Asymmetric Septal Hypertrophy Research Articles

Mitochondrial Dysfunctions Contribute to Hypertrophic Cardiomyopathy in Patient iPSC-Derived Cardiomyocytes with MT-RNR2 Mutation.

SummaryHypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young individuals. A potential role of mtDNA mutations in HCM is known. However, the underlying molecular mechanisms linking mtDNA mutations to HCM remain poorly understood due to lack of cell and animal models. Here, we generated induced pluripotent stem cell-derived cardiomyocytes (HCM-iPSC-CMs) from human patients in a maternally inherited HCM family who carry the m.2336T>C mutation in the mitochondrial 16S rRNA gene (MT-RNR2). The results showed that the m.2336T>C mutation resulted in mitochondrial dysfunctions and ultrastructure defects by decreasing the stability of 16S rRNA, which led to reduced levels of mitochondrial proteins. The ATP/ADP ratio and mitochondrial membrane potential were also reduced, thereby elevating the intracellular Ca2+ concentration, which was associated with numerous HCM-specific electrophysiological abnormalities. Our findings therefore provide an innovative insight into the pathogenesis of maternally inherited HCM.

Menarche, menopause, and pregnancy data in untreated females and females treated with agalsidase alfa in the Fabry Outcome Survey

Mucopolysaccharidosis (MPS) type III, Sanfilippo Syndrome, is an autosomal recessive lysosomal storage disorder. MPS I and II patients often develop cardiac involvement leading to early mortality, however there are limited data in MPS III. The objective of this study is to describe cardiac abnormalities in a large group of MPS III patients followed in a longitudinal natural history study designed to determine outcome measures for gene transfer trials.A single center study of MPS III patients who were enrolled in the Nationwide Children's Hospital natural history study in 2014. Two cardiologists reviewed all patient echocardiograms for anatomic, valvular, and functional abnormalities. Valve abnormalities were defined as abnormal morphology, trivial mitral regurgitation (MR) with abnormal morphology or at least mild MR, and any aortic regurgitation (AR). Abnormal left ventricular (LV) function was defined as ejection fraction < 50%. Group comparisons were assessed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher's exact tests for categorical variables.Twenty-five patients, 15 Type A and 10 Type B MPS III, underwent 45 echocardiograms. Fifteen patients (60%) demonstrated an abnormal echocardiographic finding with age at first abnormal echocardiogram within the study being 6.8 ± 2.8 years. Left-sided valve abnormalities were common over time: 7 mitral valve thickening, 2 mitral valve prolapse, 16 MR (8 mild, 8 trivial), 3 aortic valve thickening, and 9 AR (7 mild, 2 trivial). Two patients had asymmetric LV septal hypertrophy. No valvular stenosis or ventricular function abnormalities were noted. Incidental findings included: mild aortic root dilation (2), bicommissural aortic valve (1), and mild tricuspid regurgitation (3).Individuals with Sanfilippo A and B demonstrate a natural history of cardiac involvement with valvular abnormalities most common. In short-term follow up, patients demonstrated only mild progression of abnormalities, none requiring intervention. Valvular disease prevalence is similar to MPS I and II, but appears less severe. These findings raise no specific concerns for gene transfer trials in patients in this age range.

Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy

BackgorundQuantification of myocardial blood flow (MBF) by positron emission tomography (PET) is important for investigation of angina in hypertrophic cardiomyopathy (HCM). Several software programs exist for MBF quantification, but they have been mostly evaluated in patients (with normal cardiac geometry), referred for evaluation of coronary artery disease (CAD). Software performance has not been evaluated in HCM patients who frequently have hyperdynamic LV function, LV outflow tract (LVOT) obstruction, small LV cavity size, and variation in the degree/location of LV hypertrophy. AimWe compared results of MBF obtained using PMod, which permits manual segmentation, to those obtained by FDA-approved QPET software which has an automated segmentation algorithm. Methods13N-ammonia PET perfusion data were acquired in list mode at rest and during pharmacologic vasodilation, in 76 HCM patients and 10 non-HCM patients referred for evaluation of CAD (CAD group.) Data were resampled to create static, ECG-gated and 36-frame-dynamic images. Myocardial flow reserve (MFR) and MBF (in ml/min/g) were calculated using QPET and PMod softwares. ResultsAll HCM patients had asymmetric septal hypertrophy, and 50% had evidence of LVOT obstruction, whereas non-HCM patients (CAD group) had normal wall thickness and ejection fraction. PMod yielded significantly higher values for global and regional stress-MBF and MFR than for QPET in HCM. Reasonably fair correlation was observed for global rest-MBF, stress-MBF, and MFR using these two softwares (rest-MBF: r = 0.78; stress-MBF: r = 0.66.; MFR: r = 0.7) in HCM patients. Agreement between global MBF and MFR values improved when HCM patients with high spillover fractions (> 0.65) were excluded from the analysis (rest-MBF: r = 0.84; stress-MBF: r = 0.72; MFR: r = 0.8.) Regionally, the highest agreement between PMod and QPET was observed in the LAD territory (rest-MBF: r = 0.82, Stress-MBF: r = 0.68) where spillover fraction was the lowest. Unlike HCM patients, the non-HCM patients (CAD group) demonstrated excellent agreement in MBF/MFR values, obtained by the two softwares, when patients with high spillover fractions were excluded (rest-MBF: r = 0.95; stress-MBF: r = 0.92; MFR: r = 0.95). ConclusionsAnatomic characteristics specific to HCM hearts contribute to lower correlations between MBF/MFR values obtained by PMod and QPET, compared with non-HCM patients. These differences indicate that PMod and QPET cannot be used interchangeably for MBF/MFR analyses in HCM patients.

Ineffective and prolonged apical contraction is associated with chest pain and ischaemia in apical hypertrophic cardiomyopathy

To investigate the hypothesis that persistence of apical contraction into diastole is linked to reduced myocardial perfusion and chest pain. Apical hypertrophic cardiomyopathy (HCM) is defined by left ventricular (LV) hypertrophy predominantly of the apex. Hyperdynamic contractility resulting in obliteration of the apical cavity is often present. Apical HCM can lead to drug-refractory chest pain. We retrospectively studied 126 subjects; 76 with apical HCM and 50 controls (31 with asymmetrical septal hypertrophy (ASH) and 19 with non-cardiac chest pain and culprit free angiograms and structurally normal hearts). Perfusion cardiac magnetic resonance imaging (CMR) scans were assessed for myocardial perfusion reserve index (MPRi), late gadolinium enhancement (LGE), LV volumes (muscle and cavity) and regional contractile persistence (apex, mid and basal LV). In apical HCM, apical MPRi was lower than in normal and ASH controls (p<0.05). In apical HCM, duration of contractile persistence was associated with lower MPRi (p<0.01) and chest pain (p<0.05). In multivariate regression, contractile persistence was independently associated with chest pain (p<0.01) and reduced MPRi (p<0.001). In apical HCM, regional contractile persistence is associated with impaired myocardial perfusion and chest pain. As apical myocardium makes limited contributions to stroke volume, apical contractility is also largely ineffective. Interventions to reduce apical contraction and/or muscle mass are potential therapies for improving symptoms without reducing cardiac output.

Left Atrial Appendage Ostial Stenosis in a Patient with Atrial Flutter and Asymmetric Septal Hypertrophy

Left Atrial Appendage Ostial Stenosis in a Patient with Atrial Flutter and Asymmetric Septal Hypertrophy

