Tissue doppler imaging in hypertrophic cardiomyopathy without left ventricular hypertrophy

BACKGROUND: Diastolic function abnormalities determined by Doppler echo (especially those recorded by tissue velocity imaging) may be useful in determining carriers of an abnormal gene in hypertrophic cardiomyopathy who do not yet show clinical evidence of the disease. METHODS: In a single extended family, seven carriers of a mutation involving the cardiac myosin-binding protein C gene who did not show any features of the disease on 2-D echocardiography were examined by 2-D, M-mode Doppler and tissue Doppler imaging. The results were compared with a group of eight aged-matched people from the same family who did not have the gene mutation or clinical evidence of the disease. In both groups, as well as measuring the basal posterior and anteroseptal walls, the entire left ventricle was inspected for localised hypertrophy. RESULTS: Localised hypertrophy was absent from the left ventricle in both groups. There were significant differences in the tissue Doppler peak velocity measurements made at the lateral border of the mitral annulus in systole and especially early diastole. A systolic velocity of <10 cm/s was strongly suggestive of gene positivity and, if combined with an early mitral diastolic velocity (mitral E velocity) of <14 cm/s, was present only in gene-positive individuals. If the mitral E velocity was >14 cm/s, this was present only in gene-negative patients. CONCLUSION: Tissue Doppler imaging may be a valuable tool for screening first-degree relatives of patients with hypertrophic cardiomyopathy who do not show 2-D echo evidence of the disease.     

The distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: comparison to athletes and hypertensives

Cross-sectional echocardiogaphy was performed in 134 patientswith hypertrophic cardiomyopathy and 75 with secondary leftventricular hypertrophy (57 hypertensives and 18 athletes) todetermine the diagnostic sensitivity and specificity and predictivevalue of the pattern of left ventricular hypertrophy. Myocardialwall thickness was assessed in the anterior and posterior septum,free wall and posterior wall in both the upper and lower leftventricle. All patients had at least one region exceeding 2SD from normal (>l-4cm). Asymmetrical septal hypertrophy)septum to posterior wall ratio 1.5: 1 in the upper or lowerleft ventricle) was found in 75 patients with hypertrophic cardiomyopathy(56%), 11 hypertensives (18%) and 4 (22%) athletes. This patternwas more common in patients with primary compared to secondaryleft ventricular hypertrophy (P<0.01). Distal ventricularhypertrophy was only seen in patients with hypertrophic cardiomyopathy(10%). Symmetrical left ventricular hypertrophy was demonstratedin 45 patients with hypertrophic cardiomyopathy (34%), 50 hypertensives(82%) and 14 athletes (78%). This pattern was significantlymore common in patients with secondary left ventricular hypertrophy(P<0.01). Amongst those with symmetrical hypertrophy, patientswith hypertrophic cardiomyopathy had more severe hypertrophywhile the athletes had larger left ventricular cavity size.Asymmetrical septal hypertrophy was the most sensitive (56%)and distal ventricular (100%) the most specific pattern forthe diagnosis of hypertrophic cardiomyopathy with a predictivevalue of 83 and 100% respectively. Symmetrical left ventricularhypertrophy was 81% sensitive and 66% specific with a predictivevalue of 58% for the diagnosis of secondary hypertrophy. Inconclusion, the pattern of hypertrophy was of only moderatepredictive value in differentiating primary from secondary leftventricular hypertrophy.     

Diastolic intraventricular gradient in hypertrophic cardiomyopathy with apical hypertrophy

Patients with hypertrophic cardiomyopathy and additional diastolicflow abnormalities are relatively rare. This report describesa case of apical ventricular hypertrophy with complete systolicobstruction and holodiastolic intraventricular pressure gradient.     

Arrhythmogenic left ventricular apical aneurysm in hypertrophic cardiomyopathy

A 70-year old lady with prior myectomy for hypertrophic obstructive cardiomyopathy presented with sustained ventricular tachycardia. She was found to have a large left ventricular (LV) apical aneurysm. Surgical intervention was not advised, due to the risk of creating a small LV cavity after surgery and ICD was not advised based on the risk of injuring a very thin walled aneurysm. The patient's arrhythmia settled on medical therapy, but unfortunately she suffered an unwitnessed death three months later.This case represents a rare complication to a rare disease with limited management options. In such patients evidence based medicine is of little help, if any.     

