Author + information
- Received February 25, 2016
- Revision received June 29, 2016
- Accepted July 5, 2016
- Published online October 4, 2016.
- Joon Hwa Hong, MD, PhDa,
- Hartzell V. Schaff, MDa,∗ (, )
- Rick A. Nishimura, MDb,
- Martin D. Abel, MDc,
- Joseph A. Dearani, MDa,
- Zhuo Li, MSd and
- Steve R. Ommen, MDb
- aDivision of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota
- bDivision of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
- cDivision of Cardiovascular and Thoracic Anesthesia, Mayo Clinic, Rochester, Minnesota
- dDivision of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota
- ↵∗Reprint requests and correspondence:
Dr. Hartzell V. Schaff, Division of Cardiovascular Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.
Background Incidence and outcome of mitral valve (MV) surgery are unknown in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing extended transaortic septal myectomy.
Objectives This study sought to define indications and suitable operative strategy for mitral regurgitation (MR) in patients with HOCM.
Methods A total of 2,107 septal myectomy operations performed in adults from January 1993 to May 2014 at Mayo Clinic in Rochester, Minnesota, were retrospectively reviewed. Patients with prior MV operation and apical hypertrophic cardiomyopathy were excluded. Overall, 2,004 operations were performed in 1,993 patients.
Results Pre-operative MR was grade ≥3 (of 4) in 1,152 operations (57.5%). Systolic anterior motion of mitral leaflets caused the MR in most patients. However, intrinsic MV disease was identified pre-operatively in 99 patients, all of whom had MV surgery (with septal myectomy). In 1,905 operations, no intrinsic MV disease was identified pre-operatively; in 1,830 (96.1%), septal myectomy was performed without a direct MV procedure. For 75 patients, intrinsic MV disease discovered intraoperatively led to concomitant MV repair (86.7%) or replacement (13.3%). After isolated septal myectomy, the percentage of patients with MR grade ≥3 decreased from 54.3% to 1.7% (p = 0.001) on early post-operative echocardiography. Among 174 patients with concomitant MV surgery, late survival was superior with MV repair (n = 133 [76.4%]) versus replacement (10-year survival: 80.0% vs. 55.2%; p = 0.002).
Conclusions In most patients with HOCM, MR related to systolic anterior motion of the MV is relieved through adequate myectomy. Concomitant MV surgery is rarely necessary unless intrinsic MV disease is present. When MV procedures are required, repair is preferred because of improved survival compared with replacement.
Mitral valve (MV) leaflets have an important role in the pathophysiological process of left ventricular (LV) outflow tract obstruction in patients with hypertrophic obstructive cardiomyopathy (HOCM). Systolic anterior motion (SAM) of the mitral apparatus and contact of the leaflets with the hypertrophied septum narrow the LV outflow, leading to dynamic pressure gradients and, in many patients, mitral regurgitation (MR). Furthermore, studies on structural MV alterations in HOCM have shown increased mitral leaflet length and area (1,2). However, whether MV alterations continue to contribute to MR and LV outflow tract obstruction even after adequate myectomy when mitral leaflet length and area are not corrected with concomitant surgery is unknown.
Septal myectomy is the preferred treatment of most patients with HOCM, and many studies have documented relief of symptoms and satisfactory late patient survival after relief of outflow tract gradients (3–5). Surgical management of associated MR is controversial, and because prosthetic replacement of the MV also relieves LV outflow tract obstruction, some groups have advocated valve replacement with or without septal myectomy when MR is severe (6,7). Other surgeons have advocated plication of the anterior leaflet or other forms of valvuloplasty to correct associated MR caused by SAM of the MV.
When the MV is intrinsically abnormal in HOCM, valve repair or replacement may be necessary (8). However, adequate septal myectomy relieves outflow tract gradients, SAM of the MV, and MR in many patients (9). Nevertheless, several reports have described adjunctive techniques of mitral valvuloplasty aimed at eliminating SAM of the MV (10–13). Thus, the controversy regarding the optimal surgical strategy for patients with HOCM and significant MR related to SAM of the leaflets continues.
The aims of the present study were to determine: 1) how frequently additional procedures are necessary in patients who have SAM-related MR and what is the outcome of septal myectomy alone in such patients; 2) what MV problems require direct repair or replacement in addition to septal myectomy; and 3) when direct MV procedures are necessary, what are the outcomes of valve repair versus valve replacement.
From January 1993 to May 2014, a total of 2,107 operations for septal myectomy were performed in adult patients (age ≥18 years) with HOCM at Mayo Clinic’s campus in Rochester, Minnesota. In the present study, 103 patients were excluded from analysis because of nonobstructive physiological characteristics (n = 88) (14) or previous MV surgery (n = 15). The Mayo Clinic Institutional Review Board approved the study protocol.
