Progressive left ventricular remodeling in patients with hypertrophic cardiomyopathy and severe left ventricular hypertrophy

OBJECTIVES: The aim of this study was to determine the natural history of patients with hypertrophic cardiomyopathy (HCM) and severe left ventricular hypertrophy (LVH) (i.e., maximal left ventricular wall thickness [MLVWT] >/=30 mm) and whether changes in cardiac morphology influence the course of the disease. BACKGROUND: Severe LVH is common in young and rare among elderly patients with HCM. This has been explained by a high incidence of sudden death. We hypothesized that this age-related difference might be explained by left ventricular wall thinning. METHODS: A total of 106 (age 33 +/- 15 years; 71 males) consecutive patients with severe LVH underwent history taking, examination, electrocardiography, echocardiography, cardiopulmonary exercise testing, and Holter analysis. Survival data were collected at subsequent clinic visits or by communication with patients and their general practioners. In order to assess morphologic and functional changes, 71 (67.0%) patients (mean age 31 +/- 15 years; 47 males) followed at our institution underwent serial (>/=1 year) assessment. RESULTS: Of the 106 patients, the majority (78 [71.6%]) were <40 years of age. During follow-up (92 +/- 50 months [range 1 to 169]), 18 (17.0%) patients died or underwent heart transplantation (13 sudden cardiac deaths, 2 heart failure deaths, 1 heart transplantation, 1 stroke, 1 postoperative death). Five-year survival from sudden death was 90.1% (95% confidence interval [CI] 84.0% to 96.3%), and that from heart failure death or transplantation was 97.7% (95% CI 94.5 to 100). In patients serially evaluated over 85 +/- 51 months, there was an overall reduction in MLVWT of 0.6 mm/year (95% CI 0.31 to 0.81, p = 0.00004). Wall thinning >/=5 mm was observed in 41 patients (57.7%; age 35 +/- 13 years; 28 males). On multivariate analysis, the follow-up duration only predicted wall thinning (0.6 mm/year, 95% CI 0.38 to 0.85, p < 0.00001). CONCLUSIONS: Left ventricular remodeling is common in patients with severe LVH and contributes to the low prevalence of severe LVH seen in middle age and beyond.     

QT dispersion and left ventricular morphology in patients with hypertrophic cardiomyopathy

Objective: To evaluate the relation between QT variables and disproportion of left ventricular wall hypertrophy in patients with hypertrophic cardiomyopathy.     

Resting and exercise left ventricular function in patients with hypertrophic cardiomyopathy

Left ventricular ejection fraction (EF) at rest and during exercise was measured in 19 patients with hypertrophic cardiomyopathy (HCM) by means of radionuclide angiography. The results were compared to those in 20 normal subjects. Based on hemodynamic data, patients with HCM were divided into three groups. In group I, no demonstrable left ventricular outflow obstruction, there were five patients; their mean EF increased from 68% +/- 8.9 (+/- SD) at rest to 74% +/- 9.2 during exercise (p less than 0.05). In group II, latent obstruction, there were six patients; their mean EF at rest (75.2% +/- 8.2) and at peak exercise (78.7% +/- 6.7) was not statistically different (p greater than 0.05). Group III, obstruction present at rest, consisted of eight patients; EF at rest (82.6% +/- 8.5) decreased significantly during exercise (75.6% +/- 7.7, p less than 0.01). In normal subjects resting EF was 66.3% +/- 7.6; it increased to 76.4% +/- 7 (p less than 0.001). Exercise duration and heart rate-blood pressure product were lower in groups II and III. Thus there are significant differences in left ventricular systolic function both at rest and during exercise between these three major hemodynamic subgroups. These findings emphasize the importance of such a hemodynamic classification of HCM.     

Progression to left ventricular dilatation in patients with hypertrophic obstructive cardiomyopathy

Congestive heart failure with dilated left ventricle developed in two patients with symptomatic hypertrophic obstructive cardiomyopathy. Both patients previously underwent cardiac surgery for relief of their outflow obstruction. Alterations in structure and function of the left ventricle during their episode of cardiac failure and thereafter were documented by echocardiography. The findings suggest that progression to left ventricular dilatation is a potential complication in patients with hypertrophic obstructive cardiomyopathy.     

