Apical Hypertrophic Cardiomyopathy

Apical hypertrophic cardiomyopathy (AHCM) is an uncommon variant of hypertrophic cardiomyopathy (HCM) for which detectable sarcomere protein gene mutations could be less prevalent in comparison with other forms of HCM.¹ Although initially described in Japan,^2,3 where prevalence is highest,⁴ AHCM has been well documented in other Asian countries and in numerous other ethnic populations worldwide.^5–8 Importantly, sudden cardiac death is less likely to occur in patients with isolated AHCM, and overall cardiovascular morbidity may be less common compared with other HCM phenotypes.^1,5 Nonetheless, available outcomes studies are insufficiently powered for robust conclusions, and certain AHCM patients are at high risk of cardiovascular morbidity. In AHCM, thickened apical segments produce a crowded, “spade-shaped,” small apical cavity. This can be sought or detected incidentally by any of the noninvasive cardiac imaging methods⁹ in a patient with or without chest pain or heart failure symptoms, during the investigation of abnormal inverted precordial T-waves (giant or otherwise¹⁰) as seen on the 12-lead electrocardiogram (ECG) or during familial screening. In a Japanese cohort,¹¹ patients with a “true apical” phenotype (hypertrophy of only the apical segments) had improved survival over a “distal-dominant” phenotype (cases in which hypertrophy extended into the middle LV segments). This morphologic subclassification was recently recognized in North America,¹ whereas other investigators^12,13 have separated AHCM phenotypes into a “pure form” (apical segments only) and a potentially more inclusive “mixed form” (hypertrophy extending into “other” segments), the latter of which carried a worsened prognosis.

Apical hypertrophic cardiomyopathy is often first detected by transthoracic echocardiography when the degree of suspicion is high and proper imaging techniques are employed, including the use of carefully aligned (non-foreshortened) apical images, the use of apical short-axis views or various 3D cut planes; apical color Doppler; high-frequency transducer settings; and the use of intravenous echocardiography contrast agents when the apical endocardium is not clearly identified. Because familiarity and degree of suspicion may be low, AHCM is also frequently missed by echocardiography. It might even be mistaken on a casual echo exam for apical aneurysm when the interpreter's eye is drawn to the more hyperechoic epicardial layer, combined with relatively hypoechoic (dark) thick apical myocardium with an unapparent endocardial border. On the other hand, a small subset of patients with AHCM might actually develop an apical aneurysm that can also be detected, particularly with echocardiography contrast agents.¹⁴ Cardiac MRI studies using delayed gadolinium myocardial enhancement indicative of myocardial fibrosis showed apical subendocardial scar and intramural fibrosis in nonthickened segments in many patients who had minimal symptoms and a pure apical phenotype.¹⁵ Left ventricular apical “outpouchings”⁷ in AHCM are not uncommon and might or might not be related to subendocardial ischemia from pressure overload or other coronary perfusion^6,16,17 and metabolic abnormalities. In some patients, a true apical transmural scar can develop in the absence of epicardial coronary artery disease, which can increase the risk of stroke or ventricular arrhythmia.^18,19

This issue of the Texas Heart Institute Journal includes 3 AHCM cases that exemplify the potential natural history of uncomplicated and complicated AHCM. We hope that the AHCM case presentations herein lead to a greater appreciation for an uncommon (if not entirely rare) condition that might be overlooked. In most cases, the AHCM phenotypic abnormalities are detected without prior baseline data. Interestingly, the case reported by Malik²⁰ demonstrates the typical natural history of ECG, echo, and MRI changes in a young adult (age 18 years) to abnormal phenotype. Adolescence or young adulthood is thought to be the most common time for rapid AHCM development, although similar later-in-life observations have been reported,²¹ which might influence family members' screening decisions.

The case report by Angelini and colleagues¹⁴ uses multimodality imaging for the investigation of AHCM in a highly symptomatic 73-year-old woman with a severe mid-LV cavity gradient, refractory to medical management. The mid-cavity gradient of around 200 mmHg was associated with a highly pressurized (up to 300 mmHg) apical “outpouching” or aneurysm. The authors demonstrated, by spectral Doppler, a previously described^7,22 bifid early systolic and early “paradoxical” diastolic forward flow velocity, consistent with systolic and diastolic aneurysmal emptying. In this case of possible “distal-dominant” or “mixed-form” AHCM, the apical aneurysm's size and the patient's symptoms were ameliorated by subselective coronary angiography and alcohol injection into the small vessels supplying a limited segment of mid-LV obstructive muscle. Alcohol ablation in this situation has not been reported previously and was used in a palliative fashion in this particular refractory patient. Others have reported the use of surgical apical myectomy in similar circumstances, although experience is limited.²³ Alcohol ablation was recently reported to have successfully eliminated incessant monomorphic ventricular tachycardia in a patient with scarred AHCM in whom radiofrequency ablation failed.¹⁸

Finally, Kukreti and colleagues²⁴ describe a case of long-standing typical angina pectoris in a 65-year-old Indian woman who presented with a transient ischemic attack. The associated images show an absence of coronary artery disease with a prominent apical aneurysm consisting of transmural scar with mural thrombus, indicating a late phase of the disease process.

Although AHCM is unquestionably uncommon, its frequency has probably been somewhat underappreciated, as evidenced by an ongoing large number of case submissions to this journal and accelerated publications of larger case series in the world medical literature. The long-term prognosis for some morphologic subgroups of AHCM might be better than for other HCM phenotypes. However, up to 25% of individuals can develop significant late cardiovascular morbid events,^1,25 including heart failure, chest discomfort, apical fibrosis, apical aneurysm formation (with or without intracavitary obstruction), stroke, atrial fibrillation, and ventricular tachycardia. Therefore, periodic lifelong follow-up seems indicated for even initially asymptomatic patients with AHCM. Family screening should be considered.

Multimodality imaging could be increasing the detection rate for AHCM, yielding larger study populations from which to decipher mechanisms for disease and risk stratification for this uncommon and heterogeneous condition. Laboratories should strive to improve accuracy of detection with the use of the additional imaging techniques mentioned above. A consensus regarding the use of AHCM morphologic subtypes might be clinically useful.

Acknowledgment

I am grateful for Dr. A.J. Marian's review of this commentary.