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(Circulation. 2007;116:207-216.)
© 2007 American Heart Association, Inc.
Controversies in Cardiovascular Medicine |
From the Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston.
Correspondence to Michael A. Fifer, MD, Cardiology Division, Massachusetts General Hospital, 55 Fruit St, Gray/Bigelow Bldg, Ste 800, Mailstop 843, Boston, MA 02114-2696. E-mail mfifer{at}partners.org
| Introduction |
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600 000 Americans affected.
Response by Maron p 216
Several anatomic variants of HCM exist. Of these, hypertrophic obstructive cardiomyopathy (HOCM) is the variant that has been the subject of the most intense investigation. HOCM was previously termed idiopathic hypertrophic subaortic stenosis and is characterized by 4 closely related pathoanatomic features (Figure 1).1 Obstruction to left ventricular (LV) outflow is caused by bulging of the thickened septum into the left ventricular outflow tract (LVOT) during systole, with apposition of the anterior (occasionally posterior) leaflet of the mitral valve, which demonstrates systolic anterior motion. Mitral regurgitation usually is present, although the degree varies greatly among patients with HOCM. LVOT gradients may be present at rest or only during Valsalva maneuver or exercise (provocable obstruction). A recent report suggests that if patients with provocable gradients are included, most patients with HCM have the obstructive form of the disease.2
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| Management of HCM |
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| Septal Myectomy |
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| Pacing |
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| Septal Ablation |
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Because the proximal septal branches of the left anterior descending coronary artery supply the conduction system as well as the basal septum, atrioventricular block is a common complication of septal ablation. For this reason, a temporary pacemaker is placed before the procedure. With standard coronary angioplasty guiding catheters, guidewires, and balloon catheters, the most proximal septal branch that can be catheterized is entered, and the angioplasty balloon is inflated. X-ray contrast is injected through the balloon catheter to confirm filling of the septal branch and absence of backflow into the left anterior descending coronary artery itself. Correct catheter placement also is confirmed by myocardial contrast echocardiography (see below). Dehydrated ethanol, usually 1 mL at a time, is then injected slowly through the balloon catheter, causing a targeted myocardial infarction; the usual total dosage of ethanol is 1 to 3 mL. Patients receive narcotics and experience mild to moderate chest pain, usually burning in quality. The gradient can usually be reduced to <20 mm Hg (Figure 2). In some cases, ethanol is injected selectively into septal subbranches15; in others, it is injected into 2 or 3 septal branches. After delivery of ethanol, distal flow in the affected septal branch is slow or absent (no-reflow phenomenon; see Figure 3).16
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Myocardial contrast echocardiography was introduced into the procedure to localize the septal branch supplying the critical septal segment (ie, the point of mitral valve contact and maximal flow acceleration).17,18 Myocardial contrast may be achieved with agitated x-ray contrast or an echocardiographic contrast agent. Myocardial contrast echocardiography may identify inappropriate sites for injection of ethanol such as a septal branch supplying myocardium too close to the apex, papillary muscle, inferoposterior LV, or right ventricle. Incorporation of this technique reduces the number of septal branches into which ethanol is injected and may both improve success rate and lower marker release and the need for pacing.17,19
Peak creatine kinase is
500 U/L per 1 mL ethanol injected. In patients with failed septal ablation who subsequently undergo septal myectomy, we have found pathological evidence of necrosis of the vascular endothelium (Figure 4), suggesting that ethanol is toxic to both the coronary circulation and the myocardium.16
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| What Do We Know About the Efficacy and Safety of Septal Myectomy? |
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2% in young or middle-aged otherwise healthy patients undergoing isolated septal myectomy. In older patients, those with comorbid conditions, and those requiring other concomitant cardiac surgery, mortality is considerably higher.22,24,25
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Complications of septal myectomy include those peculiar to the operation (eg, ventricular septal defect [1%]20,26 and complete heart block for which a permanent pacemaker is required [3% to 10%, lower in the absence of preexisting conduction system disease]),20–22,26 and those that pertain to any cardiac operation (eg, postoperative bleeding with tamponade, sepsis, and stroke).20–22 Postoperative left bundle-branch block occurs in 40% to 56% of patients.24,26,27 When septal myectomy is successful and uncomplicated, studies with a mean follow-up of 6 to 12 years indicate that the improvement is usually sustained.20–22,25,26 Successful septal myectomy results in a decrease in LV mass that is much greater than that attributable to the removal of the septal myocardium itself and that undoubtedly results from relief of pressure overload.28
| What Do We Know About the Efficacy and Safety of Septal Ablation? |
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In association with the amelioration of the LVOT gradient, the degree of mitral regurgitation decreases,17,29,38 as does the size of the left atrium.17,39 In response to a reduction in the systolic pressure load, systolic myocardial function improves in the free wall40 and hypertrophy regresses throughout the LV (as after aortic valve replacement for aortic stenosis; Figure 5).19,39,41,42 Reduction in LVOT gradient and regression of LV hypertrophy are accompanied by improvement in diastolic LV function,17,29,43 which correlates with an increase in exercise capacity.38
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Two studies have demonstrated that, as with septal myectomy, the benefit of septal ablation in patients with provocable gradients is similar to that in patients with resting gradients.44,45 These studies provide retrospective support for Sigwarts13 performance of septal ablation in his first 3 patients, all of whom had provocable obstruction. The standard provocation for deciding whether a patient is a candidate for septal ablation is exercise. Because exercise is not practical in an instrumented patient, patients triaged to ablation on the basis of exercise-induced gradients may receive dobutamine or isoproterenol during the procedure to provide a gradient suitably high to serve as a "target" for ablation.