老年肥厚型心肌病与高血压左室肥厚患者临床特点的比较

目的 分析老年肥厚型心肌病与老年高血压左室肥厚患者的临床特点.方法 回顾性分析老年肥厚型心肌病患者(35例)与老年高血压左室肥厚患者(35例)的症状和体征及心电图、超声心动图的差异.结果 老年肥厚型心肌病患者均无高血压史.两组年龄、性别、脑血管病史及肥厚型心肌病家族史比较,差异均无统计学意义(均为P＞0.05).老年肥厚型心肌病患者中,晕厥者5例(14.3%),高血压左室肥厚患者中,无晕厥者,2组比较,差异有统计学意义(P＜0.05).老年肥厚型心肌病患者中无心脏杂音者9例(25.7%),明显少于高血压左室肥厚患者[23例(65.7%),P＜0.05].心电图示:老年肥厚型心肌病患者中,有异常Q波者10例(28.6%),较高血压左室肥厚患者的1例(2.9%)多(P＜0.05).老年肥厚型心肌病患者中心房颤动(房颤)及ST-T改变者分别为11例(31.4%)及34例(97.1%),明显多于高血压左室肥厚患者的3例(8.6%)及26例(74.3%),均为P＜0.05.超声心动图示:老年肥厚型心肌病患者的左室后壁厚度为(9.5±1.1)mm,明显薄于高血压左室肥厚患者的(12.6±1.0)mm(P＜0.01),左房内径老年肥厚型心肌病患者为(41.6±6.3)mm,高血压左室肥厚患者为(38.6±5.5)mm,两组差异有统计学意义(P＜0.05);老年肥厚型心肌病患者二尖瓣血流频谱E/A＜1者15例(42.9%),明显少于高血压左室肥厚患者的32例(91.4%),P＜0.05.老年肥厚型心肌病患者有主动脉瓣钙化者7例(20.0%),高血压左室肥厚患者20例(57.1%),二者差异有统计学意义(P＜0.05),室间隔厚度、左室内径与射血分数2组相似(均为P＞0.05).结论 老年肥厚型心肌病患者临床表现有晕厥者多,心脏有明显的杂音,心电图有异常Q波及房颤者较多,超声心动图显示左室不对称性肥厚多;高血压左室肥厚患者左室肥厚多为对称性,合并主动脉瓣钙化者多.     

Phenotypic differences between electrocardiographic and echocardiographic determination of hypertrophic cardiomyopathy in genetically affected subjects

OBJECTIVES: In the molecular era, two types of phenotypic differences are recognized between electrocardiography (ECG) and echocardiography in hypertrophic cardiomyopathy (HCM); ECG abnormalities in carriers without left ventricular hypertrophy (LVH), and normal ECG patterns in carriers with LVH. The goal of this study was to evaluate the diagnostic value of ECG for detecting carriers without LVH, and also to assess normal ECG patterns in carriers with LVH from the genetic standpoint of HCM. SETTING: A matched case-control study in a university hospital and general hospitals in Japan. PATIENTS AND DESIGN: ECG and echocardiographic findings were analysed in 173 genotyped subjects (107 genetically affected, 66 unaffected) from families with disease-causing mutations in four genes. RESULTS: ECG abnormalities were found in 18 (54.5%) of 33 nonhypertrophic carriers, but only nine (13.6%) of 66 noncarriers (P < 0.001). For detecting nonhypertrophic carriers, ST-T abnormalities showed the highest accuracy amongst the three major ECG criteria. In contrast, normal ECG patterns were found in eight (10.8%) of 74 carriers with LVH. The sensitivity of ECG for detecting carriers with LVH in families with the cardiac myosin-binding protein C, cardiac troponin T and cardiac troponin I gene mutations was 83%, 88% and 94% respectively. CONCLUSION: These findings suggest that ECG may have favourable diagnostic value even for detecting nonhypertrophic carriers. Furthermore, diagnostic value of ECG may differ according to the genes involved. Our data may contribute to interpretation of phenotypic differences between ECG and echocardiography from the viewpoint of molecular genetics of HCM.     

