Familiar Hypertrophic Cardiomyopathy Research Articles

Reversible Apical Hypertrophy in a Young Competitive Athlete with Familiar Hypertrophic Cardiomyopathy.

BACKGROUND Differential diagnosis between athlete's heart and hypertrophic cardiomyopathy is sometimes challenging in sport cardiology since endurance training can cause a distinct pattern of functional and structural changes of the cardiovascular system. It is of crucial importance to accurately diagnose it and stratify the arrhythmic risk since hypertrophic cardiomyopathy is one of the leading causes of sudden cardiac death in young athletes. Apical hypertrophic cardiomyopathy is a relatively rare form of hypertrophic cardiomyopathy that predominantly affects the apex of the left ventricle and usually has a nonobstructive physiology. Few data and studies are available on influence of aerobic training (and detraining) on morphological changes in athletes with apical hypertrophic cardiomyopathy. CASE REPORT We present the case of a 19-year-old male soccer athlete with family history for obstructive hypertrophic cardiomyopathy, with electrocardiographic and morphological left ventricular remodeling in association with sports activity. Intensive aerobic training led to marked T-wave inversion on 12-lead ECG and left ventricular hypertrophy compatible with apical hypertrophic cardiomyopathy. Genetic testing confirmed the presence of familial variant c853C>T, p.(Arg 285Cys) on TNNT2 gene. After 18 months detraining, we observed a complete regression of ECG abnormalities and a reverse remodeling of the left ventricular hypertrophy. No pharmacological therapy was indicated; periodic cardiological evaluations were advised. Monitoring devices or implantable cardioverter defibrillator were not recommended. CONCLUSIONS This case suggests that intensive aerobic training can affect the pathological hypertrophic cardiomyopathy substrate, facilitating the development of left ventricular hypertrophy and, more interesting, regression of structural changes after detraining.

GW29-e1531 The Early Diagnosis of MYH7 Gene Mutation Carriers of Hypertrophic Cardiomyopathy Using Multi-Parameter Analysis Model by Conventional 2D- Echocardiography and 3D- Speckle Tracking Imaging

To create the multi-parameter analysis model to improve the early diagnosis in different genes mutation carriers of familiar hypertrophic cardiomyopathy (HCM). Fifty-five subjects were divided into two groups:MYH7 mutation carriers without left ventricular hypertrophy (MYH7G+P-) (N=28) and MYBPC3

The early diagnosis of MYH7 gene mutation carriers of hypertrophic cardiomyopathy using multi-parameter analysis model by conventional two-dimensional echocardiography and three-dimensional speckle tracking imaging

Objective To create multi-parameter analysis model by conventional two-dimensional echorcardiography(2DE) and three-dimensional speckle tracking imaging(3D-STI) in order to improve the early diagnosis in MYH7G+ P- mutation carriers of familiar hypertrophic cardiomyopathy(HCM). Methods Twenty-eight MYH7 mutation carriers without left ventricular hypertrophy (MYH7G+ P-) were enrolled as the research group, while 27 MYBPC3 mutation carriers without left ventricular hypertrophy (MYBPC3G+ P-) were selected as the control group. The clinical data, conventional 2DE and tissue Doppler imaging(TDI) parameters of the two groups were acquired, including the maximum of the thickness of interventricular septum(IVS) and left ventricular posterior ventricular wall thickness(LVPWT) in end of diastole, mitral flow E and A velocities, E peak deceleration time(EDT), atrioventricular filling time, mitral annulus velocity of interventricular septum IVS-e′ and lateral wall L-e′, interventricular septum IVS-a′ and lateral wall L-a′ peak in diastole, calculate mean value e′ and a′, and calculate E/ e′, E/A, left atrial volume index(LAVI), left ventricular mass index(LVMI), left ventricular ejection fraction(LVEF) and isovolumic relaxation time(IVRT), isovolumic contraction time(IVCT). The global longitudinal peak strain(GLS), global radial peak strain(GRS), global circumferential peak strain(GCS) and global area peak strain(GAS) were acquired by 3D-STI. All parameters were compared between research group and control group. Results Compared with the control group, research group significantly increased in LAVI, maximum IVS and LVPWT, LVMI and GAS(P 0.05). For single parameter, the area under ROC curve(AUC) were successively LVPWT>LAVI>IVS>LVMI>GAS(0.772, 0.738, 0.733, 0.719, 0.714, respectively). AUC of multi-parameters was 0.912, the sensitivity and specificity were 85.2% and 96.3%, respectively. Conclusions Multi-parameter analysis model by conventional 2DE and 3D-STI can significantly improve the recognition efficiency of early diagnosis MYH7G+ P- of familiar HCM. With further, maximum LVPWT is an independent predictor of distinction MYH7G+ P- and MYBPC3G+ P-. Key words: Echocardiography; Cardiomyopathy, hypertrophic; MYBPC3; MYH7; Speckle tacking imaging, three-dimensional