Analysis included 2,004 operations in 1,993 patients (56% men; age at surgery: 53.6 ± 14.4 years [mean ± SD]). Before myectomy, MR severity determined by transthoracic Doppler echocardiography was grade <3 in 852 patients (42.5%) and grade ≥3 (of 4) in 1,152 patients (57.5%). Regarding clinical status, 1,728 patients (86.7%) were classified as New York Heart Association functional class III or IV because of effort dyspnea, chest pain, or syncope.
Details of our preferred techniques for septal myectomy have been described elsewhere (15,16). Intraoperative transesophageal echocardiography was used to confirm cardiac anatomy and the appearance of the ventricular septum and to assess MV morphological characteristics and function. Before cardiopulmonary bypass (CPB), intracardiac pressures were measured with needles placed directly into the aorta and the LV, and provocative maneuvers were used to elicit outflow tract gradients as necessary (17).
If no intrinsic MV disease was identified on pre-operative transthoracic echocardiography, intraoperative transesophageal echocardiography, or valve inspection through the aortotomy, we proceeded with extended septal myectomy alone regardless of the degree of MR related to SAM. We then assessed the MV using echocardiography to confirm relief of LV outflow gradients, SAM of the MV, and reduction in MR. Direct pressure measurements were then repeated after CPB to assess outflow tract hemodynamics.
Indications to resume CPB included a peak pressure gradient between the LV and the aorta >20 mm Hg with provocation, significant residual SAM, or MR with a greater than mild degree of severity. We resumed CPB for additional myectomy when the patient had SAM of the MV and residual LV outflow tract obstruction detected through direct measurement and transesophageal echocardiography, with or without MR and regardless of its grade. If the patient had MR grade ≥3 without SAM of the MV and without LV outflow tract obstruction, CPB was resumed and additional procedures were directed in MV surgery.
Data on pre-operative patient status, operative record, post-operative MR, and survival were obtained from our prospective clinical database as well as from electronic medical records. Post-operative transthoracic echocardiography was performed on all patients before hospital discharge. Vital status was determined through the Mayo Clinic registration database, which collates information from multiple sources, including correspondence from family and physicians and Accurint, an institutionally approved, Web-based resource and location service. Accurint is a subsidiary of Seisint, Inc. (Boca Raton, Florida), a private information management company that provides access to Social Security death data and a number of other data sources.
Categorical values are reported as frequency (percentage); continuous variables are reported appropriately as mean ± SD or median (range). Categorical values were compared among the patients who had MV surgery with 1 or 2 periods of CPB using chi-square test or Fisher exact test. Continuous variables were compared with 2-sample Student t test or Wilcoxon rank sum test where appropriate.
Kaplan-Meier method was used to draw survival curves and calculate 5- and 10-year survival estimates. Cox regression models were used to determine univariate and multivariate predictors of overall mortality rate. The multivariate model considered univariately significant variables (p < 0.05), and model selection was made with the stepwise method (backward and forward methods resulted in the same model). All statistical tests were 2-sided with α level set at 0.05 for significance.
Concomitant MV surgery
Of 2,004 operations, intrinsic MV disease was identified pre-operatively in 99 operations, and each of these patients had MV surgery in conjunction with transaortic septal myectomy. Among the 1,905 operations without pre-operative diagnosis of intrinsic MV disease, concomitant MV surgery was performed with myectomy in 75 patients. Thus, 174 patients (99 with and 75 without pre-operative diagnosis of intrinsic MV disease) underwent transaortic septal myectomy and concomitant MV surgery. Table 1 lists pre-operative general characteristics, intraoperative data, and post-operative results. Table 2 summarizes the intrinsic MV diseases identified in 99 patients before surgery, including chordal rupture, MV prolapse, rheumatic MV disease, healed or acute infective endocarditis, MV mass, and leaflet cleft.
All patients had transaortic myectomy. In the 99 patients with intrinsic MV disease identified pre-operatively, 68 (68.7%) had MV repair and 31 (31.3%) had MV replacement. Among the other 75 patients who had mitral surgery (3.9% of 1,905 without a pre-operative diagnosis of associated MV disease), structural valve abnormalities were discovered through intraoperative transesophageal echocardiography or direct valve inspection in 33 patients. The other 42 patients (2.2% of 1,905) had various indications for MV surgery, including redundant leaflet tissue thought to contribute to LV outflow tract obstruction, minor clefts in leaflets, and iatrogenic injury to chorda during myectomy or inadvertent injury of MV (n = 12 [0.6%]) (Table 2, Figure 1).
