The Cumulative Effects of the MYH7-V878A and CACNA1C-A1594V Mutations in a Chinese Family with Hypertrophic Cardiomyopathy

Cardiology ◽  
2017 ◽  
Vol 138 (4) ◽  
pp. 228-237 ◽  
Author(s):  
Bo Wang ◽  
Rui-Qi Guo ◽  
Jing Wang ◽  
Fan Yang ◽  
Lei Zuo ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Myocardial Fibrosis ◽  
Cumulative Effect ◽  
Left Ventricular ◽  
Chinese Family ◽  
St Segment ◽  
Asymmetric Septal Hypertrophy ◽  
Second Generation Sequencing ◽  
Septal Hypertrophy ◽  
Generation Sequencing

Aims: We investigated the pathogenesis of MYH7-V878A and CACNA1C-A1594V mutations in a Chinese family with hypertrophic cardiomyopathy. Methods: Clinical, electrocardiographic (ECG), echocardiographic, and cardiac magnetic resonance (CMR) examinations of members of a Chinese family were followed by exon and boarding intron analyses of 96 genes in the proband using second-generation sequencing. We confirmed the mutations by bidirectional Sanger sequencing in the members and in 300 healthy controls. Results: We detected MYH7-V878A and CACNA1C-A1594V mutations in this family. The members with both mutations showed inverted T-waves and ST-segment depression in ECG recordings, severe left ventricular (LV) hypertrophy in echocardiography, and myocardial fibrosis in CMR; subject II-11 did not show late gadolinium enhancement. Among those with only the MYH7-V878A mutation, subject III-7 showed abnormal ECG recordings, asymmetric septal hypertrophy, and myocardial fibrosis, and subjects II-13 and III-15 showed some abnormal repolarization, borderline LV wall thickness, and normal CMR findings. Those with only the CACNA1C-A1594V mutation showed nearly normal readings in all examinations. The members with both mutations displayed more severe LV hypertrophy and elevated LV filling pressure than those with 1 or no mutation (p < 0.05). Conclusion: Our results suggest that the pathogenesis of MYH7-V878A and CACNA1C-A1594V mutations may have a cumulative effect.

scholarly journals Echocardiographic Profile of Hypertrophic Cardiomyopathy – A Single-Centre, Observational study

2021 ◽  
Vol 14 (1) ◽  
pp. 5-11
Author(s):  
AKM Monwarul Islam ◽  
Dipal K Adhikary ◽  
Shovan Rahman ◽  
Mohsin Ahmed ◽  
Md Toufiqur Rahman ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Observational Study ◽  
Wall Thickness ◽  
Phenotypic Expression ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Left Ventricular Cavity ◽  
Asymmetric Septal Hypertrophy ◽  
Septal Hypertrophy ◽  
Bangladeshi Population

Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease of left ventricular hypertrophy (LVH). Phenotypic expression varies widely from subclinical hypertrophy to gross asymmetric septal hypertrophy causing left ventricular outflow tract (LVOT) obstruction. On top of genetic and phenotypic heterogeneity, the prevalence of different types of HCM may have geographical, as well as, ethnic variation. Methods: This observational study was carried out during 2010 to 2020 to determine the echocardiographic profile of HCM in Bangladeshi population. All patients undergoing transthoracic echocardiography (TTE) in a private consultation centre of Dhaka, Bangladesh were included. HCM was defined as the presence of a maximal end-diastolic wall thickness of e”15 mm anywhere in the left ventricle (LV), in the absence of another cause of hypertrophy in adults. HCM was further classified according to the pattern of myocardial hypertrophy and presence or absence of LVOT, or mid-left ventricular cavity obstruction. Results: Out of 76 cases, non-obstructive HCM was the commonest type (65.8%), followed by HCM causing LVOT obstruction (13.2%), HCM causing mid-LV cavity obstruction (10.5%), and the apical variety ( 10.5%). Asymmetric septal hypertrophy (ASH) was found in 42.1%, systolic anterior motion (SAM) of anterior mitral leaflet (AML) in 14.5%, mitral regurgitation (MR) in 50%, left ventricular systolic dysfunction in 5.3%, and raised pulmonary artery systolic pressure (PASP) in 15.8% of cases. Maximum LV wall thickness ≥30 mm was found in 66 out of 76 cases. Conclusion: The study highlights the clinically useful profile of HCM in Bangladeshi population based on conventional echocardiography. Further studies involving clinical, newer echocardiographic modalities and genetic analyses are warranted to discover the additional information in this ethnicity. Cardiovasc j 2021; 14(1): 5-11