Sudden cardiac death in hypertrophic cardiomyopathy

Background: Recent identification of mutations in the ß-myosinheavy chain gene (MYH7), a major responsible gene for HCM, hasprovided the opportunity to characterize genotype-phenotypecorrelation in HCM families. In this study we analysed the phenotypicexpression of two ß-myosin heavy chain (ßMHC)mutations in three unrelated HCM families. Methods: Living individuals from three unrelated HCM families(Families 1, 2, and 3) were screened by history, physical examination,electrocardiography, and two-dimensional echocardiography. Bloodwas collected from all individuals for DNA extraction. Polymerasechain reaction (PCR), restriction endonuclease digestion andchemical cleavage were utilized for detection of mutations.All mutations were confirmed by sequence analysis. Results:Identification of mutations: A missense mutation in exon 13of the ßMHC gene (Arg⁴⁰³Gln) was detected in HCM patientsfrom Families 1 and 2. PCR amplification of the exon 13 DNA,followed by Ddel digestion of the PCR product and gel electrophoresis,showed two fragments of 84 and 70 bp in normal individuals andfour fragments of 84, 70, 52 and 32 bp in HCM patients. Sequenceanalysis showed substitution of an adenine for guanine at codingposition 1208. In Family 3, a missense mutation in exon 16 ofthe ßMHC gene (Val⁶⁰⁶Met) was detected in HCM patients.Chemical cleavage of the PCR products showed an uncleaved productof 337 bp in the normal individuals, while in the affected individuals,in addition to the uncleaved product, a 90 bp cleaved productwas also detected, indicating the presence of a mismatch inone allele. Sequence analysis showed substitution of an adeninefor guanine in coding position 1817. Clinical Characteristics: Seven members of Family 1 had HCM,of whom five are alive. One patient died from sudden cardiacdeath (SCD) and another from recurrent cerebral embolL In Family2, 15 individuals had HCM of whom nine have died, seven fromSCD. The mean age at the time of SCD was 33 years. The thirdfamily is comprised of 11 affected individuals and one obligatecarrier, of whom one patient died at age 17 from progressiveheart failure. Two additional individuals in this family havealso succumbed to SCD to age 60. A variety of clinical and echocardiographicmanifestations of HCM were present in each family. Logrank test of Kaplan-Meier survival curves indicates thatArg⁴⁰³Gln mutation was associated with a poor prognosis in HCMfamilies as compared to Val⁶⁰⁶Met (P=0.034). Conclusions: ßMHC mutations despite showing variableclinical and echocardiographic manifestations of HCM are predictorsof survival in HCM families.     

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy

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Two types of left ventricular wall motion abnormalities with distinct clinical features in patients with hypertrophic cardiomyopathy

During the long-term follow-up of patients with hypertrophiccardiomyopathy (HCM), some patients develop left ventricular(LV) wall motion abnormalities in the absence of fixed coronaryartery disease. The purpose of this study is to clarify whichclinical features in patients with HCM seem to influence gradualdevelopment of LV wall motion abnormalities over an extendedperiod of time. The study investigates the incidence, mechanismand predictors of these abnormalities. In this retrospectivestudy of 162 patients with HCM, followed-up for an average of13.3 years, we focused our attention on 16 patients who graduallydeveloped two different forms of LV wall motion abnormality.In 11 of these 16 patients, apical segmental dysfunction withmidzone obstruction was recognized; the remaining five patientsshowed generalized hypokinesis, as seen in dilated cardiomyopathy.The 11 patients with apical segmental dysfunction presentedwith extensive apical hypertrophy reaching the midventricularlevel at first examination. The five patients with generalizedhypokinesis showed a slight decrease in LV contractility andreduced localized antero-apical wall motion even at initialexamination. None of the patients in either group developedthe other group's features during their clinical course. These two groups had different initial manifestations and pursueddifferent clinical courses, suggesting that the underlying mechanismscausing wall motion abnormalities are different.     

