Right Ventricular Mechanical Changes after Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy: Vector Velocity Imaging Study

Objectives: The impairment of right ventricular (RV) myocardial mechanics is evident in hypertrophic cardiomyopathy (HCM). It is independently influenced by LV mechanics and correlated to the severity of LV phenotype. We investigated the changes in RV global and regional deformation following surgical septal myectomy using vector velocity imaging (VVI). Methods: 25 HCM patients, 68% males with mean age (34.5 ± 12 years) were examined before and within two months after surgical myectomy using VVI. In addition to conventional echocardiographic parameters, peak systolic strain (εsys), strain rate (SR) and time to peak εsys (TTP) of regional RV free wall (RVFW) & septal walls were analyzed in longitudinal (long) directions from apical four-chamber view and their (∆) changes were calculated. Similar parameters were quantified in LV from apical 2 & 4 CH views. Intra-V-delay was defined as SD of TTP and inter-V dyssynchrony was estimated from TTP difference between the most delayed LV segment & RVFW. Results: All study patients showed improvement of their functional class from NYHA class III to class I and reduction of LVOT gradient to below 20 mmHg except one patient who had 30 mmHg gradients at rest. There was significant reduction of septal thickness, left atrial diameter & volume, LVOT gradient, LVMI, severity of mitral regurgitation, tricuspid annular velocities (P < 0.0001), RV diameter (P < 0.02) and increase in LV internal dimensions(P < 0.001) post myectomy. However, there was significant reduction of RV and LV systolic mechanics; RV global εsys % (from −16.1% ± 4.4% to −12.9% ± 2.9%, P < 0.0001) and LV global εsys %: from −11.6% ± 2.8% to −9.4% ± 2.2%, P < 0.0001) respectively. The magnitude of reduction of RV strain (∆RV εsys %, ∆SRsys) was directly How to cite this paper: Badran, H.M., Soltan, G., Faheem, N., Enait, M.E. and Yacoub, M.H. (2019) Right Ventricular Mechanical Changes after Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy: Vector Velocity Imaging Study. World Journal of Cardiovascular Diseases, 9, 467-488. https://doi.org/10.4236/wjcd.2019.97042 Received: March 14, 2019 Accepted: July 28, 2019 Published: July 31, 2019 Copyright © 2019 by author(s) and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access


Introduction
Hypertrophic cardiomyopathy (HCM), the most common genetically inherited heart muscle disease, affects the right ventricle (RV) because of the anatomically hypertrophied septum and conceivably by extension of the myopathic process to the RV [1]. Magnetic resonance studies by Maron et al. [2] demonstrated that the RV wall thickness was increased in patients with HCM compared to controls. In a third of patients with HCM, RV wall thickness and/or mass were increased, including about 10% with extreme RV wall hypertrophy (>10 mm).
Most patients with HCM (53%) had diffuse RV hypertrophy involving all three segments of the RV.
In hypertrophic obstructive cardiomyopathy (HOCM), invasive interventions are usually considered when pharmacotherapy either fails to control symptoms or is not tolerated [3] [4].
Recent studies have shown that cardiac dysfunction is not limited to the left ventricle, impairment of RV mechanics is evident in HCM using feature tracking. It is independently influenced by LV deformation and correlated to the severity of LV phenotype [3].
With the development of new ultrasound-based technologies to assess LV mechanics, the assessment of cardiac performance has been revolutionized. Recent speckle-tracking-based velocity vector imaging (VVI) enables the evaluation of regional or global myocardial deformation by measuring the strain, and strain rate (SR). VVI integrates frame-to-frame changes with the geometric shift of each speckle and thus allows the simultaneous evaluation of multiple components of myocardial deformation [5]. It has strikingly advanced our understanding of the pathophysiology of HCM, and added new dimension in quantifying myocardial remodeling that might occur after surgical myectomy. It improved substantively our understanding of ventricular mechanics [6].
Data on RV functional changes in HCM patients following myectomy are limited [7] [8]. More specifically, to our knowledge, no comparative study was World Journal of Cardiovascular Diseases characterizing the changes in RV strain pattern after surgical myectomy. Accordingly, in this cross-sectional study, we sought to: a) characterize regional and global RV strain in a cohort of patients with HCM before and after surgical myectomy using vector velocity imaging; b) investigate the relationship of RV strain patterns post myectomy to LV deformation and cardiac phenotype in this population.

