Hypertrophic cardiomyopathy with left ventricular apical aneurysm: the newest high-risk phenotype

This editorial refers to ‘Apical hypertrophic cardiomyopathy with left ventricular apical aneurysm: prevalence, cardiac magnetic resonance characteristics, and prognosis’, by K. Yang et al., pp. 1341--1350. Over the last two decades, the application of advanced cardiovascular imaging with cardiovascular magnetic resonance (CMR) has provided the opportunity to reliably identify hypertrophic cardiomyopathy (HCM) patients at increased risk for disease-related complications,1 and along with contemporary cardiovascular treatment strategies has helped transform this genetic heart disease to one now compatible with normal longevity and excellent quality of life.2,3 One important example of this is the relatively recent recognition of a subgroup of HCM patients with left ventricular (LV) apical aneurysm.4 This unusual phenotype is characterized by thin-walled, scarred, and dyskinetic apical rim, associated with diffuse thickening involving the mid-septum and free wall resulting in an ‘hourglass’ configuration with mid-cavity muscular narrowing. Transmural scarring of the aneurysmal rim often extends into the contiguous distal ventricular septum and/or free wall. Apical aneurysm size can vary significantly from small (6 cm).5 Although a number of echocardiographic-based case reports describing apical aneurysm formation in HCM patients were previously noted in the literature,6 it was the emergence of CMR to HCM, with its high spatial resolution and opportunity to characterize all portions of the LV chamber (including the apex) that was directly responsible in 2008 for a much more expanded understanding and appreciation for this unique HCM phenotype.4 As CMR become increasingly part of the routine evaluation of patients at HCM referral centres,1 those with LV apical aneurysm were reliably identified and followed longitudinally to understand the impact of this unique apical morphology on clinical outcome. In the largest contemporary series comprising nearly 100 HCM patients with apical aneurysm, Rowin et al.5 found that about 20% experienced potentially life-saving ICD interventions terminating ventricular tachyarrhythmias. The risk of sudden death events among aneurysm patients was noted to be five-fold greater than in those HCM patients without aneurysms, underscoring the principle that areas of myocardial scarring contiguous with the scarred aneurysm rim at the junction of viable and abnormal tissue represent an arrhythmic focus for recurrent ventricular tachyarrhythmias. In addition, thromboembolic stroke events are increased due to the formation of intracavitary thrombus within the dyskinetic/akinetic aneurysm.5 Yang et al.7 provide further evidence supporting the principle that apical aneurysms represent a high-risk phenotype within the heterogeneous HCM disease spectrum. The authors report outcome on 31 HCM patients with LV apical aneurysm followed for a median follow-up of 26 months for a composite primary outcome of adverse cardiovascular events (i.e. cardiac death, progressive heart failure, Implantable cardioverter-defibrillator (ICD) shock for ventricular tachycardia (VT)/ventricualr fibrillation (VF), stroke, and new-onset atrial fibrillation). Compared with an age- and gender-matched group of HCM patients with apical hypertrophy but no aneurysm, nearly all adverse events occurred in the patients with apical aneurysm. Notably, these data also demonstrate that the increased risk associated with apical aneurysm now extends from what has been primarily a US-based cohort experience, to a geographically and ethnically specific population of HCM patients in China. By virtue of their study design, Yang et al.7 also underscore the important differences between two very distinct apical morphologic variants in HCM (apical aneurysm vs. apical hypertrophy).8 Although both variants can involve some degree of wall thickening confined to the distal portion of the LV chamber, the presence of adverse remodelling with a scarred and thin-walled apex represents a distinctly different morphologic expression associated with unique risk and outcome compared to the largely benign patients with apical HCM (without aneurysm).8 This is a particularly relevant point since some prior studies have lumped both variants of HCM together under a single descriptive term, ‘apical HCM’, creating ambiguity surrounding nomenclature applied in clinical practice to these two markedly different phenotypic HCM subgroups.9,10 What are the clinical implications that we can take away from these data? Based on the significantly increased risk of potentially life-threatening VT and thromboembolic stroke, it is our practice to consider primary prevention ICDs and anticoagulation therapy for nearly all aneurysm patients with the understanding that these discussion often require individualization and a shared decision-making with fully informed patients.2,4,5 Although not specifically addressed by Yang et al.,7 in this report, previous studies have demonstrated that recurrent VT can uniquely be abolished with radiofrequency catheter ablation therapy directed at the arrhythmic nidus at the junction of the aneurysm rim and LV myocardium.11 With the application of these contemporary cardiovascular treatments this high-risk group of HCM patients with apical aneurysm can achieve low HCM mortality similar to that in treated HCM patients without aneurysms.5 It is also important to note that in this report, as well as other studies, no patient has incurred aneurysmal rupture and for this reason there would not appear to be a role for surgical resection specifically to mitigate this issue. It is also important to underscore that magnetic resonance imaging (MRI) and apical aneurysm are not part of the ESC risk calculator and score.12 This reflects an important limitation of the ESC score, reflective of its inherent rigidity and therefore inability to integrate new information (and risk markers) as they emerge. This is not a trivial issue since novel high-risk markers, including LV apical aneurysm, extensive late gadolinium enhancement (LGE), and systolic dysfunction (ejection fraction EF <50%) and all dependent on MRI, together account for a significant proportion (∼25%) of appropriate ICD therapies among HCM patients.13 Indeed, exclusion of apical aneurysm (and MRI), as well as these other risk markers, from the ESC risk score algorithm explains in part its low sensitivity for identifying highrisk HCM patients.13,14 This is in contrast to the enhanced ACC/AHA risk marker strategy, based on its greater flexibility, has been readily capable of incorporating novel markers into risk stratification decision-making.14 Since LV apical aneurysm in HCM may trigger important management considerations for HCM patients, reliably identification is critical. Observations from Yang et al.7 describe certain challenges in this respect. In over 60% of the HCM patients in their series, the diagnosis of apical aneurysm was missed with echocardiography but identified with CMR, particularly when the aneurysm was small. It does not appear that echocardiography contrast for LV opacification was performed, and therefore, we do not know whether this technique would have improved sensitivity for detection of aneurysms although prior studies have suggested this to be the case.4,5 Nevertheless, these data support the principle that CMR should be considered as part of the initial evaluation of nearly all HCM patients. Over the last several decades, insights gained through the advances in multi-modality imaging techniques have substantially changed our perceptions of HCM phenotype natural history and management. One of the best examples of this principle has been the LV apical aneurysms. Advanced CMR imaging has been largely responsible for defining this unusual high-risk HCM disease feature. Indeed, the data from Yang et al.7 help us to fully recognize that HCM patients with apical aneurysm represent a distinct morphologic subgroup in which the scarred aneurysm represents a structural nidus for promoting adverse events, including increased risk for sudden death, and thromboembolic stroke risk and for which contemporary treatment options (e.g. primary prevention ICDs and anticoagulation for stroke prophylaxis) reduce morbidity and mortality with the potential for normal longevity. Conflict of interest: none declared. The opinions expressed in this article are not necessarily those of the Editors of EHJCI, the European Heart Rhythm Association or the European Society of Cardiology.