INTRODUCTION

Hypertrophic cardiomyopathy (HCM) is a hereditary cardiac disease with complex genetic and phenotypic expression and an estimated prevalence of 1:500 in the general population. ^1),(2

Approximately 70% of patients with HCM present some form of dynamic obstruction (HOCM) that contributes to the development of symptoms such as dyspnea and angina. In turn, sufficient evidence shows the impact of dynamic obstruction in the development of functional and structural changes at the cardiac level, as the increase in ventricular filling pressures, pulmonary pressure and left and right atrial dilation. ^3),(4

Extended septal myectomy (ESM) has shown to be a useful strategy to improve symptoms and quality of life in patients with HOCM refractory to medical treatment. ^3),(4),(5

The purpose of this study was to evaluate the impact of this surgery on the structural changes associated with dynamic obstruction.

The objective was to analyze the short and midterm impact of ESM in structural and functional echocardiographic parameters in patients with HCM and left ventricular (LV) outflow tract dynamic obstruction.

METHODS

Echocardiographic assessment

A two-dimensional ultrasound was used to measure myocardial maximum septal thickness, left atrial (LA) anteroposterior diameter in the long parasternal axis, and atrial area and volume in apical 4-chamber view. Left atrial volume was calculated using the area-length biplane method and the LA volume index using body surface area.

Left ventricular systolic function was quantified by Simpson’s rule, in apical 2-chamber and 4-chamber views. ⁶

The apical 4-chamber view with pulsed Doppler mitral flow at the mitral valve leaflet tips was used to determine peak early (E) and late (A) diastolic wave velocities, the E/A ratio and E wave deceleration time, and to classify diastolic dysfunction according to echocardiographic quantification guidelines into normal and grade I, II and III. Early lateral and medial mitral annulus peak diastolic velocities were analyzed with tissue Doppler to assess ventricular filling pressures, considering the ratio between mitral peak E wave velocity and average peak e’ wave velocity (E/e’). ⁷

According to international recommendations, diastolic function assessment in HCM patients was considered through an integral approach, taking into account all the echocardiographic parameters that include and consider as abnormal values an E/e’ ratio >14, indexed LA volume >34 ml/m2, difference in the pulmonary vein retrograde A wave duration - transmitral flow antegrade A wave duration >30 msec, and peak tricuspid regurgitant jet velocity >2.8 m/s. Normal LA pressure and grade I diastolic dysfunction was considered if < 50 % of these variables reached cut-off values, and elevated LA pressure and grade II diastolic dysfunction when > 50% of these variables did. In case of 50% discordance, the findings were not conclusive to estimate LA pressure. Grade III diastolic dysfunction was considered in the presence of a restrictive filling pattern and reduced Doppler tissue mitral annulus velocity (septal < 7 cm/s, and lateral < 10 cm/s). ⁷

Presence of mitral regurgitation was evaluated with color Doppler ultrasound, and qualitatively graded as mild, moderate and severe, and whether its mechanism was secondary to anterior systolic mitral valve motion, or as a consequence of a valve abnormality, such as prolapse, chordal rupture, mitral valve ring calcification or incorrect positioning of a papillary muscle, or mitral subvalvular apparatus abnormalities. ⁷

To assess pulmonary artery systolic pressure (PASP), peak tricuspid regurgitant jet velocity continuous Doppler was used, added to right atrial diastolic pressure, according to the inferior vena cava diameter and its percentage of inspiratory collapse. ⁷

The obstructive gradient was identified with color Doppler and quantified with continuous Doppler according to the Bernoulli formula, at rest and with Valsalva maneuver/ exercise. ⁷

The clinical preoperative, postoperative and follow-up evaluation of patients was performed by cardiologists of the Cardiomyopathy center, and functional class for dyspnea, according to the New York Heart Association (NYHA) classification, presence or absence of angina, syncope, family history of sudden death, cardiovascular risk factors and optimal medical treatment were established (Figure 1).

Fig. 1 Echocardiographic evaluation of a patient with hypertrophic obstructive cardiomyopathy.  

RESULTS

A total of 94 patients, with mean age 57.6±13.8 years, 53% female, underwent surgery during the study period, with a median follow-up of 3.3 years (IQR 1.1- 5.1) Table 1.

All patients underwent ESM and 43 of them (45.7%) were also subjected to concomitant treatment of the mitral valve or the subvalvular mitral apparatus (9 underwent mitral valve repair, 26 mitral valve plication, 14 second order chord resection, 8 accessory muscle resection, and 3 mitral valve replacement). In addition, aortic valve replacement was performed in 3 patients (3.1%), coronary bypass surgery in 19 (20.2%) and Maze surgery in 17 (18%).

All patients presented complete left bundle branch block after the intervention, and 7.4% required definite pacemaker for complete atrioventricular block, in 5.3% of cases in patients with isolated septal myectomy. Two patients presented atrial fibrillation (AF) in the immediate preoperative and postoperative periods and 5 in the late postoperative period.

There were 3 (3.1%) interventricular septal defects related with the surgical procedure, and 30-day perioperative mortality was 1 patient (1.06%). Nine patients (9.5%) died during follow-up, 3 related to their underlying disease (3.2%)

Regarding functional class, 89% of patients were asymptomatic during the long-term follow-up.

Structural parameters showed a significant reduction in maximum septal thickness, from 21.3 mm in the preoperative period to 14 mm in the immediate postoperative period, (p < 0.001) which was maintained in the late postoperative period.

