|Year : 2019 | Volume
| Issue : 3 | Page : 836-843
Left ventricular mechanics before and after myectomy in patients with hypertrophic obstructive cardiomyopathy
Hala M Badran1, Ali M Alamin2, Naglaa F Ahmed1, Taher S Abdel Kareem2
1 Department of Cardiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Cardiology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
|Date of Submission||13-Jan-2017|
|Date of Acceptance||31-Mar-2017|
|Date of Web Publication||17-Oct-2019|
Taher S Abdel Kareem
Faculty of Medicine, Al-Azhar University, Cairo
Source of Support: None, Conflict of Interest: None
The objective of this paper is to detect changes in left ventricular (LV) mechanics after surgical myectomy in patient with hypertrophic obstructive cardiomyopathy (HOCM).
Septal myectomy is the gold standard method to relieve LV outflow tract pressure gradient in patients with HOCM. Myocardial mechanics are abnormal in those patients, demonstrating low longitudinal strain, high circumferential strain, and high apical rotation, compared with healthy patients. The aim of this study was to determine whether functional improvement after myectomy is associated with improved myocardial mechanics.
Patients and methods
A total of 15 patients (60% males and 40% female) with HOCM refractory to medical treatment were subjected to septal myectomy. Clinical data and paired echocardiographic studies before and within 6 months after myectomy were analyzed and compared. Myocardial mechanics including longitudinal and circumferential strain and rotation and LV synchronization were assessed using two-dimensional strain software (velocity vector imaging).
Results showed significant symptomatic relief. LV outflow gradient decreased dramatically from 63.13 ± 10.25 to 9.96 ± 2.72 mmHg (P < 0.0001) and left atrial volume index decreased from 37.8 ± 5.61 to 26.38 ± 3.37 cm3/m2 (P < 0.05). E/e′ decreased from 15.23 ± 2.39 to 9.18 ± 1.42 (P < 0.05). Low longitudinal strain decreased at the myectomy site (basal septum), increased in the basal inferior segment, and remained unchanged globally − 6.43 ± 6.54 to − 8.70 ± 2.30 (P = 0.232). High circumferential strain decreased from − 28.47 ± 3.35 to − 18.26 ± 2.86 (P < 0.05). High LV twist normalized from 16.52 ± 2.25 to 14.02 ± 2.27 (P < 0.05).
Patients with HOCM show mechanical adaptations to chronic elevated afterload similar to patients with severe aortic stenosis in whom there is increased circumferential strain, increased basal and apical rotation, and LV twist. However, within 6 months after myectomy, global longitudinal strain remained unchanged, circumferential strain and rotation decreased, LV twist normalized, and LV dyssynchrony showed no significant changes. Thus, improvement of symptoms after myectomy is mainly because of improvement of the predictors of diastolic function.
Keywords: hypertrophic obstructive cardiomyopathy, left ventricular outflow tract obstruction, septal myectomy, speckle tracking
|How to cite this article:|
Badran HM, Alamin AM, Ahmed NF, Abdel Kareem TS. Left ventricular mechanics before and after myectomy in patients with hypertrophic obstructive cardiomyopathy. Menoufia Med J 2019;32:836-43
|How to cite this URL:|
Badran HM, Alamin AM, Ahmed NF, Abdel Kareem TS. Left ventricular mechanics before and after myectomy in patients with hypertrophic obstructive cardiomyopathy. Menoufia Med J [serial online] 2019 [cited 2020 Feb 28];32:836-43. Available from: http://www.mmj.eg.net/text.asp?2019/32/3/836/268822
| Introduction|| |
Hypertrophic cardiomyopathy (HCM) is the commonest inherited cardiovascular disease, presenting in ∼1/500 adults in the general population . Despite its clinical heterogeneity, the main pathophysiologic substrate of HCM is consistent with mutations in sarcomeric protein genes which lead to myocardial cell disarray and fibrosis, disorders affecting the entire myocardium. This disorder is considered to be inherited in an autosomal dominant manner with variable penetrance and expressivity . Sudden cardiac death; symptoms owing to heart failure, especially in 'end stage' (or burnt-out) HCM; and stroke constitute the main clinical complications in the aforementioned patients .
Dynamic left ventricular outflow tract (LVOT) obstruction is induced by thickening of the interventricular septum and systolic anterior motion of the mitral valve . Several invasive therapeutic modalities have been developed to diminish outflow tract obstruction by reduction of the interventricular septum width . Invasive interventions are usually considered when pharmacotherapy either fails to control symptoms or is not tolerated. These invasive options include dual-chamber permanent pacing, surgical myectomy, and septal ethanol ablation .