Analysis of cardiac troponin C gene TNNC1 c. G175C mutation in a Chinese pedigree with familial hypertrophic cardiomyopathy and the correlation between genotype and phenotype

Objective: To investigate the genotype-phenotype correlation in Chinese familial hypertrophic cardiomyopathy (HCM )focusing on the cardiac troponin C gene TNNC1 c. G175C mutation. Methods: All family members of a Chinese pedigree with hypertrophic cardiomyopathy admitted in Third People's Hospital of Qingdao in February 2005 and 200 healthy volunteers were included in this study. The coding exons of 30 hypertrophic cardiomyopathy associated genes were identified by whole exons amplification and high-throughput sequencing in the proband, and the identified mutation were further detected through bi-directional Sanger sequencing in all family members and 200 healthy volunteers. Pedigree analysis included clinical manifestation, physical examination, ECG and echocardiogram. Results: A missense mutation c. G175C was identified in the TNNC1 gene in 2 family members, which resulted in a glutamic acid (E) to glutamine (Q) exchange at amino acid residue 59. A mutation c. A1319G was identified in the MYLK2 gene in 1 family member, which resulted in a lysine (K) to arginine (R) exchange at amino acid residue 440. These mutations were absent in 200 healthy controls. The proband carried the two kinds of mutations and expressed various clinical manifestations of heart failure and had history of ventricular tachycardia, paraxial atrial fibrillation, pacemaker implantation, electrocardiogram showed right bundle branch block and echocardiography examination evidenced thickened interventricular septum (23.3 mm) and apex and reduced wall motion of these segments. The daughter of the proband carried the TNNC1 c. G175C mutation and was also diagnosed with asymptomatic HCM by echocardiography with thickened interventricular septum (19 mm) and apex (15 mm). Conclusion: The novel missense mutation of TNNC1 c. G175C might be the disease-causing gene mutation in this Chinese pedigree with familiar HCM.

Abstract 20016: Genetic Anticipation in Familial Hypertrophic Cardiomyopathy

Introduction: To identify HCM at the earliest time possible, estimating the onset of disease based on diagnostic criteria is vital in timing the initiation of screening and interventions. Hypothesis: Clinic observations indicate an early diagnose of HCM in second generation of most affected families. From the pedigrees with or without mutations in beta-myosin heavy chain gene (MYH7) affected in two or more generations with hypertrophic cardiomyopathy (HCM), ages and maximal wall thickness (MWT) of left ventricles at diagnosis were evaluated to investigate the potential genetic anticipation in patients with familiar HCM (FHCM). Methods: 56 individuals from 25 families were analyzed. Linear mixed effects models were adopted to prevent misinterpretation resulting from the cohort effect. Published data containing 9 sarcomere mutations (181 individuals in 52 families) also were extracted. Results: MYH7 mutations were detected in 9 of the 25 probands, The median age of HCM diagnosis was 24 in the younger generation and 55 in the older (p < 0.001). In the parametric model, the estimated change in the expected age at diagnosis for the entire cohort was 25.8 years (p <0.001). Statistically significant earlier ages at diagnoses were also observed within subgroups of MYH7+ and MYH7- mutations, and probands older and younger than 30 years old. Although the estimated change in MWT at diagnosis for the entire cohort was only 2.161 mm (p =0.212), the subgroup of probands in the younger generation aged less than 30 years had 10.393 mm (p=0.018) thicker MWT and showed a significant reverse correlation with age. Analysis of published data also supports these findings. Conclusions: Genetic anticipation was observed in patients with FHCM. FHCM is prone to be diagnosed at an earlier age in younger generations. Patients who are younger with relatives affected by HCM, especially those who are diagnosed before 30 years of age, should continue to be tracked to offer appropriate screening modalities as earlier as possible.