Three-dimensional echocardiographic assessment of left ventricular function in takotsubo cardiomyopathy

We evaluated left ventricular (LV) function by three-dimensional echocardiography (3DE) in a patient with takotsubo cardiomyopathy (TC). An 82-year-old man was admitted to our hospital with a suspicion of acute myocardial infarction but was diagnosed as TC by coronary angiography and left ventriculography (LVG). Three-dimensional echocardiography showed circular asynergy from the midventricle to the apex associated with hyperkinesis of the base and volumetric data very close to those obtained by LVG. Thus, 3DE is a useful tool in evaluating regional wall motion abnormalities and LV volume in patients with TC.     

The natural history of left ventricular wall thickening in hypertrophic cardiomyopathy

Abstract Background: Hypertrophic cardiomyopathy (HCM) is associated with mutations of genes coding for major sarcomeric proteins, but the mechanism of hypertrophy is unknown. As hypertrophy may not develop until adolescence, an altered response to physiological growth stimuli may regulate the hypertrophy process. Aims: This study examined the relationship between age and changes in left ventricular (LV) wall thickness in patients with HCM. Methods: Forty-three patients who had definite electrocardiographic and echocardiographic evidence of HCM were studied with serial 2D and M-mode echocardiograms at least two years apart (mean interval 5.5±3.0 years). LV cavity dimensions, septal and posterior wall thicknesses, and LV mass indices were compared with data from an age- and gender-matched control group. Results: In patients with HCM aged ten to 20 years (n=9), there was an increase in septal wall thickness during the study period from 15.9±6.2 mm to 19.3 ± 2.1 mm (p<0.01). This increase (3.4±2.5 mm) greatly exceeded the change in septal thickness observed in the control group between the ages often and 20 years (0.8±0.3 mm, p<0.01). There was a lesser increase in posterior wall thickness from 9.8±2.1 mm to 11.5±3.5 mm (p=0.07). In patients with HCM aged 21–40 years (n=11), there was also an increase in septal wall thickness during the study period from 16.0±2.2 mm to 17.8±3.0 mm (p<0.05), but no change in septal thickness in the control group. In contrast, the patients aged >40 years (w=23) showed no significant change in either septal or posterior wall thickness during the study period. LV mass index increased in the ten to 20 years age group from 128 ±24 g/m² to 164±20 g/m² (p=0.01), but this increase was not observed in the older age groups. Conclusions: LV hypertrophy is progressive, particularly in the septum, during adolescence and early adult life in patients with HCM. As progressive hypertrophy may continue after somatic growth has ceased, an abnormal myocardial response to physiological growth regulators is less likely to be the principal stimulus to hypertrophy. Gene-gene interactions, changes in haemodynamic load or environmental factors may modulate the development of hypertrophy. Serial measurements of ventricular wall thickness in the first two decades of life, and probably until the fourth decade of life are advisable in patients suspected of having HCM.     

Relationship between outflow obstruction and left ventricular functional impairment in hypertrophic cardiomyopathy: a Doppler echocardiographic study

Left ventricular outflow tract (LVOT) obstruction is predictive of a worse outcome in hypertrophic cardiomyopathy (HCM). In a detailed Doppler echocardiographic study of 178 selected HCM patients, the group of patients (n = 73) with the obstructive form (resting peak gradient > or = 30 mmHg) presented more hypertrophy and poorer systolic and diastolic left ventricular (LV) functions than the HCM group (n = 105) without obstruction. LVOT peak gradient was positively correlated with hypertrophy (P < 0.0001) and negatively to tissue Doppler mitral annulus systolic (P = 0.0001) and early diastolic (P < 0.0001) velocities. The gradient significantly correlated with E/Ea ratio (r = 0.67; P < 0.0001). By multiple regression, LVOT gradient was related to E/Ea, LV maximal thickness and left atrial size. In comparison with patients without obstruction, patients with obstruction presented greater hypertrophy (P < 0.0001), lower systolic and early diastolic mitral annulus velocities (both P < 0.0001), higher E/Ea ratio (P < 0.0001) and higher global function index (P < 0.0001). In HCM, beyond the effects on hypertrophy, LVOT obstruction is an independent determinant of LV functional abnormalities.     

