Extent of Clinical Improvement After Surgical Treatment of Hypertrophic Obstructive Cardiomyopathy
Background A subgroup of patients with hypertrophic obstructive cardiomyopathy remain severely symptomatic despite optimal medical therapy. Septal myectomy reduces or eliminates left ventricular outflow obstruction and produces marked symptomatic improvement. With the recent advent of alternative methods for treatment of this disorder, such as dual-chamber pacing, it is necessary to establish the risks and benefits of septal myectomy in the modern surgical era.
Methods and Results The clinical, ECG, echocardiographic, cardiac catheterization, and surgical data were analyzed for 65 patients 20 to 70 years old with hypertrophic obstructive cardiomyopathy who had surgical treatment between 1986 and 1992. Specific symptoms and overall functional status were evaluated before surgery and at the end of the first postoperative year. Subsequent long-term clinical postoperative follow-up was also obtained. The extent of postoperative improvement was measured by the presence and severity of persistent symptoms, overall New York Heart Association (NYHA) functional class, and patients' self-perceptions of overall improvement. Of the patients, 95% were in NYHA functional class III or IV before surgery: 95% had dyspnea, 62% had angina, 63% had near-syncope, and 23% had syncope. The overall early mortality rate was 4.6%; there was no mortality among the 45 patients who underwent isolated septal myectomy. At the 1-year postoperative evaluation, 89% of survivors were in NYHA functional class I or II, and 47% believed that they had 100% improvement. Significant improvement (as defined) was seen in 67% of patients with dyspnea, 90% with angina, 86% with near-syncope, and 100% with syncope. The 5-year survival rate was 92%.
Conclusions The results of the present study reaffirm the efficacy of surgical treatment of hypertrophic obstructive cardiomyopathy in patients who are severely symptomatic despite optimal medical therapy and serve as a useful reference by which the surgical approach can be compared with new and potentially promising treatment alternatives.
The optimal treatment of patients with hypertrophic obstructive cardiomyopathy is a matter of controversy. Although medical treatment with β-blockers or calcium channel blockers is effective in relieving symptoms in some patients, a subgroup of patients remain severely symptomatic despite optimal medical therapy. Surgery with septal myectomy to relieve the dynamic left ventricular outflow obstruction has been performed in select surgical centers for the past 3 decades on patients with symptoms refractory to medical treatment1 2 3 4 but has not been universally accepted as a treatment option. Some have been reluctant to recommend surgical treatment because operative mortality in early surgical series was 10% to 19%.1 5 6 Furthermore, septal myectomy has not been shown to improve the diastolic dysfunction caused by massive myocardial hypertrophy; this dysfunction may be a major pathophysiological contributor to symptoms in some patients.
Recently, dual-chamber pacing was proposed as an appropriate therapeutic alternative for patients with hypertrophic obstructive cardiomyopathy. The lower risk and cost of this procedure and the initial beneficial results have prompted some investigators7 to advocate dual-chamber pacing in all patients with severely symptomatic hypertrophic cardiomyopathy before consideration of septal myectomy. Surgical myectomy is a technically challenging procedure with a steep learning curve. With the massive myocardial hypertrophy, continued improvements in myocardial preservation techniques may alter the risk-benefit ratio of this procedure. To reach a decision about optimal therapy for patients with hypertrophic obstructive cardiomyopathy, it is necessary to know the risks and results of the operation in the current surgical era. The purpose of the present study was to examine the clinical outcome of adult patients who had septal myectomy for hypertrophic obstructive cardiomyopathy between 1986 and 1992, with an emphasis on the presence and severity of specific symptoms.
