Hypertrophic cardiomyopathy (HCM) is the most commonly inherited cardiac disease, with estimates suggesting a prevalence approximating 1 in 500.1,2 More recently, increased awareness and genotyping has revealed a genotypic prevalence as high as 1 in 300.1 It has been linked to more than 1500 mutations in genes encoding sarcomeric proteins and is transmitted in an autosomal dominant pattern.1,3 However the penetrance, phenotypic expression, and clinical manifestations are extremely diverse even in patients with the same genotypic background.3HCM is defined as the presence of an increase in left ventricular (LV) wall thickness (usually > 15 mm in adults or two standard deviations from normal in children) in the absence of abnormal loading conditions that could elicit a similar magnitude response.4,5 Most patients with a positive phenotype are asymptomatic or minimally symptomatic.2,6 Approximately 75% of patients have an obstructive cardiomyopathy that is characterized by dynamic LV outflow tract (LVOT) obstruction at rest or on provocation most typically because of apposition of a hypertrophied basal septum with the anterior leaflet of the mitral valve. The presence of this LVOT obstruction is an independent predictor of progressive heart failure and subsequent mortality.7 Roughly 10% of patients with HCM progress to medically refractory heart failure and are candidates for septal reduction therapy with surgical myectomy or ethanol septal ablation.4,5,6 In contemporary practice, the threshold for septal reduction has reduced to include lesser degrees of heart failure, those with recurrent obstruction-related lightheadedness, those who cannot tolerate optimal doses of pharmacotherapy, and those who continue to have severe systemic hypertension.8 Favorable outcome, including a significant improvement of survival in observational experience, has further fueled interest in and performance of these procedures.
Since first performed by Cleland in 1958, surgical myectomy has been the preferred septal reduction therapy for more than 50 years, with mortality <1% in high-volume tertiary care centers.4,5,9,10 Alcohol (ethanol) septal ablation is an alternate percutaneous catheter-based procedure that has gained increasing popularity in the last two decades owing to its less invasive nature, shorter recovery period, and similar long-term clinical outcomes. Currently, patient databases suggest that in the United States alcohol septal ablation (ASA) and surgical myectomy are roughly evenly split in terms of cumulative performance volumes, whereas those in Europe and Asia strongly favor ASA over surgical myectomy.5,11
ASA was first reported in 1994 by Professor Ulrich Sigwart in a case series involving 3 patients who had failed medical therapy and pacemaker insertion and were poor surgical candidates.12 He had previously observed that balloon occlusion of the first major septal branch of the left anterior descending (LAD) coronary artery led to a temporary—yet striking—reduction in LVOT gradients in all 3 patients. Based on this evidence, he developed a protocol for permanent ablation of septal myocardial tissue using pure alcohol to create a therapeutic myocardial infarction with hopes of yielding a more sustained result.12ASA generally involves the injection of 1 to 2 mL of 98% ethanol into a proximal septal perforator branch of the LAD coronary artery to produce a myocardial infarction of the basal septum with a decrease in septal contractility (initially) and thinning (chronically). An overview of the procedure is presented in Figure 47.1. The combination eliminates turbulence in the outflow tract, resolves related mitral regurgitation, and over time widens the outflow tract to mirror the surgical myectomy result. More specifically, ASA causes necrosis of the hypertrophied part of the basal interventricular septum at the point of contact of the anterior mitral valve leaflet, causing an immediate reduction in septal contractility in 90% of patients and a subsequent fall in LVOT gradients.13 Over the next 6 to 12 months, there is LV remodeling, scar retraction and regression of the hypertrophy, leading to widening of the outflow tract, reduction in mitral regurgitation and improvement in diastolic function globally.14,15,16 Multiple studies have now shown that long-term survival of patients with HCM after successful ASA is comparable to the general disease-free population.17,18 This latter point is intriguing because it would imply improvement in both heart failure and sudden cardiac arrest-related mortality, and indeed this appears to be the case for both ASA and surgical myectomy.8
INDICATIONS AND ANATOMIC CONSIDERATIONS
The 2011 American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend that septal reduction therapy be offered to HCM patients with severe symptoms (generally New York Heart Association [NYHA] Functional Class III or IV) that persist despite optimal medical treatment utilizing negative inotropic drugs. A Class IIa recommendation is given for surgical myectomy as the treatment of choice, with ASA recommended when surgery is contraindicated (Class IIa) or considered high risk.4ASA is a Class IIb in patients who are candidates for both procedures. The more recent European Society of Cardiology (ESC) guidelines published in 2014, however, give septal reduction therapy a Class I indication and list both techniques as being comparable with the choice of therapy based on anatomy, clinical profile, patient and physician preference, and institutional experience.5,19,20 These more recent guidelines are based on intervening data suggesting equipoise between the two procedures in the absence of other surgical disease. Invasive treatments should also be considered in patients with resting or provoked gradients ≥50 mm Hg and patients that experience recurrent exertional syncope despite maximally tolerated drug therapy.4,5 As opposed to the ACC/AHA guidelines, the ESC guidelines also reduce the allowable symptoms to NYHA Class II. Septal reduction therapy should not be performed on patients who are asymptomatic with normal exercise tolerance or whose symptoms are controlled on optimal medical therapy (Class III)4; Table 47.1 illustrates indications and contraindications for ASA.
