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Antonello D'Andrea, Pio Caso, Sergio Severino, Sergio Cuomo, Giovanbattista Capozzi, Paolo Calabrò, Gennaro Cice, Luigi Ascione, Marino Scherillo, Raffaele Calabrò, Prognostic value of intra-left ventricular electromechanical asynchrony in patients with hypertrophic cardiomyopathy, European Heart Journal, Volume 27, Issue 11, June 2006, Pages 1311–1318, https://doi.org/10.1093/eurheartj/ehi688
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Abstract
Aims We sought to assess the indexes of myocardial activation delay, using Doppler myocardial imaging (DMI), as potential predictors of cardiac events in patients with hypertrophic cardiomyopathy (HCM). The distribution and magnitude of left ventricular (LV) hypertrophy are not uniform in patients with HCM, which results in heterogeneity of regional LV systolic function.
Methods and results The study population included 123 HCM patients (39.4±5.9 years) and 123 age- and sex-matched healthy subjects, followed up for 48.4±8.8 months. By use of pulsed DMI, the following regional parameters were evaluated in six different basal myocardial segments: myocardial peak velocities and systolic time-intervals; myocardial intraventricular (intra-V-Del) and interventricular (inter-V-Del) systolic delays. DMI analysis in HCM showed lower myocardial systolic and early-diastolic peak velocities of all the segments. As for time intervals, HCM showed significant inter- and intra-V delays (P<0.0001), whereas homogeneous systolic activation of the ventricular walls was assessed in controls. During the follow-up, 16 cardiac deaths (12 sudden deaths) were observed in HCM patients. InHCM, DMI intra-V-Del was the most powerful independent predictor of sudden cardiac death (P<0.0001). In particular, an intra-V-Del >45 ms is identified with high sensitivity and specificity in HCM patients at higher risk of ventricular tachycardia and sudden cardiac death (test accuracy: 88.8%).
Conclusion In HCM patients, DMI indexes of intra-V-Del may provide additional information for selecting subgroups of HCM patients at increased risk of ventricular arrhythmias and sudden cardiac death at follow-up. Accordingly, such patients may be more actively identified for early intensive treatment and survey.
Introduction
Hypertrophic cardiomyopathy (HCM) is a primary heart disease characterized by a disorganized myocardial architecture, chaotic alignment of myofibres, and areas of scaring resulting from myocyte death and repair.1–5 It is well known that the distribution and magnitude of left ventricular (LV) hypertrophy are not uniform in patients with HCM, which results in regional heterogeneity of both LV and right ventricular (RV) systolic and diastolic function.6–10 As HCM is characterized by markedly variable clinical manifestations and morphological and haemodynamic abnormalities, defining reliable clinical non-invasive markers for the diagnosis and early identification of high-risk subgroups remains a challenge.3
Doppler myocardial imaging (DMI) can provide accurate information about systolic and diastolic regional function of both the ventricles during the cardiac cycle.11–12 Recent reports have underlined the role of DMI electromechanical parameters as significant predictors of cardiac events in heart failure patients.
On these grounds, aims of the present study were (i) to evaluate by DMI regional LV and RV systolic peak velocities and activation times in HCM patients and (ii) to assess the potential prognostic value of DMI indexes in predicting cardiovascular events in HCM during a 4-year follow-up.
Methods
HCM group
Between 1999 and 2003, we prospectively examined 143 HCM patients (38.4±7.9 years), who were referred to our echocardiographic laboratories for risk stratification. Patients were enrolled in the study after their informed consent, and approval of Ethics Committee of Monaldi and Rummo Hospitals was obtained.
Diagnosis of HCM was confirmed by echocardiographic evidence ofasymmetric hypertrophy of interventricular septum (>15 mm) without any other cardiac or systemic disease capable of producing the magnitude of hypertrophy evident.3 Exclusion criteria were diabetes mellitus, arterial hypertension, coronary artery disease, sinus tachycardia, atrial fibrillation (AF), lung disease, and inadequate echocardiograms.
Of the initial 143 HCM patients, 20 were excluded from the studyfor the following reasons: eight did not meet inclusion criteria, six refused to give their consent, six because not all the required echocardiographic measurements were obtained. As a result, in our selected final population, all required measurementswere obtained in each of the subjects that were initially included.
Ten patients (8.3%) were in NYHA functional classes III–IV and 16 (13.3%) in NYHA class II. Twenty-four patients (20%) had history of unexplained syncope and 17 (14.1%) of chest pain. Twenty-three patients (19.6%) had a family history of a premature HCM-related sudden cardiac death. Twenty-eight patients (23.3%) were defined to have obstructive HCM on the basis of the evidence of LV outflow tract gradient ≥30 mmHg under basal conditions. Furthermore, allthe HCM patients had undergone stress technetium-99m-sestamibisingle photon emission computed tomography (SPECT) atleast 3 months before the enrollment in our study protocol.
Patients taking cardiac drugs, primarily beta-blockers (25.2% ofpatients) and calcium channel blockers (21.3%), withdrawn therapy at least 72 h before the echocardiogram, according to the rules of our institutional committees.
Control group
We also studied 123 age- and sex-matched subjects without detectable cardiovascular risk factor. Volunteer controls were all recruited in Naples (Italy), were selected from our departments of paediatric and adult cardiology among subjects investigated for either sport or work eligibility, and were examined in a single centre (Monaldi Hospital, Naples, Italy). None of the control subjects had cardiovascular structural or functional abnormalities or received any medication. We ensured comparability of the two groups by using frequency matching.13 Baseline characteristics such as familiar history of atherosclerothic disease, smoking behaviour, eating habits, sport activities, and body mass index were examined, and for these parameters, there were no significant differences between the two groups.
Procedures
Standard Doppler echocardiography and DMI were performed with the subjects in partial left decubitus, by either Vivid 5 or Vivid 7 ultrasound system (GE Vingmed Ultrasound, Horten, Norway) equipped with DMI capabilities. A variable frequency phased-array transducer (2.5–3.5–4.0 MHz) was used for two-dimensional, M-mode, and Doppler imaging. Doppler echocardiographic and DMI tracings were recorded on magneto-optical disk. All the measurements were analysed by two experienced readers, taking the average of three or more cardiac cycles.