Baseline Data Collection
The clinical, ECG, echocardiographic, cardiac catheterization, and surgical data of 65 consecutive adult patients 20 to 70 years old with hypertrophic obstructive cardiomyopathy (rest or provoked left ventricular outflow pressure gradient of >50 mm Hg) who underwent septal myectomy between 1986 and 1992 were reviewed. The diagnosis of hypertrophic obstructive cardiomyopathy was established by the characteristic echocardiographic findings of marked left ventricular hypertrophy and rest or provocable dynamic left ventricular outflow tract obstruction. The severity of presenting symptoms was determined; symptoms were considered mild if they occurred with high levels of activity, moderate if they interfered with normal daily activities, and severe if they occurred with minimal activity or at rest. Comprehensive two-dimensional and Doppler echocardiography8 9 was performed on all 65 patients before surgery.
Transaortic septal myectomy was performed in all patients. Additional procedures were performed in several patients.
Standard cardiopulmonary bypass techniques were used with moderate (25°C to 32°C) systemic hypothermia. Myocardial protection was achieved with cold blood (n=45) or crystalloid (n=20) potassium cardioplegia with topical cooling. The subaortic obstruction was approached by way of an aortotomy, and the septal resection was begun by making two parallel longitudinal incisions, the first beneath the nadir of the right coronary cusp and the second beneath the commissure between the right and left coronary cusps. The incisions were joined superiorly, and a bar of muscle was excised past the bulging septum to the level of the papillary muscles. Additional myocardium was removed between this resection and the lateral attachment of the anterior mitral leaflet. For the patient with midventricular obstruction, further resection was carried out below the level of the papillary muscles. The left ventricular outflow tract was then inspected and palpated for completeness of relief of outflow tract obstruction, and the aortotomy was repaired.
Early mortality was defined as death in the hospital or within 30 days after surgery. Patients were evaluated after a suitable convalescence period (≈1 year; mean, 12.1±4.4 months). This evaluation included a detailed description of each patient's perceived improvement (ie, minimal [0%, 25%], 50%, 75%, or 100%), their functional status (overall New York Heart Association [NYHA] functional class), and severity of any persisting symptoms. Significant improvement in symptoms of dyspnea and angina was defined as a change from moderate or severe symptoms before surgery to mild or no symptoms after surgery. Significant improvement in syncope and near-syncope was defined as a change from the presence of these symptoms before surgery to their absence after surgery. Subsequent long-term clinical follow-up (maximum, 73 months) was also obtained. Follow-up was achieved through return clinic visits, mailed questionnaires, correspondence with referring physicians, and telephone interviews with patients.
Survival curves were estimated with the use of the Kaplan-Meier method.
The mean±SD age of the 65 adult patients undergoing septal myectomy was 49.7±15 years (range, 20 to 70 years). Thirty-two (49%) were women. There was a family history of hypertrophic cardiomyopathy in 11 patients (17%) and a family history of sudden death in 7 (11%). Coexistent hypertension was present in 21 of the patients (32%).
All patients except 1 were symptomatic. The latter had a high resting left ventricular outflow systolic pressure gradient and a very strong family history of hypertrophic cardiomyopathy and sudden cardiac death. As shown in Fig 1⇓, dyspnea was the most common symptom (95% of patients), and two thirds of the patients with this complaint had severe dyspnea. Other symptoms included angina in 62% of patients, near-syncope in 63%, syncope in 23%, and palpitations in 46%. Arrhythmias and congestive heart failure had been documented in 17% and 28% of the patients, respectively. Of the 65 patients, 95% were in NYHA functional class III or IV. Three patients presented with acute pulmonary edema and cardiogenic shock and required emergency operation for flail mitral leaflet, which caused severe mitral regurgitation.
Various regimens of cardiac drugs had been prescribed, some of which were not well tolerated. At the time of preoperative assessment, 59 patients (91%) were taking either a β-blocker or a calcium channel blocker, and 20 (31%) were taking both drugs. β-Blockers were being used in 45 patients (69%) (two thirds of whom were taking propranolol [mean daily dose, 230 mg]), and calcium channel blockers were being used in 34 (52%) (four fifths of whom were taking verapamil [mean daily dose, 360 mg]). Seven patients (11%) were taking disopyramide.