Septal myectomy is established as the most effective and proven approach for reversing the consequences of heart failure by providing amelioration of obstruction (and relief of mitral regurgitation) at rest, with restoration of functional capacity and acceptable quality of life at any age, exceeding that achievable with long-term administration of cardioactive drugs .
The mechanics of acute unloading of a severely obstructed left ventricle (LV) have been described in patients with severe aortic stenosis (AS) with normal ejection fractions undergoing aortic valve replacement. Low preoperative longitudinal and abnormally high circumferential strain normalized after aortic valve replacement. Because chronically increased pressure overload and its surgical alleviation are similar in severe AS and hypertrophic obstructive cardiomyopathy (HOCM), we wished to define premyectomy and postmyectomy mechanics to determine whether they were altered by successful surgical myectomy .
| Patients and Methods|| |
Overall, 15 patients with symptomatic HOCM, 14 patients undergoing septal myectomy, and one patient undergoing septal myectomy with concomitant mitral valve replacement were included. Surgical myectomy was performed at Magdy Yacoub Cardiology Center (eight cases), Cardiology Academy Ain Shams University (two cases), National Heart Institute (one case), private hospitals (four patients).
Patients required full baseline clinical records, echocardiograms obtained before myectomy and within 6 months after myectomy, and echocardiographic studies adequate for strain analysis in both baseline and follow-up studies. The study was conducted at Cardiac Research Unit, Menoufia University Hospital, Menoufia, Egypt from August 2011 to August 2016. It was approved by Ethical Committee of Menoufia Faculty of Medicine. A written consent for participation at the study was taken from each patient.
Baseline (preprocedural) and follow-up (within 6 months after the procedure) transthoracic echocardiographic images were obtained. Echocardiographic studies were interpreted at the time of acquisition. All parameters including LV internal dimension end diastolic and end systolic (left ventricular end-diastolic diameter and left ventricular end-systolic diameter), LV function by M-mode (ejection fraction %), interventricular septal thickness, interventricular septum/posterior wall ratio, LV internal dimension and function, left atrial volume (LAV) and left atrial volume index (LAVI), left ventricular mass and left ventricular mass index were obtained. Moreover, two-dimensional (2D) Doppler parameters were measured according to guidelines of the American Society of Echocardiography. Good-quality echocardiograms were required for speckle-tracing analysis with minimal 2D frame rate of 40 frames/s with good LV endocardial border demarcation.
Analysis of myocardial mechanics
Baseline (preprocedural) and follow-up strain measurements were performed using 2D tissue-tracking software (Velocity Vector Imaging, version 3.0.0; Esaote Medical diagnostic systems., in Melen, 77 Genova, 16152 Italy) from archived 2D echocardiographic studies. Longitudinal wall strain and strain rate were averaged from 12-segment measurements from the apical two-chamber and four-chamber views. Circumferential strain, strain rate, and rotation velocities and angles were measured in six segments at the short-axis plane (at the basal and mid ventricular papillary muscle LV level) and in four segments at the apical level. Measurements were averaged for each short-axis level. Averaged myocardial rotation angles were used to calculate basal–apical LV twist, defined as the maximal instantaneous mid-to-apical rotation angle difference. Finally, we used time-to-peak (TTP) parameters to assess LV synchronization and the effect of myectomy.
Data were statistically analyzed using MedCalc (version 11.6.1; MedCalc Software, Mariakerke, Belgium). Data were expressed as mean ± SD. Analysis employed the Wilcoxon sign test for paired data to determine the significance of differences before and after surgical myectomy. To show the relationship between the variables in the patient groups, Spearman's rank correlation analysis was performed. Significant statistical results were considered if P value less than 0.05. Highly significant results were considered if P valueless than 0.01. Intraclass correlation coefficients with 95% confidence intervals (CIs) were calculated.
Intraobserver variability was assessed using repeated measurement performed by the same observer 2 weeks later, whereas interobserver variability was evaluated in all patient by repeated analysis by a second observer, blinded to the results of all previous measurements. The variability was assessed for longitudinal strain, circumferential strain, rotation, and twist.