Magnetic Resonance in Transthyretin Cardiac Amyloidosis

BackgroundCardiac transthyretin amyloidosis (ATTR) is an increasingly recognized cause of heart failure. Cardiac magnetic resonance (CMR), with late gadolinium enhancement (LGE) and T1 mapping, is emerging as a reference standard for diagnosis and characterization of cardiac amyloidosis. ObjectivesThe authors used CMR with extracellular volume fraction (ECV) measurement to characterize cardiac involvement in relation to outcome in ATTR. MethodsSubjects comprised 263 patients with cardiac ATTR corroborated by grade 2 to 3 99mTc-DPD (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid) cardiac uptake, 17 with suspected cardiac ATTR (grade 1 99mTc-DPD), and 12 asymptomatic individuals with amyloidogenic transthyretin (TTR) mutations. Fifty patients with cardiac light-chain (AL) amyloidosis acted as disease comparators. ResultsUnlike cardiac AL amyloidosis, asymmetrical septal left ventricular hypertrophy (LVH) was present in 79% of patients with ATTR (70% sigmoid septum and 30% reverse septal contour), whereas symmetrical LVH was present in 18%, and 3% had no LVH. In patients with cardiac amyloidosis, the pattern of LGE was always typical for amyloidosis (29% subendocardial, 71% transmural), including right ventricular LGE (96%). During follow-up (19 ± 14 months), 65 patients died. ECV independently correlated with mortality and remained independent after adjustment for age, N-terminal pro-B-type natriuretic peptide, ejection fraction, E/E′, and left ventricular mass (hazard ratio: 1.164; 95% confidence interval: 1.066 to 1.271; p < 0.01). ConclusionsAsymmetrical hypertrophy, traditionally associated with hypertrophic cardiomyopathy, was the commonest pattern of ventricular remodeling in ATTR. LGE imaging was typical in all patients with cardiac ATTR. ECV correlated with amyloid burden and was an independent prognostic factor for survival in this cohort of patients.

Contribution of mitral valve leaflet length and septal wall thickness to outflow tract obstruction in patients with hypertrophic cardiomyopathy.

We sought to examine whether elongation of the mitral valve leaflets in patients with hypertrophic cardiomyopathy (HCM) is synergistic to septal wall thickness (SWT) in the development of left ventricular outflow tract obstruction (LVOTO). HCM is a common genetic cardiac disease characterized by asymmetric septal hypertrophy and predisposition towards LVOTO. It has been reported that elongation of the mitral valve leaflets may be a primary phenotypic feature and contribute to LVOTO. However, the relative contribution of this finding versus SWT has not been studied. 152 patients (76 with HCM and 76 non-diseased age, race and BSA-matched controls) and 18 young, healthy volunteers were studied. SWT and the anterior mitral valve leaflet length (AMVLL) were measured using cine MRI. The combined contribution of these variables (SWT × AMVLL) was described as the Septal Anterior Leaflet Product (SALP). Peak LVOT pressure gradient was determined by Doppler interrogation and defined as "obstructive" if ≥ 30mmHg. Patients with HCM were confirmed to have increased AMVLL compared with controls and volunteers (p < 0.01). Among HCM patients, both SWT and SALP were significantly higher in patients with LVOTO (N = 17) versus without. SALP showed modest improvement in predictive accuracy for LVOTO (AUC = 0.81) among the HCM population versus SWT alone (AUC = 0.77). However, in isolated patients this variable identified patients with LVOTO despite modest SWT. Elongation of the AMVLL is a primary phenotypic feature of HCM. While incremental contributions to LVOTO appear modest at a population level, specific patients may have dominant contribution to LVOTO. The combined marker of SALP allows for maintained identification of such patients despite modest increases in SWT.