M- and B-modes
RV end-diastolic diameter was measured in apical four-chamber view at basal, middle, and apical levels, according to the protocol of Foale et al.15 Tricuspid annular plane systolic excursion (TAPSE) was calculated as index of global RV systolic function by the difference between end-diastolic and end-systolic measurement (in millimetre).16
Standard Doppler
Pulsed-Doppler assessment of LV inflow was performed in apical four-chamber view, with the sample volume placed at the level of valve tips. The following measurements of global LV diastolic function were determined: peak velocities of E- and A-waves (m/s) and their ratios, deceleration time of E-wave (ms), and isovolumic relaxation time (ms), measured as the time interval occurring between the end of systolic output flow and the transmitral E-wave onset, by placing pulsed-Doppler sample volume between outflow tract and mitral valve.17 Transmitral inflow was analysed also by Valsalva manoeuvre to detect pseudo-normal patterns: during the strain phase of this manoeuvre, according to a lowering preload, E-peak velocity decreased and A-peak velocity increased in 20 (16.6%) HCM patients, thus showing the evidence of pseudo-normalization.
The time for global LV activation was evaluated from the onset of QRS to the onset of aortic flow (Q-Ao). The time for global RV activation was determined from the onset of QRS to the onset of pulmonary flow (Q-Pulm). The difference between (Q-Ao) and (Q-Pulm) determined Doppler interventricular delay.18
Pulsed DMI
Pulsed DMI was performed by spectral pulsed-Doppler signal filters, by-passing high-pass filter, adjusting Nyquist limit until 15–20 cm/s (close to myocardial velocities), and using the minimal optimal gain.11 In apical four-chamber and two-chamber views, a 5 mm pulsed-Doppler sample volume was subsequently placed at the level of five different basal myocardial segments: LV posterior septum, LV inferior wall, LV anterior wall, LV lateral wall (at the level of mitral annulus), and RV lateral wall (at the level of tricuspid annulus). The apical view was chosen to obtain quantitative assessment of longitudinal regional wall motion almost simultaneous to Doppler inflow and outflow and to minimize the incidence angle between Doppler beam and longitudinal wall motion. In parasternal short-axis view, the sample volume was placed at the level of basal LV posterior wall, in order to assess regional circumferential motion. By use of DMI, the following regional parameters were evaluated in six different basal myocardial segments: systolic (Sm) and early- and late-diastolic (Em and Am) peak velocities. As the index of myocardial systolic activation was calculated: precontraction time (Q-Sm) (from the beginning of Q-wave of ECG to the onset of Sm).
Intraventricular systolic delay (intra-V-Del) was analysed by the difference between the longest and shortest Q-Sm time intervals among four different LV basal myocardial segments (posterior septum, inferior wall, anterior wall, lateral wall). Interventricular activation delay (inter-V-Del) was calculated by the difference of Q-Sm between the most delayed LV segment and RV lateral wall.19–20
Measurement of QT interval and dispersion
All resting ECGs were recorded at 25 mm/s with standard lead positions, and all records were magnified by 200% to improve resolution. QT intervals, the onset of the QRS complex to the peak of the T-wave (QTp) intervals, and QRS duration were measured in each lead of the precordial six lead ECGs (V1–V6). QT intervals were measured from the onset of the QRS complex to the end of the T-wave. The end of the T-wave was defined as the intersecting point of a tangent line on the terminal T-wave and the TP baseline. When U-waves were present, the QT interval was measured to the nadir of the curve between the T- and U-waves. The dispersion of QT was calculated as the difference between the maximum and minimum QT. Values of the QT intervals and dispersions were corrected for heart rate by using Bazett's formula.21
ECG Holter monitoring
Two-lead (D2 and V5) ECG Holter monitoring (CardioData Inc., Marlborough, MA, USA) was performed for 24 h, with patients recording in a diary the activities during the day and any relevant symptoms. The analysis of the ECG layout was performed using a CardioData Mk4 system.
Endpoints and assessment
Of 226 patients, 223 completed a mean follow-up of 4 years (mean 48.4±8.8 months; range: 16–50; median: 50). Patients were followed as outpatients at 3–6-month intervals, starting from the day of the DMI evaluation. Follow-up data was obtained through review of patient's hospital records, by periodical visit in our institution or by phone interview with the patient. In case of death, data were collected by phone contact with the same household family member. Three HCM patients were lost at follow-up (2.4%). In two patients, a cardioverter defibrillator (ICD) was implanted.
Primary endpoints were cardiovascular mortality and sudden cardiac death. The definition of cardiac-related death required documentation of significant arrhythmias or cardiac arrest, or both, or death attributable to congestive heart failure or myocardial infarction in the absence of any other precipitating factors. Sudden death was defined as death occurring within 1 h without previous worsening of cardiac symptoms. We also took unexpected deaths occurring during sleep to be sudden when patients were found dead by family members sharing the same room in the morning. We recorded non-cardiovascular death if cardiovascular events were excluded as a cause of death. For all the patients, cases of first cardiovascular event were censored at the date of death. For all the others, January 2003 was considered as the censoring date.
Statistical methods
Categorical variables are expressed in per cent, and continous variables are presented as mean±SD.
On the basis of the previous reports and of an annual event rate of 2%1–4 for the primary endpoint in patients with HCM, a sample of at least 90 patients was required to detect a 10% increase of the event rate in the group of patients with increased intra-V-Del, using a two-tailed test with a significance level of 5%, a power level of 90%, a drop-out rate of 5%, and a total follow-up period of 50 months. As the two groups were matched for age and gender, paired t-test and Wilcoxon matched-pairs test were chosen to estimate the differences between the two groups. The Pearson product-moment correlation coefficient was used to evaluate the association among DMI intra-V-Del, ECG, and standard echocardiographic measurements.
To identify significant prognostic variables in HCM patients, their individual association with follow-up events was assessed by multivariable Cox-regression analyses. The following variables were included into the analysis: clinical data (age, sex, family history of sudden cardiac death, syncope, chest pain), ECG measurements (mean heart rate, QTc dispersion, QRS duration, non-sustained episodes of ventricular tachycardia), and echocardiographic indexes (interventricular septal wall thickness, LV outflow gradient, LV EF, DMI intra-V-Del). These variables were selected according to their clinical relevance and potential impact on prognosis, as shown by earlier studies.1–4
Receiver-operating characteristic (ROC) curve analysis was performed to estimate the best discriminating value of DMI intra-V-Del for predicting a first cardiovascular event. The curves were constructed by plotting sensitivity against (one-specificity). The areas under the curves were also calculated using the method by DeLong et al.22
Variable selection was performed in the multivariable Cox regression as an interactive stepwise backward elimination method, each time excluding the one variable with the highest P-value according to Wald statistics. We analysed three final regression models: the first included only clinical variables; the second added also the Holter monitoring ECG data; and the third included the combination of clinical data, ECG, and echocardiographic measurements. The risk associated with a given variable was expressed by a hazard ratio (HR) with corresponding 95% confidence intervals (CIs). The assumption of proportionality of hazards was checked by means of Schoenfeld residuals using procedure stphtest in STATA, which is based on the methods described by Grambsch and Therneau.23 No severe deviations from parallelism were evident. The assumption of linearity was checked graphically by studying the smoothed martingal residuals from the null model plotted against the covariate variables. The linearity assumptions were satisfied.
