Continuing Education Activity

Hypertrophic cardiomyopathy patients can present with symptoms at any phase of life and may have an elevated risk of sudden cardiac death based on risk factors. To avoid delayed treatment of this condition, health care providers need guidelines for timely and appropriate management of this condition. This activity reviews treatment of patients who present with symptomatic hypertrophic cardiomyopathy and highlights the role of the interprofessional team in evaluating and treating patients with this condition.

Objectives:

• Describe the pathophysiology of hypertrophic cardiomyopathy.
• Review the indications for cardiac interventions in hypertrophic cardiomyopathy.
• Outline the contraindications for certain cardiac interventions in hypertrophic cardiomyopathy.
• Explain the importance of collaboration and communication among the interprofessional team to ensure the appropriate selection of patients with symptomatic hypertrophic cardiomyopathy for alcohol septal ablation.

Introduction

Hypertrophic cardiomyopathy (HCM) results from genetic mutations in the cardiac sarcomere gene, which in turn, codes for integral components of the contractile apparatus of the heart muscle. It is inherited in an autosomal dominant fashion with variable expressivity and penetrance. HCM is defined by an increase in the left ventricular wall thickness that is not completely explained by abnormal loading conditions. Various morphological variants of HCM are known, and present with different hemodynamic and clinical manifestations. These HCM variants include apical hypertrophic cardiomyopathy, sigmoid septal hypertrophic cardiomyopathy, symmetric septal hypertrophic cardiomyopathy, and asymmetric septal hypertrophic cardiomyopathy.[1][2][3]

Anatomy and Physiology

Hypertrophic cardiomyopathy (HCM) represents myocytes that, on histological analysis, are hypertrophied in the mix of fibrosis due to myocyte cell death secondary to small vessel ischemia. Any of the anatomical variants of HCM can cause a multitude of hemodynamic changes in the heart, which can result in ischemia of the myocardial tissue, mitral regurgitation, left ventricular outflow tract obstruction, and stiffening of the left ventricle. These hemodynamic changes can, in turn, result in symptoms of shortness of breath, chest pain, palpitations, or syncope.[4]

Further anatomical and structural changes in the intramural coronary arteries that account for these symptoms are hyperplasia of the vessel walls, which result in decreased flow reserve in the coronaries and impaired vasodilator response. The resulting myocardial substrate in HCM also predisposes patients to ventricular tachyarrhythmias that may contribute to an increased risk of sudden cardiac death.[5]

Indications

The majority of symptomatic patients with hypertrophic cardiomyopathy (HCM) develop a mechanical obstruction of the left ventricular outflow tract with dynamic gradients of greater than or equal to 30 mmHg.[5]

HCM patients can present with symptoms at any phase of life and may have an elevated risk of sudden cardiac death based on risk factors. Upon presentation, these patients should undergo transthoracic echocardiography at rest to determine if there is left ventricular outflow tract obstruction, with associated mitral regurgitation. Mitral valve anatomy and severity of regurgitation should be evaluated for the presence of systolic anterior motion (SAM) and posteriorly directed mitral regurgitation. If there is intrinsic severe mitral valve regurgitation unrelated to SAM, the patient may need surgical correction.

Transthoracic echocardiography with exercise may also be used to elicit left ventricular outflow tract obstruction severity and assess functional capacity. Further management is based on whether the patient is asymptomatic (no treatment/surveillance), mildly symptomatic (initiation of medical therapy), or severely symptomatic with drug-refractory symptoms (surgical myomectomy or alcohol septal ablation).[6] 

Cardiac intervention such as intracardiac defibrillator implantation is based on sudden cardiac death risk factor analysis (family history of HCM with sudden cardiac death, unexplained syncope, documented non-sustained ventricular tachycardia, maximal LV wall thickness greater than or equal to 30mm, abnormal exercise blood pressure response, left ventricular apical aneurysm, or sustained ventricular tachycardia/cardiac arrest) in a patient with known HCM. In patients with left ventricular apical aneurysm, radiofrequency ablation for ventricular tachyarrhythmias is an appropriate cardiac intervention as the arrhythmic focus is known.[7][8]

For patients with medication (beta-blocker, calcium channel blocker, or disopyramide) refractory symptoms and suitable anatomy, alcohol septal ablation is an established cardiac intervention. This percutaneous procedure was first described in 1995 as an alternative therapy to surgical myomectomy for left ventricular outflow tract obstruction in patients with HCM. The goal of this procedure is the reduction and, if possible, elimination of systolic thickening of the hypertrophied ventricular septum.[8]

Contraindications

Contraindications to different pharmacologic and non-pharmacologic interventions in patients with hypertrophic cardiomyopathy (HCM) are as follow:

• Antiarrhythmic drug therapy for primary prevention of sudden cardiac death in patients with HCM is not indicated due to the side effect profile and unclear benefit.
• Radiofrequency ablation in HCM patients with recurrent ventricular tachycardia is not indicated due to diffusely abnormal cardiac substrate present in these patients.
• Dobutamine to induce left ventricular outflow tract gradients is not indicated while evaluating patients for alcohol septal ablation due to its lack of specificity.
• The presence of an underlying left bundle branch block in a patient undergoing alcohol septal ablation has a high likelihood of post-procedural complete heart block and may require permanent pacemaker implantation.[9][10][11]

Equipment

Alcohol septal ablation procedure is minimally invasive and is generally performed under conscious sedation with standard radial or femoral arterial access. Ethanol (96%) is used to perform septal ablation through a standard over the wire balloon. Equipment such as a temporary pacemaker should be available to the operator performing alcohol septal ablation as this procedure is frequently known to result in electrocardiographic abnormalities most frequently right bundle-branch block.[12]

Personnel

Given the complexities involved in the evaluation and treatment of hypertrophic cardiomyopathy, therapies should be performed in tertiary care centers with expertise in the procedure.