024 Spectrum and significance of CMR findings in cardiac transthyretin amyloidosis

Background Cardiac transthyretin amyloidosis (ATTR amyloidosis) is an increasingly recognised cause of heart failure. Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) and T1 mapping is emerging as a reference standard for diagnosis and characterisation of cardiac amyloid. Objectives We used CMR with extracellular volume fraction (ECV) measurement to characterise cardiac involvement in relation to outcome in ATTR amyloidosis. Methods Subjects comprised 263 patients with cardiac ATTR amyloidosis corroborated by grade 2–3 99mTc-DPD cardiac uptake, 17 with suspected cardiac ATTR amyloidosis (grade 1 99mTc-DPD) and 12 asymptomatic individuals with amyloidogenic transthyretin (TTR) mutations. Fifty patients with cardiac AL amyloidosis acted as disease controls. Results In contrast to AL amyloidosis, asymmetric septal hypertrophy was present in 79% of ATTR patients (70% sigmoid septum and 30% reverse septal curvature), whilst symmetric left ventricular hypertrophy (LVH) was present in only 18%; 3% of patients has no LVH. In patients with cardiac amyloidosis, the pattern of LGE was always typical for amyloidosis (29% subendocardial, 71% transmural) including right ventricular LGE (96%). 65 patients died during follow-up (19±14 months). ECV independently correlated with mortality and remained independent after adjustment for age, N-terminal pro-brain natriuretic peptide, ejection fraction, E/E’ and left ventricular mass index (hazard ratio, 1.164; 95% confidence interval, 1.066–1.271; p Conclusions Asymmetric hypertrophy, traditionally associated with hypertrophic cardiomyopathy, is the commonest pattern of ventricular remodelling in ATTR amyloidosis. LGE imaging is typical in all patients with cardiac ATTR amyloidosis. ECV correlates with amyloid burden and provides incremental information on outcome even after adjustment for known prognostic factors.

Incidental spade-shaped FDG uptake in the left ventricular apex suggests apical hypertrophic cardiomyopathy.

Apical wall thickening with an "ace-of-spades" configuration is a unique sign of apical hypertrophic cardiomyopathy (AHCM). We investigated spade-shaped FDG uptake around the left ventricular apex (SSUA) incidentally found in routine oncological FDG PET. Cases showing SSUA were selected based on retrospective review. The pattern or intensity of SSUA was compared with the results of electrocardiogram (ECG), echocardiography, and stress myocardial perfusion SPECT. The diagnosis of ACHM was based on the presence of giant negative T wave in ECG, thickness of spade-shaped hypertrophy in the apex in echocardiography, and increased tracer uptake in the apex in rest SPECT. Among the 34 patients in 36 PET scans showing SSUA, SSUA was weak in 17 and intense in 17. There were isolated SSUA (n = 29) and SSUA with diffuse or other focal left ventricular uptake (n = 5). Three patients with the latter uptake pattern turned out to have coexistence of AHCM and asymmetric septal hypertrophy. Of the 16 SSUA-positive patients who underwent echocardiography, 13 (81%) were diagnosed as AHCM and the remaining 3 were regarded as borderline AHCM (apical wall thickness, 14-15mm). There were 16 patients with SSUA who also underwent PET scans after the study period among which 11 (69%) had persistent SSUA in the follow-up PET. In the remaining 5, follow-up PET scans showed diffuse left ventricular uptake and SSUA was barely visible. The intensity of SSUA was significantly or marginally associated with giant negative T wave (p < 0.01), apical asynergy (p = 0.08), and impaired coronary flow reserve (p < 0.05). There were no other factors correlated with the pattern or intensity of SSUA. SSUA incidentally found in oncological FDG PET appeared to be associated with AHCM, especially in ischemic conditions. The moderate repeatability of SSUA was probably due to obscurity by physiological uptake.

Comparison of Frequency of Ischemic Cardiovascular Events in Patients With Aortic Stenosis With Versus Without Asymmetric Septal Hypertrophy (from the SEAS Trial)

Asymmetric interventricular septum hypertrophy (ASH) has been associated with increased perioperative morbidity and mortality in patients with severe, symptomatic aortic valve stenosis (AS). Less is known about the prognostic impact of ASH during progression of AS. Clinical, echocardiographic, and outcome data from 1,691 patients with initially asymptomatic, mostly moderate AS, participating in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study was used. ASH was considered present if interventricular septum/posterior wall thickness ratio in end-diastole ≥1.5. The associations of ASH with hazard rate of ischemic cardiovascular events were tested in time-dependent Cox regression analyses. Based on the presence of ASH at study echocardiograms, the study population was grouped in to a no-ASH, nonpersistent ASH, persistent ASH, and new-onset ASH groups. During a median of 4.3years of follow-up, ASH persisted or developed in 17% of patients. Persistent or new-onset ASH was characterized by higher left ventricular mass index and ejection fraction at baseline (both p <0.05) but not with female gender or hypertension. In time-varying Cox regression analyses adjusting for these confounders, persistent or new-onset ASH was associated with higher hazard rate of ischemic cardiovascular events (hazard rate 1.45; 95% confidence interval 1.09 to 1.91, p= 0.01), in particular coronary artery bypass grafting (hazard rate 1.69; 95% confidence interval 1.17 to 2.47; p= 0.006), whereas no association with increased mortality was found. In conclusion, in patients with AS without diabetes or known renal or cardiovascular disease participating in the SEAS study, persistent or new-onset ASH during progression of AS was associated with higher rate of ischemic cardiovascular events.