Unadjusted survival data are plotted as Kaplan–Meier curves, and comparison between groups was performed using the log-rank statistic. All the tests were two sided. The 0.05 probability level was adopted to consider the significance of the association between predictive variables and events.
Reproducibility of measuring the DMI parameters was determined in 55 randomly selected subjects (30 HCM and 25 controls), according to the previously reported methods.6,8 Inter- and intraobserver variability was examined by using both the Pearson bivariate two-tailed correlations and the Bland–Altman analysis. Relation coefficients, 95% CI, and per cent errors were reported.24
The software packages were SPSS for Windows release 12.0 (SPSS Inc., Chicago, IL, USA) and STATA release 8.0 (Stata Corporation, College Station, TX, USA).
Results
Clinical characteristics of the study population
The two groups were comparable for age (39.4±5.9 years in HCM vs. 39.9±5.2 years in controls), sex (male) prevalence (66.1% in HCM; 66.3% in controls), mean blood pressure (83.5±4.5 mmHg in HCM vs. 86.2±3.8 mmHg in controls), resting heart rate (71.1±6.4 b.p.m. in controls vs. 70.8±9.2 b.p.m. in HCM), and body surface area (1.88±0.11 m in HCM vs. 1.88±0.09 m2 in controls). By SPECT analysis, 15 HCM patients had reversible myocardial perfusion defects; however, the subsequent coronary angiography showed a significant coronary stenosis only in two patients.
ECG and 24-h Holter monitoring
Mean heart rate (68.1±6.6 b.p.m. in controls vs. 71.9±10.2 b.p.m. in HCM) and QRS duration (109.3±12 ms in HCM vs. 107.6±8 ms in controls) were comparable between the two groups. Conversely, QTc (447±30 ms in HCM vs. 390± 29 ms in controls; P<0.01) and QTc dispersion (61±28 ms in HCM vs. 31±19 ms in controls; P<0.001) were increased in HCM. Ten HCM patients showed left bundle-branch block on surface ECG. In 34 HCM patients (28.3%), non-sustained episodes of ventricular tachycardia (of ≥3 b.p.m. and of at least 120 b.p.m., stopping spontaneously in <30 s) were documented, whereas no significant ventricular arrhythmias were evidenced in controls.
Standard Doppler echocardiographic analysis (Table 1)
As expected, LV mass index and septal wall thickness were higher in HCM, whereas LV end-diastolic diameter was increased in controls. All transmitral Doppler indexes were higher in controls, with increased E/A ratio. In contrast, (Q-Ao)–(Q-Pulm) was increased in HCM patients, showing a significant global Doppler interventricular delay.
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
Left ventricle | |||
Septal wall thickness (mm) | 19.8±5.2 | 9.8±0.6 | <0.00001 |
LV posterior wall thickness (mm) | 8.4±1.1 | 9.6±1 | 0.5 |
LV end-diastolic diameter (mm) | 47.4±3.7 | 50.3±3.2 | <0.05 |
LV end-systolic diameter (mm) | 27.0±4.7 | 30.6±1.8 | 0.09 |
LV EF (%) | 63.7±4.7 | 62.2±5.1 | 0.2 |
LV stroke volume (mL) | 64.7±12.5 | 66.7±6.8 | 0.1 |
LV mass index (g/m2.7) | 64±9.7 | 42.8±5.5 | <0.00001 |
Mitral peak E velocity (m/s) | 0.67±0.09 | 0.87±0.03 | <0.001 |
Mitral peak A velocity (m/s) | 0.69±0.06 | 0.44±0.03 | <0.001 |
Mitral peak E/A ratio | 0.97±0.4 | 1.5±0.8 | <0.0001 |
Mitral deceleration time (ms) | 206.4±30.9 | 175.1±13.8 | <0.001 |
Mitral IVRT (ms) | 87.0±10.5 | 79.5±9.4 | <0.001 |
RV outflow tract (mm) | 20.4±2.2 | 21.3±3.8 | 0.7 |
TAPSE (mm) | 19.1±3.5 | 20.1±2.5 | 0.6 |
(Q-Ao)–(Q-Pulm) (ms) | 32.0±10.5 | 15.4±9.9 | <0.001 |
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
Left ventricle | |||
Septal wall thickness (mm) | 19.8±5.2 | 9.8±0.6 | <0.00001 |
LV posterior wall thickness (mm) | 8.4±1.1 | 9.6±1 | 0.5 |
LV end-diastolic diameter (mm) | 47.4±3.7 | 50.3±3.2 | <0.05 |
LV end-systolic diameter (mm) | 27.0±4.7 | 30.6±1.8 | 0.09 |
LV EF (%) | 63.7±4.7 | 62.2±5.1 | 0.2 |
LV stroke volume (mL) | 64.7±12.5 | 66.7±6.8 | 0.1 |
LV mass index (g/m2.7) | 64±9.7 | 42.8±5.5 | <0.00001 |
Mitral peak E velocity (m/s) | 0.67±0.09 | 0.87±0.03 | <0.001 |
Mitral peak A velocity (m/s) | 0.69±0.06 | 0.44±0.03 | <0.001 |
Mitral peak E/A ratio | 0.97±0.4 | 1.5±0.8 | <0.0001 |
Mitral deceleration time (ms) | 206.4±30.9 | 175.1±13.8 | <0.001 |
Mitral IVRT (ms) | 87.0±10.5 | 79.5±9.4 | <0.001 |
RV outflow tract (mm) | 20.4±2.2 | 21.3±3.8 | 0.7 |
TAPSE (mm) | 19.1±3.5 | 20.1±2.5 | 0.6 |
(Q-Ao)–(Q-Pulm) (ms) | 32.0±10.5 | 15.4±9.9 | <0.001 |
IVRT, isovolumic relaxation time; Ao, aortic flow; Pulm, pulmonary flow.
