properties beyond bipolar voltage.

Severe Antenatal Hypertrophic Cardiomyopathy Secondary to ACAD9-Related Mitochondrial Complex I Deficiency

Introduction: Antenatal presentation of hypertrophic cardiomyopathy (HCM) is rare. We describe familial recurrence of antenatal HCM associated with intrauterine growth restriction and the diagnostic process undertaken. Methods: Two pregnancies with antenatal HCM were followed up. Biological assessment including metabolic analyses, genetic analyses, and respiratory chain study was performed. We describe the clinical course of these two pregnancies, antenatal manifestations as well as specific histopathological findings, and review the literature. Results: The assessment revealed a deficiency in complex I of the respiratory chain and two likely pathogenic variations in the ACAD9 gene. Discussion and Conclusion: Antenatal HCM is rare and a diagnosis is not always made. In pregnancies presenting with cardiomyopathy and intrauterine growth restriction, ACAD9 deficiency should be considered as one of the potential underlying diagnoses, and ACAD9 molecular testing should be included among other prenatal investigations.

Genetic profile and genotype-phenotype correlations in hypertrophic cardiomyopathy presenting during childhood

Genetic cardiomyopathy (CM) is a rare disease in childhood. Risk factors for outcomes remain poorly described. Our study aimed to analyse clinical and genetical aspects in a pediatric hypertrophic cardiomyopathy (HMC) population and to establish genotype-phenotype correlations. A retrospective study of all patients with “idiopathic” HCM diagnosed in southeast France, before the age of 18 years was performed. All data (clinic, echocardiography, genetic testing) were retrospectively collected. Patients who did not have complete genetic testing according to current scientific development had another DNA blood sample during the study to complete the testing. Genetic tests were considered positive if the variant found was classified as pathogenic, likely pathogenic or variant of uncertain significance. Thirty-three patients were diagnosed with “idiopathic” HCM. Median age at diagnosis was 6.8 years old [0.3–12.1]. Genetic testing was positive in 21 cases (63.6%). Patients with an identified mutation had more visceral impact (38% vs. 8%, P = 0.009), a higher rate of implantable cardiac defibrillator (24% vs. none, P = 0.025) and more frequent heart transplant (19% vs. none, P = 0.025). In our population with paediatric HCM, a positive genetic testing is associated with a worse clinical course. Those data have to be corroborated with larger-scale studies.

Genetic profile and genotype-phenotype correlations in hypertrophic cardiomyopathy presenting during childhood

Genetic cardiomyopathy (CM) is a rare disease in childhood. Risk factors for outcomes remain poorly described. Our study aimed to analyse clinical and genetical aspects in a pediatric hypertrophic cardiomyopathy (HMC) population and to establish genotype-phenotype correlations. A retrospective study of all patients with ‘idiopathic’ HCM diagnosed in southeast France, before the age of 18 years was performed. All data (clinic, echocardiography, genetic testing) were retrospectively collected. Patients who did not have complete genetic testing according to current scientific development had another DNA blood sample during the study to complete the testing. Genetic tests were considered positive if the variant found was classified as pathogenic, likely pathogenic or variant of uncertain significance. Thirty-three patients were diagnosed with ‘idiopathic’ HCM. Median age at diagnosis was 6.8 years old [0.3–12.1]. Genetic testing was positive in 21 cases (63.6%). Patients with an identified mutation had more visceral impact (38% vs. 8%, P = 0.009), a higher rate of implantable cardiac defibrillator (24% vs. none, P = 0.025) and more frequent heart transplant (19% vs. none, P = 0.025). In our population with paediatric HCM, a positive genetic testing is associated with a worse clinical course. Those data have to be corroborated with larger-scale studies.