Age-Dependent Heterogeneity of Familiar Hypertrophic Cardiomyopathy Phenotype: A Role of Cardiovascular Magnetic Resonance

In this case report, we present familiar hypertrophic cardiomyopathy with age-dependent heterogeneity of the disease phenotype among the members of one family who carry the same mutation of the myosin-binding protein C gene. Phenotypic heterogeneity is common in patients with familial forms of hypertrophic cardiomyopathy, both in clinical expression and outcome. Compared with other noninvasive cardiac imaging modalities, cardiovascular magnetic resonance provides an opportunity to more accurately characterize the varying phenotypic presentations of hypertrophic cardiomyopathy.

臨床 多彩な伝導障害と,拡張を伴う肥大を優性遺伝する家族性心筋症

臨床 多彩な伝導障害と,拡張を伴う肥大を優性遺伝する家族性心筋症

China Physiome Project: A Comprehensive Framework for Anatomical and Physiological Databases From the China Digital Human and the Visible Rat

The connection study between biological structure and function, as well as between anatomical data and mechanical or physiological models, has been of increasing significance with the rapid advancement in experimental physiology and computational physiology. The China Physiome Project (CPP) is dedicated in optimization of the connection exploration based on standardization and integration of the structural datasets and their derivatives of cryosectional images with various standards, collaboration mechanisms, and online services. The CPP framework hereby incorporates the three-dimensional anatomical models of human and rat anatomy, the finite-element models of whole-body human skeleton, and the multiparticle radiological dosimetry data of both the human and rat computational phantoms. The ontology of CPP was defined using MeSH and, with its all standardized models description implemented by M3L, a multiscale modeling language based on XML. Provided services based on Wiki concept include collaboration research, modeling version control, data sharing, online analysis of M3L documents. As a sample case, a multiscale model for human heart modeling, in which familiar hypertrophic cardiomyopathy was studied according to the structure-function relations from genetic level to organ level, is integrated into the framework and given for demonstration of the functionality of multiscale physiological modeling based on CPP.

A Homozygous MYBPC3 Gene Mutation Associated With a Severe Phenotype and a High Risk of Sudden Death in a Family With Hypertrophic Cardiomyopathy

Genetic studies can play a key role in the comprehensive evaluation of familiar hypertrophic cardiomyopathy and in the development of individualized medicine. Although only a few cases have been described, there exists a group of patients with complex genotypes that are associated with severe disease manifestations and a high risk of sudden death. We describe a family in which some members experienced the early development of systolic and diastolic dysfunction while others experienced sudden death at a young age. We identified a novel homozygous mutation (IVS6+5G>A) in the myosin-binding protein-C gene that explained the phenotype of affected individuals and that enabled us to estimate the risk in other family members and to offer genetic counseling.

Anestesia para cesariana em paciente portadora de cardiomiopatia hipertrófica familiar: relato de caso

Familiar Hypertrophic cardiomyopathy (FHC) is a rare hereditary cardiac disorder characterized by hypertrophy of the ventricular septum and variable degrees of subvalvular aortic stenosis. In this disease, the increase in myocardial contractility and reduction in peripheral vascular resistance can aggravate left ventricular outlet obstruction, leading to arrhythmias and cardiac ischemia. The objective of this report was to discuss the anesthetic management of cesarean section in a patient with FHC. A patient in the 33rd week of pregnancy and prior diagnosis of FHC presented, on the 24-hour Holter monitor, 22 episodes of non-sustained ventricular tachycardia (NSVT) and 2 episodes of sustained ventricular tachycardia (SVT). She complained of episodes of palpitation, dyspnea, and chest pain of short duration. The patient was medicated with atenolol, with control of symptoms and cardiac arrhythmias. Within 38 weeks and 5 days of gestation, the patient underwent elective cesarean section. Besides the usual monitoring, analysis of the ST segment and invasive blood pressure were also instituted. Anesthesia consisted of combined spinal-epidural technique with subarachnoidal administration of 5 microg of sufentanil followed by the administration of increasing doses of 0.375% bupivacaine until it reached the level of T6 (total of 16 mL). Metaraminol was used as a vasopressor. Perioperative maternal hypotension or other complications were not observed. General anesthesia is often used for cesarean sections in patients with FHC. Spinal-epidural anesthesia with slow installation of the blockade was a safe alternative. In those patients, one should avoid an increase in myocardial contractility and, if necessary, a a-agonist should be used to treat maternal hypotension.