FIGURE 47.1 Alcohol septal ablation procedure
Surgical myectomy is considered the gold standard therapy for LVOT obstruction reduction based on tradition and the fact that it was developed and fine-tuned decades earlier than ASA. However, no randomized controlled trial has compared the two modalities. Several observational data and single center studies have demonstrated comparable clinical efficacy in terms of functional status improvement and mortality of ASA and surgical myectomy in the long term despite an increased need for reintervention and permanent pacemaker (PPM) implantation with ASA therapy; Tables 47.2 and 47.3. At high-volume tertiary care centers and in large databases, mortality for surgical myectomy and ASA are both <1%, despite ASA patients typically having more comorbidities and being roughly 10 to 15 years older at the time of procedure.19,21
In observational experience, while surgical myectomy resulted in greater improvements in LVOT gradients than ASA, clinical efficacy was similar between strategies in terms of reduction in NYHA class, syncope, and angina.20 The difference in outcomes lies primarily in the development of conduction system abnormalities with a 2% to 3% PPM implantation rate after surgical myectomy and a 10% to 15% rate after ASA. Importantly, much of this difference is related to the age difference in the two populations, given more subclinical conduction disease in older patients and those with more comorbidities slated for ASA.4,21 More recent data from specialized and experienced centers have confirmed the procedural safety of ASA and the rarity of previously well-documented complications with ASA like heart block, ventricular arrhythmias, and need for PPM. With the refinement of the ASA technique, including the use of myocardial contrast echocardiography guidance and decreased alcohol infusion dosages, now as low as 0.5 cc, the PPM implantation rate has improved in the current era to 7% to 10%.4,19
TABLE 47.1 Indications and Contraindications for Alcohol Septal Ablation
Indications for Alcohol Septal Ablation
Symptoms that interfere substantially with lifestyle despite optimal medical therapy (New York Heart Association [NYHA] class II, III, or IV; CCS (Canadian Cardiovascular) class 2, 3, or 4 angina or recurrent gradient-related lightheadedness or syncope).
Resting or provoked left ventricular outflow tract gradient of >50 mm Hg.
Adequately sized and accessible septal branches supplying the target myocardial segment.
Absence of important intrinsic abnormality of mitral valve and of other conditions for which cardiac surgery is independently indicated.
Contraindications to Alcohol Septal Ablation
Asymptomatic disease or minimal symptoms.
Septal thickness <15 mm at point of systolic anterior motion (SAM) contact.
Patients with well-controlled symptoms on optimal medical therapy.
Children and adults aged <21 years.
Apical and mind-cavitary phenotypes are absolute and contraindications, respectively
TABLE 47.2 Study Comparison of Efficacy and Safety of Septal Ablation and Septal Myectomy
Number of Patients
Efficacy
Safety (Ablation vs Myectomy)
ASA: 41
Myectomy: 41
No difference in NYHA functional class, exercise capacity, or gradient.
Better reductions in gradient in patients with myectomy, fewer reinterventions in myectomy group.
Mortality: no difference
PPM implantation: not reported.
ASA, alcohol septal ablation; ICD, Implantable Cardioverter Defibrillator; NYHA, New York Heart Association; PPM, permanent pacemaker.
Several clinical and anatomic criteria guide the selection of either ASA or surgical myectomy for LVOT reduction and clinical improvement in HCM; Table 47.4. ASA is preferred in older patients (>60 years of age) with significant noncardiac comorbidities, adult patients of any age with particularly favorable coronary and septal anatomy, patients with gradients localized to the proximal basal septum, those with preexisting right bundle branch block (RBBB) or PPM/defibrillator, those who have recurrent obstruction after myectomy, and individuals with a strong desire to avoid open heart surgery after a thorough physician-patient discussion (Class IIb in the ACC/AHA guidelines). Surgical myectomy, on the other hand, is preferred in patients that are younger (<40 years of age), have surgically correctable cardiac comorbidities, especially intrinsic mitral valvular abnormalities, preexisting left bundle branch block (LBBB), unfavorable anatomy for ASA, or a history of failed ASA unamenable to repeat ablation.4,5,20,22 In patients under 21 years of age, ASA is contraindicated (Class III recommendation).4
TABLE 47.3 Meta-Analyses Comparing Efficacy and Safety of Septal Ablation and Septal Myectomy
Studies
Efficacy
Safety (Ablation vs Myectomy)
12 comparative studies
No difference in NYHA functional class or gradient.
Mortality: No significant difference.
PPM implantation: OR 2.57 favor myectomy.
19 ablation and 8 myectomy studies
No difference in NYHA functional class, greater improvement in gradient after myectomy.
Mortality: 2.1% vs 1.8%
SCD: 0.3% vs 0.4%
PPM Implantation:1 1% vs 5%
24 studies
Lower rate of re-intervention after myectomy.
Mortality: No difference
PPM implantation: 10% vs 4%
40 studies
Lower rates of reintervention after myectomy.
Periprocedural Mortality: 1.2% vs 2&
Long term mortality: no difference
PPM implantation: 10% vs 5%
NYHA, New York Heart Association; OR, odds ratio; PPM, permanent pacemaker; SCD, sudden cardiac death.
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