Paired sample t-test of significance was used when comparing means of repeated measurement, coefficient of variation to assess degree of variability between duplicate measurement. Bland–Altman analysis was used to assess the mean difference (bias) between two methods and their limit of agreement corresponding to ± 1.96 SD.
| Results|| |
Patient clinical characteristics are summarized in [Table 1]. The mean age at the time of surgery was 33.53 ± 10.33 years, and 60% were men and 40% were females. Most patients were treated using a combination of β blockers and/or calcium channel blockers and had New York Heart Association class III symptoms. Major symptoms included dyspnea (100%) and chest pain (6.7%).
All patients had basal septal myectomy, with concomitant surgery mitral valve replacement performed in one patient (represent 6.7% of patients). After myectomy, complete atrioventricular block necessitating permanent pacing occurred in 0% of patients, and new complete left bundle branch block occurred in 13 (86.7%) patients. After myectomy, all patients (100%) improved their functional capacity by more than one class.
Baseline and follow-up 2D Doppler echocardiographic parameters are shown in [Table 2]. At baseline, patients demonstrated asymmetric septal hypertrophy, varying levels of LVOT obstruction, moderate mitral regurgitation, and normal LV systolic function. LAVI was higher. Postmyectomy echocardiography showed a dramatic decrease in the LVOT gradient to non-obstructive levels. LV ejection fraction mildly but significantly decreased (remaining within the normal range), as there were a net decrease in LV principal strain after myectomy (nonimprovement of longitudinal strain and decreased average circumferential strain), which is the vector sum of its longitudinal and circumferential components. Associated changes included a decrease in the grade of mitral regurgitation and a reduction in the LAVI. Diastolic mitral inflow parameters were similar to premyectomy values. Tissue Doppler velocities demonstrated an increase in the lateral E′ velocity and a similar decrease in the E/E′ ratio.
|Table 2: Conventional echo characteristics premyectomy and postmyectomy of study populations (n=15)|
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Preprocedural myocardial mechanics
Preprocedural strain shows that longitudinal strain was lower than normal, increased circumferential strain, and higher than normal peak apical rotation angle and apical-to-basal twist [Table 3]. Septal wall strain measurements demonstrated a high (25 ± 3%) apical-to-basal longitudinal strain gradient, primarily owing to very low basal strain (−7.40 ± 2.2).
|Table 3: Two-dimensional ST (LS) descriptives of premyectomy and postmyectomy status of study populations|
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Postprocedural myocardial mechanics
Although there was no significant change in the average longitudinal strain, which remained lower than normal, longitudinal strain decreased at the myectomy segments and increased at the basal inferior wall segment [Table 3] and [Figure 1]. Septal strain demonstrated a nonsignificant decrease in its apical-to-basal gradient to 23.7 ± 2%. This was because of significant decrease in basal longitudinal strain from −7.40 ± 2.2 to −5.06 ± 1.75 and nonsignificant decrease in apical longitudinal strain from −10.27 ± 3.1 to −9.46 ± 3.04, without a change in overall basal strain (−7.51 ± 2.20, P = 0.188).
|Figure 1: Comparison between peak systolic strain% basal septum, basal inferior, four-chamber left ventricular (LV), and global LV premyectomy and postmyectomy.|
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Circumferential strain [Table 4] and [Figure 2] decreased to be lower than normal levels in the three short-axis levels, resulting in a lower average circumferential strain, as the decrease was unified.
|Table 4: Comparison between two-dimensional ST of average circumferential strain, apical, basal rotation, and left ventricular twist descriptives of premyectomy and postmyectomy status of study populations|
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|Figure 2: Comparison between average circumferential strain (CS) before and after surgical myectomy.|
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Rotation and twist
Supranormal baseline apical rotation significantly decreased to normal values after myectomy (11.12 ± 1.87–8.17 ± 1.88). Basal rotation was mild but showed significant decrease after surgical myectomy (−8.59 ± 1.51 to −7.82 ± 1.47) and remained nearly double the normal value. The resulting apical-to-basal twist (peak instantaneous rotation difference) largely decreased by 2.5 ± 1.04° but remained above normal [Table 4] and [Figure 3].
|Figure 3: Comparison between left ventricular (LV) twist before and after surgical myectomy.|
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Myectomy site versus nonmyectomy site mechanics
Myectomy site segment demonstrated significant decrease in both longitudinal and circumferential strain. Longitudinal strain decreased from −7.40 ± 2.2 to −5.06 ± 1.75 (P < 0.0001) and remained at −7.78 ± 5.48 at nonmyectomy sites. Basal inferior strain demonstrated a modest yet significant increase from −7.73 ± 3.15 to −9.60 ± 2.52 (P = 0.031). Circumferential strain decreased in both myectomy and nonmyectomy sites from −29.47 ± 3.35 to −18.26 ± 2.86, (P < 0.005) and from −27.47 ± 3.35 to −16.26 ± 2.86 (P < 0.005), respectively.
