Uncommon cause of a common disease.

Abstract: Myocardial infarction is a common life-threatening condition. Multiple agents can be used to treat acute coronary syndrome (ACS). These therapeutic agents pose potential life-threatening complications when used outside the realm of the acute coronary syndrome. Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder, occurring in 1 in 500 individuals, which may mimic ACS. The hypertrophy most typically involves the septum in patients with HCM. As many as 25% of Japanese patients with HCM have predominately apical involvement. Apical hypertrophic cardiomyopathy (AHC) occurs in only 1 to 2% of the non-Japanese population. Despite its low incidence, physicians caring for patients with chest pain need to consider AHC in their differential diagnosis. We present the case of a patient with chest pain and electrocardiographic changes suggestive of ACS who was later found to have AHC.

Key Words: apical hypertrophic cardiomyopathy, atrial fibrillation, hypertrophic cardiomyopathy, myocardial infarction, ventricular arrhythmias

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Key Points

* Patient presented with symptoms suggestive of acute coronary syndrome.

* HCM is one of the most common inherited cardiac disorders.

* Be aware that apical hypertrophic cardiomyopathy can present with chest pain and electrocardiographic changes suggestive of acute coronary syndrome.

Case Report

A 31-year-old man was admitted to the hospital with complaints of chest pain. The chest pain had been occurring with exercise for 2 months before admission. It radiated down his left arm and was associated with shortness of breath, diaphoresis, and nausea. His chest pain subsided with rest.

On presentation, his vital signs were as follows: temperature, 36.4[degrees]C; respiration rate, 20 breaths/min; pulse, 58 beats/min and regular; and blood pressure, 116/57 mm Hg. No jugular venous distention and no carotid bruits were appreciated. The patient's lungs, heart, abdomen, and neurologic examinations were unremarkable. His laboratory data showed a normal complete blood count and comprehensive metabolic panel. Total cholesterol and low-density lipoprotein cholesterol values were 285 mg/dl and 221 mg/dl, respectively. The patient's high-density lipoprotein level was 32 mg/dl and his triglycerides were 159 mg/dl. Three sets of cardiac isoenzymes were normal. The chest radiograph indicated mild cardiomegaly with no evidence of consolidation or effusion. Electrocardiography revealed a bradycardia and findings suggestive of left ventricular hypertrophy. ST-segment elevation of 1.5 mm was noted in leads III and aVF and 1-mm elevation was present in leads [V.sub.1] and [V.sub.2]. ST-segment depression of 0.5 to 1 mm was noted in leads I, aVL, [V.sub.3], and [V.sub.4]. Large negative T waves were present in the precordial leads (Fig. 1).

[FIGURE 1 OMITTED]

The patient was admitted to the cardiac care unit and treated with enoxaparin, nitroglycerin, aspirin, eptifibatide, and simvastatin. A [beta]-blocker was not initiated due to the patient's initial low heart rate and short asymptomatic sinus pauses. The patient became free of chest pain after treatment.

His echocardiogram showed normal left ventricle chamber diameter at the papillary muscle tips. The apical one-third was obliterated by hypertrophy with a wall thickness approaching 3 cm. The left ventricular total mass was estimated to be greater than 400 g. His ejection fraction was normal. There was no evidence of middle or basal obstructive hypertrophy. Systolic anterior movement of the anterior mitral valve leaflet was not present. The left atrium was enlarged with a diameter of 5.3 cm and an area of 26 [cm.sub.2]. The echocardiographic findings were consistent with AHC, or Yamaguchi syndrome (Figs. 2-4).

[FIGURES 2-4 OMITTED]

An exercise treadmill test was performed to evaluate his functional capacity. It was discontinued after 6 minutes, 59 seconds, because of mild chest pain and shortness of breath. The patient achieved 10 metabolic equivalents of activity, a blood pressure of 217/75 mm Hg, and a heart rate of 143 beats/min. No arrhythmia occurred. Pindolol was started at 5 mg daily, which was increased to twice daily the following day with good clinical response. The patient was discharged on pindolol. Two months after discharge, he remained free of chest pain. His electrocardiogram remained abnormal, with T-wave inversion on the precordial leads and disappearance of the ST-segment abnormalities.

The annual incidence of acute coronary syndrome in the United States is approximately 1 million. (1) Today, physicians rapidly evaluate and treat patients presenting with chest pain. (2) Multiple treatment options are available. Agents of proven benefit such as [beta]-blockers, aspirin, nitrates, angiotensin-converting enzyme inhibitors, and others are coupled with percutaneous coronary intervention, thrombolytics, and aggressive anticoagulation. (3) Although potentially life saving for patients with symptomatic coronary artery disease (CAD), the use of the same interventions could be disastrous in other conditions. Before offering anticoagulation, thrombolysis, or percutaneous coronary intervention for acute coronary syndrome (ACS), one must consider other abnormalities that can mimic symptomatic CAD. Pericardial tamponade, pneumonia, tension pneumothorax, aortic dissection, pulmonary embolism, and esophageal rupture are known to present with chest pain. These entities need to be considered as one goes through the evaluation process for a patient presenting with symptoms consistent with ACS. Hypertrophic cardiomyopathy, a less common disease, can present with chest pain, electrocardiographic (ECG) changes, and potentially abnormally elevated cardiac isoenzymes, mimicking ACS. (4)

Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disorder and the most common cause of cardiac death in children and adolescents. (5) Typically, the hypertrophy in HCM is asymmetric and involves the septum. However, muscular enlargement may occur in almost any area of the heart. (6) As many as 25% of Japanese patients with HCM have predominately apical hypertrophy. Apical hypertrophic cardiomyopathy (AHC), or Yamaguchi syndrome, occurs in only 1 to 2% of the non-Japanese population. (7) Both HCM and AHC can present initially with symptoms similar to ACS. The physician caring for patients with chest pain needs to be aware of this disorder and the fact that it is not limited to the Japanese population. (8)

Discussion

HCM is one of the most common inherited cardiac disorders. In addition to the common asymmetric septal hypertrophy with obstructive features, two other forms have been described. The first form is AHC, which was originally described in Japanese patients, in whom it constitutes up to 25% of cases of HCM. This condition occurs in less than 3% of patients in other parts of the world. (7) The other form of HCM involves midcavity obstruction.