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
Left ventricle | |||
Septal wall thickness (mm) | 19.8±5.2 | 9.8±0.6 | <0.00001 |
LV posterior wall thickness (mm) | 8.4±1.1 | 9.6±1 | 0.5 |
LV end-diastolic diameter (mm) | 47.4±3.7 | 50.3±3.2 | <0.05 |
LV end-systolic diameter (mm) | 27.0±4.7 | 30.6±1.8 | 0.09 |
LV EF (%) | 63.7±4.7 | 62.2±5.1 | 0.2 |
LV stroke volume (mL) | 64.7±12.5 | 66.7±6.8 | 0.1 |
LV mass index (g/m2.7) | 64±9.7 | 42.8±5.5 | <0.00001 |
Mitral peak E velocity (m/s) | 0.67±0.09 | 0.87±0.03 | <0.001 |
Mitral peak A velocity (m/s) | 0.69±0.06 | 0.44±0.03 | <0.001 |
Mitral peak E/A ratio | 0.97±0.4 | 1.5±0.8 | <0.0001 |
Mitral deceleration time (ms) | 206.4±30.9 | 175.1±13.8 | <0.001 |
Mitral IVRT (ms) | 87.0±10.5 | 79.5±9.4 | <0.001 |
RV outflow tract (mm) | 20.4±2.2 | 21.3±3.8 | 0.7 |
TAPSE (mm) | 19.1±3.5 | 20.1±2.5 | 0.6 |
(Q-Ao)–(Q-Pulm) (ms) | 32.0±10.5 | 15.4±9.9 | <0.001 |
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
Left ventricle | |||
Septal wall thickness (mm) | 19.8±5.2 | 9.8±0.6 | <0.00001 |
LV posterior wall thickness (mm) | 8.4±1.1 | 9.6±1 | 0.5 |
LV end-diastolic diameter (mm) | 47.4±3.7 | 50.3±3.2 | <0.05 |
LV end-systolic diameter (mm) | 27.0±4.7 | 30.6±1.8 | 0.09 |
LV EF (%) | 63.7±4.7 | 62.2±5.1 | 0.2 |
LV stroke volume (mL) | 64.7±12.5 | 66.7±6.8 | 0.1 |
LV mass index (g/m2.7) | 64±9.7 | 42.8±5.5 | <0.00001 |
Mitral peak E velocity (m/s) | 0.67±0.09 | 0.87±0.03 | <0.001 |
Mitral peak A velocity (m/s) | 0.69±0.06 | 0.44±0.03 | <0.001 |
Mitral peak E/A ratio | 0.97±0.4 | 1.5±0.8 | <0.0001 |
Mitral deceleration time (ms) | 206.4±30.9 | 175.1±13.8 | <0.001 |
Mitral IVRT (ms) | 87.0±10.5 | 79.5±9.4 | <0.001 |
RV outflow tract (mm) | 20.4±2.2 | 21.3±3.8 | 0.7 |
TAPSE (mm) | 19.1±3.5 | 20.1±2.5 | 0.6 |
(Q-Ao)–(Q-Pulm) (ms) | 32.0±10.5 | 15.4±9.9 | <0.001 |
IVRT, isovolumic relaxation time; Ao, aortic flow; Pulm, pulmonary flow.
Pulsed-DMI analysis (Tables 2 and 3)
DMI analysis in HCM detected lower Sm, Em and Em/Am ratio at the level of all the analysed myocardial segments (Figure 1). As for time intervals, the control group showed homogeneous systolic activation of ventricular walls, whereas in HCM patients significant inter- and intra-V delays were measured. These differences in time intervals remained significant even after correction for resting heart rate.
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
LV posterior septum | |||
Sm peak (m/s) | 0.07±0.03 | 0.11±0.02 | <0.01 |
Em peak (m/s) | 0.05±0.04 | 0.11±0.05 | <0.0001 |
Em/Am ratio | 0.55±0.6 | 1.4±0.5 | <0.0001 |
LV lateral wall | |||
Sm peak (m/s) | 0.08±0.02 | 0.11±0.03 | <0.01 |
Em peak (m/s) | 0.08±0.04 | 0.15±0.04 | <0.001 |
Em/Am ratio | 0.64±0.6 | 1.12±0.5 | <0.0001 |
LV inferior wall | |||
Sm peak (m/s) | 0.07±0.02 | 0.11±0.02 | <0.01 |
Em peak (m/s) | 0.09±0.04 | 0.16±0.04 | <0.0001 |
Em/Am ratio | 0.8±0.6 | 2.2±0.5 | <0.0001 |
LV anterior wall | |||
Sm peak (m/s) | 0.08±0.02 | 0.12±0.03 | <0.01 |
Em peak (m/s) | 0.08±0.04 | 0.15±0.04 | <0.001 |
Em/Am ratio | 0.67±0.6 | 1.7±0.5 | <0.0001 |
LV posterior wall | |||
Sm peak (m/s) | 0.06±0.02 | 0.09±0.03 | <0.01 |
Em peak (m/s) | 0.06±0.04 | 0.12±0.04 | <0.0001 |
Em/Am ratio | 0.7±0.6 | 1.2±0.5 | <0.001 |
RV lateral wall | |||
Sm peak (m/s) | 0.10±0.03 | 0.12±0.03 | <0.05 |
Em peak (m/s) | 0.12±0.04 | 0.15±0.04 | <0.01 |
Em/Am ratio | 1.26±0.6 | 1.6±0.6 | <0.01 |
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
LV posterior septum | |||
Sm peak (m/s) | 0.07±0.03 | 0.11±0.02 | <0.01 |
Em peak (m/s) | 0.05±0.04 | 0.11±0.05 | <0.0001 |
Em/Am ratio | 0.55±0.6 | 1.4±0.5 | <0.0001 |
LV lateral wall | |||
Sm peak (m/s) | 0.08±0.02 | 0.11±0.03 | <0.01 |
Em peak (m/s) | 0.08±0.04 | 0.15±0.04 | <0.001 |
Em/Am ratio | 0.64±0.6 | 1.12±0.5 | <0.0001 |
LV inferior wall | |||
Sm peak (m/s) | 0.07±0.02 | 0.11±0.02 | <0.01 |
Em peak (m/s) | 0.09±0.04 | 0.16±0.04 | <0.0001 |
Em/Am ratio | 0.8±0.6 | 2.2±0.5 | <0.0001 |
LV anterior wall | |||
Sm peak (m/s) | 0.08±0.02 | 0.12±0.03 | <0.01 |
Em peak (m/s) | 0.08±0.04 | 0.15±0.04 | <0.001 |
Em/Am ratio | 0.67±0.6 | 1.7±0.5 | <0.0001 |
LV posterior wall | |||
Sm peak (m/s) | 0.06±0.02 | 0.09±0.03 | <0.01 |
Em peak (m/s) | 0.06±0.04 | 0.12±0.04 | <0.0001 |
Em/Am ratio | 0.7±0.6 | 1.2±0.5 | <0.001 |
RV lateral wall | |||
Sm peak (m/s) | 0.10±0.03 | 0.12±0.03 | <0.05 |
Em peak (m/s) | 0.12±0.04 | 0.15±0.04 | <0.01 |
Em/Am ratio | 1.26±0.6 | 1.6±0.6 | <0.01 |
Sm, myocardial systolic peak velocity; Em, myocardial early-diastolic wave; Am, myocardial atrial diastolic wave.