scholarly journals P873 A rare and potentially treatable cause of left ventricular hypertrophy

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
C Y Wong
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Left Ventricular Hypertrophy ◽  
Ejection Fraction ◽  
Fabry Disease ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Valvular Regurgitation ◽  
Outflow Obstruction ◽  
Asymmetric Septal Hypertrophy ◽  
Septal Hypertrophy

Abstract Introduction A 67-year-old man was referred for care of "asymptomatic hypertrophic cardiomyopathy". He did not have hypertension. No significant positive family history could be elicited. Electrocardiogram showed sinus rhythm with voltage criteria of left ventricular hypertrophy (LVH). Outside Transthoracic Echocardiogram (TTE) reported normal ejection fraction with asymmetric septal hypertrophy without outflow obstruction. He was put on observation for few years and was not any treatment. On first encounter in our clinic, physical examination including skin and eye assessment, and laboratory tests including renal function were unremarkable. Procedure TTE was repeated in our clinic showing normal left ventricular size with ejection fraction 55%, and impaired diastolic relaxation. There was asymmetric septal hypertrophy with septal thickness 2.1 cm (Figure A). There was mild systolic anterior motion of mitral apparatus and mild mitral regurgitation, without resting or Valsalva provoked outflow obstruction. Global longitudinal strain was -7.7% with most prominent abnormalities seen at apex, mid to basal anteroseptal and anterior wall (Figure B). Further assessment by Cardiac MRI showed similar asymmetric septal wall thickening. Late gandolinium enhancement study demonstrated patchy fluffy hyperenhancement of the mid wall of the basal to mid anteroseptal segment, and mid to apical anterior segment, suggestive of myocardial fibrosis (Figure C1 and C2). Dried spot blood was sent to Taiwan for enzyme study which revealed partial acid alpha-galactosidase A deficiency. Further genetic study detected a mutation of Hemizygous NM_000169.2(GLA):c.640-801[G &gt; A] at intron 4. Finally endomyocardial biopsy was done which confirmed the cardiac involvement of Fabry disease (Figure D, myelin body shown under electron microscopy). This gentleman was referred for consideration of Enzyme Replacement Therapy (ERT). Discussion Fabry disease is an X-linked glycolipid storage disease with accumulation of globotriaosylceramide in lysosomes in multiple cell types throughout the body leading to various organ involvement. Cardiac manifestations include unexplained LVH, valvular regurgitation, conduction abnormalities etc. It occurs in up to 0.3-5% of patients with hypertrophic cardiomyopathy. Fabry disease should be considered as a differential diagnosis in all men with sporadic or non-autosomal dominant transmission of unexplained LVH, since treatment with ERT is available which may reduce LVH and improve myocardial function, although any impact on long term outcome has not yet been established. Conclusion This case illustrated a rare but potentially treatable cause of hypertrophic cardiomyopathy. Myocardial strain imaging should be integrated in routine TTE study for assessment of unexplained left ventricular hypertrophy. Multi-modality imaging and multi-specialty approach help in identifying patients of cardiac variant of Fabry disease who may benefit from ERT. Abstract P873 Figure.

