Hypertrophic Cardiomyopathy in a Young Adult with RV Aneurysm: Report of a Rare Finding and Review of the Literature.

We report a case of a 22-year-old patient with a severe form of hypertrophic cardiomyopathy involving both ventricles, for which he underwent surgical treatment. Echocardiogram and magnetic resonance imaging confirmed the presence of an aneurysm in the inferior-anterior portion of the right ventricle.

INTRODUCTION

Hypertrophic cardiomyopathy (HCM) is a well-described but difficult to define disease. HCM is a collection of similar genetic diseases that can result from one or more sarcomere mutations in a single patient. Common accelerants of ventricular hypertrophy include obesity, sleep apnea, diabetes, hypertension and aortic stenosis. Right ventricular (RV) aneurysms are very rare to occur, and we believe that they have never been reported before in association with HCM.

CASE REPORT

A 22-year-old male patient presented with a severe form of HCM involving both the ventricles. He had a history of right and left ventricular outflow tract obstruction which had required surgical intervention in the form of bilateral myectomy that was performed at the Mayo Clinic in 2004.

The patient's symptoms started at 1½ years of age at which time he presented with tachycardia and hypertrophy and was diagnosed with HCM. At 8 years of age, the patient's tachycardia necessitated intervention at which time the patient underwent a successful ablation for ectopic atrial tachycardia at Boston Children's Hospital.

At 15 years of age, the condition progressed requiring surgical intervention. At Mayo Clinic, he underwent extended septal wall myomectomy that involved surgical excision of tissue from both right and left ventricles. The result was a dramatic improvement in symptoms.

Maintenance drug is Tenormin (50 mg in the morning and 25 mg at night). The family has been against the placement of an implantable cardioverter-defibrillator (ICD), and at 22 years of age, additional testing was performed to help with risk stratification. The Holter revealed ventricular ectopy but no runs of ventricular tachycardia. His stress test confirmed the presence of an abnormal fall in BP with exercise. Magnetic resonance imaging (MRI) demonstrated an RV aneurysm with no obvious thrombus [Figures 1 and 2].

Figure 1

Inferior view of a transverse section of a MRI (Magnetic resonance imaging) showing the right ventricle (RV) and the aneurysm

Figure 2

Inferior view of a transverse section of an Magnetic resonance imaging (MRI) showing the right ventricle (RV) during contraction and the hypokinetic aneurysm

On examination, the precordium was quiet with a normal S1 and S2. There was a 2–3/6 systolic ejection murmur present at the base with radiation to the back, head and neck.

The electrocardiogram showed voltage criteria for biventricular hypertrophy.

The echocardiogram confirmed the presence of a significant dilatation of inferior-anterior portion of the right ventricle. The aneurysm was well visualized with no obvious clot formation. There was mid-cavity obliteration in systole in the right ventricle. There was no significant left ventricular outflow tract (LVOT) obstruction. The sites of the previous myectomy were well visualized. There was minor mitral and tricuspid valve insufficiency.

DISCUSSION

Review of literature

Background

HCM is a well-described but difficult to define disease. HCM is a collection of similar genetic diseases that can result from one or more sarcomere mutations in a single patient. This is complicated by variable phenotypic expression from identified and yet to be discovered variants. Other causes of LV hypertrophy can confuse the diagnosis. Common accelerants of ventricular hypertrophy include obesity, sleep apnea, diabetes, hypertension and aortic stenosis. The diagnosis can be strengthened by confirmation of a known mutation on genetic testing. The characteristic findings on echocardiography include ventricular hypertrophy, symmetric or asymmetric (ratio of septum thickness to LV wall thickness, >1.3:1), presence of a narrow LVOT with a pressure gradient suggestive of obstruction, systolic anterior motion (SAM) of mitral valve or the chordae. 70% of patients with HCM have LVOT obstruction either at rest or with exercise. When outflow tract obstruction is present, then the patient is described as having hypertrophic obstructive cardiomyopathy.

MRI plays an important diagnostic role in visualizing areas of myocardium that are inadequately evaluated by ultrasound.[1]

HCM is inherited as autosomal dominant with variable penetrance and is caused by mutations in 11 genes encoding proteins of the cardiac sarcomere (13-15). These 11 genes are: beta-myosin heavy chain, cardiac myosin-binding protein C, cardiac troponin-T, troponin I, alpha-tropomyosin, myozenin 2 (calsarcin 1), myosin light chain, myosin light chain 2, alpha-actin, titin, and telethonin. There are other genes that are thought to have an association with HCM and are as follows: myosin light chain kinase 2, alpha-myocin heavy chain, cardiac troponin C, caveolin 3 and phopholamban.[2]

Although the LV is the predominant site of involvement, RV involvement may occur in apparent isolation or in association with left-sided involvement.[3] Younger people are likely to have a more severe form of HCM.[4] Most cases are familial conditions that are genetically transmitted, but the disease can also be a spontaneous mutation.