Left ventricular synchronization
There were significant correlations between LV dyssynchrony (use TTP-SD >60 as parameter of LV dyssynchrony) and septal thickness and LVOT pressure gradient; moreover, there were significant decrease in the minimum TTP after surgical myectomy (r = 0.643, P = 0.010) but there was a nonsignificant decrease in mean TTP of global LV (r = 0.510, P = 0.052) after myectomy [Figure 4].
|Figure 4: Comparison between time-to-peak (TTP) minimum premyectomy and postmyectomy.|
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Mechanics analysis reproducibility assessment
Intraobserver agreement intraclass correlation coefficients were 0.92 for strain (95% CI, 0.85–0.96) and 0.97 for peak rotation angle (95% CI, 0.95–0.99). Interobserver intraclass correlation coefficients were somewhat lower at 0.88 for strain (95% CI, 0.74–0.96) and 0.87 for peak rotation angle (95% CI, 0.64–0.97). There was 100% agreement between observers regarding rotation direction.
| Discussion|| |
Our study demonstrate marked reduction of LA diameter, LAV, and LAVI after surgical myectomy with (r = 0.818, 0.919, and 0.831, respectively) (P < 0.0001), and this occurred mostly owing to decrease of the grade of mitral regurgitation and diastolic function with subsequent decrease in left atrial pressure that reflected on LA diameter, LAV and LAVI. Similar results were obtained by Moravsky et al.  who noticed significant reduction of LA diameter and LAVI after surgical myectomy, and also our results are concordant with Carasso et al.  who noticed significant reduction of LA dimensions and volumes after aortic valve replacement.
Moreover, there was significant improvement in other markers of diastolic function after myectomy such as tissue Doppler (E′ lateral wall and E/e′) (r = 0.221 and −0.085 respectively) (P < 0.0001), which occurred after marked reduction of pressure gradient along LVOT after surgery, and this is concordant with the results of Moravsky et al. , who noticed significant improvement of diastolic function markers after myectomy.
In the current study, there were marked symptomatic relieve and improvement of functional class after surgical myectomy owing to significant reduction of pressure gradient across LVOT, decrease in LA dimensions and volumes, and improvement of diastolic function markers, and this occurred for all of our study population (100%). These findings are in contrast with the results obtained by Moravsky et al. , who noticed only 70% of their study population showed improvement in the functional class, and this may be because our population's mean age is younger than their study population (33.53 ± 10 vs. 54 ± 13 years) or because of our small sample size (n = 15 in our study vs. 60 patients in Moravsky et al. ).
Myocardial mechanics before and after myectomy
LV emptying occurs because of myocardial contraction (measured as deformation or strain) in the longitudinal and circumferential planes as well as a wringing motion of the ventricle, measured as the degree of twist.
Before myectomy, longitudinal strain was low and circumferential strain was higher than normal . Rotation of the apex and base and LV twist were higher than normal. This likely represents a compensatory change to maintain systolic function and ejection fraction.
In our study, there was a significant decrease in longitudinal strain of the basal septum after surgical myectomy (P = 0.004), as the basal septum is the main site of myectomy. This result is concordant with that of Moravsky et al. , and discordant with the results of Lang et al.  who noticed nonsignificant increase of the basal septum longitudinal strain (12–24 months) after alcohol septal ablation, and this is mainly because there was no actual removal of myocardial tissue in alcohol septal ablation.
Moreover, there were nonsignificant increase in longitudinal strain of lateral wall segments after surgical myectomy (r = 0.479, P = 0.085). Similar results were obtained by Faber et al.  who showed nonsignificant increase in the lateral wall segments longitudinal strain in the first 12 months after alcohol septal ablation. However, Moravsky et al.  notice discordant results and explained it as the lateral wall is the least affected wall (least affected by hypertrophy, disarray, and scarring). In our study, the least affected wall is the basal inferior wall segment that shows significant improvement of its longitudinal strain after surgical myectomy with (r = 0.452, P = 0.031).
There were nonsignificant increase in global LV longitudinal strain after surgical myectomy (r = 0.143, P = 0.155), and this result is concordant with that of Moravsky et al.  who noticed nonsignificant increase in global LV strain. This suggests that most of the longitudinal abnormality in HOCM is not related solely to obstruction but rather to the basic molecular and architectural myocardial pathology, such as sarcomere dysfunction, myocardial fibrosis, fiber disarray, and abnormal microvasculature, which are unlikely to be altered by surgical myectomy. Low longitudinal strain observed in patients with nonobstructive HCM also supports this assumption.