Study Population
Twenty-five patient undergoing septal myectomy without concomitant surgery (valve repair or replacement or maze procedure) done at Aswan Hear Center

Conventional Echocardiography
Echocardiographic examinations were performed with all subjects positioned in the left lateral decubitus, by the same operator (HB) in the parasternal long, short-axis, apical 2-& 4-chamber views using standard transducer positions.
Esaote Mylab Gold 30 ultrasound system (Esaote S.p.A, Florence, Italy) equipped with a multi-frequency 2.5 -3.5 MHz phased-array transducer was utilized [9] [10]. RV end diastolic diameter and wall thickness, LV end diastolic (LVEDD), end systolic diameter (LVESD), septum (SPT), posterior wall thickness (PWT), ejection fraction (EF %) and left atrial (LA) diameter & volume and volume index were all measured in accordance with the recommendations of the American Society of Echocardiography [11]. The magnitude and extent of hypertrophy in both ventricles were assessed in all views.
Color flow mapping and continuous-wave Doppler was used to define resting LVOT, mid cavity and to estimate pulmonary artery pressure (PAP) from tricuspid regurgitation velocity (Bernoulli equation).
Additionally, the diastolic function was assessed using the standard indexes of transmitral and transtricuspid flow and TDI. The TDI program was set in pulsed-wave Doppler mode. Motion of mitral annulus was recorded in the apical four-chamber view at a frame rate of 80 to 140 frames per second [11]. Peak early (E) and late (A) transmitral (Em & Am) and trantricuspid (Et & At) filling velocities were measured from mitral and tricuspid inflow velocities. Peak systolic (S a ), early diastolic (E a ) and atrial diastolic (A a ) annular velocity were obtained using tissue Doppler imaging (TDI) by placing a myocardial TDI sample volume at the RVFW and lateral mitral annulus in the apical 4-chamber view. All velocities were recorded for three consecutive cardiac cycles during end-expiratory phase, and the results were averaged. All TDI signals were recorded at horizontal time sweep set at 50 -100 mm/s accordingly to current guidelines [12]. The E m /E am and E t /E at ratio were calculated. This ratio has been reported to correlate with LV and RV filling pressure [12] [13].

Analysis of RV and LV Deformation
LV longitudinal strain analysis was included as part of the routine TTE evaluation. Strain measurement was based on the VVI: the global myocardial deformation was evaluated from standard 2D-images at frame rate (70 ± 20 F/s) at rest and adjusted depending on the heart rate to 80 ± 23 F/s. The images were stored, during three cardiac cycles, in digital format for subsequent offline analysis. To avoid excessive translational motion seen the clips always captured with complete breath-holding during expiration. Tracking and subsequent strain calculations were performed with the software package Esaote-X-Strain based on previously validated algorithm [14] [15]. Scanning was performed from the apex to acquire best apical 2 & 3 and 4 chamber views. ECG signal and a frame rate between 40 -70 fps. They were then stored for offline analysis using X-Straine software. VVI is dedicated software that derives longitudinal myocardial velocity, strain (ε), strain rate (SR) from digitized 2D video clips. The endocardial border is automatically drawn at end-diastole using a point-and-click approach [6] [9] [12].
Right ventricular longitudinal strain data were prospectively extracted in a blinded manner from images acquired in the four-chamber view. A point and click approach was utilized to identify 3 RV anchor points (both annuli and RV apex) enabling the software to track the endocardial contour automatically.
Subsequently, tracking was visually inspected throughout systole to ensure adequate border detection and the endocardial contours adjusted manually as necessary to further optimize tracking.
Longitudinal strains (ε sys ) and strain rate (SR) during systole (SR sys ), early (SR e ) and late diastole (SR a ) for each individual segment were measured and averaged to obtain RV septal (basal mid and apical walls) and lateral RV free wall Similarly, for LV it was tracked from the septal side of the mitral annulus to lateral side in apical 4CH and from anterior to the inferior side in the apical 2CH. Velocity, strain, and SR graphics were automatically obtained [10].
To estimate LV mechanical dyssynchrony, time to peak strain (TTP) was measured from regional longitudinal strain curves for each ventricular segment, as time from the beginning of Q wave of ECG to the time to peak ε sys . Electromechanical delay (TTP-d) was measured as the difference of time to peak systolic strain in 12 LV myocardial segments and 6 RV myocardial segments (difference between the longest and shortest TTP) [9] [10] [11]. Mechanical dyssynchrony was defined as the standard deviation of the averaged time-to-peak-strain (TTP-SD) [9] [10] [11].

