Indications for and Individualization of Septal Reduction Therapy

Abstract

The importance of left ventricular outflow tract obstruction in a large subset of patients with HCM and drug-refractory symptoms, as well as the value of septal reduction therapy (surgical myectomy or alcohol septal ablation), has been demonstrated. However, determining the precise cause of symptoms in the HCM patient, and specifically implicating outflow tract obstructive physiology, can be quite challenging. Accordingly, a detailed and comprehensive morphologic and physiologic evaluation of the HCM patient is of paramount importance to determine which patients may benefit from septal reduction therapy. Patients should be considered for septal reduction therapy when (a) symptoms are clearly and primarily attributed to obstructive HCM despite optimal medical therapy; (b) symptoms encompass severe heart failure or angina (NYHA or CCS class III/IV), recurrent obstruction-related syncope, or recurrent clinical decompensation due to refractory paroxysmal atrial fibrillation; (c) a gradient ≥50 mmHg can be demonstrated on optimal medical therapy; and (d) obstruction is clearly dynamic and subvalvular, resulting mainly from septum-to-anterior mitral leaflet contact. Surgical myectomy has been the traditional gold standard invasive therapy. Alcohol septal ablation (ASA) is a minimally invasive catheter-based alternative with less patient discomfort and more rapid recovery; however, only patients with certain anatomic criteria are candidates. Evidence from nonrandomized studies suggests that ASA and surgical myectomy result in similar short- and long-term outcomes with respect to hemodynamic and functional improvements, with greater propensity for pacemaker placement with septal ablation. Based on comprehensive assessment of clinical symptoms, associated comorbidities, and echocardiographic, electrocardiographic, and angiographic features, some patients are better suited for myectomy, while others are better suited for ASA. This chapter will review indications for septal reduction therapy and how to individualize the selection of the appropriate septal reduction procedure in clinical practice.

Questions

• 1. Septal reduction therapy should be considered for which of the following patients?

  • A. Patient with severe LV outflow tract obstruction and drug-refractory symptoms, such as severe dyspnea or chest pain (usually NYHA or CCS functional class III/IV), or other important exertional symptoms (e.g., syncope)

  • B. Patients who are intolerant of optimal medical therapy

  • C. Patients in whom symptoms are clearly and primarily attributed to obstructive HCM physiology

  • D. Patients with septal thickness ≥ 15–16 mm at point of septal – mitral contact

  • E. All of the above

  Answer: E. Patients should be considered for septal reduction therapy when (a) symptoms are clearly and primarily attributed to obstructive HCM despite optimal medical therapy; (b) symptoms encompass severe heart failure or angina (NYHA or CCS class III/IV), recurrent obstruction-related syncope, or recurrent clinical decompensation due to refractory paroxysmal atrial fibrillation; (c) a gradient ≥50 mmHg can be demonstrated on optimal medical therapy; and (d) obstruction is clearly dynamic and subvalvular, resulting mainly from septum-to-anterior mitral leaflet contact. Septal wall thickness < 15–16 mm is considered a contraindication to either myectomy or ASA due to the potential risk of septal perforation with creation of a ventricular septal defect.

• 2. The following features would favor the selection of myectomy over alcohol septal ablation as the septal reduction therapy of choice, except:

  • A. Younger age

  • B. Septal hypertrophy ≥30 mm

  • C. Preexisting left bundle branch block

  • D. Prior cardiac or thoracic surgery

  • E. Atrial fibrillation that requires a maze procedure

  Answer: D. Myectomy surgery is preferred in younger patients; those with massive septal hypertrophy (e.g., ≥30 mm); those with diffuse rather than focal left ventricular hypertrophy that extends to the mid-ventricle or even apex; those with preexisting left bundle branch block (since ASA usually causes right bundle branch block, resulting in a high incidence of complete heart block); those with concomitant cardiac disease requiring surgical intervention: intrinsic severe mitral valve disease, presence of membranes, moderate/severe aortic stenosis, and coronary artery disease favoring coronary artery bypass grafting; and those with atrial fibrillation that might require a maze procedure or left atrium appendage ligation. Prior cardiac or thoracic surgery (given the risks inherent to reoperation) would favor ASA over myectomy.