In 7 patients (11%), the preoperative rhythm was atrial fibrillation. One patient had a paced rhythm, and the other 57 patients (88%) were in sinus rhythm. Left atrial enlargement (a negative terminal deflection of the P wave in lead V1 of ≥40 ms in duration) was present in 74% of the patients in sinus rhythm. The PR interval was prolonged (>200 ms) in 27% of patients and was equal to 200 ms in 27%. The shortest PR interval was 140 ms. Left bundle-branch block was present in 5 of the 65 patients (8%). Of the 60 patients without left bundle-branch block, 55% had left ventricular hypertrophy according to the criteria of Sokolow and Lyon10 : SV1 plus RV5 or RV6 of >35 mV. Two patients had giant negative T waves; these were defined as T-wave inversion of ≥10 mV. Q waves were considered abnormal if they were ≥40 ms in duration or 25% of the R wave in depth; 5 patients had pathological Q waves.
Two-dimensional and Doppler Echocardiography
The pattern of hypertrophy of the left ventricle varied; in 11 of the 65 patients (17%), there was concentric or diffuse hypertrophy. One patient had a predominantly midventricular pattern of hypertrophy. The basal two thirds or the entire septum was hypertrophied in all of the other patients (81%). The mean maximal left ventricular wall thickness was 24.6±4.2 mm (range, 18 to 33 mm). The mean peak resting left ventricular outflow pressure gradient was 66±39 mm Hg (range, 0 to 180 mm Hg). Provocation was performed in 33 patients with either amyl nitrite inhalation or the Valsalva maneuver. The mean peak provoked gradient was 89±43 mm Hg (range, 10 to 196 mm Hg). Five patients had provoked gradients of <50 mm Hg; all of these patients had significant gradients provoked at cardiac catheterization. The corrected left ventricular ejection time was prolonged (429±27 ms) and correlated weakly with the peak resting gradient (r=.33). According to the assessment of jet area with color flow imaging, mitral regurgitation was at least moderate in 40 patients (61%), mild in 18 (28%), and trivial or absent in 7 (11%). Analysis of the timing and direction of the regurgitant jet11 was performed; the mitral regurgitation was primarily due to systolic anterior motion of the mitral valve leaflet(s) in 49 patients (85%). Five patients had dense calcification of the mitral valve or annulus (or both), 3 had a flail mitral leaflet, and 1 had prolapse of the posterior leaflet of the mitral valve.
Fifty-two patients (80%) underwent coronary arteriography, and 5 (10%) were found to have significant (≥50% stenosis) coronary artery disease. The mean peak resting systolic pressure gradient between the left ventricle and aorta in 31 patients who underwent a hemodynamic study was 62.9±42 mm Hg (range, 0 to 150 mm Hg). The mean left ventricular end-diastolic pressure was 24.8±6 mm Hg (range, 12 to 35 mm Hg). Of the 30 patients who had severity of mitral regurgitation evaluated at cardiac catheterization, 6 (20%) were graded as 4/4, 3 (10%) were graded as 3/4, 6 (20%) were graded as 2/4, and 12 (40%) were graded as 1/4. The 3 other patients (10%) had no mitral regurgitation.
For the 45 patients (69%) who had only septal myectomy, the mean cross-clamp time was 32 minutes. In 16 patients, the resected septal specimen was weighed (mean weight, 2.99±1.6 g). Additional procedures were performed in 20 patients (31%) (Table⇓). The three emergency procedures were performed to replace (n=1) or repair (n=2) flail mitral valve leaflets due to chordal rupture. A second period of cardiopulmonary bypass was required in 5 patients: 2 had additional septal resection, 1 had additional resection and mitral valve repair, 1 had mitral valve replacement, and 1 had aortic valve repair after a retraction injury was recognized. No patient had a surgically induced ventricular septal defect.