Mechanocardiographic evaluation of left ventricular diastolic function in hypertrophic cardiomyopathy and hypertensive cardiomyopathy

Usefulness of computerized mechanocardiography and echocardiography in the diagnosis of impaired left ventricular diastolic function is shown in a study comparing 17 hypertrophic obstructive cardiomyopathy and 17 hypertensive cardiomyopathy patients to 20 normal subjects. Mechanocardiography allows the evaluation of three different parameters of diastolic function: isovolumic relaxation evaluated by S2a-O or better by t-dr/dt and dr/dt/A2 ratio, left ventricular compliance by the A/H ratio and time of rapid filling. All the parameters are impaired in both pathological populations. Isovolumic relaxation being more depressed in hypertensive cardiomyopathy and duration of rapid filling being prolonged especially in the hypertrophic obstructive cardiomyopathy patients. Although the differences are small indicating only trends computerized mechanocardiography gives some evidence for difference in the alteration of diastolic function in hypertrophic obstructive cardiomyopathy and hypertensive cardiomyopathy.     

Late ventricular potentials and left ventricular performance in patients with hypertrophic cardiomyopathy]

Twenty patients with hypertrophic cardiomyopathy were examined. They were found to have late ventricular potentials in the disease, which were characterized by an increase in average QRS complex duration, a decrease in voltage, and a rise in the duration of last 40 msec of the QRS complex filtered. Such patients generally exhibited lower exercise tolerance in severe asymmetric left ventricular hypertrophy, which caused a significant deterioration of cardiac pump function.     

Usefulness of real-time three-dimensional echocardiography for evaluation of myectomy in patients with hypertrophic cardiomyopathy

Real-time 3-dimensional echocardiography was performed in 10 patients with obstructive hypertrophic cardiomyopathy (HC) before and after myectomy and in 6 controls. The exact location of systolic anterior motion of the mitral leaflet was shown in all patients with HC with a predominant involvement of the medial portion in 4 patients and the middle portion in 6 patients. The smallest area of the left ventricular outflow tract was significantly smaller in patients with HC than in controls (1.4 +/- 0.7 vs 5.1 +/- 1.2 cm(2), p <0.01), significantly increased after myectomy (4.8 +/- 1.8 cm2, p <0.01) and was associated with a reduction of the pressure gradient at rest from 63 +/- 41 to 15 +/- 5 mm Hg (p <0.01).     

Provocation of left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy

Several provocation maneuvers are described in hypertrophic cardiomyopathy to Doppler echocardiographically distinguish the obstructive from the non obstructive type. No data are available about the value of orthostasis testing in comparison with nitrate application in this disease. In this study, 16 consecutive patients with hypertrophic cardiomyopathy were examined. 11 patients with hypertrophic cardiomyopathy were classified as obstructive, 5 patients with hypertrophic cardiomyopathy as non obstructive. Normal left ventricular outflow tract velocities as detected by the Doppler method were defined as < 2,0 m/s.Doppler echocardiographic measurements were performed after 10 minutes in supine position, within 10 minutes after head-up tilt and again, within 10 minutes in supine position. If systolic blood pressure during this examination exceeded 100 mm Hg 2,5 mg isosorbiddinitrate were sprayed sublingually. Measurements were done after 20 minutes in supine position and within 10 minutes after head-up tilt.Only in 7 of the 11 patients with hypertrophic obstructive cardiomyopathy maximal left ventricular outflow tract velocity in supine position measured > 2,0 m/s (2,2 ± 0,8). During head-up tilt, all patients showed increased values (3,8 ± 1,2 m/s). No differences in maximal left ventricular outflow tract velocity between head-up tilt and nitrate application in supine position (3,5 ± 1,4 m/s) were present. All patients with hypertrophic non obstructive cardiomyopathy showed maximal left ventricular outflow tract velocities < 2,0 m/s in every step of the examination.Consequently, orthostasis testing was able to identify all patients with hypertrophic obstructive cardiomyopathy and demonstrated a diagnostic value similar to nitrate application.     

Effects of nicardipine on left ventricular function in patients with hypertrophic cardiomyopathy

Calcium channel blockers have emerged as important adjuncts to pharmacotherapy of hypertrophic cardiomyopathy. Nicardipine, a new hydropyridine calcium channel blocker, was evaluated for its short-term effects (14 days, 20 mg tid) on left ventricular function in 16 patients with hypertrophic cardiomyopathy (HCM) with UCG. Results indicated that heart rate, blood pressure and systolic function changed very little after nicardipine (P greater than 0.05). However, the following changes were noted after administration: IVRT decreased (132.4 +/- 21.2----120.7 +/- 27.0, P less than 0.02); left ventricular posterior wall rapid filling amplitude and mean velocity increased (8.86 +/- 2.23----9.68 +/- 2.41, P less than 0.01; 54.96 +/- 13.6----59.66 +/- 18.36, P less than 0.05); EF slope increased (3.52 +/- 1.33----3.88 +/- 1.37, P less than 0.01); left ventricular end diastolic pressure and pulmonary capillary wedge pressure decreased (11.79 +/- 3.32----9.72 +/- 2.46, P less than 0.01; 11.11 +/- 2.97----9.19 +/- 2.42, P less than 0.01). The conclusion is that nicardipine may improve left ventricular diastolic function of patients with HCM without serious side effects. It is valuable to conduct further study.     

Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy

BACKGROUND: Conventional Doppler parameters are unreliable for estimating left ventricular (LV) filling pressures in hypertrophic cardiomyopathy (HCM). This study was undertaken to evaluate flow propagation velocity by color M-mode and early diastolic annular velocity (Ea) by tissue Doppler 2 new indices of LV relaxation, combined with mitral E velocity for estimation of filling pressures in HCM. METHODS AND RESULTS: Thirty-five HCM patients (52+/-15 years) underwent LV catheterization simultaneously with 2-dimensional and Doppler echocardiography. Pulsed Doppler echocardiography of mitral and pulmonary venous flows was obtained along with flow propagation velocity and Ea. LV preA pressure had weak or no relations with mitral, pulmonary venous velocities and atrial volumes. In contrast, preA pressure related strongly to E velocity/flow propagation velocity (r=0.67; SEE=4) and E/Ea (r=0.76; SEE=3.4). In 17 patients with repeat measurements, preA pressure changes were well detected by measuring E velocity/flow propagation velocity (r=0.68; P=0.01) or E/Ea (r=0.8; P<0.001). PreA pressure estimation with these 2 methods was tested prospectively in 17 additional HCM patients with good results (E velocity/flow propagation velocity, r=0.76; E/Ea, r=0.82). CONCLUSIONS: LV filling pressures can be estimated with reasonable accuracy in HCM patients by measuring E velocity/flow propagation velocity or E/Ea. These ratios also track changes in filling pressures.     

Impaired left ventricular rapid filling during exercise in patients with hypertrophic cardiomyopathy

The influence of exercise on left ventricular diastolic filling was evaluated in 14 patients with hypertrophic cardiomyopathy (HCM) and 14 normal controls (NC) by dynamic exercise echocardiography. Using X-Y digitizer and computer, normalized peak rate of change of the left ventricular dimension during systole (pVs) and the rapid filling phase (pVd) were determined from the left ventricular echocardiograms at rest and during exercise when heart rate reached 100 beats/min. At rest and during exercise, pVs was significantly higher in HCM (3.2 +/- 0.4/s at rest, 4.3 +/- 1.4/s during exercise) than in NC (2.4 +/- 0.5/s at rest, 3.0 +/- 0.4s during exercise) (p less than 0.001, p less than 0.001, respectively), but pVd in HCM (4.2 +/- 1.0/s at rest, 5.8 +/- 1.0/s during exercise) was not significantly different from that in NC (4.1 +/- 1.0/s at rest, 6.0 +/- 0.7/s during exercise). The ratio of pVd to pVs (pVd/pVs) in HCM did not show significant increment during exercise (1.35 +/- 0.38 to 1.43 +/- 0.35), though that ratio in NC was significantly increased by exercise (1.67 +/- 0.22/s to 1.97 +/- 0.19/s, p less than 0.001). There was no correlation between pVd and the degree of left ventricular hypertrophy. These results suggest that diastolic reserve to exercise is depressed in HCM and that other factors besides left ventricular hypertrophy may account for diastolic abnormality.     

Pressure-derived indices of left ventricular isovolumic relaxation in patients with hypertrophic cardiomyopathy.

High fidelity measurements of left ventricular pressure were made at increasing pacing rates in 21 patients with hypertrophic cardiomyopathy and a control group of 11 patients investigated for chest pain who proved to have normal hearts. In both groups the fall in pressure during isovolumic relaxation from the point of min dp/dt approximated closely to a monoexponential, and could be described by a time constant and asymptote. The time constant shortened and the asymptote increased as heart rate rose in both groups. The time constant was longer and min dp/dt less in the cardiomyopathy group than controls at all heart rates. In the cardiomyopathy patients min dp/dt, but not the time constant, was related to systolic pressure. During pacing, eight cardiomyopathy patients developed metabolic evidence of myocardial ischaemia, but indices of relaxation did not differ between these eight and the other 13 either at basal heart rate or the highest pacing rate. In 10 cardiomyopathy patients measurements were repeated at comparable pacing rates after propranolol (0.2 mg/kg). Left ventricular end-diastolic pressure and indices of contractility decreased after the drug, but the time constant did not change. Eight patients received verapamil (20 mg) after which there were substantial reductions in systolic pressure and contractility. Min dp/dt decreased in proportion to systolic pressure, but the time constant was unchanged. At the highest pacing rate before drug administration three patients had abnormal lactate extraction which was corrected by either propranolol (one patient) or verapamil (two patients). Despite abolition of metabolic evidence of ischaemia, relaxation did not improve. It is concluded that abnormal isovolumic relaxation is common in patients with hypertrophic cardiomyopathy, but its severity correlates poorly with other features of the disease. Abnormal relaxation is not the result of ischaemia, and pressure derived indices of relaxation do not improve after the administration of propranolol or verapamil.     