• 3. The following features would favor the selection of alcohol septal ablation over myectomy as the septal reduction therapy of choice, except:

  • A. Advanced age

  • B. Comorbid conditions that would increase surgical risk (e.g., pulmonary hypertension)

  • C. Presence of pacemaker/ICD

  • D. Absence or minimal intrinsic disease of mitral valve apparatus and papillary muscles and of other conditions for which cardiac surgery is indicated

  • E. Preexisting left bundle branch block

  Answer: E. Factors that favor ASA over myectomy include advanced age (>65 years), comorbid conditions that would increase surgical risk (e.g., pulmonary hypertension or severe COPD causing significant concerns about lung or airway management), preexisting right bundle branch block (because myectomy usually causes left bundle branch block and a high incidence of complete heart block), presence of pacemaker/ICD that would substantially lower the procedural risk of ASA, prior cardiac or thoracic surgery (given the risks inherent to reoperation), and focal CAD that can be treated with stenting. Myectomy is preferred in those with preexisting left bundle branch block, since ASA usually causes right bundle branch block, resulting in a high incidence of complete heart block.

• 4. In patients being considered for septal reduction therapy, what LV outflow gradient should be demonstrated?

  • A. LV outflow gradient of ≥30 mmHg with exertion.

  • B. LV outflow gradient of ≥60 mmHg at rest.

  • C. LV outflow tract gradient of ≥50 mmHg at rest, with physiologic provocation, or with exertion.

  • D. No gradient needs to be demonstrated if symptoms of severe heart failure or angina (NYHA or CCS class III/IV) are present.

  • E. LV outflow tract gradient of ≥60 mmHg at rest, with physiologic provocation, or with exertion.

  Answer: C. Candidates for septal reduction therapy must have an LV outflow tract gradient of ≥50 mmHg at rest, with physiologic provocation, or with exertion. While echocardiography is the gold standard, permitting evaluation of obstruction provoked by Valsalva maneuver or treadmill exercise, cardiac catheterization is frequently complementary and often necessary in patients with poor echocardiographic “windows” to evaluate or confirm the severity of LVOT gradient at rest and with provocative maneuvers.

• 5. If a significant resting gradient (gradient of ≥50 mmHg) is not found by echocardiography or during catheterization, the following maneuvers are recommended:

  • A. Valsalva

  • B. Induction of an extrasystolic beat to measure the Brockenbrough-Braunwald sign

  • C. Exercise (e.g., supine bicycle exercise)

  • D. Pharmacologic challenge (amyl nitrite, nitroglycerine, or isoproterenol)

  • E. All of the above

  Answer: E. If a significant resting gradient (gradient of ≥50 mmHg) is not found during catheterization, provocative maneuvers such as the Valsalva or an induction of an extrasystolic beat to measure the Brockenbrough-Braunwald sign (or a combination of both maneuvers) should then be performed. If a significant gradient is still not provoked, either exercise (e.g., supine bicycle exercise) or pharmacologic challenge (amyl nitrite, nitroglycerine, or isoproterenol) is helpful when the clinical picture strongly suggests obstructive physiology. Isoproterenol hydrochloride provides direct stimulation of the β1- and β2-receptors that simulates exercise and, therefore, may uncover a labile outflow tract gradient.

• 6. Alcohol septal ablation results in the following:

  • A. Improvement in functional class (NYHA and CCS class)

  • B. Improvement in peak oxygen consumption

  • C. Improvement in exercise capacity

  • D. Improvements in LV synchrony, microvascular function of the subendocardium, and myocardial energetics parameters

  • E. All of the above

  Answer: E. ASA results in a significant improvement in functional class (NYHA and CCS class), peak oxygen consumption , and exercise capacity for up to 8–10 years in published studies. In addition, recent studies have indicated that ASA results in improvements in LV synchrony, microvascular function of the subendocardium, and myocardial energetics parameters. HCM patients after a successful ASA procedure also appear to have long-term survival rates that are comparable to the non-HCM population.

• 7. Selective coronary angiography is required prior to alcohol septal ablation in order to demonstrate or exclude the following findings, except:

  • A. Exclude concomitant coronary disease.

  • B. Examine the size of the septal perforator arteries.

  • C. Exclude collateral circulation from septal branches to other coronary segments.

  • D. Examine the septal thickness prior to ASA.

  • E. Examine the distribution of the septal perforator arteries.