The left ventricular outflow pressure gradient was measured intraoperatively in 53 patients. The mean peak gradient in 38 patients at rest was 73.0±35 mm Hg before myectomy and 8.7±11 mm Hg after myectomy. In 15 other patients whose rest gradients before myectomy were <25 mm Hg, isoproterenol was infused and a peak provoked gradient was measured; it averaged 83.1±35 mm Hg before myectomy and 13.0±11 mm Hg after myectomy. The mean premyectomy-to-postmyectomy reduction in the intraoperative rest and provoked gradients was 67.8±33.3 and 71.6±37 mm Hg, respectively.
A second operation during the initial hospitalization was required in 4 patients: to control mediastinal bleeding in 1, for permanent pacemaker implantation in 1, for mitral valve replacement in 1, and for aortic valve replacement with placement of a left ventricular assist device in 1.
None of the 45 patients (0%) undergoing isolated septal myectomy died. Three patients who had concomitant procedures died, for an overall early mortality rate of 4.6%. One of these patients, a 66-year-old man, also underwent excision of a left atrial myxoma. He died 7 days after surgery from septicemia, with renal and hepatic failure. A 26-year-old woman with a severe form of biven-tricular hypertrophic cardiomyopathy also underwent right ventricular septal myectomy. In the postoperative period, recurrent ventricular fibrillation developed, and a left ventricular assist device was placed; however, she died after a gradual deterioration in her low cardiac output state. A 39-year-old man who also underwent mitral valve replacement died from severe diastolic heart failure 2 weeks after being discharged home. All 3 patients undergoing emergency surgery survived.
The postoperative predischarge ECG showed atrial fibrillation in 6 patients (10%) and new left bundle-branch block in 24 of 58 patients (41%). Other conduction disturbances (nonspecific intraventricular conduction delay, left anterior hemiblock, and bifascicular block) developed in 3 patients. One patient developed complete heart block, requiring implantation of a permanent pacemaker.
In the early convalescent phase (≤3 months), 1 patient had a non–Q-wave myocardial infarction (a 64-year-old man who had multivessel coronary artery bypass graft surgery at the time of septal myectomy), 1 patient had a nondebilitating stroke (a 69-year-old woman who had septal myectomy and was in atrial fibrillation and taking warfarin at the time of hospital discharge), and 1 patient had mitral valve replacement for severe mitral regurgitation (a 67-year-old woman who had had emergency mitral valve repair of a flail leaflet).
Clinical evaluation was performed at the end of the first postoperative year (12.1±4.4 months) in 61 of the 62 early survivors (98%). At this time, 90% of patients perceived an improvement of ≥50%, 76% considered themselves improved by ≥75%, and 47% believed that their improvement was 100%. Ten percent perceived no or minimal improvement. At 1 year after surgery, 89% of the patients were in NYHA functional class I or II (Fig 2⇓), and 49% (30 of 61 patients) were asymptomatic and unlimited in their activities. Overall, persistent symptoms were much less severe (Fig 1⇑). Significant improvement, defined as a change from moderate or severe symptoms before surgery to mild or no symptoms after surgery, occurred in 37 of 55 patients (67%) with dyspnea and in 27 of 30 patients (90%) with angina. Significant improvement in near-syncope and syncope, defined as a change from the presence of these symptoms before surgery to their absence after surgery, occurred in 32 of 37 patients (86%) with near-syncope and in all 14 patients (100%) with syncope. New syncope developed after surgery in two patients. The extent of clinical improvement was similar in patients who had left bundle-branch block after surgery and in those who did not (P=.71). One year after surgery, 28 patients (46%) were taking β-blockers (mean daily propranolol dose, 130 mg), and 16 (26%) were taking calcium channel blockers (mean daily verapamil dose, 230 mg).