Diffuse interstitial fibrosis assessed by cardiac magnetic resonance is associated with dispersion of ventricular repolarization in patients with hypertrophic cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy, disarray, fibrosis, and increased risk for ventricular arrhythmias. Increased QT dispersion has been reported in patients with HCM, but the underlying mechanisms have not been completely elucidated. In this study, we examined the relationship between diffuse interstitial fibrosis, replacement fibrosis, QTc dispersion and ventricular arrhythmias in patients with HCM. We hypothesized that fibrosis would slow impulse propagation and increase dispersion of ventricular repolarization, resulting in increased QTc dispersion on surface electrocardiogram (ECG) and ventricular arrhythmias. MethodsECG and cardiac magnetic resonance (CMR) image analyses were performed retrospectively in 112 patients with a clinical diagnosis of HCM. Replacement fibrosis was assessed by measuring late gadolinium (Gd) enhancement (LGE), using a semi-automated threshold technique. Diffuse interstitial fibrosis was assessed by measuring T1 relaxation times after Gd administration, using the Look–Locker sequence. QTc dispersion was measured digitally in the septal/anterior (V1–V4), inferior (II, III, and aVF), and lateral (I, aVL, V5, and V6) lead groups on surface ECG. ResultsAll patients had evidence of asymmetric septal hypertrophy. LGE was evident in 70 (63%) patients; the median T1 relaxation time was 411±38ms. An inverse correlation was observed between T1 relaxation time and QTc dispersion in leads V1–V4 (p<0.001). Patients with HCM who developed sustained ventricular tachycardia had slightly higher probability of increased QTc dispersion in leads V1–V4 (odds ratio, 1.011 [1.004–1.0178, p=0.003). We found no correlation between presence and percentage of LGE and QTc dispersion. ConclusionDiffuse interstitial fibrosis is associated with increased dispersion of ventricular repolarization in leads, reflecting electrical activity in the hypertrophied septum. Interstitial fibrosis combined with ion channel/gap junction remodeling in the septum could lead to inhomogeneity of ventricular refractoriness, resulting in increased QTc dispersion in leads V1–V4.

Comparison of hypertrophic cardiomyopathy in Afro-Caribbean versus white patients in the UK

BackgroundThis study investigated the influence of African/Afro-Caribbean (black) ethnicity on the clinical profile and outcomes in hypertrophic cardiomyopathy (HCM).Methods425 consecutive patients with HCM (163 black and 262 Caucasians (white); mean...

Twenty Years of Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy.

Hypertrophic obstructive cardiomyopathy is the most common genetic cardiac disease and is generally characterised by asymmetric septal hypertrophy and intraventricular obstruction. Patients with severe obstruction and significant symptoms that persist despite optimal medical treatment are candidates for an invasive septal reduction therapy. Twenty years after its introduction, percutaneous transluminal alcohol septal ablation has been increasingly preferred for septal reduction in patients with drug refractory hypertrophic obstructive cardiomyopathy. Myocardial contrast echocardiography and injection of reduced alcohol volumes have increased safety, while efficacy is comparable to the surgical alternative, septal myectomy, which has for decades been regarded as the ‘gold standard’ treatment. Data on medium- and long-term survival show improved prognosis with survival being similar to the general population. Current guidelines have supported its use by experienced operators in centres specialised in the treatment of patients with hypertrophic obstructive cardiomyopathy.