Preparation

A transthoracic echocardiogram is used to characterize the variant of hypertrophic cardiomyopathy (concentric, apical, septal, or asymmetric hypertrophy).HCM patients undergoing alcohol septal ablation are selected based on the following criteria:[8]

• Dynamic left ventricular outflow tract obstruction with resting gradients ≥ 30 mm Hg or ≥ 50 mm Hg with provocation in the systolic anterior motion of the mitral valve and septal hypertrophy
• Patients who have severe, drug-refractory, NYHA Class III, or Class IV symptoms
• The septal wall thickness of at least 15 mm
• No significant mitral valve disease
• No indication for the cardiac surgical procedure

Technique or Treatment

Once the association of a dynamic left ventricular outflow tract obstruction with the hypertrophied ventricular segment is made, the severity of the LVOT obstruction is measured by calculation of gradients at rest and with provocation. In patients who do not have significant LVOT obstruction at rest, provocative measures should be performed. Provocative measures include Valsalva, post-PVC accentuation, isoproterenol administration, amyl nitrate inhalation, and exercise.

Accurate measurements of the severity of LVOT obstruction is of considerable significance while evaluating HCM patients, and this is usually adequately obtained using two-dimensional transthoracic echocardiography and doppler imaging; however, further evaluation with cardiac MRI or invasive hemodynamic catheterization may be required. For patients undergoing cardiac catheterization, the most accurate method for the invasive assessment of LVOT obstruction is positioning a balloon-tipped catheter via the transseptal approach at the LV inflow and placing a pigtail catheter in the ascending aorta for simultaneous measurement of the gradient. More commonly, however, a dual lumen catheter is retrogradely inserted into the left ventricular apex from the aorta and simultaneous measurements performed.

During alcohol septal ablation, a conventional guide catheter is used to engage the left coronary artery, and guidewire used to facilitate the entry of an over the wire (OTW) balloon catheter into the targeted septal artery. Occlusion of the targeted septal artery is achieved with inflation of the OTW balloon, and the guidewire is withdrawn. Proper 1:1 balloon sizing is critical to prevent the reflux of ethanol into the distal left anterior descending artery. A left coronary artery angiogram should be performed to evaluate the complete occlusion of the septal artery with balloon inflation. Furthermore, confirmation of the proper septal artery target is performed using a transthoracic echocardiogram to localize the intended area of hypertrophied myocardium to treat while simultaneously injecting an ultrasound contrast agent through the OTW balloon.   

After confirmation, 96% ethanol is infused slowly over 3 to 5 minutes, followed by a saline flush. It is recommended not to exceed 3mL of ethanol during this procedure. The balloon is left inflated for approximately 5 to 10 minutes following the ethanol/saline infusion to reduce the risk of alcohol extravasation. Following this process, repeat left coronary angiography is performed to confirm the ablation of the targeted septal artery and to confirm the patency of the left anterior descending artery and its branches. In patients without hemodynamically significant reductions in either resting or provoked left ventricular outflow tract gradient, an attempt should be made to target other septal arteries.

Alcohol septal ablation has been shown to provide a 55-75% reduction in the LVOT gradient with procedural success rates of 80%. LVOT gradients, resting and provoked, typically continue to show reduction over the next 3-6 months after ablation, which is attributed to basal septal and ventricular remodeling.[13][14][15]

Complications

Patients undergoing cardiac interventions in hypertrophic cardiomyopathy should undergo informed consent before invasive procedures, including those undergoing alcohol septal ablation. Informed consent should include discussion regarding evidence of long-term survival after alcohol septal ablation, the need for dependency on a cardiac pacemaker, success rate based on coronary anatomy, and potential complications related to cardiac catheterization that include:[12][13]

• Coronary dissection
• CVA
• Access site bleeding/bruising
• Contrast related kidney injury

Clinical Significance

In conclusion, several studies have noted significant clinical improvement in patients undergoing septal ablation with documented improvement in patient's objective and subjective parameters, which include the patient's functional class and performance on a treadmill exercise test. Several studies in the literature have also compared overall survival of patients undergoing alcohol septal ablation versus those who undergo surgical myomectomy with follow-up ranging from 3 months to 8 years, and these studies have largely concluded similar survival rates among patients who undergo these procedures.[16][17][18][19]

Enhancing Healthcare Team Outcomes

Educating patients at risk for hypertrophic cardiomyopathy (HCM) related complications and open communication between them and their cardiologist for primary and secondary prevention can further improve the management of affected patients. Collaboration with shared decision making between the patient, primary care physician, and specialists are vital in achieving good outcomes for patients with HCM. The interprofessional care provided to the patient must use an integrated care pathway combined with an evidence-based approach to treating HCM.