  Answer: D. Selective coronary angiography should be performed to exclude concomitant coronary disease. Furthermore, in those undergoing workup for septal reduction treatment, the size and distribution of the septal perforator arteries need to be carefully evaluated. In addition, septal arteries may arise from the left main, diagonal branches and even from the right coronary artery, and thus, meticulous angiography in multiple views is imperative. It is also important to exclude the presence of the collateral circulation from septal branches to other coronary segments.

• 8. The following recommendations for septal reduction therapy have been made by the ACCF/AHA 2011 Hypertrophic Cardiomyopathy Guidelines:

  • A. In those patients who are acceptable surgical candidates, surgical myectomy should generally be preferred (class IIa).

  • B. In those patients who are acceptable surgical candidates, ASA should be preferred (class IIa).

  • C. In those patients who are not acceptable candidates for surgical intervention, ASA would be the favored treatment option (class IIb).

  • D. Patient preference for alcohol septal ablation over surgical myectomy is reasonable after a balanced and thorough discussion (class IIa).

  • E. All of the above.

  Answer: A. ACCF/AHA 2011 Hypertrophic Cardiomyopathy Guidelines recommend that in those patients who are acceptable surgical candidates, surgical myectomy should generally be preferred (class IIa) over ASA (class IIb), whereas in those patients who are not acceptable candidates for surgical intervention, ASA would be the favored treatment option (class IIa). Patient preference for alcohol septal ablation over surgical myectomy is also reasonable after a balanced and thorough discussion (class IIb). An individualized approach to selection of septal reduction therapy is commonly required, with comprehensive assessment of clinical symptoms, associated comorbidities, and echocardiographic and angiographic features that might favor one approach over another.

• 9. When comparing surgical myectomy to ASA, the following statements are correct, except:

  • A. Myectomy and ASA achieve similar early symptomatic improvements in NYHA heart failure class.

  • B. More complete gradient reduction may be achieved with myectomy.

  • C. ASA is associated with higher rate of pacemaker post-ASA.

  • D. Similar survival rates have been demonstrated when comparing ASA and surgical myectomy in multiple retrospective cohort studies and meta-analyses.

  • E. A randomized controlled trial comparing ASA to surgical myectomy has demonstrated similar symptomatic improvements in NYHA heart failure class.

  Answer: E. The early symptomatic improvements in NYHA heart failure class, syncope, angina, and LV outflow tract gradient have been shown to be similar between myectomy and ASA. There are sufficient data from retrospective cohort studies regarding rates of acute complications, LVOT gradient reduction, and short-term symptomatic improvement; both procedures are similarly efficacious in the modern era. In most reports, more complete gradient reduction is still achieved with surgery, but the magnitude does not translate into clinically meaningful differences in outcomes. ASA still lags behind the ~2–3% rates of pacemaker placement seen with surgery. However, it remains unclear whether this is solely due to the procedure itself or exacerbated by the older age at which patients are preferentially offered alcohol septal ablation. Similar survival rates when comparing ASA and surgical myectomy in multiple retrospective cohort studies and meta-analyses, with follow-up out to 8 years, have been shown. No randomized controlled trials comparing ASA to surgical myectomy have been performed, and it is unlikely that a randomized trial comparing these two therapies in patients with anatomy favorable for both procedures will ever be performed.

• 10. The following factors need to be examined when deciding regarding the appropriateness of the septal reduction therapy, except:

  • A. Symptoms should be clearly and primarily attributed to obstructive HCM physiology despite optimal medical therapy.

  • B. Symptoms of severe heart failure or angina.

  • C. Family history of sudden cardiac death.

  • D. Gradient ≥50 mmHg should be documented on optimal medical therapy.

  • E. Obstruction should clearly be subvalvular and dynamic.

  Answer: C. Patients should be deemed candidates for isolated septal reduction therapy when (a) symptoms are clearly and primarily attributed to obstructive HCM physiology despite optimal medical therapy; (b) symptoms are severe heart failure or angina (as measured by NYHA or CCS class, respectively), recurrent obstruction-related syncope, or recurrent clinical decompensation due to refractory paroxysmal atrial fibrillation; (c) a gradient ≥50 mmHg can be documented on optimal medical therapy, either at rest or with provocation; and (d) obstruction is clearly subvalvular and dynamic, from septum-to-anterior mitral leaflet contact, and not due to fixed obstructive valvular disease or membranes. Family history of sudden cardiac death should only be a factor in assessing the need for ICD therapy.