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
LV posterior septum | |||
Sm peak (m/s) | 0.07±0.03 | 0.11±0.02 | <0.01 |
Em peak (m/s) | 0.05±0.04 | 0.11±0.05 | <0.0001 |
Em/Am ratio | 0.55±0.6 | 1.4±0.5 | <0.0001 |
LV lateral wall | |||
Sm peak (m/s) | 0.08±0.02 | 0.11±0.03 | <0.01 |
Em peak (m/s) | 0.08±0.04 | 0.15±0.04 | <0.001 |
Em/Am ratio | 0.64±0.6 | 1.12±0.5 | <0.0001 |
LV inferior wall | |||
Sm peak (m/s) | 0.07±0.02 | 0.11±0.02 | <0.01 |
Em peak (m/s) | 0.09±0.04 | 0.16±0.04 | <0.0001 |
Em/Am ratio | 0.8±0.6 | 2.2±0.5 | <0.0001 |
LV anterior wall | |||
Sm peak (m/s) | 0.08±0.02 | 0.12±0.03 | <0.01 |
Em peak (m/s) | 0.08±0.04 | 0.15±0.04 | <0.001 |
Em/Am ratio | 0.67±0.6 | 1.7±0.5 | <0.0001 |
LV posterior wall | |||
Sm peak (m/s) | 0.06±0.02 | 0.09±0.03 | <0.01 |
Em peak (m/s) | 0.06±0.04 | 0.12±0.04 | <0.0001 |
Em/Am ratio | 0.7±0.6 | 1.2±0.5 | <0.001 |
RV lateral wall | |||
Sm peak (m/s) | 0.10±0.03 | 0.12±0.03 | <0.05 |
Em peak (m/s) | 0.12±0.04 | 0.15±0.04 | <0.01 |
Em/Am ratio | 1.26±0.6 | 1.6±0.6 | <0.01 |
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
LV posterior septum | |||
Sm peak (m/s) | 0.07±0.03 | 0.11±0.02 | <0.01 |
Em peak (m/s) | 0.05±0.04 | 0.11±0.05 | <0.0001 |
Em/Am ratio | 0.55±0.6 | 1.4±0.5 | <0.0001 |
LV lateral wall | |||
Sm peak (m/s) | 0.08±0.02 | 0.11±0.03 | <0.01 |
Em peak (m/s) | 0.08±0.04 | 0.15±0.04 | <0.001 |
Em/Am ratio | 0.64±0.6 | 1.12±0.5 | <0.0001 |
LV inferior wall | |||
Sm peak (m/s) | 0.07±0.02 | 0.11±0.02 | <0.01 |
Em peak (m/s) | 0.09±0.04 | 0.16±0.04 | <0.0001 |
Em/Am ratio | 0.8±0.6 | 2.2±0.5 | <0.0001 |
LV anterior wall | |||
Sm peak (m/s) | 0.08±0.02 | 0.12±0.03 | <0.01 |
Em peak (m/s) | 0.08±0.04 | 0.15±0.04 | <0.001 |
Em/Am ratio | 0.67±0.6 | 1.7±0.5 | <0.0001 |
LV posterior wall | |||
Sm peak (m/s) | 0.06±0.02 | 0.09±0.03 | <0.01 |
Em peak (m/s) | 0.06±0.04 | 0.12±0.04 | <0.0001 |
Em/Am ratio | 0.7±0.6 | 1.2±0.5 | <0.001 |
RV lateral wall | |||
Sm peak (m/s) | 0.10±0.03 | 0.12±0.03 | <0.05 |
Em peak (m/s) | 0.12±0.04 | 0.15±0.04 | <0.01 |
Em/Am ratio | 1.26±0.6 | 1.6±0.6 | <0.01 |
Sm, myocardial systolic peak velocity; Em, myocardial early-diastolic wave; Am, myocardial atrial diastolic wave.
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
IVS Q-Sm (ms) | 168.6±8.6 | 114.6±12.7 | <0.0001 |
LV lateral Q-Sm (ms) | 142.3± 8.3 | 115.6±7.6 | <0.001 |
LV inferior Q-Sm (ms) | 139.7±7.5 | 119.3±8.1 | <0.001 |
LV posterior Q-Sm (ms) | 131.7±8.5 | 113.3±8.1 | <0.01 |
LV anterior Q-Sm (ms) | 138.5±13.9 | 120.6±8.3 | <0.01 |
RV lateral Q-Sm (ms) | 128.6±10.7 | 112.5±8.1 | <0.05 |
Intraventricular delay (ms) | 37.6±8.2 | 9.8±8.8 | <0.0001 |
Interventricular delay (ms) | 39.5±10.3 | 9.5±10.6 | <0.0001 |
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
IVS Q-Sm (ms) | 168.6±8.6 | 114.6±12.7 | <0.0001 |
LV lateral Q-Sm (ms) | 142.3± 8.3 | 115.6±7.6 | <0.001 |
LV inferior Q-Sm (ms) | 139.7±7.5 | 119.3±8.1 | <0.001 |
LV posterior Q-Sm (ms) | 131.7±8.5 | 113.3±8.1 | <0.01 |
LV anterior Q-Sm (ms) | 138.5±13.9 | 120.6±8.3 | <0.01 |
RV lateral Q-Sm (ms) | 128.6±10.7 | 112.5±8.1 | <0.05 |
Intraventricular delay (ms) | 37.6±8.2 | 9.8±8.8 | <0.0001 |
Interventricular delay (ms) | 39.5±10.3 | 9.5±10.6 | <0.0001 |
Q-Sm, myocardial precontraction time; IVS, interventricular septum.