Change in MR after isolated septal myectomy
For 1,830 isolated myectomy operations without MV surgery, we compared pre-operative MR assessed through Doppler echocardiography with that observed on transthoracic Doppler echocardiography obtained before hospital discharge. The percentage of patients with MR grade ≥3 decreased from 54.3% to 1.7% (p = 0.001).
MV repair versus replacement at the time of myectomy
Of the 174 patients with concomitant MV surgery, 133 (76.4%) underwent MV repair and 41 (23.6%) underwent MV replacement. Survival of all patients who had concomitant MV surgery along with myectomy was generally similar to the expected survival of an age- and sex-matched general U.S. population (p = 0.08) (Figure 2). Table 3 shows univariate analysis of patient characteristics associated with overall mortality. In the multivariable analysis, only coronary artery disease requiring bypass (hazard ratio: 3.49; 95% confidence interval [CI]: 1.43 to 8.51; p = 0.006) and MV replacement (hazard ratio: 2.89; 95% CI: 1.22 to 6.82; p = 0.0156) were significantly associated with late mortality. The superior survival among patients who had MV repair versus replacement is shown in the Central Illustration (p = 0.002 in univariate analysis).
Impact of resuming CPB after myectomy
Among 174 patients undergoing septal myectomy and concomitant MV surgery, 116 had MV surgery during a single aortic cross clamping and CPB (single CPB group). In the other 58 patients, the aortic cross clamp was removed after initial myectomy, the patient was separated from CPB, and myectomy outcome MV was re-evaluated with intraoperative transesophageal echocardiography and direct pressure measurements. A decision for resuming CPB was made, and additional septal myectomy or MV surgery was performed on the subsequent CPBs (multiple CPB group). No difference in total bypass time or aortic cross clamp time was found between single CPB and multiple CPB groups. Post-operative ventilation time, length of intensive care unit stay, and length of hospital stay were the same in both groups (Table 4). No difference in late survival between the groups was detected (Central Illustration).
Previously, experts believed that LV outflow tract obstruction in HOCM occurred in only a small proportion of patients. However, in large referral clinics, LV outflow tract obstruction is observed in nearly 70% of patients with symptomatic HOCM (18), and patients with the obstructive physiological factors have reduced late survival (3). Septal myectomy is highly effective in relieving LV outflow tract obstruction and its associated symptoms.
In addition to contributing to outflow tract obstruction, SAM of the MV causes abnormal coaptation of the MV leaflets, resulting in valvular regurgitation of various degrees (19). In our experience, successful septal myectomy eliminates or ameliorates SAM of the MV, thus improving associated MR in most patients. However, direct MV procedures have been reported as primary treatment of both obstruction (6,20–22) and concomitant valvular abnormalities (5,23).
The present study of a large dataset suggests that in patients without evidence of intrinsic MV disease pre-operatively, only 2.1% needed concomitant MV surgery at the time of septal myectomy. More importantly, our study confirms the fact that regardless of severity, MR due to SAM of the leaflets (i.e., no intrinsic mitral disease) decreases significantly after septal myectomy alone. These results are similar to those reported by Yu et al. (9), who analyzed pre- and post-operative transesophageal Doppler echocardiograms of 93 patients undergoing septal myectomy.
Some surgeons believe that MR and outflow tract obstruction related to SAM are best treated with myectomy and concomitant MV procedures, including anterior leaflet plication (24,25), anterior mitral leaflet extension (10,26,27), and retention plasty (12,13). In contrast, Kofflard et al. (26) and van der Lee et al. (10) have proposed anterior mitral leaflet extension as a means to reduce SAM in patients for whom the surgeon determines that myectomy alone would yield a suboptimal result.
These techniques that combine mitral leaflet procedures with septal myectomy have been reported in relatively small numbers of patients (n = 8 to 36) with relatively short follow-up (2.2 to 3.4 years in studies of adult patients). More importantly, the indication to use a direct mitral leaflet procedure in addition to myectomy is based largely on surgeon experience and speculation that isolated myectomy will be inadequate to resolve the SAM. Although reported results have been satisfactory, addition of plication, patching, or retention sutures introduces additional complexity and potential complications.
In some patients, it is difficult to determine whether the MR is caused solely by SAM of the MV or is related in part to intrinsic MV disease. In the present study, 33 patients (1.7% of 1,905 patients without a diagnosis of intrinsic MV disease pre-operatively and 19.0% of 174 patients who underwent concomitant MV procedure with septal myectomy) were found to have intrinsic MV disease by intraoperative transesophageal echocardiography or direct inspection during the operation. Although this number of patients is not large, it emphasizes the importance of communication with the cardiologist or the anesthesiologist regarding intraoperative transesophageal echocardiographic findings of MV morphological characteristics in addition to the appearance of the ventricular septum, the LV outflow tract pressure gradient, and papillary muscle abnormalities that might not be apparent on the pre-operative study.