Cardiac gene activation varies between young and adult cats and in the presence of hypertrophic cardiomyopathy

Little is known about the difference of myocardial gene transcription in young and adult cats and how transcription is further modified in cats with hypertrophic cardiomyopathy (HCM) and with left atrial (LA) thrombus formation. We hypothesized that selected factors for coagulation, endothelial activation, inflammation, and remodelling are modified with age and are activated in the hearts of cats with HCM.Left atrial and ventricular (LV) samples from 12 cats with HCM (seven without (HCMwoAT] and five with LA thrombi [HCMwAT]), and six young (YC) and six adult (AC) control cats without cardiac disease were investigated for relative expression of the following genes using quantitative polymerase chain reaction: von Willebrand factor, a disintegrin and metalloproteinase with a thrombospondin type 1 motif member 13, platelet activating factor, E- and P-selectin, intercellular and vascular adhesion molecules-1, ß2-integrin, vascular endothelial growth factor, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), heat shock protein-70, and myocyte-specific enhancer factor 2C.Significant differences in gene activation were found between YC and AC, and YC and cats with HCM. Compared to AC, MCP-1 and IL-6 were significantly higher in cats with HCM. The presence of an LA thrombus was associated with higher IL-6 expression.These results illustrate the relevance of age and/or lifestyle on gene expression in the feline heart. The gene transcription pattern found in AC hearts might predispose cats to their characteristic cardiac remodelling processes and thrombus formation if disease occurs. It further supports the involvement of inflammation, but not coagulation and endothelial activation, in HCM.

C48 PROGNOSTIC IMPACT OF ECHOCARDIOGRAPHIC RESTRICTIVE FILLING PATTERN IN PATIENTS AFFECTED BY HYPERTROPHIC CARDIOMYOPATHY AND PRESERVED SYSTOLIC EJECTION FRACTION

Abstract Background “Restrictive phenotype” is an uncommon presentation of Hypertrophic Cardiomyopathy (HCM), associated with severe functional limitation and poor prognosis. For this reason, current therapeutic aims are prevention of complications through periodic follow–ups and diagnostic investigations, up to the ICD placement. Objectives The primary aim of this study was to evaluate the impact of the restrictive filling pattern in HCM on the incidence of complex composite outcome included arrhythmic events, events related to heart failure and general events, correlating it to clinical and imaging data. Methods This study is an experimental, multicentric, retrospective and non–randomized analysis, including all patients over the age of 18 suffering from classical HCM, excluding phenocopies and systolic dysfunction. Patients were followed up and selected by specialized Centers of Trieste and Turin and divided by degree of diastolic dysfunction, particularly on the basis of the presence or absence of the restrictive filling pattern. Results A total of 367 patients with HCM were included. Restrictive filling pattern was present in 23 patients (6.3%). This subgroup of patients was younger than all other patients (P &amp;lt; 0.001); percentage of ICD patients suffering from severe diastolic dysfunction at follow–up is significantly higher than patients without restrictive filling pattern (39.1% vs 4.1%, P &amp;lt; 0.001). On average, left atrial volume has larger sizes in restrictive filling pattern (109.7ml, SD 43.06 vs 82.8ml, SD 35.81, P = 0.003). Patients with restrictive filling pattern, compared to other patients, are more subjected to heart transplantation (8.7% vs 0.3%, P = 0.009) and hospitalized for heart failure (21.7% vs 7.8%, P = 0.028). Restrictive pattern was not an independent predictor of adverse events at the multivariable analysis. In our cohort, the independent predictors were found to be the left atrium diameter and the presence of LGE on CMR. Conclusions In patients with HCM and preserved EF, the evidence of a restrictive diastolic pattern identifies a poor prognosis subgroup. Severe diastolic alteration was not associated with a significant independent role either for events related to heart failure, or for arrhythmic events during a median follow up of 7 years. However, the high rate of ICD implantation in patients with severe diastolic dysfunction suggests a high clinical perception of adverse events in this subgroup.

Hypertrophic obstructive cardiomyopathy complicated with acute myocardial infarction and diffuse fibrosis: surgery or not?

BackgroundHypertrophic cardiomyopathy with extreme hypertrophy, biventricular obstruction and diffuse myocardial fibrosis complicated by myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is a rare phenotype. Evidence and guideline recommendations are still lacking for a treatment strategy.Case presentationEmergency coronary angiography was performed in a 38-year-old man with a 2-year history of nonobstructive hypertrophic cardiomyopathy (HCM) presenting with acute myocardial infarction. The coronary angiogram yielded no stenotic lesions but showed a diffusely dilated left descending artery with slow blood flow. All evidence from biomarker analysis, electrocardiography, echocardiography, and imaging supported the diagnosis of acute myocardial infarction in the left ventricular anterior wall. The echocardiogram demonstrated severe interventricular and apical hypertrophy, severe left ventricular outflow tract obstruction and mild right ventricular outflow tract obstruction. Cardiac magnetic resonance imaging showed a concentric morphological subtype of HCM with diffuse late gadolinium enhancement in the left ventricle. Extended septal myectomy was performed 1 month later, and the patient recovered well.ConclusionsHypertrophic obstructive cardiomyopathy with acute myocardial infarction is an indication for coronary angiography. Septal reduction surgery could be performed cautiously in HCM patients with extreme hypertrophy, biventricular obstruction and diffuse myocardial fibrosis complicated by MINOCA to improve the patient’s symptoms.