The arrhythmia documented most often both before and after surgery was atrial fibrillation. Seven patients had persistent atrial fibrillation before surgery; 6 of these 7 survived, and 4 of them were in sinus rhythm at 1 year after surgery. Five of 6 patients with paroxysmal atrial fibrillation before surgery were in sinus rhythm 1 year after surgery. New atrial fibrillation developed in the first postoperative year in 5 patients. Therefore, at 1 year after surgery, 8 of 61 patients (13%) were in atrial fibrillation compared with 13 of 65 patients (20%) with either persistent or paroxysmal atrial fibrillation before surgery. There was a trend toward smaller left atrial size on the predischarge postoperative echocardiogram (left atrial volume, 83±44 versus 88±43 mL before surgery, P=.06). Two patients had nonsustained ventricular tachycardia on 24-hour ambulatory ECG monitoring before surgery.
Outcome After 1 Year
The median length of long-term follow-up was 19.5 months (mean, 28.2±19.9 months; range, 4.5 to 73 months). One of 61 1-year survivors (2%) died (Fig 3⇓); this patient was undergoing chronic hemodialysis for reasons unrelated to his cardiac disease and died of pulmonary embolism 3 years after septal myectomy. Atrial fibrillation developed late (on average, 2 years after surgery) in 4 of the 53 late survivors (8%) who were in sinus rhythm at the 1-year postoperative evaluation.
At ≈2 years after surgery, 2 patients had recurrent and worsening symptoms attributable to their cardiac disease, and they received medical treatment. Further surgical treatment was necessary in 2 other patients: 1 patient underwent mitral valve replacement 6 years after myectomy for severe mitral regurgitation, and 1 patient underwent aortic valve replacement 4 years after myectomy for severe aortic regurgitation. The latter patient had required aortic valve repair after retraction trauma at the time of septal myectomy.
The results of the present study reaffirm that septal myectomy is an efficacious procedure with low risk in selected patients with hypertrophic obstructive cardiomyopathy who are incapacitated despite optimal medical treatment. The 45 patients who had only septal myectomy had an early mortality rate of 0% and a late mortality rate of 2%.
By all measures, including patients' self-perception, significant improvement occurred in most of the patients. The patients with angina or syncope, in particular, had nearly complete resolution of their symptoms. Patients who had dyspnea as the predominant presenting symptom also had improvement but not to the same extent, and 16 of the 61 patients (26%) had at least moderate residual dyspnea when evaluated 1 year after surgery. Dyspnea is a consequence of various pathophysiological processes that occur in hypertrophic cardiomyopathy, the most important contributor being abnormal diastolic function. Due to abnormal loads on the left ventricle, nonuniformity, and abnormal calcium metabolism,12 there is impaired left ventricular relaxation. The markedly hypertrophied walls may also be stiff and noncompliant. Although surgical treatment will not benefit patients with abnormal compliance, it may benefit some patients who have dyspnea by decreasing the contraction load at end systole, thus increasing the rate of early relaxation.12 Postoperative reduction in the severity of systolic anterior motion–induced mitral regurgitation as a result of septal myectomy probably also has a role in improving dyspnea.
Although surgical treatment benefits most patients with hypertrophic obstructive cardiomyopathy early after surgery, they continue to require careful long-term surveillance. New atrial fibrillation, often not well tolerated in patients with hypertrophic cardiomyopathy, occurred in 6 patients during the postoperative follow-up period of the present study. Long-term survival, in this and other surgical series,1 2 4 13 14 15 is, nevertheless, good.
