Twenty-five patient undergoing septal myectomy without concomitant surgery (valve repair or replacement or maze procedure) done at Aswan Hear Center (Aswan, Egypt) for symptomatic HOCM were studied. They were examined in a single centre (Yacoub Research Unite, Menoufia University, Egypt and as a part of the BA-HCM National Program). Patients were subjected to full baseline clinical records; echocardiograms obtained two months before myectomy and on follow-up 3 to 6 months after myectomy, and echocardiographic studies adequate for strain analysis in both baseline and follow-up studies.

The control group consisted of 33 healthy subjects without family history of hypertrophic cardiomyopathy (HCM) and normal echocardiographic findings with similar gender and age distributions. Patients were enrolled in the study after their informed consent

We excluded patients who had 1) poor echo window; 2) clinical or echocardiographic evidence of other cardiac diseases such as CAD or congenital heart disease and 3) NYHA functional class IV.

The study was approved by the Ethics Committee of Menoufia University Hospitals was obtained. The diagnosis of HCM was based on conventional echocardiographic demonstration of a non-dilated, hypertrophic LV (≥15 mm) in the absence of other cardiac or systemic diseases capable of producing the magnitude of hypertrophy evident^. [2] [3] [7] . Myectomy was offered to patients with unacceptable symptoms despite maximally tolerated pharmacotherapy with LVOT gradients ≥ 50 mm Hg at rest or after provocation (Valsalva maneuver, inhalation of amyl nitrate, or ventricular premature beat), as measured during Doppler echocardiography or cardiac catheterization [3] [7] . Patients were selected for surgical septal myectomy rather than alcohol septal ablation on the basis of their ages, comorbidities, and preferences [8] .

Traditional clinical variables of interest included demographics (age and sex), functional assessment (New York Heart Association [NYHA] class), pertinent history (family history of sudden cardiac death, history of arrhythmias, and history of unexplained syncope, Patient charts were retrospectively reviewed for clinical and demographic variables. All subjects underwent 12-lead electrocardiography, standard echocardiography (M-mode, 2-DEcho, Doppler), 2D strain imaging using VVI for measurement of RV and LV longitudinal strain (LS).

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] .

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.

Border tracking of the left ventricle (LV) and right ventricle (RV) was manually traced in the recorded clips of apical 4CH & 2CH views, with good quality 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.

Reproducibility for quantitative RV indices has been validated [12] [13] .

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 (basal, mid and apical) values. RV global longitudinal strain (GLS) was estimated by averaging septal and lateral right ventricular segmental strains.

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] .

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.

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.

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%).

After myectomy, all patients improved their functional capacity by at least one class.

Baseline and post myectomy conventional echocardiographic parameters are shown in Table 2. At baseline, patients demonstrated asymmetric septal hypertrophy, varying levels of LVOT obstruction (ranged from 115 to 56 mmHg), mild to moderate MR in 80% of patients, and normal LV systolic function. Left atrial volume index was significantly increased.

Post myectomy there was dramatic decrease in the LVOT gradient to non-obstructive levels (11.4 ± 5.6 vs 67.9 ± 14.5; p < 0.0001). There was significant decrease in LA diameter, LA volume and its volume index (LAVI) post myectomy when compared with per myectomy (39.8 ± 5.6 vs 46.4 ± 7.9; p 0.000), (62.2 ± 19.9 vs 86.5 ± 33.3; p < 0.000), and (32.8 ± 9.2 vs 46.7 ± 20.9; p < 0.000) respectively.

Similarly LVESD increased significantly post myectomy (27.1 ± 4.1 vs 22.0 ± 4.1; p < 0.000) while LVEDD the increase did not reach statistical significance (44.0 ± 6.7 vs 41.2 ± 5.9; p < 0.060). Additionally IVS, and LVPW were significantly reduced post myectomy 19.1 ± 4 vs 26.1 ± 5; p < 0.000) and (10.5 ± 2.1 vs 12 ± 3.8; p < 0.050) respectively. Consequently, there was significant decrease in LV mass (LVM) and LV mass index (LVMI) post myectomy when compared with per myectomy (318.6 ± 107.9 vs 449.5 ± 128.1; p < 0.000) and (165 ± 51.3 vs 240.4 ± 62.3; p < 0.000) respectively

LV ejection fraction modestly but significantly decreased (68.3 ± 5.4 vs 75.8 ± 8.2; p < 0.0001), however, it is remaining within the normal range. Associated changes included a decrease in the grade of mitral regurgitation and a reduction in the left atrial volume index. Diastolic mitral inflow parameters were similar to premyectomy values. Tissue Doppler velocities demonstrated an increase in mitral E’ and a similar decrease in the E/E' ratio (Table 2, Figure 1).

HR: heart rate; SBP: systolic blood pressure, DBP: diastolic blood pressure. LA: left atrium, LV: left ventricle, ESD: end systolic diameter, EDD: end diastolic diameter, FS: fractional shortening, EF: Ejection fraction, IVSd: inter-ventricular septal diameter, PWd: diastolic posterior wall diameter, LVM: left ventricular mass, LVMI: left ventricular mass index, LVOT PG: left ventricular outflow tract pressure gradient, RV: right ventricle, MR: mitral regurgitation, E: early mitral inflow diastolic velocity, A: late diastolic mitral inflow velocity, DT: deceleration time, PAP: estimated pulmonary artery pressure, S_ma: peak systolic velocity of mitral annulus; E_ma: early diastolic velocity of mitral annulus; A_ma: atrial diastolic velocity of mitral annulus; S_ta: peak systolic velocity of tricuspid annulus; E_ta: early diastolic velocity of tricuspid annulus; A_ta: atrial diastolic velocity of tricuspid annulus.

