Outcomes of an extended Morrow procedure without a concomitant mitral valve procedure for hypertrophic obstructive cardiomyopathy

The indications for a concomitant mitral valve (MV) procedure remain controversial for patients with hypertrophic obstructive cardiomyopathy (HOCM). According to previous studies, a concomitant MV surgery was required in 11–20% of inpatient operations. Thus, we aimed to study the outcomes of an extended Morrow procedure without a concomitant MV procedure for HOCM patients who had no intrinsic abnormalities of the MV apparatus. We retrospectively reviewed 232 consecutive HOCM patients who underwent extended Morrow procedures from January 2010 to October 2014. Only 10 (4.31%) patients with intrinsic MV diseases underwent concomitant MV procedures. Of the 232 patients, 230 had no to mild mitral regurgitation (MR) postoperatively. We separated the 232 patients into two groups according to preoperative MR degree. One group is mild MR, and the other is moderate or severe MR. The three-month, one-year, and three-year composite end-point event-free survival rates had no difference between two groups (p = 0.820). When we separated the patients to postoperative no or trace MR group and mild MR group, there was also no difference on survival rates (p = 0.830). In conclusion, concomitant mitral valve procedures are not necessary for HOCM patients with MR caused by systolic anterior motion, even moderate to severe extent.

Perioperative results. There were no deaths within 30 days after the operation (operative mortality, 0%).
The postmyectomy transesophageal echocardiography intraoperatively identified iatrogenic ventricular septal defects (VSDs) that were immediately repaired in three (1.3%) patients who were discharged uneventfully. A perforation of the anterolateral free wall near the apex contiguous to the anterior septum was created in one patient. It was located promptly by the surgeon and was repaired without sequela. Neither iatrogenic injury of the MV nor iatrogenic injury of the aortic valve occurred in the 232 procedures. The mean cardiopulmonary bypass and aortic cross-clamp times were 83.4 ± 28.7 and 53.9 ± 19.0 minutes. The median, 25th, 75th percentiles for the postoperative intubation time were 15 hours, 12 hours, and 18 hours, respectively.
Six (2.6%) patients received new permanent pacemakers before being discharged from the hospital because of a CAVB. Of these six patients, two had a preoperative complete right bundle branch block (CRBBB), one underwent a concomitant reduction of a right ventricular outflow obstruction, and two had an iatrogenic VSD during the operation. Almost all of the patients had no to mild MR postoperatively, except for two patients who maintained moderate MR. However, among the 101 patients with mild MR preoperatively, 51 (50.5%) patients had no or trace MR, and 49 (48.5%) had mild MR. In contrast, among the 131 patients with moderate to severe MR preoperatively, only 39 (29.8%) had no or trace MR, and 91 (69.5%) had mild MR. The patients with mild MR preoperatively had less MR postoperatively (p = 0.002).
Follow-up results. The mean clinical follow-up period was 23.8 ± 13.7 months (one to 59 months). A total of 228 (98.3%) patients accepted our telephone questionnaire. This group of patients experienced substantial symptomatic and hemodynamic improvement after the myectomy. During the follow-up, 193 (83.2%) patients remained asymptomatic or minimally symptomatic. The degree of LVOT pressure gradients decreased significant compared with the preoperative values (12.9 ± 10.1 mmHg at a recent evaluation, P < 0.001). The left atrial dimension fell to 38.7 ± 5.9 mm (P < 0.001). Eleven (4.7%) patients had a residual maximal LVOT pressure gradient > 30 mmHg, and two (0.8%) patients had a residual maximal LVOT pressure gradient > 50 mmHg. These appeared to be related to a residual obstruction of an initial myectomy rather than recurrent obstruction from muscle regrowth. All of the patients are free from any cardiac reoperation to date. Of the 46 patients with preoperative AF documented by an electrocardiogram, only 26 (56.5%) had a normal sinus rhythm during the follow-up.
To date, only one patient has died. The overall survival was 100% at three months, 100% at one year, and 99.0% at three years (Fig. 2a). The one death was a sudden cardiac death occurring 25 months after surgery. This patient was a 28-year-old woman with a global extreme hypertrophied left ventricular and a 46-mm-thick interventricular septum.
During the follow-up, 16 (6.9%) patients met the composite end-point (Table 3). The three-month, one-year, and three-year end-point event-free survival rates were 99.6%, 98.7%, and 88.7%, respectively (Fig. 2b). The most common reason for rehospitalization was heart failure symptoms (12, 75.0%). Of the 12 patients, seven were rehospitalized only once due to pneumonia and secondary reversible acute heart failure syndrome. Two patients had a residual LVOT pressure gradient > 50 mmHg. The other three patients had chronic heart failure and presented with episodes of decompensation. Of these three patients with chronic heart failure, one had iatrogenic VSD and CAVB in operation. One patient had coronary artery disease, and heart failure was always secondary to paroxysmal AF. The last patient had a complete left bundle branch block in operation, and there was a gradual cardiac enlargement after discharge. Table 3 depicts all of the end-point events.
Comparison between the patients with preoperative mild MR and moderate to severe MR. We separated the 232 patients into two groups according to the MR stage before the operation. One group included 17 patients with severe MR and 114 patients with moderate MR. The other group included 101 patients with mild MR. There were no differences in the baseline clinical characteristics between the two groups, except for the left atrial diameter, LVOT pressure gradient, and percutaneous transluminal septal myocardial ablation (PTSMA) history ( Table 1). The three-month, one-year, and three-year composite end-point event-free survival rates were 100%, 98.5%, 88.0% and 99.0%, 99.0%, 89.6%, respectively for the two groups (Tarone-Ware p = 0.820) (Fig. 3a). When we excluded the 10 patients who underwent the concomitant MV procedure, there was also no difference (100%, 98.4%, 86.9% and 99.0%, 99.0%, 89.4%, respectively, for the two groups, Tarone-Ware p = 0.682) (Fig. 3b).
If we adjusted the composite end-point event-free survival rates for the left atrial diameter, the LVOT pressure gradient, and the PTSMA history, then the differences between the two groups were not statistically significant (p = 0.487) (Fig. 3c).      (Fig. 4a). When we excluded the 10 patients who underwent the concomitant MV procedure, there was also no difference (Tarone-Ware p = 0.949) (Fig. 4b).
Predictors of end-point events. In the Cox proportional hazard models for the composite end-points, we included all 232 patients in the analysis. The data from the univariable Cox analysis are described in Table 4. Sex and variables with P < 0.05 were then entered into a stepwise multivariable analysis (Table 4). Old age, iatrogenic VSD, and postoperative AF were identified as independent predictors of worse outcomes in HOCM patients undergoing surgical treatment.