Recent reports have demonstrated a modest gradient reduction and symptomatic improvement through implantation of a dual-chamber pacemaker in patients with hypertrophic obstructive cardiomyopathy at both short- and intermediate-term follow-up.7 16 17 The mechanism of benefit is unclear but may be related to both an acute reduction in the left ventricular outflow gradient induced by alteration in septal activation and a long-term ventricular remodeling effect. There may also be a decrease in the severity of mitral regurgitation, but the left atrial size does not change.17 Questions remain regarding the efficacy of dual-chamber pacing in all patients.18 Pacing from the right ventricle acutely has been shown to cause a deterioration in diastolic function due to prolongation of relaxation and alteration of atrioventricular synchrony19 20 ; the chronic effect of long-term pacing on diastolic function is unknown. Long-term follow-up of large numbers of patients undergoing implantation of a permanent pacemaker is required to determine the ultimate role of this therapeutic modality.
Thus, the optimal treatment of the subset of patients with hypertrophic obstructive cardiomyopathy who remain severely symptomatic despite optimal medical therapy is unclear. However, based on the present as well as other recent studies,14 15 surgical treatment should be viewed as a safe, efficacious, and rational therapeutic option. It should be performed at medical centers where cardiologists and cardiac surgeons are intimately familiar with this condition and septal myectomy as well as these patients' subsequent postoperative care.
Reprint requests to Robert B. McCully, MB,ChB, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
- Received September 19, 1995.
- Revision received January 23, 1996.
- Accepted January 29, 1996.
- Copyright © 1996 by American Heart Association
Morrow AG, Reitz BA, Epstein SE, Henry WL, Conkle DM, Itscoitz SB, Redwood DR. Operative treatment in hypertrophic subaortic stenosis: techniques and the results of preoperative and postoperative assessments in 83 patients. Circulation. 1975;52:88-102.
Williams WG, Wigle ED, Rakowski H, Smallhorn J, LeBlanc J, Trusler GA. Results of surgery for hypertrophic obstructive cardiomyopathy. Circulation. 1987;76(suppl V):V-104-V-108.
Morrow AG, Epstein SE, Rodgers BM, Braunwald E. Idiopathic hypertrophic subaortic stenosis: a current assessment of the results of operative treatment. In: Wolstenholme GEW, O'Connor M, eds. Hypertrophic Obstructive Cardiomyopathy. London, UK: Churchill Livingstone; 1971:140-149.
Cooley DA, Bloodwell RD, Hallman GL, LaSorte AF, Leachman RD, Chapman DW. Surgical treatment of muscular subaortic stenosis: results from septectomy in 26 patients. Circulation. 1967;35(suppl I):I-124-I-132.
Fananapazir L, Cannon RO III, Tripodi D, Panza JA. Impact of dual-chamber permanent pacing in patients with obstructive hypertrophic cardiomyopathy with symptoms refractory to verapamil and β-adrenergic blocker therapy. Circulation. 1992;85:2149-2161.
ten Berg JM, Suttorp MJ, Knaepen PJ, Ernst SM, Vermeulen FE, Jaarsma W. Hypertrophic obstructive cardiomyopathy: initial results and long-term follow-up after Morrow septal myectomy. Circulation. 1994;90:1781-1785.
Jeanrenaud X, Goy JJ, Kappenberger L. Effects of dual-chamber pacing in hypertrophic obstructive cardiomyopathy. Lancet. 1992;2:1318-1323.
Fananapazir L, Epstein ND, Curiel RV, Panza JA, Tripodi D, McAreavey D. Long-term results of dual-chamber (DDD) pacing in obstructive hypertrophic cardiomyopathy: evidence for progressive symptomatic and hemodynamic improvement and reduction of left ventricular hypertrophy. Circulation. 1994;90:2731-2742.
Nishimura RA, Danielson GK. Dual chamber pacing for hypertrophic obstructive cardiomyopathy: has its time come? Br Heart J. 1993;70:301-303. Editorial.
Nishimura RA, Hayes DL, Ilstrup D, Holmes DR Jr, Tajik AJ. Effect of dual-chamber pacing on systolic and diastolic function in patients with hypertrophic cardiomyopathy: acute Doppler/echocardiographic and catheterization hemodynamic study. J Am Coll Cardiol.. 1996;27:421-430, 1319-1320.