Surgical Technique
All patients underwent myectomy by the standard described procedure [12]. The clinical status of patients was monitored during the follow-up visits and echocardiographic examination and strain analysis were performed within 2 months after surgical myectomy.

Statistical Analysis
Data were presented as numbers (%) or mean ± SD. Categorical variables were presented as percentages and compared with two-tailed Chi-square or Fisher's exact test, as appropriate. Continuous variables were presented as the mean ± SD and compared with unpaired Student's t-test. Quantitative variables were correlated by the use of Pearson's correlation coefficient "r". All tests were 2-tailed and p-value < 0.05 was considered statistically significant. Statistical analysis was performed using commercially available statistical software SPSS for MAC version 23.

Patients Characteristics
Surgical Myectomy was successfully done for all twenty-five (25) patients.
Twenty patients (80%) developed LBBB and one patient (4%) developed RBBB post operatively. It had been carried out at Magdi Yacoub Aswan Heart center, in the period from August 2014 to October 2018.
Clinical characteristics of the study population were depicted in Table 1. The age was ranged from 15 to 62 and mean was 34.4 ± 12.6 years, and 72% were men. All patients were treated with B blockers and (60%) were treated using a combination of b-blockers and/or calcium channel blocker, all patients had New York Heart Association class III symptoms. Major symptoms included dyspnea (96%), chest pain (12%), and syncope (4%). All patients had basal septal myectomy, with no other concomitant surgery was performed. There was no intraoperative or early mortality (within 30 days postsurgery). All patients had prominent basal septal hypertrophy.
Post-myectomy complete atrioventricular block necessitating permanent pacing occurred in 4% of patients, and new complete left bundle branch block occurred in 21 patients (84%).

Conventional Echocardiography
Baseline and post myectomy conventional echocardiographic parameters are shown in Table 2 Figure 1).

Tissue Doppler Velocities of Mitral and Tricuspid Valve Annuli
Diastolic mitral inflow parameters were similar to premyectomy values. However, tissue Doppler velocities demonstrated a significant increase in mitral annular E m post-myectomy when compared with pre-myectomy (7.3 ± 2.6 vs 6.0 ± 2; p < 0.043). This is associated with significant decrease in E/E m ratio (P < 0.03).

Right Ventricular Mechanics
RV segmental and GLS (ε sys %) pre and post-surgical myectomy of the study population are summarized in Table 3 Figures 3-6).

LV Strain
LV septal longitudinal strain was significantly attenuated post surgical myectomy (P < 0.001) as well as anterior and inferior LV walls strain (ε sys %) showed significant reduction (P < 0.05, <0.02 respectively. Post-myectomy reduction in LV global longitudinal strain was strongly evident compared with corresponding values before surgery (P < 0.001).
Comparison between LV longitudinal strain ε sys % pre and post-surgical myectomy in the study population are summarized in Table 5 and Figure 7.

Univariate Analysis of RV Strain Indexes (Table 6, Figure 8)
In HCM, The magnitude of reduction in cardiac mechanics was tested against the pre and post deformation parameters and cardiac phenotype as shown in Table 6. ∆RV septum ε sys (%) was correlated directly to pre-LVOT gradient (P < 0.03) and post-RVTTP-SD (P < 0.04). ∆Global RV ε sys (%) was directly correlated to LV MWT (P < 0.01) and negatively correlated to LV EF % (P < 0.03).
∆RV TTP SD was directly correlated to pre-RV TTP SD (P < 0.001) and negatively correlated to LV EF % (P < 0.03) and LA volume (P < 0.003). ∆RV septum SR sys was directly correlated to RV TTP post myectomy (P < 0.03) and negatively correlated to LVOT gradient (P < 0.028) while ∆Global RV SR sys was directly Table 6. Univariate analysis of ECHO parameters of RV mechanics post-myectomy.

Relationship of RV Deformation to LV Strain
There was significant reduction in longitudinal strain at the myectomy seg-

Discussion
In the current study both regional and global RV function, as measured by 2D strain imaging, evidently decline post-surgical myectomy. Despite the improvement of NYHA class, severity of mitral regurge, reduction of E/E' and LV mass, LV deformation showed marked deterioration. RV deformational decline is predominantly associated with impaired LV longitudinal strain and correlated to the severity of LV hypertrophy. Impaired RV diastolic function is correlated to severity of LVOT obstruction and PAP, while RV intraventricular dyssynchrony is mainly related to LA volume and LV EF %.