Gender Related Differences in the Clinical Presentation of Hypertrophic Cardiomyopathy-An Analysis from the SILICOFCM Database.

Background and Objectives: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease that affects approximately 1 in 500 people. Due to an incomplete disease penetrance associated with numerous factors, HCM is not manifested in all carriers of genetic mutation. Although about two-thirds of patients are male, it seems that female gender is associated with more severe disease phenotype and worse prognosis. The objective of this study was to evaluate the gender related differences in HCM presentation. Materials and Methods: This study was conducted as a part of the international multidisciplinary SILICOFCM project. Clinical information, laboratory analyses, electrocardiography, echocardiography, and genetic testing data were collected for 362 HCM patients from four clinical centers (Florence, Newcastle, Novi Sad, and Regensburg). There were 33% female patients, and 67% male patients. Results: Female patients were older than males (64.5 vs. 53.5 years, p < 0.0005). The male predominance was present across all age groups until the age of 70, when gender distribution became comparable. Females had higher number of symptomatic individuals then males (69% vs. 52%, p = 0.003), most frequently complaining of dyspnea (50% vs. 30%), followed by chest pain (30% vs. 17%), fatigue (26% vs. 13%), palpitations (22% vs. 13%), and syncope (13% vs. 8%). The most common rhythm disorder was atrial fibrillation which was present in a similar number of females and males (19% vs. 13%, p = 0.218). Levels of N-terminal pro-brain natriuretic peptide were comparable between the genders (571 vs. 794 ng/L, p = 0.244). Echocardiography showed similar thickness of interventricular septum (18 vs. 16 mm, p = 0.121) and posterolateral wall (13 vs. 12 mm, p = 0.656), however, females had a lower number of systolic anterior motion (8% vs. 16%, p = 0.020) and other mitral valve abnormalities. Conclusions: Female patients are underrepresented but seem to have a more pronounced clinical presentation of HCM. Therefore, establishing gender specific diagnostic criteria for HCM should be considered.

COX16 deficiency causes a novel mitochondrial disorder with lethal infantile presentation and complex IV deficiency

Objective: To investigate the underlying genetic aetiology in two unrelated Caucasian patients with lethal infantile presentation of hypertrophic cardiomyopathy, encephalopathy, severe lactic acidosis, and complex IV deficiency in skeletal muscle.

Mega Coronary Arteries with Obstructive Coronary Artery Disease in Hypertrophic Obstructive Cardiomyopathy: A Case Report and Literature Review

We report a rare case of hypertrophic obstructive cardiomyopathy (HOCM) presenting with mega coronary arteries with obstructive coronary artery disease. Interestingly, the patient had large septals, large diagonals, large obtuse marginal with a large left atrial branch, and a large conus almost mimicking a duplicate right coronary artery. Because of massive left ventricular hypertrophy, to overcome the supply-demand mismatch, coronary arteries may become large or with more arborization in hypertrophic cardiomyopathy but the same is rarely encountered in routine clinical practice. Our case is a rare illustration of the simultaneous presence of mega coronary arteries and critical obstructive coronary artery disease in HOCM in a young male of 38 years of age.