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). Similarly, S_t, E_t and A_t of tricuspid annular velocity were significantly increased post myectomy (8.7 ± 3.6 vs 12.6 ± 2.6; p < 0.000), (6.8 ± 2.4 vs 11.6 ± 5; p < 0.001) and (10.3 ± 3 vs 14.8 ± 5.2; p < 0.002) respectively (Figure 2).

RV segmental and GLS (ε_sys %) pre and post-surgical myectomy of the study population are summarized in Table 3. Pre-procedural RV mechanics: septal strain was significantly lower compared with RVFW segments and particularly demonstrated a high (−27% to 11%) basal-to-apical gradient.

Post myectomy, there was significant reduction in RV septum strain (−10.7 ± 3.3 vs −12.3 ± 3.8; p < 0.05), RVFW basal segment (−20.6 ± 8.2 vs −27.3 ± 13; p 0.008), mid (−15.5 ± 5.3 vs −20.4 ± 10.3; p < 0.01) segments, apical segment (−15.7 ± 4.7 vs −19.9 ± 8.2; p < 0.007) and global RV ε_sys % (−12.9 ± 2.9 vs −16.1 ± 4.7; p < 0.000) when compared with pre-myectomy. No significant change in RV electromechanical delay (TTP-d) or RV intra-ventricular dyssynchrony following surgical myectomy (Table 3, Figures 3-6).

Table 4 is demonstrating changes in RV peak systolic strain rate (SR_sys), early (SR_e) and late (SR_a) diastolic strain rate following myectomy. Post operative,

ε_sys: Peak systolic strain; TTP: time to peak systolic strain, TTP-d: electromechanical delay; TTP-SD: standared deviation of mean time to peak.

Comparison between Right ventricular strain rate parameters pre- and post-myectomy; RV: right ventricle, sept.: septum, RVFW: right ventricular free wall, SRsys: peak systolic strain rate, SRe: early diastolic strain rate, SRa: atrial diastolic strain rate.

there was significant reduction in segmental and global RV SR_sys, SR_e, and SR_a (−13.4 ± 4.6 vs −19.8 ± 9.4; p 0.002), and (−12.1 ± 2.8 vs −16.4 ± 4.7; p: 0.0001) respectively.

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.

LV: left ventricular, ε_sys (%): peak longitudinal strain, sept: septum.

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

ε_sys: Peak systolic strain; TTP: time to peak systolic strain, TTP-d: electromechanical delay; TTP-SD: standared deviation of mean time to peak. RVFW: right ventricular free wall, SRsys: peak systolic strain rate, SRe: early diastolic strain rate, SRa: atrial diastolic strain rate.

correlated to age (P < 0.02). Regarding diastolic parameters, ∆septum SR_{e and} ∆global SR_e were inversely correlated with end diastolic diameter (P < 0.04 and <0.03) respectively. Meanwhile, reduction in atrial contractile function (∆septum SR_a and ∆global SR_a) was directly correlated to LVOT gradient (P < 0.001, <0.002) and PAP (P < 0.001, <0.003) respectively.

There was significant reduction in longitudinal strain at the myectomy segments, averaged IVS and global LV longitudinal strain, which remained lower than normal, Pearson correlation coefficient of global RV (ε_sys %) showed modest correlation to LV ε_sys % (r = 0.39, P < 0.047) postmyectomy. However, no significant correlation was detected between other RV deformation parameters and LV ε_sys %, RV SR_sys (r = 0.31_. P < 0.07), RV SR_e (r = 0.098, P = 0.84) or RV SR_a (r = 0.198, P = 0.63) post myectomy.

GLS assessed using speckle-tracking echocardiography (STE) is an emerging 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.

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] .

In the present study 2D strain imaging was used to characterize the changes in RV mechanics post myectomy. Both segmental and global RV mechanics showed marked decline especially with proved RV dysfunction before myectomy. A variety of hypotheses have been proposed to explain the reduction of RV function even following uncomplicated cardiac surgery. Such theories include pericardial disruption, injury to the right atrium from venous cannulation, ischemic injury to the RV due to incomplete myocardial protection while on cardiopulmonary bypass, and formation of adhesions between the right ventricle and surrounding mediastinal tissues [26] [27] . These factors are superimposed on already impaired RV dysfunction due to hypertrophic myopathic process.

The reduced RV contractile function in our study was associated with the reduction in LV function. Generally, LV function may be impaired by cardioplegia-induced myocardial arrest and ischemia-reperfusion injury, especially in those patients with hypertrophic cardiomyopathy. Alternatively, LV function may improve on long term follow up when afterload is reduced following myectomy and resolution of LVOTO. The right ventricle (RV), however, experiences cardioplegic arrest without benefiting from improved loading conditions [28] .

Unlike patients with aortic valve replacement, where LV function improved after replacement of a stenotic aortic valve as demonstrated by improved longitudinal strain; LV function post myectomy is deteriorated. In the current study, 80% developed complete LBBB and 4% developed RBBB after surgery which might be the real underlying cause of LV mechanical dysfunction and electromechanical dyssynchrony detected in HCM patients post myectomy [28] [29] .

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.

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, 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.