Prevalence and clinical features of Fabry disease in Japanese male patients with diagnosis of hypertrophic cardiomyopathy

BackgroundThe prevalence of Fabry disease (FD) in Japanese patients presenting with unexplained left ventricular hypertrophy (LVH) has remained unclear. MethodsWe measured plasma α-galactosidase A activity in 177 men with a diagnosis of hypertrophic cardiomyopathy (HCM) (maximum LV wall thickness ≥15mm). ResultsTwo patients (1.1%) showed very low α-galactosidase A activity [0.0 and 0.3nmol/hr/ml (normal range: 3.6–17.6nmol/hr/ml)], and a clinical diagnosis of cardiac variant of FD was finally made. One patient was a 55-year-old man who came to our hospital because of abnormal results of electrocardiography and showed concentric LVH in echocardiography. A missense mutation, R112L, was identified. The other was a 74-year-old man who had been diagnosed with HCM at the age of 60 years in another hospital and was referred for evaluation of repeated hospitalization for heart failure. Although echocardiography revealed asymmetric septal hypertrophy (ASH) with interventricular septal wall thickness of 16mm and posterior wall thickness of 11mm and reduced LV ejection fraction with hypokinetic posterior wall motion, his echocardiographic findings at the initial diagnosis of HCM were not ASH but concentric LVH with normal LV systolic function. A splicing mutation, IVS4+919G>A, was identified. ConclusionsThe prevalence of FD in Japanese male patients with a clinical diagnosis of HCM was found to be 1.1%. These patients showed late onset and concentric LVH at initial presentation.

Is the Increased Septal Perfusion the Signal of Asymmetrical Septal Hypertrophy?

In this study, we have compared scintigraphic and echocardiographic data in order to investigate whether increased septal perfusion represents asymmetrical septal hypertrophy (ASH), which is a symptom followed in the scintigraphy of myocardial perfusion. The study consists of a total of 186 patients (120 females and 66 males with an average age of 59.45 ± 11.54 years) who had normal myocardial perfusion scintigraphy and echocardiography examinations. Statistical comparison of septal wall thickness measurements obtained from echocardiography and septal-to-lateral wall ratios (S/L ratio) was performed scintigraphically. Left ventricular mass values were obtained as both scintigraphic and echocardiographic data and their correlations were evaluated in order to assess the presence of left ventricular hypertrophy (LVH). In statistical analyses, the values of interventricular septal thickness in diastole (IVSd), left ventricle posterior wall thickness in diastole (LVPWd), left ventricle mass (LVM), and left ventricle mass index (LVMI) were found to be significantly higher in group 2 (S/L ratio >1) compared to group 1 (S/L ratio <1). In addition, S/L ratio is significantly correlated with echocardiographic IVSd, LVPWd, LVM, LVMI, and scintigraphic LVM (rest) values. Furthermore, echocardiographic LVM and LVMI values were significantly correlated with LVM and LVMI values obtained from scintigraphy. It should be known that increased S/L ratio that can be monitored during scintigraphic studies can be an indicator of septal hypertrophy and/or LVH, however, further examination and close follow-ups should be performed in necessary cases.

Cardiovascular magnetic resonance demonstration of the spectrum of morphological phenotypes and patterns of myocardial scarring in Anderson-Fabry disease.

BackgroundAlthough it is known that Anderson-Fabry Disease (AFD) can mimic the morphologic manifestations of hypertrophic cardiomyopathy (HCM) on echocardiography, there is a lack of cardiovascular magnetic resonance (CMR) literature on this. There is limited information in the published literature on the distribution of myocardial fibrosis in patients with AFD, with scar reported principally in the basal inferolateral midwall.MethodsAll patients with confirmed AFD undergoing CMR at our center were included. Left ventricular (LV) volumes, wall thicknesses and scar were analyzed offline. Patients were categorized into 4 groups: 1) no wall thickening; 2) concentric hypertrophy; 3) asymmetric septal hypertrophy (ASH); and 4) apical hypertrophy. Charts were reviewed for clinical information.ResultsThirty-nine patients were included (20 males [51 %], median age 45.2 years [range 22.3–64.4]). Almost half (17/39) had concentric wall thickening. Almost half (17/39) had pathologic LV scar; three quarters of these (13/17) had typical inferolateral midwall scar. A quarter (9/39) had both concentric wall thickening and typical inferolateral scar. A subgroup with ASH and apical hypertrophy (n = 5) had greater maximum wall thickness, total LV scar, apical scar and mid-ventricular scar than those with concentric hypertrophy (n = 17, p < 0.05). Patients with elevated LVMI had more overall arrhythmia (p = 0.007) more ventricular arrhythmia (p = 0.007) and sustained ventricular tachycardia (p = 0.008).ConclusionsConcentric thickening and inferolateral mid-myocardial scar are the most common manifestations of AFD, but the spectrum includes cases morphologically identical to apical and ASH subtypes of HCM and these have more apical and mid-ventricular LV scar. Significant LVH is associated with ventricular arrhythmia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12968-016-0233-6) contains supplementary material, which is available to authorized users.