A significant reduction was observed in the left atrial size; its anteroposterior diameter decreased from 49.7 mm to 48.2 mm in the immediate postoperative period (p < 0.001) to 46.2 mm in the late postoperative period (p < 0.001). Left atrial volume indexed by body surface area decreased from 57.6 ml/m2 to 51.2 ml/m2 (p < 0.001) in the immediate postoperative period, and to 46.1 ml/m2 (p < 0.001) in the late postoperative period. Moreover, left atrial area decreased from 30.1 cm2 to 28.2 cm2 (p < 0.001) in the immediate postoperative period, and to 26.3 cm2 (p < 0.001) in the late postoperative period (Table 2 and Figure 2).

Fig. 2 Extended septal myectomy and changes in left atrial volume and E/e´ ratio. IQR: Interquartile range.LA: Left atrial. 

Regarding functional parameters, the intraventricular gradient at rest decreased from 49.2 mmHg to 6.4 mmHg (p < 0.001), and then to 4.6 mmHg (p=0.224) in the immediate and late postoperative periods, and with the Valsalva maneuver from 93.9 mmHg to 8.7 mmHg (p < 0.001), and 7.2 mmHg (p=0.226), respectively. Diastolic function was assessed as grade II in 59.3% of patients in the preoperative period, in 51.6% in the immediate postoperative period, and in 29% in the late postoperative period (Figure 3). Similarly, a change in the E/e´ ratio and pulmonary artery systolic pressure was evidenced. Moderate to severe mitral regurgitation decreased from 53.1% in the preoperative period to 8.7% in the late postoperative period and pulmonary pressure from 32 mmHg to 27 mmHg, respectively. Left ventricular ejection fraction (LVEF) decreased from 65% to 60% (p < 0.001) in the immediate postoperative period and remained at 60% (p=0.953) in the late postoperative period.

Fig. 3 Modifications in the transmitral filling pattern. POP: postoperative 

DISCUSSION

The importance of the results obtained in this work is the significant impact of ESM on the different hemodynamic parameters studied by echocardiography and the clinical improvement of patients. We would like to highlight 4 findings.

First, from a structural point of view, a reduction was evidenced in the LA size measured in all its forms, which appears to be intensified with the passage of time. The probable mechanisms that we understand are involved in this phenomenon are the reduction of mitral regurgitation and of LV filling pressure. In relation to the first, patients undergoing surgery for isolated mitral regurgitation usually show this phenomenon, correlated in the case of mitral valve repair surgery with the degree of residual mitral regurgitation. Regarding filling pressures, the reduction of the dynamic gradient has a verified impact at the level of end-diastole pressure and contributes to this phenomenon. From a prognostic viewpoint, LA size is an independent risk factor for adverse outcomes in patients with HCM, and increased LA volume is associated with an increased risk of atrial fibrillation, thromboembolic stroke, heart failure and cardiovascular mortality, which appears to represent much more than a simple structural change. ^{8),(9),(10),(11),(12),(13),(14),(15),(16),(17),(18} Our findings have been previously reported by Tower-Rader et al., who in a review of 25 patients observed a significant decrease in atrial volume 2 years after myectomy. ¹⁹ Similarly, Finocchiaro et al. demonstrated a marked reduction of LA volume in a cohort of 40 patients undergoing septal reduction therapy (myectomy or alcohol septal ablation). ²⁰ In a cohort of 44 operated-on patients, Kyung Eun Ha et al. observed a reduction in atrial volume and increased strain of this chamber, consistent not only with the reduction in size but with an improvement in fiber function. ²¹

Second, echocardiographic “hemodynamic” assessment showed a reduction in the E/e´ ratio and changes in the transmitral filling pattern. These modifications seem to be related with the reduction in LV end diastolic pressure, secondary to the significant reduction that the procedure achieved in the dynamic left ventricular outflow tract gradients both at rest and with Valsalva maneuver. Evidence of this is that the changes are noticeable in the immediate postoperative period. Moreover, both variables tend to improve even more in the late postoperative period, a fact that could be explained by the gradual recovery in diastolic function produced by the relief of the obstruction. This has been also reported by others, such as Nguyen et al, who found in a cohort of 656 patients an improvement in the E/e' ratio, which occurred in the early postoperative phase and was maintained in the long-term follow-up. ²² There is evidence that correlates dynamic obstruction with the development of myocardial ischemia and interstitial fibrosis, so we hypothesize that this relief could be generating a retrograde phenomenon. ^23),(24

Third, the LVEF drop in the immediate postoperative period could be associated with the impact of the pump used for cardiopulmonary bypass during surgery, but above all to the development of left bundle branch block due to the myectomy. This last phenomenon causes mechanical dyssynchrony and a drop in ejective volume, without ruling out that it has an impact on the reduction of the dynamic gradient. The analysis of the late postoperative period shows a numerical though not significant recovery, requiring greater follow-up for analysis. ^{23),(24),(25),(26} Along the same line, Ha et al. observed a relationship between postmyectomy QRS duration and the drop in LVEF, accompanied by a reduction in non-septal LV longitudinal strain. ²¹

Fourth, patients showed a reduction in echocardiographic assessed pulmonary artery systolic pressure that deepened over time. This fact shows that changes in left filling pressures and improvement in diastolic function have an impact on the pulmonary circuit and right chambers, which probably contributes to explaining the clinical improvement of patients. ^25),(26

CONCLUSIONS

In this cohort of patients with HOCM, ESM was associated with a significant improvement in LV diastolic function, reduction in filling and pulmonary pressures and degrees of mitral regurgitation, and reverse remodeling of the left atrium.

It is possible that this combination of effects explains the clinical benefits of the intervention.