Management of a Critically Ill Patient With Severe Hypertrophic Obstructive Cardiomyopathy Presenting for Emergent Craniotomy Due to Subdural Hemorrhage

Hypertrophic obstructive cardiomyopathy (HOCM) is an inherited cardiac disorder characterized by asymmetric thickening of the myocardium, most commonly of the interventricular septum. Perioperative considerations for patients with HOCM undergoing surgical procedures are discussed, so as to avoid worsening the existing left ventricular outflow tract (LVOT) obstruction, leading to potential cardiovascular collapse. Of particular interest is managing these patients when confronted with vascular aneurysmal disease or hemorrhagic comorbidities with conflicting hemodynamic goals. In this case report, we present the case of a 77-year-old female with known HOCM and severe LVOT obstruction, presenting with intracranial hemorrhage (ICH), acute on chronic subdural hematoma, and potential cerebral aneurysm, undergoing decompressive craniectomy and hematoma evacuation. Anesthetic management of a patient with HOCM presenting for emergent ICH can be challenging given the complex hemodynamic management goals, often conflicting with a patient's comorbidities. Here we describe the prioritization of the patient's underlying HOCM pathology and favored maintenance of afterload given the potentially lethal risk of cardiovascular collapse if LVOT obstruction was encountered.

Management of growth failure and other endocrine aspects in patients with Noonan syndrome across Europe: A sub-analysis of a European clinical practice survey

To date, there is a lack of international guidelines regarding the management of the endocrine features of individuals with Noonan syndrome (NS). The aim was to develop a clinical practice survey to gather information on current treatment and management of these patients across Europe. A group of 10 experts from three clinical specialities involved in the management of NS patients (clinical geneticists, paediatric endocrinologists, and paediatric cardiologists) developed a 60-question clinical practice survey. The questionnaire was implemented in Survey Monkey and sent to physicians from these three specialities via European/national societies. Contingency tables and the Chi-Squared test for independence were used to examine differences between specialities and countries. In total, responses of 364 specialists (paediatric endocrinologists, 40%; geneticists, 30%; paediatric cardiologists, 30%) from 20 European countries were analysed. While endocrinologists mostly referred to national growth charts for the general population, geneticists mostly referred to NS-specific growth charts. Approximately half of the endocrinologists perform growth hormone (GH) stimulation tests in short patients with low IGF1 levels. Two thirds of endocrinologists begin GH treatment for short patients in early childhood (4-6.9 years), and over half of them selected a threshold of -2 standard deviation score (SDS) according to national growth charts. The main concerns about GH treatment appear to be presence of hypertrophic cardiomyopathy (HCM) (59%), increased risk of malignancy (46%), and limited efficacy (31%). When asked if they consider HCM as a contraindication for GH treatment, one third of respondents skipped this question, and among those who replied, two thirds selected 'cannot answer', suggesting a high level of uncertainty. A total of 21 adverse cardiac responses to GH treatment were reported. Although most respondents had not encountered any malignancy during GH treatment, six malignancies were reported. Finally, about half of the endocrinologists expected a typical final height gain of 1-1.5 SDS with GH treatment. This survey describes for the first time the current clinical practice of endocrine aspects of NS across Europe and helps us to identify gaps in the management but also in the knowledge of this genetic disorder.

Anesthesia Management in a Hypertrophic Cardiomyopathy Patient with Brain Tumor: A Case Report

Background: Brain tumour surgeries are high-risk because of their potential for postoperative fetal complications. This risk is exaggerated in the presence of hypertrophic cardiomyopathy (HCM). Hypertrophic cardiomyopathy includes asymmetric left ventricular hypertrophy with mitral valve dysfunction that obstructs the left ventricular outflow tract. Various postoperative factors may accelerate this obstruction and lead to life-threatening consequences. Hypertrophic obstructive cardiomyopathy (HOCM) is a type of HCM that obstructs the left ventricular outflow tract. The most important parameters are preload, afterload, and ventricular contraction, resulting from the surgical method, anesthesia factors, and changes in intravascular volume that are prone to fluctuations in HOCM patients in the postoperative period. These cases increase the risk of arrhythmias and myocardial ischemia and significantly increase patients' morbidity and mortality after surgery. It should avoid lowering blood pressure, increasing heart rate, and reducing preload and afterload in these patients. Cases Report: In this study, we reported a 59 years old man who complained of a speech disorder that had worsened three months ago and mentioned a history of hypertrophic cardiomyopathy. The patient underwent brain tumor surgery and was discharged from the hospital with proper management of anesthesia. Conclusion: Loading and maintaining sinus rhythm are recommended to prevent complications. We presented the intraoperative management of a patient with HCM undergoing a brain tumour resection and discussed its complications.