Asymmetrical septal hypertrophy and hypertrophic cardiomyopathy in infant of diabetic mother: A reversible cardiomyopathy

Hypertrophic cardiomyopathy (HOCM) that includes thickening of one or both of the ventricular walls, hypertrophy of the interventricular septum; systolic and diastolic dysfunction, transient hypertrophic sub-aortic stenosis is a well-recognized comorbidity in infants of diabetic mothers. This cardiac complication in the infant of the diabetic mother has recently been named as pathological ventricular hypertrophy to avoid confusion with the autosomal dominant form of congenital HCM. We report a neonate that was diagnosed as case of asymmetrical septal hypertrophy and hypertrophic cardiomyopathy and was born to mother who had poor glycemic control and was treated successfully with propranolol and showed resolution of hypertrophy in follow-up echocardiography.

Clinical profile and echocardiographic findings of patients with cardiomyopathy at a tertiary care hospital

Cardiomyopathy is a primarily disorder of the heart muscle that causes abnormal myocardial performance and is not the result of disease or dysfunction of other cardiac structures. It is an important and heterogeneous group of diseases. We conducted this study at a tertiary care center with the aim to study the clinical profile and echocardiographic findings of cardiomyopathy patients. This study was a descriptive cross-sectional study conducted over a period of 18 months from September 2013 to August 2015. 50 consecutive patients of cardiomyopathy, attending out-patient department and admitted in tertiary care hospital and meeting inclusion and exclusion criteria were selected. Microsoft Office® Excel software was used for data entry and IBM SPSS 18 was used for descriptive statistics. In our study maximum number of patient belonged to age group of 30 to 49 years (n= 25, 50%). The mean age of presentation was 45.16 years where as mean age for male patients was 45.68 and for female patients was 45.18 years. Male to female ratio was 3.16:1.Dilated cardiomyopathy (n= 26, 52%) was most common type of cardiomyopathy. In DCM patients most common symptom was dyspnea (n=26,84.6%) and most common sign was pedal edema (n=14,53.8%). Among HCM patients, dyspnea (33.3%) was the commonest presenting complaint but large number of patients were asymptomatic (28.6 %) and commonest sign was pedal edema (n=5, 23.8%). In DCM patients common ECG findings include Left ventricular hypertrophy (34.6%), Left axis deviation (30.8%), Left bundle branch block (23.1%), atrial fibrillation (23.1%), sinus tachycardia (23.1%) and ventricular premature complex (11.5%). Common ECGfinding in HCM patients were Left ventricular hypertrophy (47.6%), giant T wave inversion in V2- V6 (42.9%), Left axis deviation (33.3%), ventricular premature complex (14.3%), Left bundle branch block (9.5%) and atrial fibrillation (9.5%). Echocardiography findings for DCM patients in our study were, LV systolic dysfunction (Mean LVEF: 26.3±10.3%), Global hypokinesia, Dilation of all four chambers (Mean LVIDd: 66.4±3.4mm and LVIDs 54.6±3.5mm), Mitral regurgitation (30.8%), Pulmonary hypertension (38.5%), Pericardial effusion (11.5%) and LV thrombus (7.7%).Echocardiographic findings in HCM patients showed marked LV hypertrophy, LVOT obstruction (38.1%), Asymmetric septal hypertrophy (52.4%), Apical hypertrophy (47.6%) and Systolic anterior motion of mitral valve (23.8%). In HCM patients, most common pattern of LV hypertrophy was pattern 3 (42.8%) i.e. Apical hypertrophy with any other segment hypertrophy followed by Pattern 1 (38.1%) i.e. Septal hypertrophy alone, pattern 2 (14.3%) i.e. septal and other segment hypertrophy excluding apex; and pattern 4 (4.8%) i.e. apical hypertrophy alone.