scholarly journals Cardiac amyloidosis: The great masquerader

2018 ◽  
Vol 2018 (2) ◽  
Author(s):  
Jubran Rind ◽  
Nagib Chalfoun ◽  
Richard McNamara
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Cardiac Mri ◽  
Cardiac Amyloidosis ◽  
Ventricular Hypertrophy ◽  
Left Ventricular Outflow Tract ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Asymmetric Septal Hypertrophy ◽  
Left Ventricular Outflow ◽  
Septal Hypertrophy

Cardiac amyloidosis is an elusive condition that is notorious for mimicking various cardiovascular conditions that present with left ventricular hypertrophy (LVH). The hypertrophy in amyloidosis is typically diffuse; however, rare reports of echocardiographic resemblances with hypertrophic cardiomyopathy (HCM) exist, such as asymmetric septal hypertrophy and left ventricular outflow tract obstruction. Cardiac MRI can help differentiate amyloidosis from hypertrophic cardiomyopathy in unclear situations. This differentiation from HCM and other forms of cardiomyopathy has important treatment implications. Here we present the case of a 76-year-old man with cardiomyopathy who had echocardiographic features of asymmetric hypertrophic cardiomyopathy but was correctly diagnosed with amyloidosis with the help of cardiac MRI and ECG.

Modified Septal Myectomy Using a Curved Knife for Left Ventricular Septal Hypertrophy

2014 ◽  
Vol 17 (5) ◽  
pp. 269
Author(s):  
Shinya Takahashi ◽  
Taiichi Takasaki ◽  
Futoshi Tadehara ◽  
Takahiro Taguchi ◽  
Keijiro Katayama ◽  
...  
Keyword(s):  
Blood Flow ◽  
Chest Pain ◽  
Aortic Valve ◽  
Cross Section ◽  
Left Ventricular ◽  
Chest Discomfort ◽  
Septal Myectomy ◽  
Asymmetric Septal Hypertrophy ◽  
Septal Hypertrophy ◽  
Septal Myocardium

An 86-year-old woman presented with chest pain and discomfort. Echocardiography revealed severe aortic valve stenosis and asymmetric septal hypertrophy. Aortic valve replacement and myectomy were performed using a curved knife. The blade was U-shaped in cross-section, and was curved upward along the long axis. Hypertrophic septal myocardium was removed along the long axis of the left ventricle (LV), and a groove for blood flow was constructed. The patient was discharged uneventfully without recurrence of her chest discomfort. Our result suggested that a curved knife is a reasonable option for transaortic septal myectomy in patients with obstructive LV hypertrophy.

scholarly journals Predictive values of multiple non-invasive markers for myocardial fibrosis in hypertrophic cardiomyopathy patients with preserved ejection fraction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yumin Li ◽  
Jia Liu ◽  
Yukun Cao ◽  
Xiaoyu Han ◽  
Guozhu Shao ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ejection Fraction ◽  
Myocardial Fibrosis ◽  
Troponin I ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Predictive Values ◽  
Non Invasive ◽  
Potential Biomarker

AbstractMyocardial fibrosis assessed by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with cardiovascular outcomes in hypertrophic cardiomyopathy (HCM) patients, but little is known about the utility of non-invasive markers for detecting LGE. This study aims to explore the association between cardiac-specific biomarkers, CMR myocardial strain, left ventricular (LV) hypertrophy and LGE in HCM patients with preserved ejection fraction (EF) and investigate the predictive values of these indexes for LGE. We recruited 33 healthy volunteers and 86 HCM patients with preserved EF to undergo contrast-enhanced CMR examinations. In total, 48 of 86 HCM patients had the presence of LGE. The LGE-positive patients had significant higher serum high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro b-type natriuretic peptide (Nt-proBNP) levels and lower global longitudinal (GLS) and circumferential (GCS) strains than the LGE-negative group. The LGE% was independently associated with the Nt-proBNP levels, GCS, LV end-diastolic maximum wall thickness (MWT) and beta-blocker treatment. In the receiver operating characteristic curve analysis, the combined parameters of Nt-proBNP ≥ 108.00 pg/mL and MWT ≥ 17.30 mm had good diagnostic performance for LGE, with a specificity of 81.25% and sensitivity of 70.00%. These data indicate that serum Nt-proBNP is a potential biomarker associated with LGE% and, combined with MWT, were useful for identifying myocardial fibrosis in HCM patients with preserved EF. Additionally, LV GCS may be a more sensitive indicator for reflecting the presence of myocardial fibrosis than GLS.