Acquired cardiomyopathy

The most common cause for acquired cardiomyopathy is myocarditis due to viral infections. Other causes include: cocaine, interleukin 2 or viral infections (coxsackievirus, adenovirus, parvovirus, HIV), bacterial (diphtheria, meningococcus, psittacosis, streptococcus), rickettsial (typhus, Rocky Mountain spotted fever), fungal (aspergillosis, candidiasis), and parasitic (chagas disease, toxoplasmosis) and giant cell myocarditis.[5]

Secondary cardiomyopathy

The causes of secondary cardiomyopathy include, but are not limited to, amyloidosis, Gaucher's disease; hemochromatosis, Fabry's; endomyocardial fibrosis and hypereosinophilic syndrome; sarcoidosis, Diabetes Mellitus; Noonan syndrome; Friedreich's ataxia and Duchenne–Becker muscular dystrophy; pellagra; systemic lupus erythematosis and scleroderma; doxorubicin and radiation.[5]

Thickening of the myocardium occurs most commonly at the inter-ventricular septum. The thickened septum may cause a narrowing that can block or reduce the blood flow from the LV to the aorta, a condition called “outflow tract obstruction” often mimicking aortic stenosis. This type of HCM may be called hypertrophic obstructive cardiomyopathy.

Natural history

HCM is the most common genetic heart disease, the leading cause of sudden cardiac death in the young, and a cause of heart failure symptoms and death at any age.[6-12]

HCM can be considered obstructive or non obstructive, depending on the presence of LVOT gradient, either at rest or with provocative maneuvers.[13] Younger patients often have more diffuse hypertrophy and reversal of septal curvature, whereas older patients tend to have focal proximal septal hypertrophy, with a sigmoid septal morphology.[614-17] These may be two different disease processes because subjects with reversal of septal curvature were found to have an almost 80% yield for screening for HCM-associated mutations but those with a sigmoid septum had less than a 10% correlation. Hypertrophy often develops or worsens during the adolescent growth spurt. An apical variant of HCM also exists.

LV hypertrophy usually involves thickening of the proximal portion of the interventricular septum, resulting in narrowing of the LVOT.

SAM may occur if the mitral valve leaflets are pulled or dragged anteriorly toward the ventricular septum during ventricular contraction due to Bernoulli Effect.[18-21] SAM results in LVOT obstruction and mitral regurgitation. Consequently, the left ventricle has to generate higher pressures to overcome the LVOT obstruction. Premature closure of the aortic valve may occur, caused by the decline in pressure distal to the LVOT obstruction.[31122]

The obstruction that occurs with HCM is dynamic, therefore the degree of obstruction depends more on cardiac contractility and loading conditions than on fixed obstructions. An underfilled left ventricle results in greater obstruction because there is less space between the mitral valve and interventricular septum. Augmenting cardiac contractility also increases LVOT obstruction because a more vigorous contraction is more likely to cause the obstructing components to come together. Most patients with HCM have a favorable prognosis.[31123-25]

HCM has a variable course in which most patients are asymptomatic. The most common symptom is dyspnea on exertion; others include chest pain on exertion, syncope and palpitations.

Diagnosis and treatment

Diagnosis

Chest radiograph may suggest LV hypertrophy.

Electrocardiogram could show LV hypertrophy.[26]

Echocardiography is the gold standard for diagnosing HCM.[311]

Transthoracic echocardiogram: The septum can be well visualized and measured in the parasternal long, apical long, apical four-chamber, and parasternal short axis views.[27-29]

Stress echocardiography is performed in patients with HCM to assess the functional significance of LVOT obstruction.

Transesophageal echocardiography can be conducted in subjects with technically limited imaging or as part of intraoperative monitoring during surgical intervention.

MRI plays an important diagnostic role in its ability to visualize areas of myocardium that are inadequately evaluated by ultrasound.

Lifestyle modifications

HCM subjects should avoid strenuous activity because it will increase the afterload to the myocardium and can worsen hypertrophy,[30] and maintain adequate hydration.

Medical therapy

Beta blockers are the first-line therapy for symptomatic HCM. Beta blockers decrease the contractile force which leads to decrease in the outflow gradient and decreased oxygen demand. Beta blockers also lengthen diastolic filling by slowing the heart rate.[2631-36]

Calcium channel blockers are second-line therapy because of their negative inotropic effect.[37-42]

The second-line agents are the Class IA antiarrhythmic agents that have negative inotropic effects.[43-46]

Surgical interventions and procedures

Septal myectomy decreases LVOT gradients and improves the symptoms.[47-56]

Percutaneous alcohol septal ablation consideration is always second line because of formation of scar tissue in the myocardium.

CONCLUSIONS

RV aneurysms associated with HCM is a rare condition. The possible cause would be the pathologic process that causes myocyte disarray in HCM, increasing the thickness of the ventricular wall and also leading to local ventricular atrophy.[57] Regardless of the etiology, the treatment strategies remain the same.

Radionuclide imaging with analysis of viability utilizing Fluorine-18–Labeled Deoxyglucose Positron Emission Tomography (18F-FDG-PET) could provide additional information on the pathogenesis of RV aneurysm. Patients with RV aneurysms and HCM are at increased risk for life-threatening ventricular tachyarrhythmia and sudden death,[58] in which management strategies should be directed toward prevention of these risks.