Catheter-Based Management of Hypertrophic Cardiomyopathy

Anatomy and Physiology

Patients with HCM are symptomatic due to dynamic LVOT obstruction, causing arrhythmias, diastolic dysfunction, ischemia, and autonomic dysfunction. HCM causes asymmetric septal hypertrophy and abnormal mitral valve Morphology and function, resulting in a pathologic pressure gradient that impairs cardiac output. Left ventricular hypertrophy varies in anatomic distribution, but most commonly affects the basal anterior septum and anterior free wall.

Hypertrophy impedes the systolic anterior motion of the mitral valve, predominantly the anterior mitral leaflet, worsening LVOT gradient and mitral regurgitation, thereby increasing intracavitary pressure and exacerbating diastolic heart failure. LVOT obstruction is clinically significant if the peak LVOT gradient is 30 mm Hg or greater and usually produces ischemic symptoms.[5] Please see StatPearls' companion article on Hypertrophic Cardiomyopathy. 

Indications

In patients with symptomatic obstructive HCM, beta-blockers or nondihydropyridine calcium channel blockers are used initially, and increased as indicated to maximum doses. If symptoms persist while using this regimen, disopyramide may be added in an effort to reduce the LVOT gradient and improve function. SRT is considered in patients whose symptoms are refractory to or not well controlled with medical management.

Severe obstruction and/or severe symptoms, such as recurrent syncope, are indications for SRT. Approach to SRT, surgical myomectomy, or catheter-based alcohol ablation, factors in patient preference, comorbidities, and risk for open surgical procedures. Surgical myomectomy is recommended for symptomatic individuals undergoing cardiac surgery for other conditions, like multi-vessel coronary artery disease or hemodynamically significant valvular disease, to be performed at a comprehensive HCM center by experienced surgeons. Alcohol septal ablation is recommended for persons with high surgical risk, advanced age, or those refusing open-heart surgery.[2]

Criteria for ASA include:

• Severe symptoms, New York Heart Association class III–IV, including severe dyspnea or chest pain, or recurrent presyncope or syncope during exertion, interfering with daily activities
• Peak LVOT gradient of ≥50 mm Hg at rest or with provocation in patients with septal hypertrophy and systolic anterior motion of the mitral valves
• Septal wall thickness ≥15 mm
• Presence of a septal perforator that supplies the part of the septum causing the obstruction, which can be targeted during catheterization

Contraindications

Ideal outcomes depend on Appropriate patient selection. Children and young adults with high resting peak gradients of 100 mm Hg or greater should undergo surgical myomectomy. ASA is contraindicated in the following:

• Septal thickness ≥ 30 mm.
• Asymptomatic individuals with good exercise capacity
• LVOT peak gradient of ≥100 mm Hg
• Septal thickness <15 mm due to increased risk of ventricular septal defect 
• HCM with septal hypertrophy but without a major septal perforator vessel
• A septal perforator that supplies other areas of the myocardium, risking extensive necrosis
• Unusual location of hypertrophy 
• LVOT obstruction primarily attributable to mitral valve abnormalities
• Conduction pathology that would risk post-procedural complete heart block
• Mitral valve anatomic anomaly
• Other associated cardiac conditions, like aortic stenosis, intrinsic mitral valve pathology, severe valve disease, anomalous papillary muscle, or severe coronary artery disease, requiring surgical repair [2] 

Equipment

Alcohol septal ablation can be performed in a cardiac catheterization laboratory under moderate sedation or with anesthesia assistance. A coronary angiogram is required to assess any significant coronary artery disease and locate the septal perforator in the region of interest. Both right and left systems must be interrogated to identify any anomalous arterial supply. 