scholarly journals Prognostic significance of cardiac magnetic resonance-based markers in patients with hypertrophic cardiomyopathy

2021 ◽  
Author(s):  
Zsofia Dohy ◽  
Liliana Szabo ◽  
Attila Toth ◽  
Csilla Czimbalmos ◽  
Rebeka Horvath ◽  
...  
Keyword(s):  
Cardiac Magnetic Resonance ◽  
Hypertrophic Cardiomyopathy ◽  
Magnetic Resonance ◽  
Myocardial Fibrosis ◽  
Ventricular Arrhythmias ◽  
Prognostic Significance ◽  
Strain Analysis ◽  
Left Ventricular ◽  
Icd Therapy ◽  
Lv Mass

AbstractThe prognosis of patients with hypertrophic cardiomyopathy (HCM) varies greatly. Cardiac magnetic resonance (CMR) is the gold standard method for assessing left ventricular (LV) mass and volumes. Myocardial fibrosis can be noninvasively detected using CMR. Moreover, feature-tracking (FT) strain analysis provides information about LV deformation. We aimed to investigate the prognostic significance of standard CMR parameters, myocardial fibrosis, and LV strain parameters in HCM patients. We investigated 187 HCM patients who underwent CMR with late gadolinium enhancement and were followed up. LV mass (LVM) was evaluated with the exclusion and inclusion of the trabeculae and papillary muscles (TPM). Global LV strain parameters and mechanical dispersion (MD) were calculated. Myocardial fibrosis was quantified. The combined endpoint of our study was all-cause mortality, heart transplantation, malignant ventricular arrhythmias and appropriate implantable cardioverter defibrillator (ICD) therapy. The arrhythmia endpoint was malignant ventricular arrhythmias and appropriate ICD therapy. The LVM index (LVMi) was an independent CMR predictor of the combined endpoint independent of the quantification method (p < 0.01). The univariate predictors of the combined endpoint were LVMi, global longitudinal (GLS) and radial strain and longitudinal MD (MDL). The univariate predictors of arrhythmia events included LVMi and myocardial fibrosis. More pronounced LV hypertrophy was associated with impaired GLS and increased MDL. More extensive myocardial fibrosis correlated with impaired GLS (p < 0.001). LVMi was an independent CMR predictor of major events, and myocardial fibrosis predicted arrhythmia events in HCM patients. FT strain analysis provided additional information for risk stratification in HCM patients.

Predictive Values of Multiple Non-Invasive Markers for Myocardial Fibrosis in Hypertrophic Cardiomyopathy Patients With Preserved Ejection Fraction

2020 ◽  
Author(s):  
Yumin Li ◽  
Jia Liu ◽  
Yukun Cao ◽  
Xiaoyu Han ◽  
Guozhu Shao ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ejection Fraction ◽  
Myocardial Fibrosis ◽  
Troponin I ◽  
Myocardial Strain ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Predictive Values ◽  
Non Invasive ◽  
Potential Biomarker