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
IVS Q-Sm (ms) | 168.6±8.6 | 114.6±12.7 | <0.0001 |
LV lateral Q-Sm (ms) | 142.3± 8.3 | 115.6±7.6 | <0.001 |
LV inferior Q-Sm (ms) | 139.7±7.5 | 119.3±8.1 | <0.001 |
LV posterior Q-Sm (ms) | 131.7±8.5 | 113.3±8.1 | <0.01 |
LV anterior Q-Sm (ms) | 138.5±13.9 | 120.6±8.3 | <0.01 |
RV lateral Q-Sm (ms) | 128.6±10.7 | 112.5±8.1 | <0.05 |
Intraventricular delay (ms) | 37.6±8.2 | 9.8±8.8 | <0.0001 |
Interventricular delay (ms) | 39.5±10.3 | 9.5±10.6 | <0.0001 |
Variable . | HCM (123 patients) . | Controls (123 patients) . | P-value . |
---|---|---|---|
IVS Q-Sm (ms) | 168.6±8.6 | 114.6±12.7 | <0.0001 |
LV lateral Q-Sm (ms) | 142.3± 8.3 | 115.6±7.6 | <0.001 |
LV inferior Q-Sm (ms) | 139.7±7.5 | 119.3±8.1 | <0.001 |
LV posterior Q-Sm (ms) | 131.7±8.5 | 113.3±8.1 | <0.01 |
LV anterior Q-Sm (ms) | 138.5±13.9 | 120.6±8.3 | <0.01 |
RV lateral Q-Sm (ms) | 128.6±10.7 | 112.5±8.1 | <0.05 |
Intraventricular delay (ms) | 37.6±8.2 | 9.8±8.8 | <0.0001 |
Interventricular delay (ms) | 39.5±10.3 | 9.5±10.6 | <0.0001 |
Q-Sm, myocardial precontraction time; IVS, interventricular septum.
In HCM patients, intra-V-Del was positively associated with both septal wall thickness (r=0.69, P<0.0001) and LV outflow gradient (r=0.51, P<0.001). In addition, the same intra-V-Del was inversely related to LV stroke volume (r=−0.55, P<0.001). As for ECG measurements, a significant direct correlation was observed between intra-V-Del and QTc dispersion, whereas no significant association was detected between intra-V-Del and QRS duration (Figure 2).
Reproducibility of DMI measurements
Interobserver variability
Pearson's correlations: Sm: r=0.97, P<0.00001; Em:r=0.98, P<0.00001; Intraventricular delay: r=0.96, P<0.00001.
Bland–Altman analysis: Sm (95% CI±1.8, per cent error 3.3%); Em (95% CI±1.2, per cent error 3.1%); Intraventricular delay (95% CI±3.5, per cent error 4.3%).
Intraobserver variability
Pearson's correlations: Sm: r=0.98, P<0.00001; Em:r=0.98, P<0.00001; Intraventricular delay: r=0.97, P<0.00001.
Bland–Altman analysis: Sm (95% CI±1.3, per cent error 2.2%); Em (95% CI±1, per cent error 2.3%); Intraventricular delay (95% CI±3.1, per cent error 4.1%).
Events during the follow-up
Among the HCM patients, during the follow-up period, there were one non-cardiovascular death and 16 cardiovascular deaths (13.3%): 12 sudden deaths and four pump-failure deaths.
By Cox's multivariable proportional-hazards regression analyses, family history of sudden cardiac death (HR: 1.22; 95% CI: 1.08–1.34; P<0.001), non-sustained episodes of ventricular tachycardia (HR: 2.51; 95% CI: 1.3–4.6; P<0.0001), and DMI intra-V-Del (HR: 3.6; 95% CI: 1.4–4.3; P<0.0001) were the only independent predictors of sudden cardiac death (Tables 4 and 5). The global χ2 of this combined clinical, Holter ECG and DMI test model was 64.3 (P<0.00001) (Figure 3).
Variable . | SD HCM (12 patients) . | No SD HCM (111 patients) . | P-value . |
---|---|---|---|
Family history for SD (%) | 58.5 | 18.5 | <0.0001 |
NYHA class II (%) | 14.2 | 13.8 | 0.8 |
Syncope (%) | 16.5 | 11.3 | 0.08 |
Chest pain (%) | 15.1 | 13.8 | 0.7 |
Non-sustained VT (%) | 57.1 | 28.5 | <0.0001 |
QTc dispersion (ms) | 64±18 | 59±22 | 0.09 |
Interventricular septum (mm) | 20.8±5.1 | 18.6±6.1 | 0.6 |
Obstructive HCM (%) | 24.2 | 22.3 | 0.8 |
Intraventricular delay (ms) | 54.6±5.5 | 29.4±5.8 | <0.0001 |
Perfusion defects (SPECT) (%) | 11.2 | 12.3 | 0.8 |
Use of beta-blockers (%) | 23.6 | 26.4 | 0.3 |
Variable . | SD HCM (12 patients) . | No SD HCM (111 patients) . | P-value . |
---|---|---|---|
Family history for SD (%) | 58.5 | 18.5 | <0.0001 |
NYHA class II (%) | 14.2 | 13.8 | 0.8 |
Syncope (%) | 16.5 | 11.3 | 0.08 |
Chest pain (%) | 15.1 | 13.8 | 0.7 |
Non-sustained VT (%) | 57.1 | 28.5 | <0.0001 |
QTc dispersion (ms) | 64±18 | 59±22 | 0.09 |
Interventricular septum (mm) | 20.8±5.1 | 18.6±6.1 | 0.6 |
Obstructive HCM (%) | 24.2 | 22.3 | 0.8 |
Intraventricular delay (ms) | 54.6±5.5 | 29.4±5.8 | <0.0001 |
Perfusion defects (SPECT) (%) | 11.2 | 12.3 | 0.8 |
Use of beta-blockers (%) | 23.6 | 26.4 | 0.3 |
SD, sudden death; VT, ventricular tachycardia.