Usefulness of brain natriuretic peptide levels in the clinical evaluation of patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HC) is associated frequently with heart failure symptoms and diastolic dysfunction. Although the influence of brain natriuretic peptide (BNP) levels in the management of patients with systolic dysfunction is evolving, there are few data on the role of BNP in the management of patients with HC. BNP was compared with clinical and echocardiographic variables, including measures of diastolic filling, in 217 patients with HC. BNP values were correlated with New York Heart Association classification, echocardiographic estimates of diastolic filling pressure, and right ventricular systolic pressure even after adjusting for age, gender, renal function, and body habitus. However, the overlap of the BNP levels in these respective categories was notable. BNP values did not correlate with objective measures of exercise capacity, and serial BNP values did not track changes in clinical status. In conclusion, BNP levels in patients with HC are associated with similar subjective and objective measures as have been observed in patients with left ventricular systolic dysfunction, but these correlations are relatively weak and do not allow the precise characterization of clinical status.     

Absence of progression of left ventricular hypertrophy in adult patients with hypertrophic cardiomyopathy

Development or progression of left ventricular hypertrophy has recently been described in children with hypertrophic cardiomyopathy. To determine whether similar changes in magnitude and distribution of left ventricular hypertrophy may also occur in adult patients with this disease, serial assessment of left ventricular wall thickness was obtained with M-mode and two-dimensional echocardiography in 65 patients with hypertrophic cardiomyopathy who were 23 to 50 years of age. The follow-up period was 3 to 6 years (mean 4). None of the 65 patients showed a substantial increase (greater than or equal to 5 mm) in left ventricular wall thickness; however, 9 (14%) demonstrated a substantial decrease (5 to 9 mm). Wall thinning most commonly involved the anterior ventricular septum (seven patients), but was also identified in the posterior septum (six patients), lateral free wall (two patients) and posterior free wall (one patient). In the nine patients with wall thinning, left ventricular end-diastolic diameter increased significantly (from 44 +/- 6 to 51 +/- 6 mm; p less than 0.001); however, in seven of the nine, absolute cavity size remained within normal limits (less than or equal to 52 mm) at the most recent evaluation. Eight of the nine patients with left ventricular wall thinning and relative cavity enlargement were severely symptomatic and one was mildly symptomatic. In conclusion, substantial progression of left ventricular hypertrophy was not identified in any of the study patients. Hence, if such progression occurs in adults with hypertrophic cardiomyopathy, it is probably rare. Conversely, an important minority of adult patients with hypertrophic cardiomyopathy may show progressive left ventricular wall thinning and relative cavity enlargement, which are usually associated with severe cardiac symptoms.     

肥厚性心肌病患者左心室形态学改变与QT间期离散度的关系

目的探讨体表心电图上QT间期离散度（QTd）与肥厚性心肌病（HCM）左心室形态学改变的关系。方法43例HCM患者,均经二维超声心动图确诊。根据心室肥厚的部位不同,将患者分为4组:A组（室间隔肥厚）16例、B组（室间隔肥厚及左室前壁肥厚）10例、C组（室间隔肥厚、左室前壁肥厚及左室侧壁肥厚）10例、D组（室间隔肥厚及广泛左室壁肥厚）7例。在安静状态下记录同步12导联心电图（ECG）,人工测量各导联的QT间期、QRS波时间,并计算QT及QRS离散度（QTd及QRSd）。结果超声心动图检查D组的左室后壁厚度（PWT）明显大于A、B、C组,D组的室间隔厚度（IVST）/PWT明显小于A、B、C组。A、B组的QTd明显大于C、D组,差异有显著性意义。结论QTd不仅反应了左心室复极的不均一性,也反应了左心室肥厚的形态学改变的不均性。