Left Ventricular Apex Involvement in Hypertrophic Cardiomyopathy.
Case series.
Parato VM, MD*, Olivotto I, MD**, Pandian NG, MD# and Maron MS, MD##
*Chest Pain Unit and Echocardiography, Madonna del Soccorso Hospital, San Benedetto del Tronto and Politecnica delle Marche University, Ancona, Italy**Referral Center for Cardiomyopathies, Careggi University Hospital, Florence, Italy #Heart Valve Clinic, Tufts Medical Center, Boston, USA
##Hypertrophic Cardiomyopathy Center, Tufts Medical Center, Boston, USA
Abstract. Hypertrophic Cardiomyopathy (HCM) is the most frequent inherited heart muscle disease, characterized by extreme clinical and morphological heterogeneity. All segments of the left ventricular (LV) wall may be hypertrophied in HCM, although a basal
anteroseptal localization of hypertrophy is by far the most common pattern. Apical left ventricular (LV) hypertrophy is present in a minority of consecutive HCM patients, and often underestimated by transthoracic echocardiography. Furthermore, the apex may be involved in the HCM disease process by aneurysm formation, often associated with mid-ventricular obstruction. We here present a series of three HCM patients reflecting the spectrum of LV apex involvement and discuss the implications of these uncommon clinical variants.
Key words: hypertrophic cardiomyopathy, left ventricular apex, atherosclerotic epicardial coronary disease
Introduction
Hypertrophic cardiomyopathy (HCM) is a genetically transmitted disease with broad morphologic and clinical spectrum. [1-4]. The most common presentation involves asymmetric basal anteroseptal left ventricular (LV) hypertrophy with outflow tract
obstruction due to systolic anterior motion of the mitral valve. Less common variants are represented by mid-ventricular and apical HCM. These forms are usually defined as “sub-basal HCM” and have been associated with apical aneurysm formation [15]. There is no universal classification of the LV hypertrophy pattern in HCM [11,12]. According to a “four-patterns” model proposed by Helmy [10], four different patterns are identified: pattern 1 is characterized by septal hypertrophy alone; pattern 2 involves the septum and adjacent segments but spares the apex; pattern 3 involves the apex in combination with other LV segments and pattern 4 consists of an apical hypertrophy alone (figure 1). Isolated apical HCM (pattern 4) is a rare variant in the non-Japanese population (1% to 2%). We here present 3 HCM patients in whom the LV apex is variously involved, reflecting atypical localization of hypertrophy or the consequences of the mid-ventricular obstruction, and discuss the clinical implications of these rare variants.
Clinical Cases
Case A. The patient was male, 62 y-o, with negative clinical history. He was diagnosed at our institution following ECG for sport pre-participation screening, and was completely asymptomatic and event-free. The ECG showed T wave inversion and ST-T depression in leads V4-6, D1 and aVL (figure 2,A). TT echocardiography showed apical hypertrophy (maximum thickness: 22 mm) extended to the whole lateral wall (maximum thickness: 21 mm). There was no intra-ventricular obstruction. LV cavity volume was 64 ml/m2 (end-diastolic) and 27 ml/m2 (end-systolic) with LVEF: 58% (figure 2,B-C). CMR (figure 2, D,E) confirmed the apical localization of hypertrophy and identified areas of late gadolinium enhancement (LGE) within the inferior wall which was hypokinetic. Because of this finding, the patient underwent CT coronary angiogram showing a significant lesion of the proximal right coronary artery (RCA) plus non significant lesions of the circumflex and anterior descending left coronary artery. The proximal RCA lesion, confirmed by angiography, was treated by PTCA and stenting . To date, he remains asymptomatic and in good health. Case B. The patient was a male, 63 y-o, who presented to the emergency department (ED) with acute onset of chest pain. He was diagnosed with NSTEMI due to a left
circumflex coronary artery (LCx) culprit lesion and treated by PCI/stenting. The ECG on subsequent controls showed very high voltages and an impressive ST depression plus very deep T waves inversion on the precordial leads (figure 3,A). The echocardiographic picture (figure 3,B-C) was that of an evident apical HCM, with a maximum diastolic
thickness of 21 mm. There was complete apical obliteration in systole, confirmed by CMR (figure 3, D-E). During follow-up, the patient required a further PCI/stenting procedure on a critical stenosis of the LAD coronary artery. After this procedure, patient remained
asymptomatic on antiplatelet agents, beta blockers, RAS inhibitors and statins.