Variable . | SD HCM (12 patients) . | No SD HCM (111 patients) . | P-value . |
---|---|---|---|
Family history for SD (%) | 58.5 | 18.5 | <0.0001 |
NYHA class II (%) | 14.2 | 13.8 | 0.8 |
Syncope (%) | 16.5 | 11.3 | 0.08 |
Chest pain (%) | 15.1 | 13.8 | 0.7 |
Non-sustained VT (%) | 57.1 | 28.5 | <0.0001 |
QTc dispersion (ms) | 64±18 | 59±22 | 0.09 |
Interventricular septum (mm) | 20.8±5.1 | 18.6±6.1 | 0.6 |
Obstructive HCM (%) | 24.2 | 22.3 | 0.8 |
Intraventricular delay (ms) | 54.6±5.5 | 29.4±5.8 | <0.0001 |
Perfusion defects (SPECT) (%) | 11.2 | 12.3 | 0.8 |
Use of beta-blockers (%) | 23.6 | 26.4 | 0.3 |
Variable . | SD HCM (12 patients) . | No SD HCM (111 patients) . | P-value . |
---|---|---|---|
Family history for SD (%) | 58.5 | 18.5 | <0.0001 |
NYHA class II (%) | 14.2 | 13.8 | 0.8 |
Syncope (%) | 16.5 | 11.3 | 0.08 |
Chest pain (%) | 15.1 | 13.8 | 0.7 |
Non-sustained VT (%) | 57.1 | 28.5 | <0.0001 |
QTc dispersion (ms) | 64±18 | 59±22 | 0.09 |
Interventricular septum (mm) | 20.8±5.1 | 18.6±6.1 | 0.6 |
Obstructive HCM (%) | 24.2 | 22.3 | 0.8 |
Intraventricular delay (ms) | 54.6±5.5 | 29.4±5.8 | <0.0001 |
Perfusion defects (SPECT) (%) | 11.2 | 12.3 | 0.8 |
Use of beta-blockers (%) | 23.6 | 26.4 | 0.3 |
SD, sudden death; VT, ventricular tachycardia.
Variable . | Model χ2 . | P-value . | Variables selected (HR; 95% CI; P-value) . |
---|---|---|---|
Sudden cardiac death | |||
Clinical | 35.3 | 0.001 | Family history for SD (1.28; 1.1–1.39; P<0.001) |
Clinical+Holter ECG | 44.2 | 0.0001 | Family history for SD (1.26; 1.2–1.4; P<0.001) |
QTc dispersion (3.26; 1.2–8.4; P<0.01) | |||
Non-sustained VT (2.59; 1.4–4.6; P<0.0001) | |||
Clinical+Holter ECG+Echo/DMI | 64.3 | 0.00001 | Family history for SD (1.22; 1.08–1.34; P<0.001) |
Non-sustained VT (2.51; 1.3–4.6; P<0.0001) | |||
DMI intraventricular delay (3.6; 1.4–4.3; P<0.0001) |
Variable . | Model χ2 . | P-value . | Variables selected (HR; 95% CI; P-value) . |
---|---|---|---|
Sudden cardiac death | |||
Clinical | 35.3 | 0.001 | Family history for SD (1.28; 1.1–1.39; P<0.001) |
Clinical+Holter ECG | 44.2 | 0.0001 | Family history for SD (1.26; 1.2–1.4; P<0.001) |
QTc dispersion (3.26; 1.2–8.4; P<0.01) | |||
Non-sustained VT (2.59; 1.4–4.6; P<0.0001) | |||
Clinical+Holter ECG+Echo/DMI | 64.3 | 0.00001 | Family history for SD (1.22; 1.08–1.34; P<0.001) |
Non-sustained VT (2.51; 1.3–4.6; P<0.0001) | |||
DMI intraventricular delay (3.6; 1.4–4.3; P<0.0001) |
SD, sudden death; VT, ventricular tachycardia.
Variable . | Model χ2 . | P-value . | Variables selected (HR; 95% CI; P-value) . |
---|---|---|---|
Sudden cardiac death | |||
Clinical | 35.3 | 0.001 | Family history for SD (1.28; 1.1–1.39; P<0.001) |
Clinical+Holter ECG | 44.2 | 0.0001 | Family history for SD (1.26; 1.2–1.4; P<0.001) |
QTc dispersion (3.26; 1.2–8.4; P<0.01) | |||
Non-sustained VT (2.59; 1.4–4.6; P<0.0001) | |||
Clinical+Holter ECG+Echo/DMI | 64.3 | 0.00001 | Family history for SD (1.22; 1.08–1.34; P<0.001) |
Non-sustained VT (2.51; 1.3–4.6; P<0.0001) | |||
DMI intraventricular delay (3.6; 1.4–4.3; P<0.0001) |
Variable . | Model χ2 . | P-value . | Variables selected (HR; 95% CI; P-value) . |
---|---|---|---|
Sudden cardiac death | |||
Clinical | 35.3 | 0.001 | Family history for SD (1.28; 1.1–1.39; P<0.001) |
Clinical+Holter ECG | 44.2 | 0.0001 | Family history for SD (1.26; 1.2–1.4; P<0.001) |
QTc dispersion (3.26; 1.2–8.4; P<0.01) | |||
Non-sustained VT (2.59; 1.4–4.6; P<0.0001) | |||
Clinical+Holter ECG+Echo/DMI | 64.3 | 0.00001 | Family history for SD (1.22; 1.08–1.34; P<0.001) |
Non-sustained VT (2.51; 1.3–4.6; P<0.0001) | |||
DMI intraventricular delay (3.6; 1.4–4.3; P<0.0001) |
SD, sudden death; VT, ventricular tachycardia.
In particular, an intra-V-Del cut-off value of >45 ms well identified HCM patients at higher risk of sudden cardiac death (85.5% sensitivity; 90.4% specificity; positive predictive value: 66.9%; negative predictive value: 96.7%; test accuracy: 88.8%). The cumulative 4-year mean survival time, free of sudden death, was 57.7 months (95% CI: 54.3–60) in the intra-V-Del <45 ms group and 39.8 months (95% CI: 24.8–51.2) in the intra-V-Del >45 ms group (log-rank: 55.4; P<0.00001) (Figure 4).
Discussion
The present study confirms the usefulness of pulsed DMI to analyse myocardial pattern of both LV and RV in pathological LV hypertrophy.
In our previous reports, we have already compared LV and RV myocardial diastolic indexes of HCM with the ones obtained in normal sedentary subjects.6,8,12,25 However, the present study highlights the existence of extreme myocardial systolic non-uniformity and asynchrony in patients with HCM, in contrast with homogeneous myocardial systolic activation assessed in controls. Furthermore, in HCM patients, DMI parameters of intra-LV electromechanical asynchrony were the most powerful predictors of sudden cardiac death in the subsequent 5 years and provided significant incremental prognostic value when compared with clinical information and other instrumental data.
To the best of our knowledge, such association between delayed intramyocardial activation and increased risk of sudden cardiac death has not been previously described in HCM.
Myocardial systolic peak velocities in either pathological or physiological LV hypertrophy
In the present study, despite normal indexes of global ventricular systolic function (i.e. LV EF, TAPSE), lower myocardial systolic and early-diastolic velocities were observed in HCM at the level of both hypertrophied and non-hypertrophied ventricular walls.
