Continuing Education Activity

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac condition characterized by left ventricular muscular hypertrophy in the absence of other cardiac, systemic, or metabolic conditions. Septal reduction therapy (SRT) effectively reduces LVOT gradients in HCM patients due to LVOT obstruction. SRT can be done by surgical myomectomy or by percutaneous catheter-directed alcohol septal ablation. This activity reviews the evaluation and treatment options for HCM patients. It highlights the interprofessional team's role in catheter-directed management of HCM as an alternative option to surgical myomectomy.

Objectives:

• Outline the indications of catheter management of hypertrophic cardiomyopathy.
• Review the contraindications of catheter management of hypertrophic cardiomyopathy.
• Describe the equipment needed for catheter management of hypertrophic cardiomyopathy.
• Explain the procedure of catheter management of hypertrophic cardiomyopathy.

Introduction

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac condition characterized by left ventricular muscular hypertrophy in the absence of other cardiac, systemic, or metabolic conditions like hypertension, aortic stenosis, amyloidosis, glycogen storage diseases, or lysosomal storage diseases. The diagnosis is established by non-invasive imaging modalities such as two-dimensional echocardiography (ECHO) or cardiovascular magnetic resonance (CMR), or cardiac computed tomography (CT). The maximal end-diastolic wall thickness of ≥1.5 cm or 1.3 to 1.4cm with a positive family history or positive genetic test without other obvious cause is diagnostic of HCM.[1][2] 

Septal reduction therapy (SRT), either percutaneously or surgically, is effective in reducing LVOT gradients. Even though there is increased mortality among HCM patients with LVOT obstruction, the evidence lacks SRT in asymptomatic patients to improve survival. SRT is recommended in symptomatic patients despite maximal medical therapy in a comprehensive HCM center.[3] It can be done by either surgical myomectomy (SM) or percutaneous catheter-directed alcohol septal ablation (ASA).[4] Here, we will discuss the catheter management of HCM with ASA.

Anatomy and Physiology

HCM patients are symptomatic due to dynamic left ventricular outflow tract (LVOT) obstruction, arrhythmias, diastolic dysfunction, ischemia, and autonomic dysfunction. Dynamic LVOT obstruction is due to left ventricular (LV) septal hypertrophy and abnormal morphology of mitral valve or sub-mitral valvular apparatus. LV hypertrophy can be observed in any pattern and distribution, with a basal anterior septum and anterior free wall being the most predominant location. It causes the systolic anterior motion of the mitral valve (SAM), mostly the anterior mitral leaflet, resulting in worsening of LVOT gradient and mitral regurgitation. This further leads to high intracavitary pressure built up and exacerbation of diastolic heart failure and ischemic symptoms. LVOT obstruction is considered significant if the peak LVOT gradient is ≥30 mm Hg. The ECHO finding in HCM, SAM, and LVOT gradients are illustrated in the images below.

Indications

In patients with symptomatic obstructive HCM, beta-blockers or non-dihydropyridine calcium channel blockers are used first at maximally tolerated doses. Either adding disopyramide to the regimen or SRT should be considered in patients who continue to have symptoms despite medical management. However, patients' preferences, age, and comorbid conditions should be considered when selecting the type of SRT. SM is recommended for symptomatic patients requiring cardiac surgery for other conditions like multi-vessel coronary artery diseases (CAD), hemodynamically significant valvular disease at a comprehensive HCM center by experienced surgeons. As an alternative, ASA is recommended in comprehensive HCM centers by an experienced operator for prohibitive or high surgical risk patients with associated comorbid conditions or advanced age or patients refusing open-heart surgery.[2]

The following criteria have to be met before considering ASA:

1. Septal reduction therapy is recommended in patients with clinical symptoms like severe dyspnea or chest pain (NYHA III or class IV), or symptoms like presyncope or syncope during exertion interfering with daily activities due to LVOT obstruction and peak gradient of ≥50mmHg at rest or with provocation in patients with septal hypertrophy and SAM of mitral valves.
2. Targeted anterior septal wall thickness>15mm. Septal thickness>30mm will result in a suboptimal outcome.
3. A septal perforator perfusing the septal area of interest, causing dynamic LVOT obstruction and gradient.
4. No significant CAD.

Contraindications

The procedural outcomes depend on correctly identifying the eligible patients. Children and young adults with very high resting peak gradients of ≥100mmHg should undergo SM. ASA is not preferred in the following situations:[2]

1. Asymptomatic patients with good exercise capacity.
2. LVOT peak gradient of ≥100mmHg leads to suboptimal results.  
3. Septal thickness <15mm due to increased risk of VSD. 
4. HCM with septal hypertrophy but without a major septal perforator vessel
5. Septal perforator giving collateral blood supply to other areas of the myocardium. 
6. Septal perforator supplying the larger area of the myocardium than the focused area. 
7. LVOT obstruction is mainly contributed by mitral valve pathology.
8. Other associated cardiac conditions like aortic stenosis, intrinsic mitral valve pathology, or anomalous papillary muscle require surgical repair.