Usually, transthoracic, transesophageal, or intracardiac echo guidance is used to localize the septal perforator by using ultrasound-enhancing contrast agent injection, monitor LVOT gradients and myocardial septal activity, and electrocardiogram monitoring is used to assess electrical activity during the procedure.[6] ASA with echo guidance has resulted in greater success, reduced procedure time, and fewer complications like complete heart blocks and inadvertent infarctions.[7]

Additional equipment:

• 6F guide catheter
• Anticoagulation, such as heparin or bivalrudin
• 300 cm guide wire
• Over-the-wire balloon 
• 100% ethanol
• Normal saline

Personnel

ASA is performed in a high-volume tertiary center with expertise in HCM, by interventional cardiologists with experience in 20 to 50 ASA procedures, working in a well-equipped catheterization laboratory with the support of experienced personnel. Cardiac surgeons should be on standby for any unexpected complications.[8]

Preparation

Invasive hemodynamics and a complete angiogram are performed as final preparation for the ASA procedure. A right heart catheterization assesses disease severity and any concurrent pulmonary pathology. The left ventricular outflow tract is interrogated to identify the areas of maximal obstruction. Resting and dynamic obstruction are assessed. The aortic valve is also evaluated for the presence of severe stenosis, which would require intervention. The target septal artery and its branches are identified. 

Informed consent should be obtained. Major complications—vascular access, contrast injury, risk of myocardial infarction due to alcohol, complications from guide catheter, risk of conduction abnormalities, including the risk of sedation, and possible deaths should be explained well in advance, including the need for repeat intervention in 7% to 20% of patients with residual obstruction.[9] In preparation for the alcohol septal ablation, a temporary transvenous pacemaker is placed in anticipation of any conduction abnormality.[10]

Technique or Treatment

A temporary transvenous pacemaker should be placed and left in place for 2 or 3 days after the procedure. The lead is placed apically, well out of the way of the site of intervention.[11] Dual arterial access is obtained. Angiography is performed again to confirm the anatomy of the septal vessel and any branches.

The target of the ablation is the left ventricular side of the septum at its base. A septal vessel must be at least 1.25 mm in diameter to allow access by a catheter. A 6F or 7F guide catheter is used to access the left main coronary artery, and the other access site is used to introduce a 5F or 6F pigtail catheter into the left ventricle for measurement of the ventricle, LVOT, and aortic gradients.

Anticoagulation is administered. A 300-cm coronary guidewire is advanced to the first septal perforator via a guide catheter in the left main artery. A 6 mm to 8 mm over-the-wire balloon is advanced over the wire to the septal perforator a couple of millimeters beyond its insertion point, and inflated to completely occlude the vessel.

The guidewire is removed, and angiography is performed through the catheter to confirm balloon occlusion, and then contrast is injected through the balloon lumen to assess for leaks into the left anterior descending (LAD) directly or traveling through any collateral vessels to any vessel not selectively targeted. Concurrent transthoracic echocardiography (TTE) is conducted using contrast injected into the septal branch to confirm the location of the selected basal septal area. After confirming the targeted myocardium, 1 to 2 cc of 100% ethanol is slowly injected over 1 to 3 minutes into the septal perforator via the balloon, followed by a saline flush. 

While TTE is performed, the balloon is left inflated for 5 minutes. The TTE should show decreased motion and ethanol enhancement of the targeted area. Left ventricle-to-aorta and LVOT gradients are measured using the pigtail and TTE, respectively, and should demonstrate a reduction in gradient with successful ablation.

Adjacent myocardium is assessed to ensure these areas were not affected by the ethanol. The patient's hemodynamics and cardiac electrical activity are continuously monitored. Another 1 cc to 2 cc alcohol infusion can be repeated if a less than 50% reduction in gradients is noted. The balloon should be inflated for 10 minutes after the last alcohol infusion. A completion coronary angiogram is performed to visualize the LAD for unintended consequences and to confirm the effectiveness of ablation.

Additional experimental and lesser-known techniques for septal ablation are described. Alternative materials and techniques, including glue, microspheres, coil embolisation, and covered stents, have shown some success, but all rely on inducing myocardial ischaemia. A study using coil embolisation demonstrated effective gradient reduction with minimal complications, though long-term outcomes remain unknown.[12]

Septal scoring along the midline endocardium (SESAME) is a novel transcatheter intervention designed to replicate surgical myectomy. SESAME uses catheters to create a myectomy in the thickened myocardium using radiofrequency energy.  Not all patients with HCM are suitable for this procedure, and a multidisciplinary heart team determines candidacy. Radio frequency technology can also be used for transcatheter mitral valve replacement and in those with a subaortic membrane. The technique is relatively new, and its long-term efficacy remains uncertain.[13] 

Complications

Complete heart block requiring a permanent pacemaker is the most common complication and can occur several days after the procedure. A myocardial infarction can occur during the procedure due to extravasation of the ethanol. Additional complications from imprecise ethanol placement include ventricular septal rupture, coronary dissection, tachyarrhythmia, and cardiac tamponade.[11]

Additional complications secondary to cardiac catheterization included vascular access site hematoma, coronary artery dissection, thromboembolism, stroke, acute limb ischemia, right ventricular perforation from pacemaker insertion, and contrast injuries to the kidneys. Sedation can lead to respiratory failure, memory loss, and aspiration pneumonia.[14] The complication rate from alcohol septal ablation in centers of excellence is very low, and heart block is typically the only postprocedural event.