RV Strain Using Speckle Tracking as a Measure of Cardiac Function
GLS assessed using speckle-tracking echocardiography (STE) is an emerging World Journal of Cardiovascular Diseases technique for detecting and quantifying subtle disturbances in cardiac mechanics. GLS reflects the longitudinal contraction of the myocardium and its accuracy has been validated against tagged magnetic resonance imaging (MRI) [13]. This method is operator independent, more reproducible than conventional parameters, easily measured and integrated to standard echocardiogram method [14].
In the general population and patients with heart failure, GLS was shown to be a superior predictor of cardiac events and all-cause mortality compared to EF [13] [15]. More recently, GLS was found to be a robust prognostic marker following cardiac surgery [16] [17] [18]. GLS predicted postoperative mortality, myocardial dysfunction, and the need for prolonged inotropic support in cardiac surgical patients, though GLS was measured preoperatively by TTE in many recent research studies [19] [20].
In the present study, we characterized the change in RV function following myectomy using established deformational RV 2D strain techniques.

RV Function Following Cardiac Surgery
While RV function is an important determinant of cardiac surgical outcomes, there are few known predictors of postoperative dysfunction. Studies demonstrate that RV fractional area change (FAC) < 35% is associated with the greatest risk of postoperative mortality [21] [22] and that among patients with preserved RV FAC, those with abnormal longitudinal strain are at higher risk for post-operative mortality [23]. Despite our finding that all patients have symptomatic improvement, RV longitudinal indices including strain and strain rate showed significant deterioration post myectomy and after few months post-operative that ensure patient recovery, which might predict persistent dysfunction.
Using the feature tracking VVI, RV global longitudinal strain not only measures contraction but is also able to reflect interstitial myocardial changes such as fibrosis, which are one of main histopathological changes following cardiac surgery [24] [25].

Mechanisms of Post Myectomy RV Dysfunction
In the present study 2D strain imaging was used to characterize the changes in Furthermore, in HCM patients another explanation can be added which is replacement fibrosis of LV myocardial segments following surgical excision of septal segments which is completely different from valve replacement without interference in myocardial architechture or myocardial vasculature.
To our knowledge, this is the most inclusive study of changes in RV systolic function and diastolic function postoperatively with correlation of changes in 2D strain imaging with regional and global LV strain. We demonstrate that postoperative RV systolic function significantly declines across all parameters few months following surgery; in particular, GLS which significantly predict persistant subnormal RV function that predicts poor outcome. Meanwhile, our measurements were taken longtime after surgery, which suggests that changes in RV indices were due to both functional and geometric changes.
Unlike Doppler interrogation, strain measured by 2D is angle independent.
Therefore, it may be more accurate and easily applied than tissue Doppler interrogation (TDI). However, 2D STE is dependent on image quality and has lower temporal resolution than TDI. While 2D STE is used to demonstrate subclinical LV dysfunction independent of changes in ejection fraction, it is not yet routinely used to characterize RV dysfunction [30] [31]. Our study demonstrates that it is feasible to use strain as a comparable index to predict RV function in the postoperative period [32] [33].
RV strain may be an important index to detect RV dysfunction and provide postoperative risk stratification that might have important clinical implications.
Nevertheless, it remains unclear precisely when and why these indices of RV systolic function are reduced.

Study Limitations
There were several limitations to this study. First, the RV is difficult to image in its entirety in one view and is difficult to model. A 3D RV function analysis, such as 3D speckle tracking, might have been superior to 2D only. Second Subtle changes in other areas of the RV myocardium might have been detected. Third, World Journal of Cardiovascular Diseases only longitudinal strain was analyzed, whereas analysis of radial or circumferential strain might have provided some additional clues into whether contraction patterns change in response to myectomy or surgery itself. Additionally, patients did not undergo long-term follow-up with a transthoracic echocardiogram to assess whether any aspect of recovery was apparent at a later date or whether any changes in contraction patterns evolved in the face of a persistent depression of LV longitudinal strain.

Conclusion
Surgical myectomy deteriorates RV function, as measured by two-dimensional myocardial strain imaging. The magnitude of RV function decline is proportionate to LV dyfunction and severity of cardiac phenotype. Worsening of RV strain, however, and its clinical implications in HCM population require further exploration. The feasibility, high reproducibility, and validated reference values of deformation imaging may support more routine post operative use of this modality in the TTE examination of HCM patients.