We have generally avoided direct MV surgery during septal myectomy because LV outflow tract obstruction, SAM of the MV, and related MR resolve in most patients after adequate myectomy. Indeed, in the present study, the prevalence of regurgitation grade ≥3 was 54.3% before myectomy and only 1.7% afterward. Thus, our practice for patients without intrinsic MV disease has been to first perform extended myectomy and to second assess MV function through transesophageal Doppler echocardiography after discontinuation of CPB.
In our experience, the most common cause of residual SAM, MR, and recurrent LV outflow tract obstruction is inadequate myectomy (28). If a residual outflow tract gradient and SAM are present, we resume CPB to perform additional septal resection. Exploration of the MV is reserved for patients with suspected mitral prolapse secondary to injury to the supporting chordae. With this strategy, we have avoided unnecessary MV surgery, and the percentage of patients who have had concomitant MV surgery with myectomy is small compared with other series (29).
Among patients who required concomitant MV repair or replacement, removing the cross clamp and administering subsequent CPB for this additional procedure did not prolong total aortic cross clamp time, CPB time, or length of hospital stay compared with patients who had undergone the valve operation during the first period of cardioplegic arrest. Furthermore, survival was not different between the patients who underwent surgery with a single period of CPB and the patients who required 2 or more periods of CPB.
The rate of MV repair in patients undergoing MV operation during myectomy was higher (76.4% of all concomitant MV operations) in this investigation than in other studies (29). In fact, the rate of MV repair versus replacement was similar in patients with mild, moderate, or severe valve leakage (p = 0.70). These findings support the findings reported by Wan et al. (23) that concomitant MV repair with myectomy can be performed with a low mortality rate and low risk of causing SAM and LV outflow tract obstruction. More importantly, the present study also showed that patients who underwent myectomy and concomitant MV repair had better survival than patients who had concomitant MV replacement. These findings support the large body of evidence showing improved late survival of patients undergoing operation for repair of degenerative MV disease versus MV replacement (30,31). The explanation for superior survival is unclear because we do not have complete information on causes of late death. Nevertheless, it seems best to proceed with concomitant valve repair whenever possible for patients with MR not corrected with adequate septal myectomy.
Several abnormalities in MV anatomy have been described in patients with HOCM, including increased leaflet area, longer leaflet length, and papillary muscle thickening and displacement (1,2). Additional procedures during myectomy should be considered for papillary muscle abnormalities that contribute to LV outflow tract obstruction, although not every papillary muscle abnormality contributes to such obstruction or leads to functional abnormalities. Specifically, some abnormal papillary muscles insert near the free edge of the anterior leaflet and thereby provide support, and excision of these functioning papillary muscles may result in MR. Although anatomic alterations may exist in the MV leaflet, we believe that the functional and clinical impacts of these abnormalities are minimal when an adequate myectomy is performed.
This is a retrospective study with the usual associated limitations of such investigations. We do not have late echocardiographic assessment of MR to correlate with operative methods. In addition, we do not have precise morphometric measurements of the MV to allow correlation of leaflet length with outcome.
Most MR related to SAM in patients with HOCM resolves after adequate subaortic septal myectomy, and concomitant MV surgery is rarely required unless the patient has intrinsic MV disease. In the absence of diagnosis of intrinsic MV disease, direct MV surgery for SAM and related MR can be safely avoided through the strategy of initially performing adequate myectomy, re-evaluating the result with intraoperative transesophageal echocardiography, and proceeding with any necessary additional MV procedures during a subsequent period of CPB. When MV surgery is required, late outcome is better with MV repair than with replacement.
COMPETENCY IN MEDICAL KNOWLEDGE: In patients with HOCM, adequate myectomy decreases MR substantially, and MV surgery usually is not necessary unless there is intrinsic disease of the MV independent of SAM. In patients requiring concomitant MV surgery, valve repair yields better results than valve replacement.
TRANSLATIONAL OUTLOOK: Future studies should focus on the response of symptoms to medication therapy directed at SAM-mediated MR and the identification of patients with severe MR who benefit from earlier myectomy.
Dr. Hong is now with the Department of Thoracic and Cardiovascular Surgery, Heart Research Institute, Chung-Ang University College of Medicine, Seoul, South Korea. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- cardiopulmonary bypass
- hypertrophic obstructive cardiomyopathy
- left ventricle
- mitral regurgitation
- mitral valve
- systolic anterior motion
- Received February 25, 2016.
- Revision received June 29, 2016.
- Accepted July 5, 2016.
- American College of Cardiology Foundation
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