Equipment

ASA can be performed in a cardiac catheterization laboratory under moderate sedation or with anesthesia assistance if needed. A coronary angiogram is required to assess any significant coronary artery diseases and locate the septal perforator in the region of interest. Usually, transthoracic or transesophageal, or intracardiac echo guidance is needed to localize the septal perforator by using ultrasound-enhancing contrast agent injection and monitoring LVOT gradients during the procedure.  ASA with echo guidance has resulted in greater success, reduced procedure time, and lower complications like heart blocks and infarct size.[5]

Personnel

The procedures should be performed in a high-volume tertiary center by trained interventional cardiologists in a well-equipped catheterization laboratory with the support of experienced personnel. Also, cardiac surgeons should be on standby for any unexpected complications. Experienced operators are operators with at least 20 ASA procedures or working in comprehensive HCM centers with a cumulative 50 ASA procedures.[6]

Preparation

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 7-20% of patient with residual obstruction.[7]

Technique or Treatment

A temporary transvenous pacemaker should be placed and kept for 2 or 3 days after the procedure. Dual arterial access should be obtained. A 6F or 7F left coronary guide catheter is used to engage the left main coronary artery, and another access is used to introduce a 5F or 6F pigtail catheter to LV for measurement of LV, LVOT, and aortic gradients. A coronary wire is advanced to the first septal perforator via a guide catheter in the left-main. Then, the wire balloon (OTW) is advanced over the wire and inflated at the proximal portion of the septal perforator to completely occlude the vessel.

After that, the dye is injected into the septal branch to ensure no reflux into the left anterior descending artery (LAD) and no collaterals supplied by this septal branch. Echocardiographic contrast dye is injected into the septal branch to spot the area of interest by a transthoracic echocardiogram (TTE). After delineating the targeted myocardium, 1 to 2 cc of absolute alcohol is injected into the septal perforator via OTW balloon. LV to the aorta and LVOT gradients are measured by pigtail and TTE, respectively. Another 1 to 2 cc alcohol infusion can be repeated if a <50% reduction in gradients is noted. The OTW balloon should be inflated for around 10 minutes after the last alcohol infusion. Then, a coronary angiogram is performed to view LAD for any unintended consequences.

Complications

The complications associated with ASA are ventricular septal defect, injury to LAD from the backflow of alcohol, tachyarrhythmia, and complete heart block. Other anticipated complications related to left heart catheterization included vascular access site complications, coronary artery dissection, thromboembolism like stroke/acute limb ischemia, right ventricular perforation from pacemaker insertion, and contrast injuries kidneys and pericardial tamponade. Also, sedation can lead to respiratory failure, memory loss, and aspiration pneumonia.

Clinical Significance

The successful septal reduction is defined as a >50% reduction in LVOT peak gradient. Continuous improvement in gradient is expected along with cardiac remodeling over a period of few years. ASA avoids the anxiety related to the surgery, reduces the recovery time and residual discomfort associated with surgery.  However, between 5 to 15% of patients may fail ASA therapy. Repeat ASA can be performed in patients with suitable anatomy and inadequate reduction of LVOT gradient. The meta-analysis published by Agrawal et al. showed ASA and SM had similar mortality rates and functional capacity post-intervention.  However, an increased rate of conduction abnormalities and higher LVOT gradient requiring reintervention was noted in the ASA group.[8] There are currently no randomized controlled trials comparing ASA and SM.

Enhancing Healthcare Team Outcomes

ASA performed by experienced interventional cardiologists in comprehensive HCM centers will undoubtedly enhance the procedural outcomes. Studies have shown the overall mortality from the procedures is <1%, and the survival rate is similar to SM.[7][9][10]

Appropriate patient selection is the key to procedural success. Highly trained nursing staff will aid in identifying the potentially life-threatening complications augmenting the need for immediate intervention. A skilled and experienced surgeon should also be on standby to handle any potential procedure-related complications. This requires a collaboration of qualified staff support and a multidisciplinary team at every level to achieve great procedural success. A full discussion of the available treatment options should be held with symptomatic patients.

The success rates, risks, and benefits should be explained in detail. Referral to centers with comprehensive HCM care with excellent clinical outcomes should be made appropriately for eligible patients for SRT. [Level 1] For severely symptomatic eligible patients 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 risk and benefits of all available treatment options. [Level 2]

Nursing, Allied Health, and Interprofessional Team Interventions

The expert and prudent ancillary staff's support is always vital. Patient hemodynamics should be monitored throughout the procedure. Correct catheter and sheath size, appropriate balloons, and optimal contrast delivered by the support staff are crucial for procedural success. Unfractionated heparin should be given to achieve the therapeutic activated clotting time of 250 to 300 seconds. Astute ECHO technicians should be available to monitor pericardial effusion during the procedure. Vascular access sites should be monitored for any concern for bleeding. In addition, physicians should be notified immediately if any complications are noted.

Nursing, Allied Health, and Interprofessional Team Monitoring

After the procedure, the patient should be transferred to the intensive care unit for further monitoring up to 4 to 7 days before discharge. The transvenous pacemaker should be left for 2 to 3 days. Patients should be monitored for the following signs.

1. Any access site complications like groin hematoma and retroperitoneal hematoma
2. Arrhythmias or heart blocks
3. Hemodynamic instability 
4. Stroke/TIA
5. Contrast nephropathy
6. Myocardial ischemia

TTE should be done to assess LVOT gradient and mitral regurgitation before discharge. Patients should be followed up in the clinic and should be checked for any signs of access site complications like arteriovenous (AV) fistula, femoral artery pseudoaneurysm, hematoma, or infection. Appropriate, timely follow-ups should be arranged along with repeat ECHO within 3 to 6 months after the procedure to assess LVOT gradients.[11]