Left Ventricular Hypertrophy in Asymptomatic Nonsevere Aortic Stenosis

Increased biomechanical stress on cardiomyocytes because of outflow obstruction secondary to aortic stenosis (AS) is thought to induce reexpression of the fetal gene program, which modifies myocyte efficiency, sarcomere composition, and regulation of extracellular matrix, as well as various nuclear signal transduction pathways resulting in autocrine production and secretion of cytokines, neurohormones and growth factors that ultimately promote ventricular hypertrophy.1,2 See Article by Gerdts et al The traditional view of adaptative concentric left ventricular hypertrophy (LVH) because of parallel replication of new sarcomeres is that wall thickness increases to normalize LV systolic wall stress and preserve systolic performance. This view, accepted for the past 40 years3 and perhaps counterintuitively expected to mitigate the effects of LV pressure overload on cardiovascular morbidity and mortality, has begun to be challenged by new clinical data, suggesting that moderate or severe LVH may be associated with adverse outcomes in AS4,5 and that inappropriately increased LV mass, found in 17% of patients with mild to moderate AS6 and in 67% of patients with asymptomatic severe AS, was associated with a 4.5-fold increased risk of cardiovascular events.7 Conversely, the absence of hypertrophy in one third of the patients with severe AS seems to have no adverse effects on systolic function or survival.8,9 Experimental studies in genetically modified animal models are consistent with clinical observations.10 In addition, no association was found between AS severity and the magnitude or pattern of LVH using cardiac magnetic resonance.11 Thus, it seems that the presence, severity, and the geometric pattern of LVH in AS vary widely, are …

Whole exome sequencing combined with integrated variant annotation prediction identifies a causative myosin essential light chain variant in hypertrophic cardiomyopathy

BackgroundThe development of candidate gene approaches to enable molecular diagnosis of hypertrophic cardiomyopathy (HCM) has required extensive and prolonged efforts. Whole exome sequencing (WES) technologies have already accelerated genetic studies of Mendelian disorders, yielding approximately 30% diagnostic success. As a result, there is great interest in extending the use of WES to any of Mendelian diseases. This study investigated the potential of WES for molecular diagnosis of HCM. MethodsWES was performed on seven relatives from a large HCM family with a clear HCM phenotype (five clinically affected and two unaffected) in the Kanazawa University Hypertrophic Cardiomyopathy Registry. Serial bioinformatics filtering methods as well as using combined annotation dependent depletion (CADD) score and high heart expression (HHE) gene data were applied to detect the causative variant. Moreover, additional carriers of the variant were investigated in the HCM registry, and clinical characteristics harboring the variant were collected and evaluated. ResultsWES detected 60020 rare variants in the large HCM family. Of those, 3439 were missense, nonsense, splice-site, or frameshift variants. After genotype–phenotype matching, 13 putative variants remained. Using CADD score and HHE gene data, the number of candidates was reduced to one, a variant in the myosin essential light chain (MYL3, NM_000258.2:c.281G>A, p.Arg94His) that was shared by the five affected subjects. Additional screening of the HCM registry (n=600) identified two more subjects with this variant. Serial assessments of the variant carriers revealed the following phenotypic characteristics: (1) disease-penetrance of 88%; (2) all clinically affected carriers exhibited asymmetric septal hypertrophy with a substantial maximum left ventricular wall thickness of 18±3mm without any obstruction. ConclusionsWES combined with CADD score and HHE gene data may be useful even in HCM. Furthermore, the MYL3 Arg94His variant was associated with high disease penetrance and substantial interventricular septal hypertrophy.