Apical Hypertrophic Cardiomyopathy Presenting as Recurrent Unexplained Syncope

Discussion

Apical hypertrophic cardiomyopathy (AHC) is a rare variant of hypertrophic cardiomyopathy first described in Asian patients.1,3 It is more common in Asia, although it is also seen in the Western nations.2 It is predominantly a hereditary disease, although it can also be present in patients with no family history.4–6 In our case the patient was adopted, and no information related to his biological family was available. In the Japanese population AHC accounts for about 13% to 25% of the cases of hypertrophic cardiomyopathy,7 but it is less prevalent in the western population.8 Diagnostic modalities include ECG, ventriculography, nuclear myocardial perfusion studies, and MRI, which is emerging as the preferred modality.8–10

Apical hypertrophic cardiomyopathy can be asymptomatic or present with syncope, chest pain (symptoms similar to those of acute coronary syndromes have been described), palpitations, and dyspnea.11 In western patients there seems to be a varied presentation as far as clinical and ECG features are concerned, compared to the classic AHC as defined in the Asian population.11–13 Given its diverse presentation forms, plain clinical evaluation alone cannot be relied upon. In such situations, understanding the unique ECG features of AHC can be of assistance in the diagnostic process of this uncommon condition.

The presence of ECG findings indicative of left ventricular hypertrophy with giant T-wave inversions (especially in precordial leads) and loss of septal Q-wave should raise strong suspicions of AHC. These are considered pathognomnic for this disorder.1,14 The lack of septal Q-waves is thought to be due to intra-ventricular conduction defects, whereas the giant T-wave inversions are thought to result from the reversal of repolarization order within the distal left ventricular septum and apex. The reason for the loss of Q-waves is thought to be dysfunctional activation of the ventricle, but the exact mechanism is unknown.1 Although giant T-wave inversions in the setting of left ventricular hypertrophy are considered pathognomnic for AHC, it is relevant to have a low threshold to rule out other more frequent causes of ST-T wave abnormalities that can present with syncopal episodes as well, such as coronary heart disease, neurological diseases (eg, subarachnoid hemorrhage), medication effect (eg, digoxin), and conditions with electrolyte derrangements (eg, hypomagnesaemia). Based on the numerous potential differential diagnoses to consider, comprehensive evaluation by cardiac imaging is necessary to confirm the diagnosis of AHC.8–10

Echocardiography has been universally accepted as the first-line imaging modality in investigation of patients with suspected AHC, due to its non-invasiveness, versatility, and well-established cost/benefit ratio. This continues to be true, despite its being an operator-dependent study, as well as the significant variation that might exist between the different exploratory windows.15 Use of contrast-enhanced echocardiography can be an option in an effort to better delineate the anatomy, minimizing the above-described limitations.16,17 A case in point is the better visualization of the left ventricular apical hypertrophy and aneurysm seen in our patient, compared to standard echocardiography, in which the apical aneurysm could not be well appreciated. Cardiac MRI is now emerging as “the gold standard” study in the diagnostic process of AHC given the limitations of echocardiography, the superiority in the assessment of the left ventricular anatomy, and its ability to detect the disease in early stages.8,9,18,19

Although the prevailing consensus is that AHC has a benign prognosis,11–14 there is emerging data showing increased risk for sudden cardiac arrest, fatal arrhythmias, heart failure, and ischemic events in patients with AHC.19–25 A recent study showed a substrate for monomorphic ventricular tachycardia to exist within the hypertrophied muscle component of AHC.24 Management of this condition includes watchful waiting, medical treatment, or invasive interventions such as myomectomy, arrhythmia ablation, and intracardiac cardioverter defibrillator (ICD) placement.24–26