Temporary complete atrioventricular block occurs during the procedure in approximately half of the patients.17,29,46–48 After the procedure, right bundle-branch block is present in approximately half of the patients.17,18,27,29,46,48 A corollary is that patients with preexisting left bundle-branch block usually require permanent pacing after ablation.48 Another corollary is that patients who undergo sequential septal ablation and septal myectomy (which frequently causes left bundle-branch block) also are likely to require permanent pacing.49 Although the rate of permanent pacemaker placement was as high as 38% early in the septal ablation experience,29 it has fallen with the introduction of myocardial contrast echocardiography and the use of lower dosages of ethanol, with 1 group reporting an incidence of <10%.17,19,48
In-hospital mortality is 0% to 4%.19,29,30 Deaths have been due to coronary dissection,30 pulmonary embolism,17 refractory ventricular fibrillation,36 right ventricular perforation by the temporary pacemaker,36 pump failure,15 and heart block.29 In-hospital sustained ventricular tachyarrhythmias occur in
5% of cases.16 The theoretical concern that after septal ablation, arrhythmic sudden death resulting from superimposition of a myocardial infarction on a cardiomyopathic substrate would be common has fortunately not been realized in clinical practice. In patients with preexisting risk factors for sudden death, an implantable cardioverter–defibrillator may be placed before septal ablation.
Other complications of the procedure are remote myocardial infarction caused by aberrant ethanol injection14 or collateral circulation50 and ventricular septal rupture.19 Because of the latter potential complication, septal ablation should not be performed if septal thickness at the site of planned ethanol delivery is <15 mm.
| Comparison of Septal Ablation and Septal Myectomy |
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In an institution at which both procedures were regularly performed, patients were triaged according to clinical factors, so the groups were not comparable.49 In particular, the 25 patients undergoing septal ablation were older and had a higher prevalence of comorbid conditions than did the 26 patients undergoing myectomy. At the 3-month follow-up, the gradient reduction was more complete in the surgical cohort, whereas the 2 groups had similar reductions in symptoms, septal thickness, and degree of mitral regurgitation. No deaths occurred in either group.
In the second study from 2 hospitals that each favored 1 of the procedures, patients were triaged according to institutional preference.51 In this study, it was possible to match patients for age and LVOT gradient. Forty-one patients were included in each group. At the 1-year follow-up, severity of symptoms, maximal oxygen uptake, LVOT gradient, septal thickness, and degree of mitral regurgitation were similar for the 2 therapies. There was 1 death during septal ablation as a result of coronary dissection.
A third study compared the effects of septal ablation in 20 patients with those of septal myectomy in 24 patients.53 Patients who underwent myectomy were younger than those who had ablation. There was 1 death in each group. Although improvements in LVOT gradient and New York Heart Association (NYHA) class were similar in the 2 groups, the increase in maximal oxygen uptake was higher in the patients who underwent surgery.
In a fourth study, patients were triaged to ablation or surgery on the basis of age and other clinical factors.53 The outcomes of 54 patients undergoing septal ablation were compared with those of 48 patients undergoing septal myectomy. Relief of symptoms was more complete in the surgical group. More late deaths occurred in the ablation group.
A comparison of echocardiographic indexes of diastolic function an average of 5 months after intervention demonstrated no difference between septal ablation and septal myectomy.54
| Which Patients Are Candidates for Mechanical Therapy for HOCM? |
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Optimal therapy consists of β-blockade titrated to symptom relief, heart rate, or an adverse reaction. In patients with substantial symptoms despite optimal β-blockade, disopyramide, starting as 150 mg BID in the controlled-release form, may be added. Although disopyramide administration is sometimes limited by QT prolongation, a retrospective multicenter study provides some evidence against a proarrhythmic effect of the drug in patients with HOCM.55 In patients with noncardiac side effects of β-blockade, verapamil usually is substituted.