Case C. The patient was female, 60 y-o, with unremarkable past clinical history. She presented to the ED due to chest pain, palpitations and dyspnea. The ECG showed rapidly conducted atrial fibrillation, associated with hypotension (90/60) and mild TnT/hs elevation. Urgent DC shock cardioversion was performed. The ECG after cardioversion (figure 4,A) showed ST elevation in leads V1-5. A TT-echocardiogram showed clear evidence of HCM with a 28 mm systolic muscular apposition of the septum and LV free wall at the mid-ventricle associated with a pressure gradient between the apical and basal chambers (figure 4,B-C). Mid-ventricular gradients were 13 mmHg in diastole and 60 mmHg in systole. An ‘hourglass’ shaped LV with a large apical aneurysm (28x20 mm sized) was evident. There was a clear bulging of the thinned basal septum (video 1). The aneurysm was more clearly detectable by CMR (figure 4, D-E), which also showed transmural late gadolinium enhancement (LGE) due to extensive myocardial scarring at this level. The basal LV cavity was enlarged with concave appearance of the
interventricular septum. The patient underwent ICD implantation for primary prophylaxis and was started on warfarin, amiodarone, beta-blockers and a statin. She remained asymptomatic at .. years follow-up, with no further recurrences of atrial fibrillation.
Discussion
HCM patients with LV apex involvement represent an under-recognized subset in the heterogeneous HCM disease spectrum with important clinical implications. The detection of apical involvement often requires a high index of suspicion, given the low diagnostic accuracy of echocardiography (57%) [14,16]. Cardiovascular Magnetic Resonance is often necessary to confirm the diagnosis, although contrast-enhanced echocardiography is an elegant bedside alternative to assess left ventricular apical segments [3].
There are some special features of HCM with apex involvement. First, when the apex is involved, ECG evidence of LV hypertrophy is virtually always detectable. In Helmy’s study it was present in 100% of patients with patterns 3 and 4 [10]; likewise, in our patients the ECG was distinctively abnormal.
This contains a clear message: in patients with ECG repolarisation abnormalities without an obvious ischaemic cause, routine echocardiography without contrast may not exclude apical HCM. Definitive exclusion of this important diagnosis requires further imaging such as CMR or contrast echocardiography [3]. Our first two patients had also an epicardial coronary disease. We don’t know if this finding could have contributed to determine ECG alterations.
Our first patient can be labelled as having a pattern 3 according to Helmy [10]. These forms are generally judged to have a favourable outlook, without very low risk of
developing obstruction or apical aneurysm. Patients usually are asymptomatic and the diagnosis is made following routine ECG. Indeed, this patient had a critical RCA lesion treated with PTCA/stenting. Our second patient can be labelled as having a pattern 4, which is associated with an elevated risk of apical aneurysm [16]. Of note, the clinical course in this patient was also complicated by epicardial coronary disease, including an acute coronary syndrome due to LCx lesion and subsequent PTCA/stenting on LAD artery because of recurrent angina. These first two patients allow us to focus on coronary artery disease (CAD) in hypertrophic cardiomyopathy.
Myocardial ischemia in the absence of epicardial coronary atherosclerosis is a
well-recognized phenomenon in patients with HCM. Approximately 25% of HCM patients have evidence of ischemia during daily activity [20]. The presence of ischemia has been
associated with a worse prognosis in HCM [21,22]. The mechanisms of ischemia are complex and include distortion of the arteriolar architecture, intramural small-vessel disease, a high prevalence of myocardial bridging, impairment of endothelium-dependent vasodilation, and an imbalance of myocardial oxygen supply and demand due to the hypertrophied myocardium and ventricular loading conditions [22]. There also is evidence that coronary blood flow is maximal or near maximal in most HCM patients (ie, impaired coronary reserve)[23]. As result of ischemia, myocardial fibrosis in HCM is a progressive and fast phenomenon and it can be identified by CMR - late gadolinium enhancement (LGE) detection. We know that LGE increment, related to a worse clinical status, is more extensive in apical hypertrophy than in other patterns (4).