Abstract Myocardial fibrosis assessed by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with cardiovascular outcomes in hypertrophic cardiomyopathy (HCM) patients, but little is known about the utility of non-invasive markers for detecting LGE. This study aims to explore the association between cardiacspecific biomarkers, CMR myocardial strain, left ventricular (LV) hypertrophy and LGE in HCM patients with preserved ejection fraction (EF) and investigate the predictive values of these indexes for LGE. We recruited 33 healthy volunteers and 86 HCM patients with preserved EF to undergo contrast-enhanced CMR examinations. In total, 48 of 86 HCM patients had the presence of LGE. Serum high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro b-type natriuretic peptide (Nt-proBNP) levels were elevated in LGE-positive patients compared with LGE-negative patients. The LGE-positive patients had lower global longitudinal (GLS) and circumferential (GCS) strains than the LGE-negative group and the healthy controls. The LGE% was independently associated with the Nt-proBNP levels, GCS, MWT and beta-blocker treatment. In the receiver operating characteristic curve analysis, the combined parameters of Nt-proBNP≥108 pg/mL and MWT≥17.3 mm had good diagnostic performance for LGE, with a specificity of 81.3% and sensitivity of 70.0%. These data indicate that serum Nt-proBNP is a potential biomarker associated with LGE% and, combined with MWT, were useful for identifying myocardial fibrosis in HCM patients with preserved EF. Additionally, LV GCS may be a more sensitive indicator for reflecting the presence of myocardial fibrosis than GLS.

Abstract 15921: Correlation Between Repolarization Changes in Signal Averaged Electrocardiography and Myocardial Fibrosis in Adults With Hypertrophic Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ramses Ramirez Damera ◽  
Hernan L Vera-Sarmiento ◽  
David Hurtado-de-Mendoza ◽  
Ketty Dolores-Cerna ◽  
Muhammad I Khan ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Myocardial Fibrosis ◽  
Ventricular Arrhythmias ◽  
Interstitial Fibrosis ◽  
Objective Assessment ◽  
Left Ventricular ◽  
Noninvasive Technique ◽  
Arrhythmogenic Substrate ◽  
Study Results ◽  
Replacement Fibrosis

Introduction: Hypertrophic Cardiomyopathy (HCM) is known as one of the most common causes of sudden cardiac death. Its propensity to lethal arrhythmias is a result of myocardial remodeling leading to aberrant conduction and increased reentrant electrical activity. Previous studies suggest an association between the amount of myocardial fibrosis found on Cardiac Magnetic Resonance (CMR) and the risk of these ventricular arrhythmias. Signal Average Electrocardiography ( SAECG) is a noninvasive technique used to detect subtle conduction abnormalities that can be missed on standard Electrocardiography ( ECG ). Hypothesis: Non-uniform conduction through fibrotic tissue seen in CMR leads to unsynchronized myocardial depolarization which correlates with further repolarization abnormalities that can be detected by SAECG. Method: In this retrospective study, results of SAECG were used to classify 73 HCM patients into Normal or Abnormal groups based on the presence of two or more of three predetermined criteria (fQRS, RMS40, LAS40). Replacement fibrosis was assessed by measuring late gadolinium enhancement (LGE) . Interstitial fibrosis was assessed by measuring T1 relaxation times, using the Look-Locker sequence. Results: A statistically significant association between the presence of myocardial fibrosis on CMR and abnormal SAECG was found with a difference of proportions of 41.3% between the subgroups. Left ventricular mass index was found to be significantly higher in the abnormal subgroup (Normal: 61.2 ± 19.6; Abnormal: 82.4 ± 37.1; p = <0.003, CI 95% [2.93; 39.47]). The presence of T wave inversions on standard ECG was only seen in those who had an abnormal SAECG exam. Conclusion: Abnormal SAECG in patients with HCM is associated with the presence of LGE on CMR. This study showed a subset of patients with absence of LGE despite having abnormal SAECG, which implies that there are other complex mechanisms besides replacement fibrosis, that predisposes this population to ventricular arrhythmias. This can also be highlighted by the fact that there was no difference between the two groups in the T1 mapping time. We believe that SAECG could be an objective assessment of the arrhythmogenic substrate present in patients with HCM.

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