In patients without resting LVOT gradients of at least 30 to 50 mm Hg, exercise may bring out a provocable gradient. Patients with obstruction at rest or during exercise are candidates for mechanical therapy if they have symptoms that interfere substantially with their lifestyles despite truly optimal medical therapy. Published guidelines suggest that patients undergoing mechanical therapy should be in NYHA class III or IV.56 Because patients in NYHA class II have, by definition, symptoms during ordinary physical activity,57 some of these patients also are appropriate candidates for either septal ablation or septal myectomy. Patients in class II are, in fact, often managed with either septal ablation36,37,51,53 or septal myectomy.20–22,24–26,51,53 On the other hand, some patients in NYHA class III choose to live with their symptoms rather than undergo interventional or surgical management.
Retrospective studies have suggested that prognosis in HCM is related to the presence of a resting LVOT gradient58 and that prognosis in HOCM is favorably affected by septal myectomy.23 In the absence of conclusive prospective data to indicate that reducing or abolishing the gradient improves prognosis, however, mechanical therapy should not be offered to patients, even those with large gradients, if they have no or mild symptoms.
In some cases, HOCM is associated with intrinsic abnormalities of the mitral valve. These and other patients who require concomitant valve surgery or coronary bypass grafting should undergo septal myectomy rather than septal ablation. Surgery also should be considered for patients with atrial fibrillation who might benefit from a concomitant maze procedure.
| Advantages of Septal Myectomy |
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| Advantages of Septal Ablation |
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| What We Do Not Know |
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Thus, although some have expressed strong, well-reasoned opinions in support of either septal ablation60 or septal myectomy61 as the procedure of choice, existing data are inconclusive, so the management decision in many cases depends critically on patient choice.
| Application to Patient Care |
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Case 1: A 43-year–old man had exertional dyspnea and angina despite β-blockade. Septal thickness was 16 mm, and LVOT gradient 72 mm Hg. On the combination of a β-blocker and disopyramide, his symptoms remitted.
Case 2: A 61-year–old man had severe lightheadedness and exertional dyspnea despite optimal medical therapy in association with HOCM and pulmonary fibrosis. Septal thickness was 22 mm, and LVOT gradient 116 mm Hg. Because of his pulmonary disease, the patient underwent septal ablation.
Case 3: A 27-year–old man had presyncope and progressive exertional angina and dyspnea despite optimal medical therapy. Septal thickness was 26 mm, and LVOT gradient 184 mm Hg. His symptoms were refractory to medical therapy. Because of his young age and marked hypertrophy, the patient underwent septal myectomy.
Case 4: A 73-year–old woman had severe bisided heart failure in association with HOCM and chronic obstructive pulmonary disease. Septal thickness was 24 mm, and LVOT gradient 121 mm Hg. Diuresis was limited by hypotension and azotemia. Because she was in need of immediate relief of outflow obstruction and despite her concomitant pulmonary disease, the patient underwent septal myectomy.
Case 5: A 46-year–old woman had disabling angina, dyspnea, and lightheadedness despite optimal medical therapy. Septal thickness was 19 mm, and LVOT gradient 121 mm Hg. Both mechanical options—septal ablation and septal myectomy—were offered to the patient.
For patients like the last one, clinical decision making is not informed by clear-cut data demonstrating that either septal ablation or septal myectomy is superior. For such "gray-area" patients, the principle of patient autonomy dictates that it is appropriate for the properly informed patient to choose between the 2 procedures.
| What to Tell Patients |
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90% to 95%) is higher than that for septal ablation (
80% to 90%).
1% to 2%).
10% to 15%) than after septal myectomy (
5%). | What Patients Will Choose |
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Similarly, and for the same reasons, most gray-area patients with HOCM choose septal ablation over septal myectomy. Patients are of course influenced by the information presented to them by physicians. It is important to emphasize that not all patients fall into the gray area; as illustrated above by the case examples, many patients exist for whom the cardiologist should direct the management to either septal ablation or septal myectomy. It is also critical that gray-area patients be allowed to choose between the options in an unhurried, unpressured environment and to seek counsel from family, friends, other patients with HCM, and other physicians.
| Conclusions |
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Future comparisons of the results of septal ablation and septal myectomy would be aided by adoption of a standard definition of success of the procedures. One possible definition would be improvement by
1 NYHA or Canadian Cardiovascular Society class and gradient reduction by
50% at 3 months after the procedure. Clinical equipoise would allow performance of a multicenter randomized trial comparing septal ablation and septal myectomy.62,63 Because mortality is low after both procedures, selection of a primary end point such as exercise capacity is advisable.
| Acknowledgments |
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Disclosures
Dr Fifer has received honoraria for speaking on HCM in general and on septal ablation in particular.
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