Adult patients with hypertrophic cardiomyopathy (HCM) may develop concomitant atherosclerotic epicardial coronary artery disease. Reports on the prevalence of CAD in HCM have varied, but up to 20% of adult HCM patients have been shown to have
coexistent CAD [19]. Epicardial coronary disease is one of several etiologic mechanisms that contribute to myocardial ischemia in patients with HCM. There is a paucity of data on the clinical outcomes of HCM patients who have CAD [18]. Sorajja’s investigation [18] revealed an adverse prognosis for HCM patients undergoing routine coronary angiography who were found to have severe CAD. Compared with HCM patients without severe CAD, those with severe CAD had a significantly greater risk of death that was evident despite a normal left ventricular ejection fraction.Optimal treatment of these patients with combined disease remains to be determined, as in the quoted study there was no apparent survival benefit for revascularization (PCI or CABG) versus those who were treated medically. The third patient had an apical aneurysm due to mid-ventricular obstruction (type 2 of Helmy’s pattern). This indirect apical involvement includes different and more serious clinical implications [16]. An LV apical aneurysm may be defined as a discrete thin-walled dyskinetic or akinetic segment of the most distal portion of the chamber with a relatively wide communication to the LV cavity. The incidence of concealed apical aneurysm with mid-ventricular cavity obliteration is approximately 1-2% of all HCM cases [16].
The mechanisms responsible for the formation of apical aneurysms in HCM patients remain unresolved while several causes have been hypothesized, such as an increased LV wall stress as a result of mid-cavitary LV obstruction and elevated intracavitary systolic pressures, genetic predisposition and myocardial bridging of the left anterior descending coronary artery. Also the massive hypertrophy of the LV apex alone (Helmy’s pattern 4) could be at risk of aneurism formation probably due to a microvascular myocardial ischemia causing myocardial scarring. In a previous study, 32% of patients with apical aneurysm had distal hypertrophy alone [16].
The formation of apical aneurysm in HCM represents a very serious complication. Often, LV systolic function is depressed and thrombi may develop inside the aneurysm leading to embolic events. Ventricular tachycardia arising from the scarred apical wall may also occur, predisposing to sudden death. High-risk HCM patient subgroups identified with CMR include those with thin-walled scarred LV apical aneurysms (which prior to CMR imaging in HCM remained largely undetected) [14]. We know that echocardiography without contrast has a low accuracy (57%) in detecting LV aneurysm [16].
Specific complications are common in association with large or medium aneurysms: sudden death , LV systolic dysfunction, progressive heart failure symptoms , embolic stroke due to LV apical thrombus formation. Small aneurysms are usually free of
complications. Patients with large apical aneurysm have an high risk of sudden death and they need ICD implantation. Mid-ventricular obstruction may be treated by transaortic myectomy, transapical approach and combined trans-aortic and trans-apical incision. A transapical approach allows an excellent exposure for midventricular myectomy and relief of intraventricular gradients and related symptoms [1]. However, the correct treatment of these forms remains uunresolved.
Conclusions
In patients with ECG or TT-Echocardiography evidence of LV hypertrophy it is very
important to accurately investigate the LV apex. CMR or contrast-enhanced trans-thoracic echocardiography may improve accuracy of LV apex assessment.
In HCM patients LV apex may be involved in different ways. Whereas the apex hypertrophy together with any other segment involment may be a benign condition, massive hypertrophy of the apex alone could be at risk of aneurism formation probably due to a microvascular myocardial ischemia causing myocardial scarring.
Serious prognostic implications may be related to LV apical aneurysm. Its formation is frequent in patients with a mid-ventricular obstruction. Only a correct diagnosis of the apical involvement allows us to plan a correct interventional strategy.
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Figure Legend
Figure 1. The four different patterns (P1 to P4) of HCM as proposed by Sherif M. Helmy (10) Figure 2. Case A. A. Basal ECG. B. TT-echo, 4-Ch view, systolic phase. C. TT-echo, 4-Ch view,
diastolic phase. D. CMR image (L-A). E. CMR image (S-A). F,G. CMR images (4-Ch, diastole)
Figure 3. Case B. A. Basal ECG. B. TT-echo, 4-C view, diastolic phase. C. TT- echo, 4-Ch view,
Figure 4. Case C. A.ECG during atrial fibrillation. B. Basal ECG in sinus rythm. C. TT-echo image,
4-Ch view. D. CW-doppler: midventricular gradient measurement. E,F. CMR images showing the apical aneurysm in diastolic (E) and systolic (F) phase.
FIGURES
Figure 1.
Figure 2.