AHC is often clinically benign with no demonstrable genetic transmission. (9) Overall survival at 15 years after diagnosis is 95%. (10,11) Individuals with AHC can present with angina, dyspnea, and ECG changes suggestive of ischemia. In a retrospective study of 105 patients treated during a 25-year period, the most common cardiac problems to occur were atrial fibrillation (12% of patients) and myocardial infarction (10% of patients). (11) In rare cases, ventricular tachycardia or ventricular fibrillation may complicate the course of this disease. (12) Age younger than 41 years, left atrial enlargement, and New York Heart Association functional Class II or higher increase the risk for symptomatic AHC. (11) An unusual complication seen in AHC is the formation of apical aneurysms, which seem to be associated with ventricular arrhythmias and ST-segment changes. (10,13)

In patients with AHC, the electrocardiogram frequently has large negative T waves in the midprecordial leads that may "wax and wane" with time. (14) Transition from normal T waves to negative T waves can occur acutely or can take several years. Our patient presented with T-wave and ST-segment abnormalities. Although his ST-segment findings could support an infarct in the distribution of a large right coronary artery that wraps around the left ventricular apex, the concave upward ST segments are atypical of an infarct. [V.sub.5] and [V.sub.6] would have been the leads with greater ST-segment elevation than in [V.sub.1] and [V.sub.2]. However, proximal right carotid artery occlusion can cause ST-segment elevation in [V.sub.1].

AHC can be visualized by echocardiography that can be enhanced with the use of contrast agents. (15) Magnetic resonance imaging can also be used. (16) On two-dimensional echocardiography, the ventricle usually shows a symmetric apical hypertrophy, and the left ventricular chamber has a spadelike appearance. (17) This can be seen on left ventriculograms during cardiac catheterization. (4,17) Although patients with AHC may present with myocardial infarction, the coronary arteries are generally normal on angiographic scans, despite stress nuclear imaging showing perfusion defects. (18) A variety of mechanisms may contribute to the production of angina pectoris, including the imbalance between oxygen supply and demand as a consequence of the increased myocardial mass in the setting of normal coronary arteries. (1)

AHC is often a benign disease compared with obstructive hypertrophic cardiomyopathy. Generally, no treatment is needed. In patients with chest pain or high blood pressure, [beta]-blockers, verapamil, and disopyramide have been used. (9) Losartan can be used and is expected to reduce the hypertrophy. Amiodarone can be used in patients with ventricular and supraventricular arrhythmias. (19) In rare cases of serious ventricular arrhythmias, automatic implantable cardiac defibrillator placement may be necessary. (12,20)

Physicians should be mindful of this uncommon entity when dealing with a young patient. Chest pain typical of ACS, ECG abnormalities, and multiple cardiac risk factors in a young patient still has a greater likelihood of being an uncommon disease, certainly more so than in an elderly patient where multiple risk factors and typical presentations have a relatively high pretest probability of CAD.

References

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(14.) Yamanari H, Saito D, Mikio K, et al. Apical hypertrophy associated with rapid T wave inversion on the electrocardiogram. Heart Vessels 1995; 10:221-224.

(15.) Soman P, Swinburn J, Callister M, et al. Apical hypertrophic cardiomyopathy: Bedside diagnosis by intravenous contrast echocardiography. J Am Soc Echocardiogr 2001;14:311-313.

(16.) Ibrahim T, Schwaiger M. Diagnosis of apical hypertrophic cardiomyopathy using magnetic resonance imaging. Heart 2000;83(1):el.

(17.) Keren G, Belhassen B, Sherez J, et al. Apical hypertrophic cardiomyopathy: Evaluation by noninvasive and invasive techniques in 23 patients. Circulation 1985;71:45-56.

(18.) Abinader EG, Sharif D, Shefer A, et al. Novel insights into the natural history of apical hypertrophic cardiomyopathy during long-term follow-up. Isr Med Assoc J 2002;4:166-169.

(19.) Gavaliatsis IP, Kouvousis NM, Rallidis LS, et al. Recurrent atrial flutter in apical hypertrophic cardiomyopathy. Jpn Heart J 1992;33:499-504.

(20.) Dohlemann C, Hebe J, Meitinger T, et al. Apical hypertrophic cardiomyopathy due to a de novo mutation Arg719Trp of the [beta]-myosin heavy chain gene and cardiac arrest in childhood: A case report and family study. Z Kardiol 2000;89:612-619.

From the Veterans Affairs Medical Center, Mountain Home, TN, and the Division of Cardiology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN.

We have no commercial or proprietary interest in any drug, device, or equipment mentioned in this article.

Reprint requests to Said B. Iskandar, MD, 1616 Seminole Drive, Apt. 216, Johnson City, TN 37604. Email: [e-mail]

Accepted April 23, 2003.