Discussion
Dr. W. P. Cleland, a British surgeon, reported the first myotomy in 1958 7 . Thereafter, the surgical treatment for HOCM was developed at several North American and European centers [8][9][10] . Currently, the most widely used surgical method is myectomy via an aortic approach, which is called an extended Morrow procedure 11 . Recently, the European Society of Cardiology (ESC) guideline and American College of Cardiology Foundation (ACC)/ American Heart Association (AHA) guidelines on the management of HCM stated that a surgical septal myectomy is the gold standard and primary treatment option for patients with HOCM and severe symptoms of heart failure 12,13 . The outcomes of the septal myectomy in our consecutive 232 HOCM patients were as good as those reported by other famous centers 5 with no perioperative death, while one HCM-related death occurred during the follow-up, and a total of 16 (6.9%) HCM-related rehospitalizations occurred after discharge. One hundred ninety-three (83.2%) of the patients remained asymptomatic or minimally symptomatic (NYHA class I) during the intermediate follow-up.
Although a transaortic septal myectomy has a good prognosis for HOCM patients 5,10 , some controversy remains concerning the surgery, especially the management of MR 14 . Dr. Klues recognized that there were diverse structural MV alterations in HOCM 15 . Several adjunctive procedures, including realignment of papillary muscles 16 , anterior mitral leaflet plication 17 , and anterior mitral leaflet extension 18 , are used to eliminate SAM and decrease MR. Our study suggests that a concomitant MV procedure is not necessary for HOCM patients without intrinsic MV disease. On one hand, an extended Morrow procedure alone is effective to alleviate even moderate to severe MR caused by SAM. Only 10 (4.3%) patients of this population underwent a concomitant MV procedure, which is less than that previous reported 19 . In 230 (99.1%) of 232 patients, the MR was decreased to mild or less postoperatively. Of the 131 patients with moderate or severe MR preoperatively, 130 (99.2%) had no to mild MR postoperatively. On the other hand, mild MR postoperatively was acceptable and did not increase the adverse cardiovascular event rate. During the follow-up, there was no difference in end-point events-free survival between the patients with no or trace MR and patients with mild MR. Thus, the sufficient elimination of LVOT obstruction and an appropriate dissociation of abnormal attachments provided excellent surgery outcomes for HOCM patients with no intrinsic pathological MV changes. A resection distally toward the left ventricular apex as far as possible is important. A normal left ventricle geometry created by surgery may improve the flow of blood during the period from end diastole to isovolumic systole to eliminate SAM 20 . Dissociation at the base of the papillary muscles from around hypertrophy myocardial tissue and the excision of abnormal fibrous or muscular attachment structures can result in fair mobility of the papillary muscle and the anterior leaflet of MV 14 .
Both preoperative AF and postoperative AF are predictors of composite end-point events. Postoperative AF is an independent predictor of the composite end-point events. In other studies, AF was always identified as the risk factor of worse outcomes 21 ; however, the reason is not entirely clear. The residual AF, which induces a loss of atrial mechanical function, can indeed reduce cardiac output 22 . Some reports demonstrate that AF could trigger ventricular tachycardia 23 . In this cohort, adjunctive surgical ablation of AF was conducted in only five patients with persistent AF. All five patients maintained sinus rhythm during the follow-up with no end point events. Therefore, a MAZE procedure might be conducted in every patient with AF ever recorded by electrocardiogram.  Old age was always determined as a risk factor associated with worse outcomes 24 . However, contrary to other studies, we found that procedures performed concomitant with the myectomy did not increase the possibility of the composite end-point events 25 . There are still some limitations. This is a retrospective study; all of the surgeries were performed by one experienced surgical team. There was no concomitant MV procedure, such as a leaflet plication or anterior leaflet extension, conducted to eliminate SAM and MR. Nevertheless, these conclusions still may be valid and clinically relevant. As previously reported, the survival rate of the HOCM patients after surgery was excellent. However, more attention should be focus on HOCM-related rehospitalization. The question of whether surgery could abolish the risk for progression to the end-stage phase of heart failure requires further study.
Our results prove that the extended Morrow procedure can successfully improve the symptoms of HOCM patients. Concomitant MV procedures are not necessary for patients who have even moderate to severe MR caused by SAM. Residual mild MR postoperatively does not influence the outcome of these patients. Old age, iatrogenic SVD, and postoperative AF are independent predictors of worse outcomes.