Abnormalities of LV long-axis function have been already reported in patients with different kinds of cardiomyopathy.6,9,10,12,25–27 Previous report demonstrated that both systolic and early-diastolic regional velocities are directly dependent on myocardial structure, characterized by the per cent of interstitial fibrosis and the myocardial beta-adrenergic receptor density assessed by endomyocardial biopsy.28 Therefore, the impairment of myocardial indexes in our patients with HCM can be easily explained as a consequence of a direct involvement of ventricular walls by myopathic process, which is characterized by extensive areas of interstitial and perivascular fibrosis, particularly involving the LV subendocardium.
Prognostic value of intraventricular myocardial activation delay in HCM
In our study protocol, we evaluated in HCM patients three useful indexes of systolic activation delay: (i) QRS width by surface ECG; (ii) (Q-Ao)–(Q-Pulm) by standard echo-Doppler; and (iii) intra- and interventricular delay by DMI. Despite the absence of intraventricular conduction defects by surface ECG in most of HCM patients, DMI measurements of myocardial systolic dyssynchrony were all prolonged in patients with HCM. In particular, no significant association was observed between ECG QRS duration and intra-V-Del, whereas direct correlations of the same intra-V-Del with QTc dispersion, septal wall thickness, and LV outflow gradient were detected. These results are not surprising, considering that recent DMI studies in patients with dilated cardiomyopathy have confirmed that the relation between QRS duration and LV myocardial dyssynchrony is poor, indicating that QRS width does not seem to be a a reliable identifier of patients likely to benefit from resynchronization therapy.29,30
In our study, an intra-V-Del >45 ms (a cut-off value properly assessed by ROC curve analysis) selected with high sensitivity and specificity in HCM patients at higher risk of both ventricular tachyarrhythmias and sudden cardiac death at follow-up. Intra-V-Del provided incremental value for risk stratification, in addition to clinical and ECG Holter monitoring data, as indicated by the increase of the χ2 of the incremental model by the use of DMI echocardiographic data (Figure 3). These results are in accordance with the findings of Bader et al.19 who have underlined the role of DMI electromechanical parameters as significant predictors of cardiac events in heart failure patients, independent of the QRS width and LV EF.
Previous invasive angiocardiographic and electrophysiological studies have suggested that complex ventricular tachyarrhythmias, emanating from an electrically unstable myocardial substrate and resulting from re-entry, are the most common mechanism by which sudden cardiac death occurs in HCM. In particular, Watson et al.31 described the presence of multiphasic local ventricular electrocardiograms in HCM patients at higher risk of cardiac events, whereas Betocchi et al.32 reported systolic and diastolic asynchronyin50% of HCM patients undergoing biplane left ventriculography.
Several hypotheses have been considered regarding the mechanism of LV arrhythmias in HCM, such as: (i) changes in intrinsic properties caused by myocardial disarray and fibrosis33; (ii) temporal non-uniformity of relaxation and contraction at the respective walls caused by regional differences in the distribution of LV hypertrophy34; and (iii) myocardial replacement scarring as a repair process following cell death due to intramural small vessel disease or muscle mass-to-coronary flow mismatch.5,35 By our findings, the impairment of intraventricular systolic synchronicity in HCM patients is strongly associated on one hand with the degree of LV hypertrophy, and on the other with increased risk of non-sustained ventricular tachycardia on ambulatory Holter ECG recording and, therefore, with two instrumental data both described as clinical markers of higher risk of sudden death in the ACC/ESC Consensus Document.3 In addition, in recent reports, we have already observed a close relation between myocardial systolic activation delay and increased risk of ventricular arrhythmias in patients with HCM, dilated cardiomyopathy, and late after repair of Tetralogy of Fallot.21,36,37
Therefore, myocardial heterogeneity results in HCM in ananatomical and electrical substrate that may on one hand determine a non-uniform dispersion of cardiac impulse (i.e. increased QTc dispersion) and a regional delay in systolic activation of LV ventricular wall (i.e. prolongation of intra-V delay) and on the other establish a single macroscopic or multiple microscopic re-entrant circuits, generating polymorphic life-threatening ventricular tachyarrhythmias and sudden cardiac death.
Study limitations
The first limitation, intrinsic to Doppler technique, is the angle dependence of pulsed DMI and the possible presence of artefacts.11
However, we used the same angle incidence of transmitral Doppler and our DMI reproducibility was good. We have also to point out that cardiac overall motion in the space influences DMI regional velocities, thus limiting the myocardial heterogeneity evaluation. In our study, however, the concept of an impaired myocardial function rises from comparison of regional DMI variables between two different groups.
As our paper was the first study reporting the incremental prognostic value of DMI indexes in HCM patients, in our protocol, we selected a control group of healthy subjects. However, further studies could be necessary to analyse the prognostic value of DMI measurements also in different forms of pathological (hypertensive) or physiological (athletes) secondary LV hypertrophy.
Finally, our analysis was perfomed in a population of HCM patients who were referred to our echocardiographic laboratories coming from four different hospitals. Even if the ACC/AHA/NASPE 2002 guidelines have designed the ICD for primary prevention of sudden death as a class IIb indication and for secondary prevention after a cardiac arrest as a classI indication,3 in our population only two patients hada cardioverter defibrillator implanted during the follow-up. As HCM is characterized by markedly variable clinical manifestations, in our country, physician and patient attitudes toward ICD vary among different hospitals and have an important impact on the decision-making in HCM. In fact, there is, at present, an understandable reluctance on the part of several cardiologists to implant such devices chronically in patients for primary prevention, especially in young patients.
Conclusions
Pulsed DMI may represent an effective non-invasive and easy-repeatable technique for assessing the severity of regional delay in the activation of LV walls in patients with pathological LV hypertrophy. In HCM patients, DMI analysis may provide additional information for selecting subgroups of patients at increased risk of ventricular arrhythmias and sudden cardiac death that may benefit from more accurate risk stratification, by taking into account the overall clinicalprofile, and eventually from prophylactic implantable cardioverter defibrillator.
Supplementary material
Supplementary material is available at European Heart Journal online.
Conflict of interest: none declared.
References
The present paper was partially presented in a speech during the ESC Congress in Stockholm (September 2005).
- holter electrocardiography
- hypertrophic cardiomyopathy
- myocardium
- sudden death
- tachycardia, ventricular
- sudden cardiac death
- left ventricle
- cardiac event
- heterogeneity
- diastole
- follow-up
- heart ventricle
- systole
- heart
- hypertrophy
- patient prognosis
- ventricular arrhythmia
- myocardial imaging
- homogeneity
- peak arterial velocity