After surgical myectomy, there were significant decreases in average global LV circumferential strain (r = 0.499, P < 0.0001), basal rotation (r = 0.974, P < 0.0001), apical rotation (r = 0.936, P < 0.0001), and LV twist (r = 0.965, P < 0.0001). This occurred owing to marked elimination of LV afterload after surgical myectomy (normalization of the compensatory mechanisms). Similar results were obtained by Moravsky et al.  who showed normalization of average circumferential strain and LV twist after surgical myectomy.
These changes (which is the significant decrease of the average global LV circumferential strain, LV twist, and nonsignificant increase of the global LV longitudinal strain) translate into a net decrease in LV principal strain (the vector sum of its longitudinal and circumferential components) and are compatible with the observed decrease in LV ejection fraction (r=−0.046, P = 0.010).
Left ventricular synchronization
The severity of dyssynchrony is significantly related to LV mass, septal wall thickness, posterior wall thickness, and left ventricular end-diastolic diameter .
Although LV mechanical dyssynchrony was more severe in patients with HOCM than in patients with HCM without significant LVOT obstruction and LV dyssynchrony (septal to lateral mechanical delay) was strongly related to increased septal thickness and LV outflow gradient , our study did not show any improvement in LV dyssynchrony after surgical myectomy.
In our study, there was a nonsignificant decrease in TTP-SD of global LV (r = 0.189, P = 0.499), but there was a significant decrease in the minimum TTP after surgical myectomy (r = 0.643, P = 0.010). These results are discordant with those of Chen et al. , who showed significant improvement of LV dyssynchrony after alcohol septal ablation. This may be because of a very small sample volume of our study and short period of follow-up (within 6 months after surgical myectomy), which are the main limitations of our study, or because Chen et al.  use gated single photon emission computed tomography myocardial perfusion imaging, the most sensitive method for detection of LV synchronization.
Comparison with valvular aortic stenosis
Abnormal systolic mechanics have been demonstrated previously in conditions with chronic elevation of LV afterload, such as severe AS. In patients with AS and normal ejection fractions, most studies have also shown low longitudinal strain and higher circumferential strain and apical rotation. This phenomenon is again likely a compensatory mechanism preserving LV ejection fraction .
In symptomatic patients with severe AS, alleviating obstruction by valve replacement resulted in an increase in longitudinal strain to near normal values and normalization of compensatory increased circumferential strain and apical rotation. We found that HOCM mechanics before and after myectomy were similar to severe AS mechanics before and after aortic valve replacement, but not identical. Compared with patients with severe symptomatic AS (before aortic valve replacement), average longitudinal strain was not as low. This may be because of higher LVOT gradients and longer duration of fixed obstruction in surgical patients with AS, as opposed to patients with HCM with dynamic obstruction.
Finally, despite a small decrease in LV ejection fraction, unchanged global longitudinal strain, and decreased circumferential strain, patients dramatically improved clinically because of improved LV diastolic function. This may come through relief of obstruction, decrease in LV wall stress because intracavitary LV systolic pressures are markedly decreased, and relief or reduction in mitral regurgitation. When these factors improve, there is less or no need for compensatory mechanisms to be normalized.
The main limitations of our study is the (a) relatively small number of patients examined, which is owing to relatively rare cases in a single referral tertiary center; (b) short period of follow-up; and (c) absence of a gold standard method cardiovascular magnetic resonance (CMR) for the detection of the extent of myocardial fibrosis and disarray to compare between the extent of myocardial involvement in each segment and its actual response after surgical myectomy. Nevertheless, we report several significant observations.
| Conclusion|| |
In patients with HOCM, surgical myectomy improves symptoms, relieves LVOT obstruction, and decreases LAVI. Myocardial mechanics showed opposing changes in myectomy and nonmyectomy longitudinal strain, resulting in no change in its average and reductions of circumferential strain and rotation dynamics. These changes differ somewhat from those in patients with AS undergoing valve replacement and provide insights to the different mechanical adaptation to chronic elevated afterload observed in HOCM.
Although both groups of patients develop hypertrophy and compensatory myocardial mechanics in response to LV pressure overload, relief of LVOT obstruction does not reverse the additional structural abnormalities in patients with HCM. Disease extent and the presence of diastolic dysfunction seem to be related to symptomatic response to myectomy.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]