Comprehensive contrast and 3-dimensional echocardiographic imaging of left ventricular noncompaction cardiomyopathy

A 62-year-old woman with a history of heart failure, hypertensionand stroke presented to hospital with dyspnea. Transthoracicechocardiography revealed significant left ventricular dysfunction;with contrast-enhanced 2- and 3-dimensional echocardiography,extensive hypetrabeculation of the left ventricular myocardiumwas visualized, leading to a diagnosis of noncompaction cardiomyopathy.Apical thrombi were excluded with contrast imaging; however,the patient was systemically anticoagulated owing to the presenceof noncompaction cardiomyopathy in the setting of prior stroke.This case report demonstrates remarkable imaging of the leftventricular myocardium achieved with contrast-enhanced 3-dimensionalechocardiography in the setting of noncompaction cardiomyopathy.     

Diagnostic accuracy of a 2D left ventricle hypertrophy score for familial hypertrophic cardiomyopathy.

AIMS: To study the diagnostic value of a new 2D left ventricle hypertrophy (2D LVH) score in families with hypertrophic cardiomyopathy (HCM) in comparison with the conventional maximal wall thickness (MWT) measurement (>13 mm in adults), which is limited by a low sensitivity in relatives. METHODS AND RESULTS: The study was performed in 237 adults from genotyped families with HCM. Population A (derivation sample) comprised 109 adults and population B (validation sample) comprised 128 adults. MWT and 2D LVH scores (sum of thicknesses of four segments) were determined by echocardiography. Genotyping was the gold standard for diagnosis. In population A, a theoretical value for LVH score was determined in the healthy population by a multiple linear regression model including age, sex, and body surface area. An abnormal cut-off value was defined as an LVH score above a maximum theoretical value according to receiver operating characteristic analysis. Sensitivity and specificity were, respectively, 73 and 96% for 2D LVH score and 62.5 and 100% for MWT. Improvement of sensitivity was particularly important in adults <50 years of age (69 vs. 54%, respectively, P<0.04). These results were validated in population B: sensitivity and specificity of LVH score were, respectively, 75 and 96% in this sample and 67 and 97%, in the subgroup <50 years. In the latter, sensitivity of LVH score increased when compared with that of MWT (67 vs. 53%, P<0.03). CONCLUSIONS: The LVH score has a higher diagnostic value for HCM than the conventional criterion of MWT, particularly in young adults. This echographic parameter may be proposed as an alternative diagnostic criterion for familial screening.     

Longitudinal left ventricular strain in hypertrophic cardiomyopathy: correlation with nonsustained ventricular tachycardia

Aims: Stratifying risk of sudden death is a major issue in the management of hypertrophic cardiomyopathy (HCM). Existing risk factors have low positive predictive value and new parameters are needed. Determination of myocardial deformation (strain) by 2D Speckle tracking is a new methodology for determining LV regional function and could correlate with myocite disarray and fibrosis. The aim of this study was to assess the relationship between strain analysis and nonsustained ventricular tachycardia (NSVT) in patients with HCM. Methods: Thirty‐two consecutive patients with HCM (mean age 55, 17–78) were studied. All underwent standard echocardiographic and two‐dimensional strain examination. Twenty‐four‐hour Holter monitoring was performed and echocardiographic parameters were correlated with NSVT. Results: Nine patients (28%) had one or more episodes of NSVT. Patients with NSVT had a higher value of maximal LV thickness (23.6 mm vs. 19.4 mm, P = 0.027). There were no significant associations between NSVT on Holter monitoring and LV outflow gradient left atrial diameter, E/Em or left ventricle ejection fraction. Patients with HCM and NSVT had significant reductions in mid septal, apical‐septal, apical‐lateral strain, and in mean longitudinal strain. Midseptal strain >–10.5% had a sensitivity of 89% and a specificity of 74% (area under the curve, 0.787; P < 0.0013) for predicting NSVT independently of age or maximum wall thickness. Conclusion: Lower end‐systolic peak longitudinal strain obtained by 2D speckle tracking was a predictor of NSVT in HCM patients. This parameter could become a useful tool in stratifying SCD risk in this population. (Echocardiography 2011;28:709‐714)