Autonomic cardiac control in animal models of cardiovascular diseases II. Variability analysis in transgenic rats with α-tropomyosin mutations Asp175Asn and Glu180Gly

Animal models of cardiovascular diseases allow to investigate relevant pathogenetic mechanisms in detail. In the present study, the mutations Asp175Asn and Glu180Gly in alpha-tropomyosin (TPM1), known cause familiar hypertrophic cardiomyopathy (FHC) were studied for changes in hemodynamic parameters and spontaneous baroreflex regulation in transgenic rats in comparison to transgenic and non-transgenic controls by telemetry. Heart rate variability (HRV) and blood pressure variability (BPV) were analyzed using time- and frequency domain, as well as non-linear measures. The dual sequence method was used for the estimation of the baroreflex regulation. In transgenic rats harboring mutated TPM1, changes in HRV were detected during exercise, but not at rest. Both mutations, Asp175Asn and Glu180Gly, caused increased low frequency power. In addition, in animals with mutation Asp175Asn a reduced total HRV was observed. BPV did not show any differences between all transgenic animal lines. During exercise, a strong increase in the number of bradycardic and tachycardic fluctuations accompanied with decreased baroreflex sensitivity (BRS) was detected in animals with either TPM1 mutation, Asp175Asn or Glu180Gly. These data suggest, that the analysis of cardiac autonomic control, particularly of baroreflex regulation, represents a powerful non-invasive approach to investigate the effects of subtle changes in sarcomeric architecture on cardiac physiology in vivo. In case of mutations Asp175Asn or Glu180Gly in TPM1, early detection of alterations in autonomic cardiac control could help to prevent sudden cardiac death in affected persons.

Cardiovascular remodelling and red blood cell Li+/Na+ countertransport in patients with type 1 diabetes and essential hypertension

Patients with type 1 (insulin-dependent) diabetes may develop a specific cardiac disease characterized by functional and structural abnormalities. The pathogenesis of the cardiac disease is poorly understood but cardiac and renal complications may coexist. Patients with overt diabetic nephropathy have increased red cell Li+/Na+ countertransport (CT), which reflects abnormal kinetic properties of the red cell membrane Na+/H+ exchange. Since the activation of Na+/H+ exchange has a key role in cell proliferation and cell growth, as well as in the regulation of cell sodium and cell pH and in the renal reabsorption of Na+ and bicarbonate, we have looked for relationships between red cell Li+/Na+ CT, Na+/H+ exchange and cardiovascular remodeling in patients with type 1 diabetes, essential hypertension and idiopathic familiar cardiomyopathy. In type 1 diabetes the maximal velocity of Li+/Na+ CT is positively correlated with interventricular septum thickness and the left ventricular wall to lumen ratio. Similar results were obtained in patients with essential hypertension. In these patients an increased Li+/Na+ CT is also associated with severe and drug-resistant hypertension and with significant vascular remodelling, estimated by the minimal post-ischaemic vascular resistance in the calf. Finally, Li+/Na+ CT is negatively correlated with diastolic relaxation of the left ventricle in familiar hypertrophic cardiomyopathy. From these data it appears that widespread abnormal kinetic properties of Na+/H+ exchange, estimated by increased red cell Li+/Na+ CT, may have epistatic effects on the pathogenesis of cardiac complications of type 1 diabetes and essential hypertension.