Although there are no randomized controlled trials specifically in AHC populations, the management of each patient relies on the risk stratification as specified in the 2002 ACC/ESC/ HRS practice guidelines for management of hypertrophic cardiomyopathy.27 Risk stratification in the general hypertrophic cardiomyopathy (HCM) population is aimed at identifying individuals who are at high risk for sudden cardiac death (SCD) and would benefit from ICD placement. Factors associated with high risk of SCD among patients with HCM are: recurrent unexplained syncope, ventricular tachyarrhythmias, massive hypertrophy (wall thickness of 30 mm or more), previous cardiac arrest, abnormal blood pressure response on treadmill stress test, high-risk mutant gene, and family history of premature HCM-related sudden death. It is recommended that all patients with HCM undergo an annual risk assessment to evaluate for presence of any of these factors.27 Presence of each of these factors in a patient under the age of 60 years, denotes high risk for SCD and is, hence, an indication for ICD placement. This is consistent with the 2008 ACC/ESC/HRS practice guidelines for device-based therapy of cardiac rhythm abnormalities.27–31 Our patient was 47-years-old and had recurrent, unexplained syncope which placed him at high risk for SCD; for this reason ICD placement was indicated.

In addition to the features mentioned previously, another factor that has an effect on cardiovascular outcome is the presence of apical aneurysm, which our patient had. Patients with AHC and apical aneurysm have been observed to be at higher risk of SCD, embolic stroke, and progressive cardiac failure. Although not actually recognized as an independent risk factor for indication of ICD placement, its presence should be taken into consideration when a decision about ICD placement is being made. There are limited data on whether these patients might also benefit from chronic anticoagulation in order to reduce the risk of embolic phenomena.14,25,32

Beta-adrenergic blocking (BB) agents were among the first drugs used for the treatment of symptomatic HCM (heart failure symptoms, chest pain, and arrhythmias). The real benefit of BB remains debatable, due to lack of large randomized trials. It could even be questionable in the AHC subgroup, especially in absence of any other indication for its use, such as systemic hypertension, cardiac arrhythmias, or coronary heart disease. Until now, use of BB and non-dihydropyridine calcium channel blockers has been, and remains, the initial drug treatment of choice for symptomatic patients, with the aim of alleviating symptoms.29 Potential mechanisms of these benefits include their capacity to reduce heart rate at rest and exercise, negative inotropy, and the reduction on left ventricular wall stress, which consequently reduces myocardial oxygen consumption. Patients’ responses remain variable, and the role of BB in asymptomatic individuals is far from established and is empiric at best. In our case, the presence of angiographically significant coronary artery disease and the concern of possible underlying ventricular tachyarrhythmia justified the use of BB. In such patients there has been demonstrable clinical benefit.27,29

A small group of patients with HCM are considered to be candidates for surgical intervention (myectomy). This includes patients with marked septal hypertrophy and left ventricular outflow tract obstruction, presenting with severe exertional dyspnea, NYHA class III–IV heart failure, and refractoriness to maximum medical therapy. In these types of cases the main goal is to eliminate the portion of ventricular muscle (normally the interventricular septum) that is generating the obstruction. Although some reports are available, very little is known about the utility and benefit of myectomy in patients with the AHC variant.26,27,29 Other non-pharmacological therapies for the treatment of patients with HCM, like dual chamber pacing and ethanol septal ablation, were designed specifically (and only) to be used in the subset of patients where the site and extent of cardiac hypertrophy obstructs the left ventricular outflow. Based on the particular anatomical conditions necessary to implement these therapies, there is no room for their use in patients with the AHC variant where, by definition, no outflow tract obstruction is observed.

In 1895, Willem Einthoven reported the first accurate recording of the ECG and introduced its utility as a clinical tool. Since then the ECG has become a fundamental element in the daily diagnostic process of cardiac diseases. This is a simple study, easy to do, very available, and fairly simple to interpret, with an excellent cost/benefit ratio; in other words, is a very low cost study, and the information that it provides is invaluable. In our case, the diagnosis was almost completely established with only the classical ECG findings that had been previously overlooked. We believe that the consequence of a missed diagnosis for this patient resulted in multiple traumatic events that could have been avoided if the appropriate interpretation of the ECG had been achieved in a timely fashion. This case demonstrates a very infrequent disease in our population, and at the same time underscores the vital emphasis that must be placed on training programs, primary care physicians, and other providers involved in the evaluation and treatment of patients with syncope, in developing appropriate and adequate ECG interpretation skills.