Study population. This study was approved by the Human Research Ethics Committee of the Fuwai
Hospital and was performed in accordance with the Declaration of Helsinki and the approved guidelines. Oral informed consent was obtained from all of the patients via a telephone questionnaire. We retrospectively reviewed all of the 232 consecutive HOCM patients who underwent a transaortic extended septal myectomy in the ninth department of surgery in our institution from January 2010 to October 2014. The diagnosis of HCM was based on clinical and echocardiographic features with the presence of a hypertrophied non-dilated left ventricular in the absence of other cardiac or systemic disease capable of producing the magnitude of the hypertrophy evident 26 . These patients had severe symptoms and an LVOT pressure gradient greater than 50 mmHg at rest or after exercise, despite treatment with a β -blocker, diltiazem, singly or in combination titrated to a maximum tolerated  dose. Intrinsic MV pathological changes were defined as rheumatic disease, degeneration, prolapse, and infective endocarditis. This study was approved by the Fuwai Institutional Review Board.
Echocardiographic evaluation. All of the patients underwent comprehensive echocardiogram examinations with commercially available instruments. All of the transthoracic echocardiography procedures were performed by the same professional doctor. Echocardiographic parameters were acquired using standard views and protocols 27 . The LV wall thickness was measured at the end-diastole. The LVOT peak velocity was measured with a continuous-wave Doppler, and the LVOT pressure gradient was estimated using a simplified Bernoulli equation 28 . The exercise-induced LVOT pressure gradient was assessed in patients with resting LVOT pressure gradients < 50 mmHg. MR was graded by a color flow Doppler method according to the regurgitant jet area 29 (see Supplementary Table S1).

Univariable
Stepwise Multivariable  Transaortic septal myectomy. An intraoperative transesophageal echocardiography is a pre-requisite for surgery because it allows the detection of the ventricular septal anatomy and its thickness, the evaluation of the MV function, and the identification of other abnormalities. The chest is opened with a complete standard median sternotomy. To sufficiently expose the subaortic septum, an oblique aortotomy much closer to the sinotubular junction than that usually performed for an aortic valve replacement is made and carried to the midpoint of the noncoronary sinus 30 . We begin the first incision from the basal region toward the apex of the heart approximately 5 mm left of the membranous septum to avoid complete atrioventricular block (CAVB). The incision is extended leftward to the anterolateral free wall of the left ventricle near the MV annulus. The trough is then continued in the apical direction beyond the bases of the papillary muscles. Importantly, all of the papillary muscle fusions to the septum or ventricular free wall are divided to increase mobility of the papillary muscle. Abnormal chordal structure and anomalous fibrous or muscle attachments of the MV apparatus to the ventricular septum should be excised. Before the patient is weaned from cardiopulmonary bypass, a transesophageal echocardiography is repeated to remeasure the LVOT pressure gradient, the continuity of the septum and the MV function.
Follow-up. All of the follow-up data were obtained between January and May 2015. During the follow-up, the time and cause of death were provided to the immediate families. The end-point was a composite of all causes of death, resuscitation from sudden death, syncope, documented stroke, arrhythmia or congestive heart failure requiring hospitalization 25 . HCM-related death was defined as the sudden death, death or heart transplantation as a result of progressive heart failure. The definition of sudden death was an unexpected sudden collapse occurring < 1 hour from the onset of symptoms in patients who had previously experienced a relatively stable or uneventful clinical course 25 .
Statistical Analysis. Continuous data were expressed as the mean ± standard deviation and compared using a Student's t test or analysis of variance. Categorical data were expressed as percentages and were compared with a chi-square test. A Cox proportional hazards model was used to identify the risk factors of composite end-points. A stepwise multivariable Cox proportional hazards model was developed to determine the independent risk factors. The proportional hazards assumption in the Cox model was assessed with models including time-by-covariate interactions. Cumulative event rates were calculated using a Kaplan-Meier method, and different event curves of outcomes were compared using a Log-Rank or Tarone-Ware test. All of the P values were reported two-sided, and P < 0.05 was considered statistically significant. Statistical analyses were performed using SPSS version 20 (IBM SPSS Inc., Chicago, IL).