Clinical Significance

The successful septal reduction is defined as a greater than 50% reduction in LVOT peak gradient. Ongoing improvement in the gradient, along with cardiac remodeling, is expected over the next few years. A postprocedural echocardiogram demonstrates akinesis of the targeted septum.

Several months following the procedure, a repeat echocardiogram demonstrates septal thinning. Hemodynamic function may still require pharmacologic support until full remodeling and functional improvement have been achieved. Compared with open surgery, ASA reduces the recovery time and discomfort. 

However, between 5% to 15% of patients fail ASA therapy. Repeat ASA can be performed in patients with suitable anatomy and inadequate reduction of the LVOT gradient. A meta-analysis by Agrawal et al showed ASA and surgical myomectomy had similar mortality rates and functional capacity postintervention, but an increased rate of conduction abnormalities and higher LVOT gradient requiring reintervention was noted in the ASA group.[15] No randomized controlled trials are comparing ASA and surgical myomectomy.

Enhancing Healthcare Team Outcomes

ASA performed by experienced interventional cardiologists in comprehensive HCM centers demonstrates excellent outcomes with minimal complications. Study results have shown that overall mortality from the procedures is less than 1%, and the survival rate is similar to that of surgical myomectomy.[9][16][17] Appropriate patient selection is the key to procedural success.

Specialized nursing staff ensure appropriate pre- and postprocedural monitoring and minimize potentially life-threatening complications or the need for urgent intervention. An experienced surgeon is on standby to handle any potential procedure-related complications. A successful and safe alcohol septal ablation requires collaboration with qualified staff and a trained interdisciplinary team at every stage. 

Candidates for surgical or ablative intervention should be given full autonomy and introduced to all treatment options. The risks and benefits should be explained in detail. Referral to centers with comprehensive HCM care and excellent clinical outcomes should be standard. For severely symptomatic eligible individuals with LVOT obstruction due to HCM, SRT can be performed as an alternative to an escalation of medical therapy after shared decision-making and explaining the risks and benefits of all available treatment options.

Nursing, Allied Health, and Interprofessional Team Interventions

The Interprofessional team is vital to the success of complex cardiac interventions. Patient hemodynamics are monitored preceding, during, and following the procedure. Correct catheter and sheath size, prepared in the correct order, appropriate balloons, contrast, and anticoagulation delivered by the support staff are crucial for procedural success.

Unfractionated heparin is given to achieve the therapeutic activated clotting time of 250 to 300 seconds. Astute echocardiogram technicians should be available to monitor pericardial effusion and hemodynamics during the procedure. Vascular access sites are monitored for bleeding, and timely communication of any complications is paramount.

Nursing, Allied Health, and Interprofessional Team Monitoring

After the procedure, the patient is transferred to the cardiac intensive care unit for close telemetry monitoring, serial electrocardiograms, and cardiac enzymes to track the progression of the induced infarction for the first 48 hours. The transvenous pacemaker is left for 2 to 3 days. Patients are monitored for the following:

• Access site complications, such as groin or retroperitoneal hematoma
• Arrhythmias or heart blocks
• Hemodynamic instability 
• Stroke/transient ischemic attack
• Contrast nephropathy
• Myocardial ischemia

Following the initial 48 hours, the risk for an acute event is substantially decreased, and the stable patient can transfer to a telemetry floor. Persons most at risk for postprocedural heart block include older adults, those with preexisting conduction abnormalities, and women. TTE is done to assess LVOT gradient and mitral regurgitation before discharge. Patients follow up in the clinic where they are assessed for general well-being and any signs of access site complications like arteriovenous fistula, femoral artery pseudoaneurysm, hematoma, or infection. Patients undergo a repeat echocardiogram within 3 to 6 months to assess the LVOT gradient.[18]